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Daratumumab SC Ver1

Description: Chemotherapy Protocol Myeloma Daratumumab Subcutaneous Regimen • Myeloma – Daratumumab (SC) Indication • Daratumumab monotherapy is recommended as an option for treating relapsed and
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VR-RituximabVenetoclaxCycle_1_VenetoclaxDoseTitration

Description: Chemotherapy Protocol Chronic Lymphocytic Leukaemia VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration Regimen • CLL – VR Rituximab Venetoclax (high risk) Cycle 1 – Venetoclax dose titration Indication • Venetoclax with rituximab is indicated for the treatment of adult patients with previously treated chronic lymphocytic leukaemia (CLL) who have had at least one previous therapy. • This protocol is to be used for dose titration of venetoclax to 400mg daily. Once this dose is reached rituximab can be added using protocol for cycle 2 onwards. Toxicity Drug Adverse Effect Rituximab See cycle 2 protocol Upper respiratory tract infection, neutropenia, anaemia, Venetoclax hyperphosphataemia, electrolyte disturbances, tumour lysis syndrome (TLS), gastrointestinal disturbance, raised blood creatinine, fatigue. The adverse effects listed are not exhaustive. Please refer to the relevant summary of product characteristics for further details. Monitoring Drugs • FBC, U&Es and LFTs on cycle one day 1, 2, 8, 9, 15, 16, 22, 23, 29 and 30 (to include phosphate, calcium and LDH). These parameters must be checked prior to any dose increase. • FBC, U&Es (including potassium, phosphate, LDH, adjusted calcium and uric acid) and LFTs should be measured prior to starting therapy and pre-existing electrolyte abnormalities corrected. For patients at risk of tumour lysis syndrome (TLS), potassium, uric acid, phosphate, adjusted calcium, LDH and creatinine should be monitored at 6 to 8 hours and at 24 hours after the first dose and during each dose increase of venetoclax. Electrolyte abnormalities should be corrected promptly. The next venetoclax dose should not be administered until the 24-hour blood chemistry results have been evaluated (see section on TLS below). Consider admitting the patient for monitoring for TLS monitoring and treatment. • Tumour burden assessment, including radiographic evaluation (e.g. CT scan) must be performed for all patients prior to starting venetoclax therapy. • Viral screening is required before starting treatment including Hepatitis B surface antigen, core antibody and HIV status. Version 1(December 2019) Page 1 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration Dose Modifications The dose modifications listed are for haematological, liver and renal function and drug specific toxicities only. Dose adjustments may be necessary for other toxicities as well. Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. Haematological Consider blood transfusion or the use of erythropoietin according to NICE TA323 if patient symptomatic of anaemia or has haemoglobin of less than 8g/dL (80g/L). Treatment with venetoclax should be withheld for grade 3 or 4 febrile neutropenia (neutrophils less than 1x109/l) and/or infection, or other grade 4 haematological toxicities (neutrophils less than 0.5x109/l or platelets less than 25x109/l), except lymphopenia. Once the toxicity has resolved to grade 1 or baseline level (recovery), therapy with venetoclax may be restarted at the same dose. If the toxicity recurs, the dose reduction guidelines in Table 2 should be followed when resuming treatment with venetoclax following recovery. A larger dose reduction may occur at the discretion of the physician. Discontinuation of venetoclax should be considered in patients who require dose reductions to less than 100 mg for more than 2 weeks Hepatic Impairment No dose adjustments are required for either rituximab or venetoclax in patients with mild or moderate hepatic impairment. These patients should be monitored more closely for signs of toxicity at initiation and during the dose-titration phase of venetoclax as a trend for increased adverse events was observed in patients with moderate hepatic impairment in a population pharmacokinetic analysis. It is not recommended to administer venetoclax to patients with severe hepatic impairment as safety in this patient group has not been established. A dose reduction of at least 50% throughout treatment is recommended for patients with severe hepatic impairment (Child Pugh C or bilirubin more than 3xULN). These patients should be monitored more closely for signs of toxicity. Renal Impairment No dose adjustments are required for either rituximab or venetoclax for patients with mild or moderate renal impairment. However, patients with reduced renal function (CrCl less than 80 ml/min) may require more intensive prophylaxis and monitoring to reduce the risk of tumour lysis syndrome at initiation and during the dose-titration phase. Safety in patients with severe renal impairment or on dialysis has not been established, and a recommended dose for these patients has not been determined. Venetoclax should be administered to patients with severe renal impairment (creatinine clearance less than 30ml/min) only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS. Version 1(December 2019) Page 2 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration Other Venetoclax Tumour Lysis Syndrome (TLS) Venetoclax can cause a rapid reduction in tumour, and thus poses a risk for tumour lysis syndrome in the initial 5-week dose-titration phase. Changes in electrolytes consistent with tumour lysis syndrome that require prompt management can occur as early as 6 to 8 hours following the first dose of venetoclax and at each dose increase. It is strongly recommended to admit the patient for monitoring if at risk of TLS. The risk of tumour lysis syndrome is a continuum based on multiple factors, including comorbidities. Patients with high tumour burden (e.g., any lymph node with a diameter greater than or equal to 5cm or high absolute lymphocyte count greater than or equal to 25x109/L) are at greater risk of tumour lysis syndrome when initiating venetoclax and should be treated as high risk. Reduced renal function (creatinine clearance less than 80ml/min) further increases the risk. The risk may decrease as tumour burden decreases with venetoclax treatment. Drug interactions may also contribute. Always check for drug interactions. Concomitant use of venetoclax with strong CYP3A inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, ritonavir) at initiation and during the dose-titration phase is contraindicated due to increased risk for TLS. At initiation and during the dose-titration phase, concomitant use of venetoclax with moderate CYP3A inhibitors (e.g., ciprofloxacin, diltiazem, erythromycin, fluconazole, verapamil) should be avoided. Alternative treatments should be considered. If a moderate CYP3A inhibitor must be used, the initiation dose of venetoclax and the doses for the titration phase should be reduced by at least 50%. Patients should be monitored more closely for signs and symptoms of TLS. Prior to initiating venetoclax, tumour burden assessment, including radiographic evaluation (e.g. CT scan), must be performed for all patients. Blood chemistry (potassium, uric acid, phosphate, adjusted calcium, LDH and creatinine) should be assessed and pre-existing abnormalities corrected. The prophylaxis measures listed below should be followed. Patients should be adequately hydrated during the dose-titration phase. Patients should be instructed to drink plenty of water daily starting 2 days before and throughout the dosetitration phase. Patients should be particularly instructed to drink 1.5 to 2L of water daily, 2 days prior to and the days of dosing at initiation and each subsequent dose increase. Intravenous fluids should be administered as indicated based on overall risk of tumour lysis syndrome or for those who cannot maintain an adequate level of oral hydration. For high risk patients the anti-hyperuricemic plan is rasburicase 7.5mg used prophylactically at initiation and for the first dose increase then start allopurinol before the third dose increase and continue until dose titration is complete. For low risk patients use separate protocol – initiate allopurinol two days before starting venetoclax and continue until dose titration is complete. Table 1 - Tumour Lysis Syndrome (TLS) Management Venetoclax Abnormality Dose Modification and Management Hyperkalaemia Potassium more than or equal to 0.5mmol/l Hold venetoclax until resolution increase from prior value (and within upper Recheck calcium, creatinine, phosphate, Version 1(December 2019) Page 3 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration Abnormality Dose Modification and Management limit of normal (ULN)) potassium and uric acid in 1hour. If further 0.2mmol/l or more rise in potassium do an ECG and consider calcium gluconate and calcium resonium in line with local hyperkalaemia policy. Continue to monitor for TLS every 2 hours Resume protocol testing if change in potassium is less than 0.2mmol/l and no other evidence of TLS resume venetoclax. Potasssium more than ULN but less than Hold venetoclax until resolution 6.0mmol/l Do an ECG and consider calcium gluconate and calcium resonium in line with local hyperkalaemia policy. Recheck calcium, creatinine, phosphate, potassium and uric acid in 1 hour. If potassium less than ULN continue to monitor for TLS 2 and 4 hours later Potassium more than or equal to 6.0mmol/l Hold venetoclax until resolution and/or symptomatic (e.g. muscle cramps, Refer to local hyperkalaemia guideline and weakness, paraesthesia, nausea, vomiting or seek advice from renal team. diarrhoea) Recheck calcium, creatinine, phosphate, potassium and uric acid every hour Hyperuricaemia Uric acid more than or equal to Hold venetoclax until resolution. 476micromol/l Consider giving rasburicase if not given in last 24 hours. Hypocalcaemia Adjusted calcium less than 1.75mmol/l or Hold venetoclax until resolution. patient symptomatic (e.g. muscle cramps, Administer calcium gluconate 10% 10 to hypotension, tetany, cardiac arrhythmias) in 20ml in 100ml sodium chloride 0.9% over the presence of hypocalcaemia. 15minutes with ECG monitoring. Recheck calcium, creatinine, phosphate, potassium and uric acid every one to two hours. Hyperphosphataemia Phosphate more than 1.45mmol/l and less Withold venetoclax until resolution than 1.67mmol/l Does not require treatment. Recheck calcium, creatinine, phosphate, potassium and uric acid in 1 hour. Phosphate 1.67 to 2.1mmol/L Withold venetoclax until resolution to less than 1.45mmol/l Discuss with renal team as a phosphate binder may be necessary (e.g. calcium carbonate, sevelamer, lanthanum) Recheck calcium, creatinine, phosphate, potassium and uric acid in 1 hour. Phosphate more than 2.1mmol/l Withold venetoclax until resolution to less than 1.45mmol/l Discuss with renal team as a phosphate binder or haemodialysis may be required. Recheck calcium, creatinine, phosphate, potassium and uric acid in 1 hour. Version 1(December 2019) Page 4 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration Abnormality Dose Modification and Management Creatinine Increase of more than or equal to 25% from Hold venetoclax until resolution baseline. Administer intravenous fluids. Recheck potassium, phosphate, uric acid, calcium and creatinine in 1 to 2 hours LDH Increase of more than 50% from baseline Hold venetoclax until level is back to baseline (check level weekly). Restart at previous dose level. If occurred on first dose restart at 10mg daily. If biochemical changes suggestive of tumour lysis syndrome occur, the next venetoclax dose should be withheld and remainder of the rasburicase treatment dose 0.2mg/kg/day (less 7.5mg prophylactic dose) should be given. Blood electrolytes (potassium, phosphate, uric acid, calcium and creatinine) should be carefully monitored and responded to every 2 hours to assess TLS response or progression until patient stable. If the changes resolve within 24 to 48 hours of the last dose, treatment with venetoclax can be resumed at the same dose. If clinical tumour lysis syndrome or biochemistry changes occur, that require more than 48 hours to resolve, treatment should be resumed at a reduced dose (see table below). When resuming treatment with venetoclax after interruption due to tumour lysis syndrome, the instructions for prevention of tumour lysis syndrome should be followed. Table 2 – Venetoclax dose modifications if resolution of TLS sign takes more than 48hours Dose modification for TLS and other toxicities during venetoclax treatment Dose at interruption (mg) Restart dose (mga) 400 300 300 200 200 100 100 50 50 20 20 10 aThe modified dose should be continued for 1 week before increasing the dose. Version 1(December 2019) Page 5 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration Regimen Cycle 1 (35 day cycle venetoclax dose titration). 1 cycle will be set in ARIA. For cycle 2 see VR-Rituximab-Venetoclax cycle 2 onwards protocol. This cycle will be set up on ARIA in 7 day blocks that can be prescribed independently Drug Dose 20mg* Days 1, 2, 3, 4, 5, 6, 7 Administration Venetoclax 50mg* 8, 9, 10, 11, 12, 13, 14 100mg* 15, 16, 17, 18, 19, 20, 21 Oral 200mg* 22, 23, 24, 25, 26, 27, 28 400mg* 29, 30, 31, 32, 33, 34, 35 *Day 1, 8, 15, 22 and 29 will be dispensed as a separate supply to allow evaluation for TLS on day 2, 9, 16, 23 and 30 Version 1(December 2019) Page 6 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration Dose Information • Venetoclax is available as 10mg, 50mg and 100mg film-coated tablets. • For patients who have had a dosing interruption lasting more than 1 week during the first 5 weeks of dose titration or more than 2 weeks when at the daily dose of 400mg, tumour lysis syndrome risk should be reassessed to determine if restarting at a reduced dose is necessary. Administration Information • Venetoclax film-coated tablets are for oral use. Patients should be instructed to swallow the tablets whole with a meal and water at approximately the same time each day. The tablets should not be chewed, crushed, or broken before swallowing. • During the dose-titration phase, venetoclax should be taken in the morning to facilitate laboratory monitoring. • It is imperative that the time of administration of the venetoclax is recorded on ARIA and the correct blood tests are taken at the correct time as part of any increase in the dose. • If a patient misses a dose of venetoclax within 8 hours of the time it is usually taken, the patient should take the missed dose as soon as possible on the same day. If a patient misses a dose by more than 8 hours, the patient should not take the missed dose and should resume the usual dosing schedule the following day. Additional Therapy • Antiemetics As take home medication - metoclopramide 10mg three times a day when required oral • Anti-infective prophylaxis including: - aciclovir 400mg twice a day oral - consider co-trimoxazole 960mg once a day oral on Monday, Wednesday and Friday only • Allopurinol 300mg once a day oral for 28 days oral starting on day 12 of cycle 1 to continue for 28 days. • Calcium carbonate 1.5g or 1.25g (in line with local protocol) three times a day for 28 days oral starting on day 1 of cycle 1 only. Used as a phosphate binder to reduce the risk of dose delay due to hyperphosphataemia during the initial titration phase. Dose should be taken with food. Version 1(December 2019) Page 7 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration • Rasburicase 7.5mg intravenous infusion in 50ml sodium chloride 0.9% over 30 minutes on cycle 1 days 1, 2, 8 and 9. • Patients should be adequately hydrated during the dose-titration phase to reduce the risk of TLS. Patients should be instructed to drink plenty of water daily starting 2 days before and throughout the dose-titration phase. Patients should be particularly instructed to drink 1.5 to 2L of water daily, 2 days prior to and the days of dosing at initiation and each subsequent dose increase. Additional intravenous fluids should be administered as indicated based on overall risk of TLS or for those who cannot maintain an adequate level of oral hydration. • Sodium chloride 0.9% 1000ml over 4 hours to starting at least one hour prior to the administration of venetoclax on cycle 1 days 1 and 8. Advise patient to drink an additional litre of water during the day. • Sodium chloride 0.9% 500ml over 2 hours starting at least one hour before administration of venetoclax on cycle 1 days 2 and 9. • Gastric protection with a proton pump inhibitor or a H2 antagonist may be considered in patients considered at high risk of GI ulceration or bleed. • Rituximab pre-medication - See cycle 2 onwards which includes rituximab element. Additional Information • The National Patient Safety Alert on oral chemotherapy (NPSA/2008/RRR001) must be followed in relation to venetoclax. • It must be made clear to all staff, including those in the community, that venetoclax must only be prescribed under the supervision of a consultant haematologist. • Venetoclax interacts with many other medications. Always check for drug interactions. • Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with venetoclax. Coding • Procurement – X71.5 (cycles 1 and 8 to 27); X70.8 (cycles 2 to 7) • Delivery – X71.3 (cycles 1 and 8 to 27); X72.9 (cycles 2 to 7) References 1.Abbvie Limited (2016) Venetoclax film-coated tablets Summary of Product Characteristics. Online at http://www.medicines.org.uk/emc/medicine/32650, accessed 29 October 2019. 2. NICE guidance TA561 Venetoclax with rituximab for previously treated chronic lymphocytic leukaemia. 4. Wessex Blood and Marrow Transplant Tumour Lysis Prevention and Management Policy (Adults) version 1.0 Version 1(December 2019) Page 8 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration REGIMEN SUMMARY Cycle 1 VR-Rituximab-Venetoclax (high risk) Day 1 1. Warning – Check in-patient administration Administration Instructions If the patient has been admitted for monitoring please check what was prescribed and administered either on the inpatient electronic or / and paper system and adjust this prescription accordingly. This prescription is designed for out-patient use and may not be used for an in-patient. 2. Rasburicase 7.5mg intravenous infusion in 50ml sodium chloride 0.9% over 30 minutes Administration Instruction Administer after baseline blood sample has been taken 3. Sodium chloride 0.9% 1000ml intravenous infusion over 240 minutes Administration Instruction Advise patient to drink an additional litre of water during the day. Patients should be adequately hydrated during the dose-titration phase to reduce the risk of TLS. Patients should be instructed to drink plenty of water daily starting 2 days before and throughout the dose-titration phase. Patients should be particularly instructed to drink 1.5 to 2L of water daily, 2 days prior to and the days of dosing at initiation and each subsequent dose increase. Intravenous fluids should be administered as indicated based on overall risk of TLS or for those who cannot maintain an adequate level of oral hydration 4. Warning – Administer venetoclax Administration Instructions Administer venetoclax as per the dosage in the take home medicines, please record the time of administration by administering this warning in ARIA. This is to facilitate the diagnosis of TLS from the blood results. Administer the venetoclax at least one hour after the start of the sodium chloride 0.9% infusion. Ensure all the correct blood tests have been taken at the correct time. Take with or after food. Take with a full glass of water. Oral chemotherapy. Take Home Medicines (day 1) 5. Venetoclax 20mg once a day for 1 day oral Administration Information Administer 20mg once a day on day 1 only, please record the time of administration by administering the “warning – administer venetoclax” in ARIA. This is to facilitate the diagnosis of TLS from the blood results. Administer the venetoclax one hour after the start of the sodium chloride 0.9% infusion. Ensure all the correct blood tests have been taken at the correct time. Dispense only one dose Take with or after food. Take with a full glass of water. Oral chemotherapy 6. Metoclopramide 10mg three times a day when required for the relief of nausea oral Administration Instructions Please supply 28 tablets or nearest equivalent pack size 7. Calcium carbonate One tablet three times a day oral Administration instructions Take with or after food. This is being used as a phosphate binder, it is essential it is taken with meals Please dispense an original pack as per local formulary eg;calcium carbonate 1.25g or calcium carbonate 1.5g 8. Aciclovir 400mg twice a day for 35 days oral Administration Instructions Please supply 35 days or an original pack if appropriate. Version 1(December 2019) Page 9 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration Day 2 9. Rasburicase 7.5mg intravenous infusion in 50ml sodium chloride 0.9% over 30 minutes 10. Sodium chloride 0.9% 500ml intravenous infusion over 120 minutes Administration Instruction Advise patient to drink an additional 1.5 litres of water during the day. Take Home Medicines (day 2 only) 11. Venetoclax 20mg once a day for 6 days oral Administration Information Start on day 2 of the cycle. Dispense six days only. Take with or just after food. Take with a full glass of water. Oral chemotherapy Day 8 12. Warning – Check in-patient administration Administration Instructions If the patient has been admitted for monitoring please check what was prescribed and administered either on the inpatient electronic or / and paper system and adjust this prescription accordingly. This prescription is designed for out-patient use and may not be used for an in-patient. 13. Rasburicase 7.5mg intravenous infusion in 50ml sodium chloride 0.9% over 30 minutes Administration Instruction Administer after baseline blood sample has been taken 14. Sodium chloride 0.9% 1000ml intravenous infusion over 240 minutes Administration Instruction Advise patient to drink an additional litre of water during the day. Patients should be adequately hydrated during the dose-titration phase to reduce the risk of TLS. Patients should be instructed to drink plenty of water daily starting 2 days before and throughout the dose-titration phase. Patients should be particularly instructed to drink 1.5 to 2L of water daily, 2 days prior to and the days of dosing at initiation and each subsequent dose increase. Intravenous fluids should be administered as indicated based on overall risk of TLS or for those who cannot maintain an adequate level of oral hydration. 15. Warning – Administer venetoclax Administration Instructions Administer venetoclax as per the dosage in the take home medicines, please record the time of administration by administering this warning in ARIA. This is to facilitate the diagnosis of TLS from the blood results. Administer the venetoclax at least one hour after the start of the sodium chloride 0.9% infusion. Ensure all the correct blood tests have been taken at the correct time. Take with or after food. Take with a full glass of water. Oral chemotherapy Take Home Medicines (day 8) 16. Venetoclax 50mg once a day for 1 day oral Administration Information Administer 50mg once a day on day 8 only, please record the time of administration by administering the “warning – administer venetoclax” in ARIA. This is to facilitate the diagnosis of TLS from the blood results. Administer the venetoclax one hour after the start of the sodium chloride 0.9% infusion. Ensure all the correct blood tests have been taken at the correct time. Dispense only one dose Take with or after food. Take with a full glass of water Oral chemotherapy Version 1(December 2019) Page 10 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration Day 9 17. Rasburicase 7.5mg intravenous infusion in 50ml sodium chloride 0.9% over 30 minutes 18. Sodium chloride 0.9% 500ml intravenous infusion over 120 minutes Administration Instruction Advise patient to drink an additional 1.5 litres of water during the day Take Home Medicines (day 9 only) 19. Venetoclax 50mg once a day for 6 days oral Administration Information Start on day 9 of the cycle. Dispense 6 days only. Take with or just after food. Take with a full glass of water. Oral chemotherapy 20. Allopurinol 300mg once a day for 28 days oral Administration information Start on day 12 of the cycle. Day 15 21. Warning - Administer venetoclax Administration Instructions Administer venetoclax as per the dosage in the take home medicines, please record the time of administration by administering this warning in ARIA. This is to facilitate the diagnosis of TLS from the blood results. Ensure all the correct blood tests have been taken at the correct time and that the patient is drinking a minimum of 2 liters of fluid a day. Take with or after food. Take with a full glass of water. Oral chemotherapy Take Home Medicines (Day 15 only) 22. Venetoclax 100mg once a day for 1 day oral Administration information Administer 100mg once a day on day 15 only. If appropriate please record the time of administration in the journal in ARIA. This is to facilitate the diagnosis of TLS from the blood results. Ensure all the correct blood tests have been taken at the correct time. Dispense only one dose Take with or after food. Take with a full glass of water Oral chemotherapy Take Home Medicines (Day 16 only) 23. Venetoclax 100mg once a day for 6 days oral Administration Information Start on day 16 of the cycle. Dispense 6 days only. Take with or just after food. Take with a full glass of water. Oral chemotherapy Day 22 24. Warning - Administer venetoclax Administration Instructions Version 1(December 2019) Page 11 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration Administer venetoclax as per the dosage in the take home medicines, please record the time of administration by administering this warning in ARIA. This is to facilitate the diagnosis of TLS from the blood results. Ensure all the correct blood tests have been taken at the correct time and that the patient is drinking a minimum of 2 liters of fluid a day. Take with or after food. Take with a full glass of water. Take Home Medicines (Day 22 only) 25. Venetoclax 200mg once a day for 1 day oral Administration information Administer 200mg once a day on day 22 only. If appropriate please record the time of administration in the journal in ARIA. This is to facilitate the diagnosis of TLS from the blood results. Ensure all the correct blood tests have been taken at the correct time. Dispense only one dose Take with or after food. Take with a full glass of water Oral chemotherapy Take Home Medicines (Day 23 only) 26. Venetoclax 200mg once a day for 6 days oral Administration Information Start on day 23 of the cycle. Dispense 6 days only. Take with or just after food. Take with a full glass of water. Oral chemotherapy Day 29 27. Warning - Administer venetoclax Administration Instructions Administer venetoclax as per the dosage in the take home medicines, please record the time of administration by administering this warning in ARIA. This is to facilitate the diagnosis of TLS from the blood results. Ensure all the correct blood tests have been taken at the correct time and that the patient is drinking a minimum of 2 liters of fluid a day. Take with or after food. Take with a full glass of water. Take Home Medicines (Day 29 only) 28. Venetoclax 400mg once a day for 1 day oral Administration information Administer 400mg once a day on day 29 only. If appropriate please record the time of administration in the journal in ARIA. This is to facilitate the diagnosis of TLS from the blood results. Ensure all the correct blood tests have been taken at the correct time. Dispense only one dose Take with or after food. Take with a full glass of water Oral chemotherapy Take Home Medicines (Day 30 only) 29. Venetoclax 400mg once a day for 6 days oral Administration Information Start on day 30 of the cycle. Dispense 6 days only. Take with or just after food. Take with a full glass of water. Oral chemotherapy Version 1(December 2019) Page 12 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration DOCUMENT CONTROL Version Date Amendment Written By Approved By 1 December 2019 None Harriet Launders Pharmacist Dr Andrew Duncombe Consultant Haematologist This chemotherapy protocol has been developed as part of the chemotherapy electronic prescribing project. This was and remains a collaborative project that originated from the former CSCCN. These documents have been approved on behalf of the following Trusts; Hampshire Hospitals NHS Foundation Trust NHS Isle of Wight Portsmouth Hospitals NHS Trust Salisbury NHS Foundation Trust University Hospital Southampton NHS Foundation Trust Western Sussex Hospitals NHS Foundation Trust All actions have been taken to ensure these protocols are correct. However, no responsibility can be taken for errors that occur as a result of following these guidelines. These protocols should be used in conjunction with other references such as the Summary of Product Characteristics and relevant published papers. Version 1(December 2019) Page 13 of 13 CLL-VR-RITUXIMAB-VENETOCLAX (high risk) Cycle 1 – Venetoclax dose titration
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Blinatumomab

Description: Chemotherapy Protocol Acute lymphoblastic leukaemia (ALL) Blinatumomab (3, 4 day) Regimen • ALL – Blinatumomab (3, 4 day schedule) Indication • Treatment of Philadelphia-chromosome-negative relapsed or refractory B-precursor acute lymphoblastic leukaemia. Toxicity Drug Adverse Effect Blinatumomab Cytokine release syndrome, tumour lysis syndrome, neurological toxicity, elevated liver enzymes. The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Monitoring • FBC, U&Es and LFTs on day 1 of the cycle • Hepatitis B, C and HIV serology prior to cycle one Dose Modifications • Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. • Consideration to discontinue blinatumomab temporarily or permanently as appropriate should be made in the case of the following severe (NCI-CTC grade 3) or life-threatening (NCI-CTC grade 4) toxicities. For example, cytokine release syndrome, tumour lysis syndrome, neurological toxicity, elevated liver enzymes and any other clinically relevant toxicities. • If the treatment is interrupted for more than four hours it is recommended that the patient is examined by a heathcare professional. If the interruption of treatment after an adverse event is 7 days or less, continue the same cycle to a total of 28 days of infusion inclusive of days before and after the interruption in that cycle. If an interruption due to an adverse event is longer than 7 days, start a new cycle. If the toxicity takes more than 14 days to resolve, discontinue blinatumomab permanently, except if described differently in the table below: Version 1 (July 2017) Page 1 of 14 ALL-Blinatumomab (3, 4 day schedule) Toxicity Action Cytokine release Grade 3 syndrome, Interrupt blinatumomab until resolved, then restart at 9micrograms/day. tumour lysis Escalate to 28micrograms/day after 7 days if the toxicity does not recur. syndrome Grade 4 Discontinue blinatumomab permanently. Neurological toxicity Convulsion Discontinue blinatumomab permanently if more than one convulsion occurs. Grade 3 • Interrupt blinatumomab until no more than grade 1 (mild) and for at least 3 days, then restart blinatumomab at 9micrograms/day. Escalate to 28micrograms/day after 7 days if the toxicity does not recur. • On re-initiation, pre-medicate with a 24mg dose of dexamethasone. Then reduce dexamethasone step-wise over 4 days. • If the toxicity occurred at 9micrograms/day, or if the toxicity takes more than 7 days to resolve, discontinue blinotumumab permanently. Grade 4 Discontinue blinatumomab permanently. Elevated liver enzymes Grade 3 If clinically relevant, interrupt blinatumomab until no more than grade 1 (mild), then restart blinatumomab at 9micrograms/day. Escalate to 28micrograms/day after 7 days if the toxicity does not recur. Grade 4 Consider discontinuing blinatumomab permanently. Other clinically relevant (as determined by treating physician) adverse reactions Grade 3 Interrupt blinatumomab until no more than grade 1 (mild), then restart blinatumomab at 9micrograms/day. Escalate to 28micrograms/day after 7 days if the toxicity does not recur. Grade 4 Consider discontinuing blinatumomab permanently. *Based on the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 3 is severe, and grade 4 is life-threatening. Haematological No dose modifications for haematological toxicity are necessary for blinatumomab. If treatment with blinatumomab is not tolerated it should be stopped. Version 1 (July 2017) Page 2 of 14 ALL-Blinatumomab (3, 4 day schedule) Hepatic Impairment Based on pharmacokinetic analyses, dose adjustment is not necessary in patients with mild to moderate hepatic dysfunction. The safety and efficacy of blinatumomab have not been studied in patients with severe hepatic impairment. See table above. Renal Impairment Based on pharmacokinetic analyses, dose adjustment is not necessary in patients with mild to moderate renal dysfunction. The safety and efficacy of blinotumumab have not been studied in patients with severe renal impairment. Patients with evidence of impaired renal function should be carefully monitored as they are prone to additional myelosuppression. Elderly No dose adjustment is necessary in elderly patients (greater than or equal to 65 years of age). There is limited experience with blinatumomab in patients greater than or equal to 75 years of age. Other Dose reductions or interruptions in therapy are not necessary for those toxicities that are considered unlikely to be serious or life threatening. For example, alopecia, altered taste or nail changes (see table above). Cytokine Release Syndrome (CRS) and Infusion Related Reactions Premedication with dexamethasone is intended to prevent CRS events associated with blinatumomab treatment. Serious adverse events that may be signs and symptoms of CRS included pyrexia, asthenia, headache, hypotension, total bilirubin increased, and nausea. The median time to onset of a CRS event was 2 days. Patients should be closely monitored for signs or symptoms of these events. Disseminated intravascular coagulation and capillary leak syndrome (e.g. hypotension, hypoalbuminaemia, oedema and haemoconcentration) have been commonly associated with CRS. Patients experiencing capillary leak syndrome should be managed promptly. Infusion Related Reactions Infusion reactions may be clinically indistinguishable from manifestations of CRS and include symptoms such as rash, wheezing, flushing, breathlessness, hypotension, facial swelling. The infusion reactions were generally rapid, occurring within 48 hours after initiating infusion. However some patients reported delayed onset of infusion reactions or in later cycles. Patients should be observed closely for infusion reactions, especially during the initiation of the first and second treatment cycles and treated appropriately. Anti-pyretic use (e.g. paracetamol) is recommended to help reduce pyrexia during the first 48 hours of each cycle. Version 1 (July 2017) Page 3 of 14 ALL-Blinatumomab (3, 4 day schedule) Neurological In the pivotal study 52% of patients experienced one or more neurologic adverse reactions (including psychiatric disorders). NCI-CTC grade 3 or higher neurologic events following initiation of blinatumomab administration included encephalopathy, seizures, speech disorders, disturbances in consciousness, confusion, disorientation, and coordination and balance disorders. The median time from initiation of blinatumomab to onset of a neurologic event was 9 days. The majority of events resolved after treatment interruption. It is recommended that a neurological examination be performed in patients prior to starting therapy and that patients be clinically monitored for signs and symptoms of neurologic events (e.g. writing test). Management of these signs and symptoms to resolution may require either temporary interruption or permanent discontinuation of treatment. Elderly patients experience a higher rate of neurological events. Counsel patients on the potential neurologic effects and advise patients not to drive, use heavy machinery, or engage in hazardous activities while on treatment and to promptly report any neurological symptoms. Tumour lysis syndrome Tumour lysis syndrome (TLS), which may be life-threatening or fatal (grade equal to or greater than 4) has been observed in patients receiving blinatumomab. Appropriate prophylactic measures including aggressive hydration and anti-hyperuricaemic therapy (such as allopurinol or rasburicase) should be used for the prevention and treatment of TLS during treatment, especially in patients with higher leukocytosis or a high tumour burden. Patients should be closely monitored for signs or symptoms of TLS, including renal function and fluid balance in the first 48 hours after the first infusion. In clinical studies, patients with moderate renal impairment showed an increased incidence of TLS compared with patients with mild renal impairment or normal renal function, Management of these events may require either temporary interruption or discontinuation of blinatumomab. Regimen 42 day cycle for up to 5 cycles Patients will receive an initial 2 cycles of treatment. Patients who have achieved complete remission after 2 cycles may receive up to 3 additional cycles, based on an individual benefits-risks assessment. Consider the administration of pre-phase corticosteroid treatment prior to cycle one if the peripheral blast count is greater than 15% or bone marrow blasts are greater than 50%. This is not included on ARIA Version 1 (July 2017) Page 4 of 14 ALL-Blinatumomab (3, 4 day schedule) Cycle 1 Drug Dose Blinatumomab 9 micrograms/day 28 micrograms/day Days 1 to 7 (7 days) 8 to 28 (21 days) Administration Continuous intravenous infusion in 240ml sodium chloride 0.9% at a rate of 2.5ml/hour via a pump (please see administration instructions below for days the pump is changed). Cycle 2, 3, 4, 5 Drug Dose Blinatumomab 28 micrograms/day Days 1 to 28 (28 days) Administration Continuous intravenous infusion in 240ml sodium chloride 0.9% at a rate of 2.5ml/hour via a pump (please see administration instructions below for days the pump is changed). Dose Information • Blinatumomab is a set dose and does not require dose banding • Dosing errors have been observed with blinatumomab treatment. It is very important that the instructions for administration are strictly followed to minimise this risk. • The administration period must not exceed 28 days in total in any given cycle Administration Information • Central venous access is required. Infuse through a dedicated lumen. • Blinatumomab should be administered as a continuous intravenous infusion delivered at a constant flow rate using a pump system. All infusions will contain sufficient volume and drug for a 96 hour infusion, although they will be administered over alternate 72 and 96 hours. The bag will contain; - 9microgram/day – 41.25microgram in 275ml - 28microgram/day – 133.75microgram in 275ml • ARIA has been set up to administer the first, third, fifth and seventh infusions of the same cycle over 72 hours. This means that treatment must start on a Monday, Tuesday or Friday. The infusion will contain sufficient drug and volume for 96 hours and must be programmed to stop after 72 hours. The bag must then be discarded. The second, fourth, sixth and eighth infusion of each cycle will be administered over 96 hours. Ensure the pump is set to stop at the correct times. • Do not flush infusion lines into the patient, as it will cause an inadvertent bolus of blinatumomab to be administered. The line must be replaced with every change of the infusion bag. Version 1 (July 2017) Page 5 of 14 ALL-Blinatumomab (3, 4 day schedule) • Administer blinatumomab through a Polyolefin, PVC non-DEHP, or EVA intravenous infusion line with a low protein-binding 0.2µm in-line filter. • The administration period must not exceed more that 28 days in any given cycle • The days of administration may need to be adjusted on ARIA depending on the time of the start of the day one infusion. Additional Therapy • Consider the administration of pre-phase corticosteroid treatment prior to cycle one if the peripheral blast count is greater than 15% or bone marrow blasts are greater than 50%. This is not included on ARIA • Dexamethasone 20mg or equivalent intravenous 60 minutes prior to day 1 blinatumomab on every cycle • Paracetamol 1000mg four times a day for the first 48 hours of the day 1 blinatumomab on every cycle oral • Allopurinol 300mg daily for 7 days (cycle 1 only) oral • Anti-infective prophylaxis with - aciclovir 400mg twice a day oral - co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays oral - fluconazole 50mg once a day oral • For the treatment of infusion related reactions - chlorpheniramine 10mg intravenous when required - hydrocortisone 100mg intravenous when required - pethidine 12.5-25mg when required for rigors following instruction from a medical practitioner - salbutamol 2.5mg nebulised when required - pethidine 12.5-25mg intravenous when required for rigors • Gastric protection with a proton pump inhibitor or a H2 antagonist may be considered in patients considered at high risk of GI ulceration or bleed. Additional Information • Patients should be encouraged to drink at least three litres of fluid per 24 hours • Cycle one and two are started in the hospital setting. It is recommended the patient remain an in-patient for the first 9 days of cycle one and at least two days of cycle two. Take home (supportive) medicines have been included in this protocol. If an inpatient stay is necessary these must be prescribed on the in-patient chart Version 1 (July 2017) Page 6 of 14 ALL-Blinatumomab (3, 4 day schedule) Coding • Procurement – X71.3 • Delivery – X72.2 References 1. National Institute for Health and Clinical Excellance (2017). Blinatumomab for previously treated Philadelphia-chromosomenegative acute lymphoblastic leukaemia. Technology appraisal guidance [TA450] Published date: 28 June 2017 2. Kantarilan H, Stein A, Gokbuget N et al. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Eng J Med 2017; 376 (9):836-847. Version 1 (July 2017) Page 7 of 14 ALL-Blinatumomab (3, 4 day schedule) REGIMEN SUMMARY Blinatumomab (3, 4 day schedule) Cycle 1 Day 1 1. Warning – Check Supportive Medicines Prescribed (if I/P) Administration Instructions If an in-patient ensure the following medicines are prescribed; 1. Paracetamol 1000mg four times a day for the first 48 hours then as required oral (see below) 2. Aciclovir 400mg twice a day 3. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only oral 4. Fluconazole 50mg once a day oral 5. Allopurinol 300mg once a day for 7 days oral 6. Chlorphenamine 10mg intravenous when required for infusion related reactions 7. Hydrocortisone 100mg intravenous when required for infusion related reactions 8. Salbutamol 2.5mg nebulised when required for infusion related reactions 9. Pethidine 12.5-25mg intravenous when required for rigors (following medical instruction) 2. Dexamethasone 20mg or equivalent intravenous Administration Instructions Administer 20mg or equivalent dose intravenously 60 minutes before the start of the blinatumomab infusion 3. Paracetamol 1000mg oral Administration Instructions Administer 60 minutes before the start of the blinatumomab infusion. Check if the patient has already taken paracetamol (maximum dose is 4000mg/24 hours) 4. Blinatumomab 9micrograms/day by continuous intravenous infusion in 240ml sodium chloride 0.9% at a rate of 2.5ml/hour for 72 hours via a pump Administration Instructions Central venous access is required. Infuse through a dedicated lumen. Blinatumomab should be administered as a continuous intravenous infusion delivered at a constant flow rate using a pump. All infusions will contain sufficient volume and drug for a 96 hour infusion, although they will be administered over alternate 72 and 96 hours. The bag will contain; - 9microgram/day – 41.25microgram in 275ml - 28microgram/day – 133.75microgram in 275ml ARIA has been set up to administer the first, third, fifth and seventh infusions of the same cycle over 72 hours. This means that treatment must start on a Monday, Tuesday or Friday. The pump will contain sufficient drug and volume for 96 hours and must be programmed to stop after 72 hours. The bag must then be discarded. The second, fourth, sixth and eighth infusion of each cycle will be administered over 96 hours. Ensure the pump is set to stop at the correct times. Do not flush the remaining volume left in the infusion line into the patient, as it will cause an inadvertent bolus of blinatumomab to be administered. The line must be replaced with every change of pump. Administer blinatumomab through a Polyolefin, PVC non-DEHP, or EVA intravenous infusion line with a low proteinbinding 0.2µm in-line filter. The administration period must not exceed more that 28 days in any given cycle. The day of administration may need to be adjusted on ARIA depending on the time of the start of the day one infusion 5. Chlorpheniramine 10mg intravenous when required for the relief of infusion related reactions 6. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions Version 1 (July 2017) Page 8 of 14 ALL-Blinatumomab (3, 4 day schedule) 7. Pethidine 25mg when required for the relief of rigors Administration Instructions For the relief of rigors following a verbal confirmation from a doctor that the dose is to be given. 8. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions Cycle 1 Day 4 9. Blinatumomab 9micrograms/day by continuous intravenous infusion in 240ml sodium chloride 0.9% at a rate of 2.5ml/hour for 96 hours via a pump Administration Instructions Central venous access is required. Infuse through a dedicated lumen. Blinatumomab should be administered as a continuous intravenous infusion delivered at a constant flow rate using a pump. All infusions will contain sufficient volume and drug for a 96 hour infusion, although they will be administered over alternate 72 and 96 hours. The bag will contain; - 9microgram/day – 41.25microgram in 275ml - 28microgram/day – 133.75microgram in 275ml ARIA has been set up to administer the first, third, fifth and seventh infusions of the same cycle over 72 hours. This means that treatment must start on a Monday, Tuesday or Friday. The pump will contain sufficient drug and volume for 96 hours and must be programmed to stop after 72 hours. The bag must then be discarded. The second, fourth, sixth and eighth infusion of each cycle will be administered over 96 hours. Ensure the pump is set to stop at the correct times. Do not flush the remaining volume in the infusion line into the patient, as it will cause an inadvertent bolus of blinatumomab to be administered. The line must be replaced with every change of pump. Administer blinatumomab through a Polyolefin, PVC non-DEHP, or EVA intravenous infusion line with a low proteinbinding 0.2µm in-line filter. The administration period must not exceed more that 28 days in any given cycle. The day of administration may need to be adjusted on ARIA depending on the time of the start of the day one infusion 10. Chlorpheniramine 10mg intravenous when required for the relief of infusion related reactions 11. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 12. Pethidine 25mg when required for the relief of rigors Administration Instructions For the relief of rigors following a verbal confirmation from a doctor that the dose is to be given. 13. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions Cycle 1 Days 8, 15, 22 14. Blinatumomab 28micrograms/day by continuous intravenous infusion in 240ml sodium chloride 0.9% at a rate of 2.5ml/hour for 72 hours via a pump Administration Instructions Administration Instructions Central venous access is required. Infuse through a dedicated lumen. Blinatumomab should be administered as a continuous intravenous infusion delivered at a constant flow rate using a pump. All infusions will contain sufficient volume and drug for a 96 hour infusion, although they will be administered over alternate 72 and 96 hours. The bag will contain; - 9microgram/day – 41.25microgram in 275ml - 28microgram/day – 133.75microgram in 275ml Version 1 (July 2017) Page 9 of 14 ALL-Blinatumomab (3, 4 day schedule) ARIA has been set up to administer the first, third, fifth and seventh infusions of the same cycle over 72 hours. This means that treatment must start on a Monday, Tuesday or Friday. The pump will contain sufficient drug and volume for 96 hours and must be programmed to stop after 72 hours. The bag must then be discarded. The second, fourth, sixth and eighth infusion of each cycle will be administered over 96 hours. Ensure the pump is set to stop at the correct times. Do not flush the remaining volume left in the infusion line into the patient, as it will cause an inadvertent bolus of blinatumomab to be administered. The line must be replaced with every change of pump. Administer blinatumomab through a Polyolefin, PVC non-DEHP, or EVA intravenous infusion line with a low proteinbinding 0.2µm in-line filter. The administration period must not exceed more that 28 days in any given cycle. The day of administration may need to be adjusted on ARIA depending on the time of the start of the day one infusion 15. Chlorpheniramine 10mg intravenous when required for the relief of infusion related reactions 16. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 17. Pethidine 25mg when required for the relief of rigors Administration Instructions For the relief of rigors following a verbal confirmation from a doctor that the dose is to be given. 18. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions Cycle 1 Days 11, 18, 25 19. Blinatumomab 28micrograms/day by continuous intravenous infusion in 240ml sodium chloride 0.9% at a rate of 2.5ml/hour for 96 hours via a pump Administration Instructions Central venous access is required. Infuse through a dedicated lumen. Blinatumomab should be administered as a continuous intravenous infusion delivered at a constant flow rate using a pump. All infusions will contain sufficient volume and drug for a 96 hour infusion, although they will be administered over alternate 72 and 96 hours. The bag will contain; - 9microgram/day – 41.25microgram in 275ml - 28microgram/day – 133.75microgram in 275ml ARIA has been set up to administer the first, third, fifth and seventh infusions of the same cycle over 72 hours. This means that treatment must start on a Monday, Tuesday or Friday. The pump will contain sufficient drug and volume for 96 hours and must be programmed to stop after 72 hours. The bag must then be discarded. The second, fourth, sixth and eighth infusion of each cycle will be administered over 96 hours. Ensure the pump is set to stop at the correct times. Do not flush the remaining volume left in the infusion line into the patient, as it will cause an inadvertent bolus of blinatumomab to be administered. The line must be replaced with every change of pump. Administer blinatumomab through a Polyolefin, PVC non-DEHP, or EVA intravenous infusion line with a low proteinbinding 0.2µm in-line filter. The administration period must not exceed more that 28 days in any given cycle. The day of administration may need to be adjusted on ARIA depending on the time of the start of the day one infusion 20. Chlorpheniramine 10mg intravenous when required for the relief of infusion related reactions 21. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions Version 1 (July 2017) Page 10 of 14 ALL-Blinatumomab (3, 4 day schedule) 22. Pethidine 25mg when required for the relief of rigors Administration Instructions For the relief of rigors following a verbal confirmation from a doctor that the dose is to be given. 23. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions Take Home Medicines (day 1 only) 24. Paracetamol 1000mg four times a day for days 1 and 2 of the cycle then 1000mg four times a day as required 25. Allopurinol 300mg once a day for 7 days oral 26. Aciclovir 400mg twice a day for 42 days oral 27. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 42 days 28. Fluconaole 50mg once a day for 42 days oral Cycle 2, 3, 4, 5 Day 1 29. Warning – Check Supportive Medicines Prescribed (if I/P) Administration Instructions If an in-patient ensure the following medicines are prescribed; 10. Paracetamol 1000mg four times a day for the first 48 hours then as required oral (see below) 11. Aciclovir 400mg twice a day 12. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only oral 13. Fluconazole 50mg once a day oral 14. Allopurinol 300mg once a day for 7 days oral 15. Chlorphenamine 10mg intravenous when required for infusion related reactions 16. Hydrocortisone 100mg intravenous when required for infusion related reactions 17. Salbutamol 2.5mg nebulised when required for infusion related reactions 18. Pethidine 25mg intravenous when required for rigors (following medical instruction) 30. Dexamethasone 20mg or equivalent intravenous Administration Instructions Administer 60 minutes before the start of the blinatumomab infusion 31. Paracetamol 1000mg oral Administration Instructions Administer 60 minutes before the start of the blinatumomab infusion. Check if the patient has already taken paracetamol (maximum dose is 4000mg/24 hours) 32. Blinatumomab 28micrograms/day by continuous intravenous infusion in 240ml sodium chloride 0.9% at a rate of 2.5ml/hour for 72 hours via a pump Administration Instructions Administration Instructions Central venous access is required. Infuse through a dedicated lumen. Blinatumomab should be administered as a continuous intravenous infusion delivered at a constant flow rate using a pump. All infusions will contain sufficient volume and drug for a 96 hour infusion, although they will be administered over alternate 72 and 96 hours. The bag will contain; - 9microgram/day – 41.25microgram in 275ml - 28microgram/day – 133.75microgram in 275ml ARIA has been set up to administer the first, third, fifth and seventh infusions of the same cycle over 72 hours. This means that treatment must start on a Monday, Tuesday or Friday. The pump will contain sufficient drug and volume for 96 hours and must be programmed to stop after 72 hours. The bag must then be discarded. The second, fourth, sixth and eighth infusion of each cycle will be administered over 96 hours. Ensure the pump is set to stop at the correct times. Version 1 (July 2017) Page 11 of 14 ALL-Blinatumomab (3, 4 day schedule) Do not flush the remaining volume left in the infusion line into the patient, as it will cause an inadvertent bolus of blinatumomab to be administered. The line must be replaced with every change of pump. Administer blinatumomab through a Polyolefin, PVC non-DEHP, or EVA intravenous infusion line with a low proteinbinding 0.2µm in-line filter. The administration period must not exceed more that 28 days in any given cycle. The day of administration may need to be adjusted on ARIA depending on the time of the start of the day one infusion 33. Chlorpheniramine 10mg intravenous when required for the relief of infusion related reactions 34. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 35. Pethidine 25mg when required for the relief of rigors Administration Instructions For the relief of rigors following a verbal confirmation from a doctor that the dose is to be given. 36. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions Days 8, 15, 22 37. Blinatumomab 28micrograms/day by continuous intravenous infusion in 240ml sodium chloride 0.9% at a rate of 2.5ml/hour for 72 hours via a pump Administration Instructions Central venous access is required. Infuse through a dedicated lumen. Blinatumomab should be administered as a continuous intravenous infusion delivered at a constant flow rate using a pump. All infusions will contain sufficient volume and drug for a 96 hour infusion, although they will be administered over alternate 72 and 96 hours. The bag will contain; - 9microgram/day – 41.25microgram in 275ml - 28microgram/day – 133.75microgram in 275ml ARIA has been set up to administer the first, third, fifth and seventh infusions of the same cycle over 72 hours. This means that treatment must start on a Monday, Tuesday or Friday. The pump will contain sufficient drug and volume for 96 hours and must be programmed to stop after 72 hours. The bag must then be discarded. The second, fourth, sixth and eighth infusion of each cycle will be administered over 96 hours. Ensure the pump is set to stop at the correct times. Do not flush the remaining volume left in the infusion line into the patient, as it will cause an inadvertent bolus of blinatumomab to be administered. The line must be replaced with every change of pump. Administer blinatumomab through a Polyolefin, PVC non-DEHP, or EVA intravenous infusion line with a low proteinbinding 0.2µm in-line filter. The administration period must not exceed more that 28 days in any given cycle. The day of administration may need to be adjusted on ARIA depending on the time of the start of the day one infusion 38. Chlorpheniramine 10mg intravenous when required for the relief of infusion related reactions 39. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 40. Pethidine 25mg when required for the relief of rigors Administration Instructions. For the relief of rigors following a verbal confirmation from a doctor that the dose is to be given. 41. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions Version 1 (July 2017) Page 12 of 14 ALL-Blinatumomab (3, 4 day schedule) Cycle 2, 3, 4, 5 Days 4, 11, 18, 25 42. Blinatumomab 28micrograms/day by continuous intravenous infusion in 240ml sodium chloride 0.9% at a rate of 2.5ml/hour for 96 hours via a pump Administration Instructions Central venous access is required. Infuse through a dedicated lumen. Blinatumomab should be administered as a continuous intravenous infusion delivered at a constant flow rate using a pump. All infusions will contain sufficient volume and drug for a 96 hour infusion, although they will be administered over alternate 72 and 96 hours. The bag will contain; - 9microgram/day – 41.25microgram in 275ml - 28microgram/day – 133.75microgram in 275ml ARIA has been set up to administer the first, third, fifth and seventh infusions of the same cycle over 72 hours. This means that treatment must start on a Monday, Tuesday or Friday. The pump will contain sufficient drug and volume for 96 hours and must be programmed to stop after 72 hours. The bag must then be discarded. The second, fourth, sixth and eighth infusion of each cycle will be administered over 96 hours. Ensure the pump is set to stop at the correct times. Do not flush the remaining volume in the infusion line into the patient, as it will cause an inadvertent bolus of blinatumomab to be administered. The line must be replaced with every change of pump. Administer blinatumomab through a Polyolefin, PVC non-DEHP, or EVA intravenous infusion line with a low proteinbinding 0.2µm in-line filter. The administration period must not exceed more that 28 days in any given cycle. The day of administration may need to be adjusted on ARIA depending on the time of the start of the day one infusion 43. Chlorpheniramine 10mg intravenous when required for the relief of infusion related reactions 44. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 45. Pethidine 25mg when required for the relief of rigors Administration Instructions For the relief of rigors following a verbal confirmation from a doctor that the dose is to be given. 46. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions Take Home Medicines (day 1 only) 47. Paracetamol 1000mg four times a day for days 1 and 2 of the cycle then 1000mg four times a day as required 48. Aciclovir 400mg twice a day for 42 days oral 49. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 42 days 50. Fluconaole 50mg once a day for 42 days oral Version 1 (July 2017) Page 13 of 14 ALL-Blinatumomab (3, 4 day schedule) DOCUMENT CONTROL Version Date Amendment Written By Approved By 1 July 2017 None Stuart Martin Pharmacist Dr Deborah Wright Pharmacist Dr Christopher Dalley Consultant Haematologist This chemotherapy protocol has been developed as part of the chemotherapy electronic prescribing project. This was and remains a collaborative project that originated from the former CSCCN. These documents have been approved on behalf of the following Trusts; Hampshire Hospitals NHS Foundation Trust NHS Isle of Wight Portsmouth Hospitals NHS Trust Salisbury NHS Foundation Trust University Hospital Southampton NHS Foundation Trust Western Sussex Hospitals NHS Foundation Trust All actions have been taken to ensure these protocols are correct. However, no responsibility can be taken for errors that occur as a result of following these guidelines. Version 1 (July 2017) Page 14 of 14 ALL-Blinatumomab (3, 4 day schedule)
Url: /Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/ALL/Blinatumomab.pdf

Whooping cough study - volunteers information sheet

Description: Chief Investigator Professor R. C. Read Southampton National Institute for Health Research Wellcome Trust Clinical Research Facility Southampton Centre for Biomedical Research Southampton General Hospital Tremona Road Southampton SO16 6YD Tel (Reception): 023 8120 4989 Fax: 023 8120 5023 Email: UHS.RecruitmentCRF@nhs.net A human controlled infection study to establish a safe, reproducible and practical human Bordetella pertussis colonisation model for the identification of correlates of protection against colonisation. Volunteer information sheet – Phase A We would like to invite you to take part in a research study. Before making a decision about whether or not to take part, please take the time to read this information sheet and discuss it with friends, relatives and your General Practitioner (GP) if you wish. One of our study team will go through the information sheet with you and answer any questions you may have. In summary In this study, we are trying to find out how we can best protect people against the disease Whooping Cough and stop it spreading from person to person. To do this, we will be performing a deliberate controlled infection of the nose, so that the body is transiently infected with the agent that causes this disease. You do NOT have to take part. Before you join we will explain in the following pages exactly what it entails (the procedures, investigations, time commitment and a short balanced presentation on risk and benefits) but first we want to highlight key points that we think you should know before making a decision. If you are still interested in joining our study, we’ll then get into more detail. * You’ll be given a small dose of live bacteria into your nose * You’ll be admitted in the research unit for 17 days and have investigations to measure the course of the infection and your immune response to it * There is a small chance you will get the symptoms of whooping cough but we will closely monitor you and treat early * You musn’t have had any past problems with your immune system * We must confirm eligibility through your GP If you are intersted, the following pages will explain more about the study. What is Bordetella pertussis? Whooping cough, also called pertussis, is a bacterial infection of the lungs and airways. It is caused by a bacterium called Bordetella pertussis (B. pertussis). Whooping cough can cause repeated coughing bouts that can last for two to three months or more. Young babies under six months of age are typically affected and are in the age group that is most vulnerable to serious complications. In older children and adults it tends to be less serious, although it can still be unpleasant and frustrating. In some adults who are infected there may be no symptoms at all, so that the infection passes unnoticed. B. pertussis is spread in the droplets produced when someone with the infection coughs or sneezes. Therefore you can catch whooping cough if you come into close contact with someone with the infection. The first symptoms are similar to those of a cold, such as a runny nose, red and watery eyes, a sore throat, and a slightly raised temperature. Intense coughing bouts typically start about a week later. Antibiotics will help stop the infection spreading to others, and usually (but do not always) reduce the symptoms. If antibiotics are given during the early phase of the infection, it is believed that the cough can be prevented, but there are exceptions to this rule and it is possible that people who are given antibiotics even during the early phase of illness may go on to develop the cough. Although a pertussis vaccine is offered to all babies in the UK, the vaccine does not offer lifelong protection. In fact, protection by the vaccine seems to be less nowadays in comparison to 15 years ago. What is the purpose of this study? This study is part of a project that aims to develop a better vaccine against whooping cough. To do this we need to know more about the immune response generated against B. pertussis and what kind of immune response protects against whooping cough. This study is designed to look at those particular questions by inoculating healthy volunteers with nose drops containing B. pertussis, then monitoring their immune response before giving them an antibiotic to clear B. pertussis. Previous studies, which have been performed with an attenuated (`weakened`) live B. pertusiss have shown that giving nose drops can result in colonisation – when the bacteria live in the nose and throat of the volunteer without causing any disease. In these previous studies, those volunteers who were successfully colonised were seen to produce an immune (antibody) response to the bacteria, in a similar way to producing an immune response after a vaccination. This has never been done with non-attenuated B. pertussis before. In this study we are aiming to cause colonisation with B. pertussis and analyse the immune response triggered by this colonisation, without causing the volunteers to become unwell. The study is comprised of two phases. In phase A we will give nasal drops with B. pertussis at a low dose of bacteria, with the aim of achieving colonisation in most, but not all, volunteers. If that dose works, then all subsequent volunteers will receive the same dose. If it doesn’t work then subsequent volunteers will receive progressively higher doses until colonisation is reproducibly achieved. If we find the dose is too high in initial volunteers (because it results in colonisation in all of them) the subsequent volunteers will receive a lower dose. In phase B we will give the optimised dose of nose drops to 30 healthy volunteers and a sham inoculum (salty water only, with no bacteria) to 15 volunteers. All volunteers in Phase A who have been inoculated with B. pertussis will be admitted to the NIHR Wellcome Trust Clinical Research Facility at University Hospital Southampton for a maximum of 17 days. Am I eligible to take part? In order to be involved in this study you must be: * A healthy adult aged 18 to 45 years inclusive on the day of screening * Fully conversant in the English language * Able to communicate easily by both mobile telephone and text messaging * Able and willing (in the investigator’s opinion) to comply with all study requirements * Willing to give written informed consent to participate in the trial * Willing to take a curative antibiotic regimen after inoculation with B. pertussis according to the study protocol * Willing to be admitted to the NIHR-WTCRF Southampton for 17 days for phase A (from inoculation until two days after the eradication therapy is given) and for the duration necessary for phase B (maximum of 17 days; dependant on phase A results) * Able to answer all questions on the informed consent quiz correctly Acceptable forms of contraception include: * Established use of oral, injected or implanted hormonal methods of contraception * Placement of an intrauterine device or intrauterine system * Total hysterectomy * Barrier methods of contraception (condom or occlusive cap with spermicide) * Male sterilisation if the vasectomised partner is your only partner * True abstinence when this is in line with your preferred and usual lifestyle You cannot participate in this study if: * You have inviolable commitments within 3 months of discharge from the inpatient phase of the study to make contact with: * unimmunised or partially immunised children and infants aged < 1 year * pregnant women >32 weeks who have not received pertussis vaccination at least a week prior to contact * You have household contacts working with * unimmunised or partially immunised children and infants aged < 1 year * pregnant women >32 weeks who have not received pertussis vaccination at least a week prior to contact * Phase A only: You have had recent B. pertussis infection * B. pertussis is detected on nasopharyngeal swab taken before the challenge * You have signs of a current infection at the time of inoculation with B. pertussis * You have participated in other interventional clinical trials in the last 12 weeks * You have a history of receiving B. pertussis vaccination in the last 5 years * You are a current smoker * You have received systemic antibiotics within 30 days prior to the challenge or plan to during the study period * You have a confirmed or suspected immunosuppressive or immune-deficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed) * You have received immunoglobulins or blood products within the 3 months prior to enrolment * You have a history of allergic disease or reactions likely to be exacerbated by any component of the inoculum * You are not allowed to use azithromycin or macrolides for medical reasons * You are pregnant, breast-feeding or are planning to become pregnant during the study * You have any clinically significant abnormal finding on screening investigations or clinical examination - in the event of abnormal test results, confirmatory repeat tests will be requested * You have any other significant disease, disorder, or characteristic which in the opinion of the investigator, may (i) significantly increase the risk to you if you participate in the study, (ii) affect your ability to participate in the study or (iii) impair interpretation of the study data. Examples include recent surgery to the nasopharynx, or evidence of recreational drug use. If you have private medical or travel insurance you are advised to contact your insurance company before participating in this trial, because involvement in this study may affect the cover provided by private insurance. Do I have to take part? No. It is up to you to decide whether or not to take part. If you are interested in taking part, a member of the study team will discuss the study with you and answer any questions you may have. You will then be asked to sign a consent form. You are free to withdraw from the study at any time without giving a reason, but you may be asked to come to a follow up visit for safety reasons. What will happen if I take part? This study involves a nasal inoculation and a period of admission to the NIHR Wellcome Trust Clinical Research Facility at University Hospital Southampton. Volunteers in phase A will all receive nasal inoculation with B. pertussis and will be admitted to the for 17 days followed by 4 follow up visits. At the moment we are only looking for volunteers for phase A. The study timetable for phase A is summarised in the tables below: Table 1: Visits and procedures phase A In phase B the volunteers will be split into two groups. Group 1 will receive nasal inoculation with B. pertussis and will be admitted for approximately seven days (depending on Phase A results) followed by five follow up visits. Group 2 will receive a sham inoculum (salty water with no bacteria present). Persons in Group 2 will not be admitted but will come to the unit for six follow up visits. You may be able to choose which group you are in as long as there are places available. Screening visit If you are interested in taking part in this study you will be invited to attend a screening appointment at the NIHR-Wellcome Trust Clinical Research Facility at University Hospital Southampton. This will take place up to 30 days prior to inoculation and will last up to one hour. The purpose of this visit is for us to discuss the trial with you and for you to decide if you wish to participate. You will be asked to fill in a questionnaire to make sure that you fully understand the study. You will be shown where you will be admitted if you decide to participate and are eligible. If you decide to participate then you will be asked to sign a consent form. We then need to check that you do not have any health conditions that affect your eligibility for the study or make the study unsafe for you. A doctor will ask you some medical questions and examine you. We will ask you to fill in the General Health Questionnaire to screen for personality or psychiatric disorders. We will take a nasopharyngeal swab, take a blood sample, make an ECG (heart-tracing) and do a urine test (including a pregnancy test for females). We will send a letter to your GP asking to confirm your medical history to make sure this study is safe for you and we will provide them with information about what the study involves. Pre-inoculation visit If you are eligible for the study, we will ask you to come for a pre-inoculation visit 7 days before inoculation to check that you are still not carrying natural B. pertussis and take some base line samples. Once this is confirmed you will be asked to return on the day of the inoculation for admission to the research unit. Inoculation day We will ask you not to eat or drink anything other than water for the hour prior to your inoculation. We will check that you are still happy to continue in the study and that nothing has changed with your medical history. Prior to the inoculation we will take some blood tests. Females will also have another pregnancy test. You will then be given the inoculation of B. pertussis. You will be asked to lie on your back with your neck extended back and 0.5ml of fluid containing a carefully measured amount of bacteria will be dripped slowly into each nostril over approximately 1 minute for each nostril. You will be able to breathe through your mouth during this procedure. Following the inoculation you will be asked to remain lying down for 5 minutes and then you will be observed for a total of 15 minutes. Admission to the research facility Immediately following the inoculation, volunteers who have been inoculated with B. pertussis will be admitted to the research unit. Volunteers in phase A will be admitted for 17 days. During admission you will have frequent reviews by the study doctors and nurses and regular nasal and blood samples will be taken to look for successful colonisation and an immune response. The shedding of B. pertussis be assessed daily after challenge using analyses of the face mask you are wearing, sampling the air in your bedroom, taking samples from surfaces in the room, dipping your fingertips in a small dish with water and by letting you cough/talk inside a coughbox. This coughbox is like a glass cupboard which you can sit in while we take air samples. Eradication and discharge Prior to discharge you will be given a three day course of an antibiotic called azithromycin to clear colonisation of B. pertussis from your nose and throat. We will check that B. pertussis has been successfully cleared by performing a nasopharyngeal swab 24 and 48 hours after eradication. In phase A this treatment will be given on days 14, 15 and 16. If we suspect that you are developing whooping cough then we will start treatment immediately and will discharge you after the last dose of antibiotics. Follow up visits Participants will be asked to return on Day 28, 56, 183 and Day 365 after inoculation for follow up visits. We will repeat the nasal and throat samples and also take some blood tests, to look for an immune response to B. pertussis. Investigations: Nasopharyngeal swabs This test involves passing a cotton wool swab on a stick into your nose so that it touches the back of your throat. This can feel a little uncomfortable, but not painful, and may lead to a sensation of gagging which lasts no more than a couple of seconds. Nasal fluid samples We collect nasal fluid in two different ways. Firstly we will use a small piece of filter paper, which is placed on the inside of your nostril and left for 5 minutes. After this time it will have collected a small amount of fluid, which we will analyse in the laboratory. Secondly we will perform a nasal wash, which will involve warm salty water being instilled from a syringe into each nostril, 5 ml (1 teaspoon) at a time. We will then ask you to tip your head forward to let the fluid back out and collect it for analysis. Throat swabs This test involves passing a cotton wool swab on a stick into throat so that it touches the back of your throat. This can feel a little uncomfortable, but not painful, and may lead to a sensation of gagging which lasts no more than a couple of seconds. Saliva samples This test involves rubbing small sponge on a stick on the inside of your mouth for about 25 seconds.This can feel a little uncomfortable, but not painful. Environmental samples Environmental samples that will be collected include sampling the air in your bedroom, taking samples from surfaces in the room, dipping your fingertips in a small dish with water and coughing/talking inside a coughbox. This is not considered to be uncomfortable. Where will I be staying? To prevent infecting other people, especially vulnerable people, with B. pertussis volunteers will be admitted to a dedicated area of the NIHR Wellcome Trust Clinical Research Facility which is located on C level of University Hospital Southampton. While admitted, volunteers will have access to dedicated rooms, toilets, shower and a recreational area. Volunteers will be able to leave the designated area during daytime for a maximum of two hours two times a day, providing that they follow the necessary infection prevention measures. They will be required to stay inside from 18.00 till 8.00 and meals, drinks, snacks and entertainment will be provided. To protect you from developing illness outside the research unit and to prevent possible cross infection of other people the volunteer will have to adhere to the following rules: 1. You are only allowed to leave the NIHR-WTCRF with the permission of the clinical team during admission and are allowed to leave the designated area during daytime for a maximum of two hours twice a day. 2. When you leave your personal room the isolation area at the NIHR-WTCRF unit you will have to wear a surgical mask to cover your nose and mouth. 3. When you are in the recreational room you will have to wear a surgical mask to cover your nose and mouth 4. You are not to enter the room of other admitted volunteers 5. Starting at inoculation until 3 months after discharge you are not allowed have contact with a. healthcare workers working with one of the groups mentioned below b. unimmunised or partially immunised children and infants aged < 1 year. c. pregnant women >32 weeks who have not received pertussis vaccination at least a week prior to contact 6. You need to wash your hands before leaving your room and are not allowed to have direct face-to-face contact (< 2 metre distance) for greater than a cumulative period of 1 hour with other people during the admission period. 7. You are not allowed to have any direct contact that could involve transfer of respiratory secretions to anyone during the admission period. 8. When you leave the unit you must be carrying a mobile phone with the study emergency phone number programmed in, and contact the clinical study team if necessary. 9. You must be able to be return in the NIHR-WTCRF within 30 minutes. 10. You will have to be contactable by telephone while outside the NIHR-WTCRF. 11. You may receive a maximum of two guests at a time between 8.00 and 22.00, who must wear masks covering nose and mouth while in close proximity to you and must adhere to strict infection control procedures. What are the risks of taking part? Blood tests The maximum total volume of blood taken during the study is approximately 580 ml over a year. The amount taken on one day will be a maximum of 65 ml (13 teaspoons). The volume of blood being taken over the course of the trial should not cause any problems in healthy people. There may be some temporary mild discomfort, such as bruising and tenderness at the site where the blood tests are taken. You may experience faintness as a result of the blood test. We will give you a copy of your blood test results if you request them, and will only send the results to your GP if you wish us to and will not report them to anyone else without your permission. Nasopharyngeal swabs, throat swabs, saliva samples and nasal fluid samples These procedures can be a little uncomfortable or cause gagging but this will resolve quickly and should not be painful or pose any risk to you. Inoculation The inoculation with fluid containing B. pertussis may cause some irritation of the nose that will disappear within a few seconds. Whooping cough Although the aim of the challenge model is to establish colonisation of B. pertussis, but not to cause whooping cough, there is a possibility that whooping cough may occur as a result of the inoculation. Initial symptoms of whooping cough in adults include a runny nose, sneezing and ‘flu like symptoms, hoarseness, sinus pain, headaches and a persistent cough. If you have one or more of these symptoms we will review you immediately. If we suspect you are having a normal cold we will keep an extra close watch on you for the next 48 hours and take extra safety blood tests . If we suspect that you are developing whooping cough then we will start treatment immediately. We expect such early treatment to reduce the illness in comparison to natural infection where treatment is often delayed due to the typically mild and non-specific presentation. However there are always exceptions to every rule and we cannot exclude the possibility that you may be left with a lengthy cough as a result of taking part in the project. In adults who develop whooping cough, coughing episodes may disturb sleep or result in vomiting, and occasionally cause whooping. Adults can develop complications from pertussis, but they occur less frequently and are usually less severe than in children. Reported complications of pertussis disease include urinary incontinence (during the coughing bouts) , rib fractures, collapsed lungs, inguinal hernias, aspiration, pneumonia, seizures and ear infections. These complications have only been reported in children, or in debilitated adults who suffer from other diseases or who are older than 65 years. Eradication An antibiotic called azithromycin will be used to eradicate B. pertussis colonisation at the end of the experimental colonisation period. It is a licenced drug in the UK for the treatment of pertussis, and the treatment consists of a dose of 500 mg once daily for three days. We will need to watch you taking the doses. Azithromycin is generally well tolerated, but may occasionally cause some side effects. The side effects include: Common: Abdominal discomfort; diarrhoea; nausea; vomiting Uncommon: Jaundice; liver dysfunction; rash Rare: Antibiotic-associated colitis; heart rhythm problems; pancreatitis; Stevens-Johnson syndrome; toxic epidermal necrolysis (serious skin conditions) Frequency not known: Reversible hearing loss (sometimes with tinnitus) can occur after large doses If you experience any of these symptoms you should contact a doctor immediately, and then inform us. Azithromycin does not interfere with the contraceptive pill. Are there any benefits to taking part? It is possible that taking part in this study will result in you having a degree of immunity to whooping cough but we cannot be certain that you will benefit directly from this study. We hope that the information gained from this study will help inform the development of vaccines to prevent pertussis and the associated serious complications in the future. You may gain some general information about your health as part of this study. If abnormal results or undiagnosed conditions are found in the course of the study these will be discussed with you and your GP will be informed. For example, a new diagnosis of anaemia or a psychological disorder might be made. Any newly diagnosed conditions will be looked after by your GP within the NHS. Will my taking part in this study be kept confidential? Yes, all information that we collect about you will be coded with a study number and kept confidential. The information will be available to the study team, safety monitors, sponsor, government regulatory agencies and external monitors who can ask to audit or monitor the study. All study information will be held in paper form in a locked room in the NIHR-Wellcome Trust Clinical Research facility or in electronic form on a secure server. Any information that leaves the hospital will have sufficient information removed so that you cannot be identified. What will happen to the results of the research study? We intend to publish the results of this study in scientific journals and present the results at scientific meetings. All results in journals and presentations will be anonymous. An annual report will be published on the study website for volunteers. Who is organising and funding this study? This research is being organised by the University of Southampton and funded by The Periscope project, which has received funding from the European Union Innovative Medicines Initiative. It is being sponsored by University of Southampton. There are no conflicts of interest for any of the research team working on this study. Who has reviewed this study? All research in the NHS is reviewed by an independent Research Ethics Committee to protect your interests. The study has been reviewed and approved by the Health Research Authority. Samples taken during the study may be used in future research only after this future research is ethically approved. Expenses and payments Volunteers will be compensated for their time and for the inconvenience caused by procedures at a rate of £15 per visit plus additional £6 travel expenses per visit. Admission will be compensated for at a rate of £200 per day. The maximum individual volunteers will be compensated is £3526 and the minimum £15. Volunteers who withdraw from the study prior to its completion will be offered financial re-imbursement corresponding to the number of visits or days attended. What if there is a problem? The study team are available 24 hours a day, during admission. After discharge you can contact the study team on 02381 20 4989 (working hours only) or 077 71674842 (24 hours). If you were to fall ill and require medical help after your discharge from the research facility we would advise you to contact your GP in the first instance and inform us once convenient. We will provide you with a letter explaining the study, which will contain the contact number for the research team. The doctor who reviews you would be encouraged to contact the study team if there were any concerns about your health during the study. The investigators recognise the important contribution that participants make to medical research, and will make every effort to ensure your safety and well-being. The University of Southampton, as sponsor of this study, has insurance in place to cover any negligent harm caused within the research activity as stated in the protocol. While the University will cooperate with any claim, you may wish to seek independent legal advice to ensure that you are properly represented in pursuing any complaint. At any time during the study you will be entirely free to change your mind about taking part, and to withdraw from the study. This will not affect your subsequent medical care in any way. What if I wish to complain about the way the study was conducted? If you have cause to complain about any aspect of the way in which you have been approached or treated during the course of this study, the normal National Health Service complaints mechanisms are available to you and your normal medical care will not be compromised in any way because you have taken part in a research study. Contact details for the study team and the independent Patient Support Service located within the hospital are at the end of this information sheet. What will happen if I don’t want to carry on with the study? If you wish to withdraw from the study you are free to do so at any time, but you may be asked take medicine to treat possible carriage with B. pertussis and have a telephone contact follow up for safety reasons. In such an event we would continue to use any data we collected up to the point of your withdrawal. Your compensation would be paid as a proportion of the total compensation according to the length of your participation. What if relevant new information becomes available? Sometimes during the course of a research project, new information becomes available. If this happens, we will tell you about it and discuss whether you want to or should continue in the study. If you decide to continue in the study you will be asked to sign an updated consent form. On receiving new information, we might consider it to be in your best interests to withdraw you from the study. Prevention of ‘Over Participating’ Participants participating in this study must not be concurrently receiving medications or vaccines in another study. In order to check this, you will be asked to provide your National Insurance or Passport number (if you do not have a NI number). This will be entered on to a national database, which helps prevent participants from taking part in too many clinical trials. More information can be found at www.tops.org.uk. Your national insurance or passport number is also required to allow processing of compensation payments. Contact for further information If you are interesting in taking part in this study please contact the study team: Email: uhs.recruitmentCRF@nhs.net Tel: 023 8120 3853 Fax: 023 8120 5023 If you have any questions regarding this research study please contact the clinical research fellow Dr. Hans de Graaf or the Chief Investigator Professor R. Read. Email: h.de-graaf@soton.ac.uk Tel: 023 8120 4989 Fax: 023 8120 5023 If you are a volunteer participating in the study and you would like to contact us in case of an emergency we can be contacted 24 hours a day, 7 days a week on: 077 71674842 In the event that you wish to discuss this project with an independent third party, please contact the hospital’s Patient Support Service (available 9am to 4.30pm Monday to Friday) Patient Support Service C Level Centre Block Mailpoint 81 Southampton General Hospital Tremona Road Southampton SO16 6YD Tel no. 023 81 20 6325 Email: PatientSupportService@uhs.nhs.uk A human controlled infection study to establish a safe, reproducible and practical human Bordetella pertussis colonisation model for the identification of correlates of protection against colonisation. VIS phase A, V2.0, 15/2/2017 RHM MED1396, IRAS ID 219496, REC Ref: 17/SC/006Page 2 of 13
Url: /Media/Southampton-Clinical-Research/Patient-information-sheet/Whooping-cough-study-volunteers-information-sheet.docx

Isatuximab VRD weekly

Description: Chemotherapy Protocol Myeloma Isa-VRD weekly Isatuximab-Lenalidomide-Bortezomib-Dexamethasone (20) Regimen Myeloma – Isa-VRD weekly Isatuximab-Lenalidomide-Bortezomib-Dexamethasone (20
Url: /Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Myeloma/Isatuximab-VRD-weekly-Ver1.pdf

SETT Centre Theme Lead in Medical Technology_JD_Oct2025

Description: Southampton Emerging Therapies and technologies (SETT) Centre Job Role Version 4 Job Title: Directorate/ department: Grade: Hours per week: Accountable to: Key working relationships SETT Theme Lead Research and Development, Trust HQ Consultant or equivalent 1 PA Director of R&D Clinical Director R&D and Director SETT Centre Director of R&D Deputy Director of R&D Divisional Research Leads SETT Centre Manager SETT delivery teams R&D delivery teams Researchers and research teams Main purpose: Job Summary: To work actively as part of the leadership team within the Southampton Emerging Therapies and Technologies (SETT) Centre to support the aims of the Centre in catalysing research and innovation, focused on NHS needs, in catalysing research and innovation, focused on NHS needs, in emerging areas with significant potential to develop future clinical services, and with substantial growth opportunity for research and innovation. Provide strong leadership in the development and delivery of the Theme portfolio ensuring growth in line with the Trust approved investment case (2020) and R&D Strategy (23-28) Actively engage UHS clinicians, academics and external partners in relation to the Theme ensuring UHS reputation as a centre of excellence. Promote a culture of research and innovation throughout UHS supporting the Trust’s strategic ambition to be a leading university teaching hospital with a growing, reputable, innovative research and development portfolio that attracts the best staff and efficiently delivers the best possible treatments and care for our patients. 1. To lead the development and delivery of the SETT programme of in their designated Theme 2. Contribute to the overall strategic management of SETT in conjunction with the Director collaborating and coordinating activities with other themes 3. To determine resources required to develop and deliver projects and research activities within their Theme, to work with the SETT Manager to ensure budgets are realistic, provide value for money and appropriately managed to ensure financial balance. 4. Work with the Theme specific Research Project Managers to ensure the effective design and delivery of research on time, to target and within budget. 5. To support clinical fellows/innovation fellows within the designated theme 6. Deliver growth within the Theme in line with Trust Investment case and R&D Strategy, increasing the volume of high-quality research delivered and associated patient recruitment, publications, impact and external income. Performance Indicators: 7. Work with the SETT Manager to develop and deliver theme-specific capacity development plans. 8. Work to ensure PPIEP is integral to all stages of the research life cycle. 9. Work to ensure that industry engagement and partnership are integral to all stages of the research Theme. 10. To ensure the Theme’s research programme incorporates opportunities to engage across research infrastructure for example Secure Data Environment (SDE programme), CRF, TRCs, ARC WESSEX, NIHR BioResources and NIHR CRUK CTU. Where relevant, to link with other infrastructures that is theme specific (e.g. Data Science links with HIC). 11. To engage with other participants along the pathways, including basic scientists within University of Southampton and implementation specialists within ARC Wessex. 12. To develop the Theme’s programme to incorporate opportunities to engage relevant academics from HEIs, NHS Trusts, public health, local authorities and the third sector where applicable including promoting cross-disciplinary working. 13. Support SETT with the timely completion of periodic reports and annual plans. 14. Identify the need for any significant changes to the Theme direction and seek approval from the SETT Clinical Director for any proposed changes. 15. Contribute to the integrated approach to research governance and management upholding standards of good governance within SETT and R&D. 16. To lead on, or contribute, as appropriate, to the leadership of cross SETT programmes of work as the opportunity arises. 17. To contribute to the development and delivery of SETT engagement in order to enhance external understanding and appreciation of SETT locally, regionally, nationally and globally. 18. To deputise for the SETT Director at regional and national meetings and events as necessary. 1. Compliance with Trust Board KPIs. 2. Adherence to DHSC/NIHR High-Level Objectives and national metrics for recruitment, study setup, and delivery. 3. Increased submissions of high-quality grant applications within SETT Theme 4. Increased publications which showcase trust research innovation and capability within SETT Theme 5. Growth in commercial income from participation in contract commercial research. 6. Contribution to R&D annual research plan 7. Support for development and delivery of SETT delivery plans 8. Regular engagement with stakeholders to explore innovation opportunities relevant to Theme 9. Participation in SETT Meetings as required. Note: Performance indicators will be reviewed at the annual appraisal.
Url: /Media/Southampton-Clinical-Research/Downloads/SETT-Centre-Theme-Lead-in-Medical-Technology-JD-Oct2025.pdf

DRD Daratumumab-Lenalidomide-Dexamethasone

Description: Chemotherapy Protocol Myeloma DRD Daratumumab-Lenalidomide-Dexamethasone Regimen • Myeloma – DRD Daratumumab-Lenalidomide-Dexamethasone Indication • Daratumumab in combination with lenalidomide and dexamethasone is recommended for use within the Cancer Drugs Fund as an option for treating untreated multiple myeloma patients who are ineligible for an autologous stem cell transplant. • This regimen was based on MAIA trial and has been slightly modified to simplify the schedule (i.e. SC instead of IV Daratumumab and two divided doses of dexamethasone instead of once weekly dosing). • Cancer Drug Fund approval – BLUETEQ is required prior to treatment. • The Cancer Drug Fund stipulates that the patient is contraindicated for thalidomide containing chemotherapy or intolerant to thalidomide. Toxicity Drug Daratumumab Dexamethasone Lenalidomide Adverse Effect Infusion related reactions, hypotension, headache, rash, urticaria, pruritus, nausea, vomiting, respiratory tract infections (including pneumonia), neutropenia, thrombocytopenia, anaemia, lymphopenia, peripheral neuropathy, diarrhoea, muscle spasms, fatigue, pyrexia and peripheral oedema, blood transfusion related events Weight gain, gastrointestinal disturbances, hyperglycaemia, CNS disturbances, Cushingoid changes, glucose intolerance. Peripheral neuropathy, bone marrow suppression, pneumonia, infection, venous thrombotic events, respiratory dysfunction, rashes, hypokalaemia, hypomagnesaemia, hypocalcaemia, teratogenic risk, GI disturbances, flu-like symptoms. The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Monitoring Bloods • FBC, U&Es, Ca2+ and LFTs prior to day one of each cycle of treatment. Version 1 (October 2023) Page 1 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone • Paraprotein and / or light chains prior to each cycle. • All patients should be tested for hepatitis B virus (HBV) before initiating treatment with daratumumab. Those patients who test positive for HBV infection should be discussed with a consultant specialising in HBV prior to initiating treatment with daratumumab to plan monitoring requirements whilst on treatment. Patients may also be tested for hepatitis C, CMV and HIV at the same time if clinically appropriate. • Send a blood sample to transfusion and inform patient and transfusion laboratory that patient is due to commence daratumumab. Patient will require red cell phenotyping as cross match fails due to binding of daratumumab to red cells. • Regular monitoring of blood glucose is considered good practice due to dexamethasone use. • Pregnancy testing in women of childbearing potential. A negative pregnancy test must be obtained within 3 days of starting lenalidomide the test must be repeated every 4 weeks (every 2 weeks in women with irregular menstrual cycles) with the final test 4 weeks after the last dose of lenalidomide. Dose Modifications The dose modifications listed are for haematological, liver and renal function and drug specific toxicities only. Dose adjustments may be necessary for other toxicities as well. In principle all dose reductions due to adverse drug reactions should not be re-escalated in subsequent cycles without consultant approval. It is also a general rule for chemotherapy that if a third dose reduction is necessary treatment should be stopped. Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. Haematological No dose reductions of daratumumab are recommended. Dose delay may be required to allow recovery of blood cell counts in the event of haematological toxicity. Always refer to the responsible consultant, as any dose delays will be dependent on clinical circumstances and treatment intent. Low counts can be a consequence of bone marrow infiltration as well as drug toxicity. Consider blood transfusion or the use of erythropoietin according to NICE TA323 if patient symptomatic of anaemia or where the haemoglobin is less than 8g/dL (80g/L). Consider growth factor support as an alternative to the options below, particularly where there is evidence of bone marrow suppression. To initiate a new cycle of daratumumab, the neutrophil count should be 1x109/L or greater and the platelet count should be 50x109/L or greater, unless the low counts are due to bone marrow infiltration with myeloma. In this situation the daratumumab may be administered at the discretion of the treating consultant haematologist with the appropriate blood product and growth factor support. Version 1 (October 2023) Page 2 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone Dose Reduction Steps Starting Dose Dose Level -1 Dose Level -2 Dose Level -3 Dose Level -4 Dose Level -5 Lenalidomide 25 mg 20 mg 15 mg 10 mg 5 mg 2.5 mg Neutrophils (x109/L) Dose Modifications (Lenalidomide) Fall to less than 1.0 First Occurrence Interrupt lenalidomide treatment and monitor FBC weekly. Consider G-CSF treatment. Return to 1.0 with no other observed toxicity Return to 1.0 or greater and dosedependent haematological toxicities other than neutropenia are observed Resume at 25 mg daily Resume at the next lower dose Subsequent Occurrence Fall to less than 1.0 Interrupt lenalidomide treatment and monitor FBC weekly. Consider G-CSF treatment. Return to 1.0 or greater Resume at the next lower dose Platelets (x109/L) Fall to less than 30 Returns to 30 or greater Dose Modifications First Occurrence Interrupt lenalidomide treatment and monitor FBC weekly. Consider transfusion. Resume at the next lower dose Version 1 (October 2023) Page 3 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone Fall to less than 30 Returns to 30 or greater Subsequent Occurrence Interrupt lenalidomide treatment and monitor FBC weekly. Consider transfusion. Resume at the next lower dose Hepatic Impairment Drug Lenalidomide Daratumumab Bilirubin μmol/L N/A AST/ALT units/L N/A Dose (% of original dose) No formal studies conducted. No specific dose recommendations. No formal studies of daratumumab in patients with hepatic impairment have been conducted. Based on population pharmacokinetic analysis no dosage adjustments are necessary for patients with hepatic impairment Renal Impairment Drug Lenalidomide Daratumumab Creatinine Clearance Dose (ml/min) (% of original dose) 10 mg daily 30 and 50 The dose may be escalated to 15 mg after 2 cycles if patient is not responding to treatment and tolerates the dose Less than 30 7.5 mg daily or 15 mg every other day Less than 30 with Dialysis 5 mg daily Administer after dialysis No formal studies of daratumumab in patients with renal impairment have been conducted. Based on population pharmacokinetic analysis no dosage adjustments are necessary for patients with renal impairment Other Dose reductions or interruptions in therapy are not necessary for those toxicities that are considered unlikely to be serious or life threatening. For example, alopecia, altered taste or nail changes. Lenalidomide In general, lenalidomide treatment should be stopped when the patient develops NCI-CTC grade 3 or 4 toxicities. Restart at next lower dose level when toxicity has resolved to grade 2 or lower depending on the physician’s discretion. Allergic or hypersensitivity reactions that occur at NCI-CTC grade 2, withhold treatment until the symptoms have resolved to NCI-CTC grade 1 or below. Treatment may be cautiously Version 1 (October 2023) Page 4 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone restarted at a daily dose of 15mg. For NCI-CTC grade 3 or above reactions discontinue the lenalidomide. Thromboembolism The combination of lenalidomide with dexamethasone is associated with an increased risk of venous thromboembolism. Appropriate thromboprophylaxis is recommended, especially in patients with additional thrombotic risk factors. Patients and their carers should be made aware of the symptoms of thromboembolism and advised to seek a medical advice if they develop shortness of breath, chest pain or swelling of a limb. If the patient develops thromboembolic events, treatment must be discontinued. Once the patient has been stabilised on the anticoagulation treatment and any complications of the thromboembolic event have been managed, the lenalidomide treatment may be restarted at the original dose dependent upon a benefit risk assessment. Skin Rash Lenalidomide should be interrupted or discontinued for NCI-CTC grade 2 or 3 skin rash. Allergic or Hypersensitivity Reactions Cases of allergic reactions including angioedema, anaphylactic reaction and severe cutaneous reactions including SJS, TEN and DRESS have been reported in patients treated with lenalidomide (see section 4.8). Patients should be advised of the signs and symptoms of allergic and hypersensitivity reactions and should be instructed to seek medical attention immediately if they develop these symptoms. Lenalidomide must be discontinued for angioedema, anaphylactic reaction, exfoliative or bullous rash, or if Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is suspected and should not be resumed following discontinuation for these reactions. Interruption or discontinuation of lenalidomide should be considered for other forms of skin reaction depending on severity. Patients who had previous allergic reactions while treated with thalidomide should be monitored closely, as a possible cross-reaction between lenalidomide and thalidomide has been reported in the literature. Patients with a history of severe rash associated with thalidomide treatment should not receive lenalidomide. Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) has been reported with lenalidomide. Patients should be monitored for new or worsening neurological symptoms, cognitive or behavioural signs and symptoms. If PML is suspected, further dosing must be suspended until PML has been excluded. If PML is confirmed, lenalidomide must be permanently discontinued. Version 1 (October 2023) Page 5 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone Teratogenicity Lenalidomide is highly teratogenic. All prescribers, patients and pharmacy staff must comply with the manufacturer’s Pregnancy Prevention Programme. Women of child-bearing potential taking thalidomide must use one agreed effective method of contraception for at least 4 weeks before starting thalidomide, while on Lenalidomide and for one month after. They must have a negative pregnancy test within 3 days prior to starting treatment. Pregnancy testing should be repeated monthly thereafter until one month after stopping Lenalidomide (or every 2 weeks in women with irregular menstrual cycles). If a woman taking Lenalidomide thinks she may be pregnant she must stop the drug immediately and seek medical advice. Men taking Lenalidomide must use a barrier method of contraception throughout treatment and for one week after stopping, if their partner is capable of bearing children. Other Dexamethasone For patients who are elderly or unable to tolerate the standard dose of dexamethasone the dose given the day after bortezomib alone may be reduced. Please note the doses before and the day after each daratumumab are to reduce the risk of infusion related reactions and as a steroid component of the triple combination. Infusion related reactions (IRR) Daratumumab solution for subcutaneous injection can cause severe and/or serious IRRs, including anaphylactic reactions. In clinical studies, approximately 11% (52/490) of patients experienced an IRR. Most IRRs occurred following the first injection and were Grade 1-2. IRRs occurring with subsequent injections were seen in less than 1% of patients. The median time to onset of IRRs following daratumumab injection was 3.7 hours (range 0.15-83 hours). The majority of IRRs occurred on the day of treatment. Delayed IRRs have occurred in less than 1% of patients. Signs and symptoms of IRRs may include respiratory symptoms, such as nasal congestion, cough, throat irritation, allergic rhinitis, wheezing as well as pyrexia, chest pain, pruritus, chills, vomiting, nausea, and hypotension. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnoea, hypertension and tachycardia. Patients should be pre-medicated with antihistamines, antipyretics, and corticosteroids as well as monitored and counselled regarding IRRs, especially during and following the first and second injections. If an anaphylactic reaction or life-threatening (Grade 4) reactions occur, appropriate emergency care should be initiated immediately. Daratumumab therapy should be discontinued immediately and permanently. To reduce the risk of delayed IRRs, oral corticosteroids should be administered to all patients following Daratumumab injection. Patients with a history of chronic obstructive pulmonary disease may require additional post-injection medicinal products to manage respiratory complications. The use of post-injection medicinal products (e.g. short- and long- Version 1 (October 2023) Page 6 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone acting bronchodilators and inhaled corticosteroids) should be considered for patients with chronic obstructive pulmonary disease. Interference with Serological Testing Daratumumab binds to CD38 in red blood cells and results in a positive indirect antiglobulin test (Coombs test). Daratumumab mediated positive indirect antiglobulin test may persist for up to six months after the last daratumumab infusion. Daratumumab bound red blood cells masks detection of antibodies to minor antigens in the patient serum. The determination of a patient ABO and Rh blood type are not impacted. Blood transfusion must be informed that a patient is receiving daratumumab. Patients must be typed and screened prior to daratumumab. All patients must be given an identification card that should be carried for six months after stopping therapy and agree to inform all healthcare professionals who treat them that they have received daratumumab. Daratumumab is a human IgG kappa monoclonal antibody detectable on both the serum electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in all patients with IgG kappa myeloma. Reactivation of Hepatitis B Virus Hepatitis B virus reactivation has been reported in patients treated with daratumumab and lenalidomide. All patients must be screened for hepatitis B before initiation of treatment. This includes all patients with unknown serology who are on treatment already. Monitoring is required for patients with positive serology for clinical and laboratory signs of hepatitis B reactivation during treatment and for at least six months after completion of daratumumab. Those with positive serology must seek medical help immediately if they experience symptoms of hepatitis B. Daratumumab and lenalidomide must be stopped if hepatitis B reactivation occurs during treatment. Regimen Cycles 1 to 2 Drug Dose Daratumumab 1800mg Dexamethasone 20mg PO (this includes dexamethasone pre-meds) i.e. on daratumumab days, the premed dose of dexamethasone is sufficient. On nondaratumumab days, 20mg is Days Days 1, 8, 15 and 22 Days 1, 2, 8, 9, 15, 16, 22 and 23 Administration Subcutaneous 20mg Oral 10mg oral (or iv dose equivalent) for over 75yrs and less than BMI 18.5 Version 1 (October 2023) Page 7 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone to be administered. Lenalidomide 25mg PO Days 1 to 21 (NOCTE) Oral Cycles 3 to 6 Drug Daratumumab Dexamethasone Lenalidomide Dose 1800mg 20mg PO (this includes dexamethasone pre-meds) i.e. on daratumumab days, the premed dose of dexamethasone is sufficient. On nondaratumumab days, 20mg is to be administered. 25mg PO Days Days 1, and 15 Days 1, 2, 15 and 16 Days 1 to 21 (NOCTE) Administration Subcutaneous 20mg Oral 10mg oral (or iv dose equivalent) for over 75yrs and less than BMI 18.5 Oral Cycles 7 and further cycles Drug Daratumumab Dexamethasone Lenalidomide Dose 1800mg 20mg PO (this includes dexamethasone pre-meds) i.e. on daratumumab days, the premed dose of dexamethasone is sufficient. On nondaratumumab days, 20mg is to be administered. 25mg PO Days Day 1 Days 1 and 2 Days 1 to 21 (NOCTE) Administration Subcutaneous 20mg Oral 10mg oral (or iv dose equivalent) for over 75yrs and less than BMI 18.5 Oral Cycle Frequency Version 1 (October 2023) Page 8 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone 28-day cycle until disease progression or intolerance Dose Information • Dexamethasone is available as 2mg and 500microgram tablets and 3.3mg in 1ml injection (equivalent to 4mg orally) • Lenalidomide is available as 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg, and 25mg capsules Administration Information • The first dose of daratumumab should be administered in an environment where resuscitation facilities are available. • For first dose a cannula should be inserted to allow emergency treatment of anaphylaxis • Pre-medications (oral or intravenous) should be administered to reduce the risk of IRRs to all patients 1-3 hours prior to every administration of Daratumumab. • For patients with a history of chronic obstructive pulmonary disease, the use of postinjection medicinal products including short and long-acting bronchodilators, and inhaled corticosteroids should be considered. • Inject 15 mL daratumumab solution for subcutaneous injection into the subcutaneous tissue of the abdomen approximately 7.5 cm to the right or left of the umbilicus over approximately 3-5 minutes. Do not inject daratumumab solution for subcutaneous injection at other sites of the body as no data are available. • First dose daratumumab that the patient should be observed with hourly observations for 4 hours following subcutaneous administration. If no infusion-related reactions following the first dose then neither cannulation nor additional post injection observations are needed with subsequent doses. If IRR with first dose then continue to observe for 4 hours following subsequent doses until IRRs subside. Following the first four injections, if the patient experiences no major IRRs, inhaled postinjection medicinal products may be discontinued at the discretion of the physician. • If the patient experiences no major IRRs after the first three injections, post-injection corticosteroids (excluding any background regimen corticosteroids) may be discontinued. • No modification to rate or dose of daratumumab administration was required to manage IRRs in clinical studies. • Injection sites should be rotated for successive injections. • Daratumumab solution for subcutaneous injection should never be injected into areas where the skin is red, bruised, tender, hard or areas where there are scars. • Pause or slow down delivery rate if the patient experiences pain. In the event pain is not alleviated by slowing down the injection, a second injection site may be chosen on the opposite side of the abdomen to deliver the remainder of the dose. Version 1 (October 2023) Page 9 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone • During treatment with daratumumab solution for subcutaneous injection, do not administer other medicinal products for subcutaneous use at the same site as Daratumumab. • Lenalidomide should be taken at night to avoid daytime drowsiness • Lenalidomide prescriptions must be accompanied by a completed Prescription Authorisation Form Additional therapy • Consider allopurinol 300mg once a day for seven days for the first cycle only oral • Anti-emetics - Metoclopramide 10mg three times a day when required oral (this is not included in the regimen on ARIA but can be added from favourites if required) • Premedication required 1 to 3 hours before every daratumumab infusion: - Dexamethasone – see regimen for dose details - Chlorphenamine 4mg oral - Paracetamol 1000mg oral - Montelukast 10mg oral for the first four doses only • Thromboprophylaxis according to local formulary choice. For example; - Dalteparin 5000units once a day subcutaneous injection - Enoxaparin 40mg once a day subcutaneous injection - Heparin 5000units twice a day subcutaneous injection - Apixaban 2.5mg twice a day oral (unlicensed use) - Aspirin 75mg once daily (patients with no or one risk factor) • Bisphosphonates in accordance with local policies. • Mouthwashes according to local or national policy on the treatment of mucositis. • Laxatives as required for Lenalidomide-induced constipation. • Gastric protection with a proton pump inhibitor or an H2 antagonist may be considered in patients considered at high risk of GI ulceration or bleed. • As required for the treatment of infusion related reactions for patients at high risk of respiratory complications: - Salbutamol 2.5mg nebulised - Hydrocortisone sodium succinate 100mg intravenous - Chlorphenamine 10mg intravenous - Paracetamol 1000mg oral - Oxygen as required Version 1 (October 2023) Page 10 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone Additional Information • All instances of infusion related reaction must be recorded on ARIA. • Daratumumab interferes with indirect antiglobulin tests as it binds to CD38 on red blood corpuscles (RBCs) and interferes with compatibility testing, including antibody screening and cross matching. Daratumumab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt daratumumab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kell-negative units should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered. • Daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, consider other methods to evaluate the depth of response. • The National Patient Safety Agency alert NPSA/2008/RRR001 must be followed when prescribing, dispensing or administering oral chemotherapy. • Patients should be assessed for suitability for oral chemotherapy prior to starting treatment. • For all patients taking lenalidomide; the patient, prescriber and supplying pharmacy must comply with an appropriate pregnancy prevention programme. Reference 1. eMC (2023). Apixaban 2.5mg film-coated tablets. Available at: https://www.medicines.org.uk/emc/product/14534. Accessed [15/10/2023]. 2. eMC (2023). Darzalex 1800mg solution for injection. Available at: https://www.medicines.org.uk/emc/search?q=daratumumab. Accessed [15/10/2023]. 3. eMC (2023). Revlimid 25mg Hard Capsules. Available at: https://www.medicines.org.uk/emc/product/10047/smpc Accessed [15/10/2023]. 4. Facon, T., Kumar, S. et al (2019). Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. Available at: https://www.nejm.org/doi/full/10.1056/nejmoa1817249. Accessed [15/10/2023]. 5. IMWG Guidelines (2023). IMWG Guidelines for the Prevention of Thalidomide and Lenalidomide-Associated Thrombosis in Myeloma. Available at: https://www.myeloma.org/resource-library/imwg-guidelines-preventionthalidomide-lenalidomide-associated-thrombosis-myeloma. Accessed [15/10/2023]. 6. Moik, F., et al (2020). Direct oral anticoagulants compared to low‐molecular‐weight heparin for the treatment of cancer‐associated thrombosis: Updated systematic review and meta‐analysis of randomized controlled trials. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292654/ [Accessed 15/10/2023] REGIMEN SUMMARY Myeloma – DRD Daratumumab-Lenalidomide-Dexamethasone Version 1 (October 2023) Page 11 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone Cycle 1 Day 1 1.Warning – Inform blood transfusion Administration Instructions Daratumumab interferes with indirect antiglobulin tests as it binds to CD38 on red blood corpuscles (RBCs) and interferes with compatibility testing, including antibody screening and cross matching. Daratumumab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt daratumumab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kell-negative units should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered. Daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, consider other methods to evaluate the depth of response Please inform blood transfusion when a patient is prescribed daratumumab 2.Antihistamine oral Administration Instructions Oral antihistamine according to local formulary choices. To be taken 1 -3 hours prior to daratumumab infusion For example; Chlorphenamine 4mg Oral Loratadine 10mg Oral Cetirizine 10mg Oral Fexofenadine 120mg Oral Acrivastine 8mg Oral 3.Dexamethasone 20mg oral Administration Instructions To be taken 1 -3 hours prior to daratumumab infusion. Can be administered as 20mg intravenous. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 4.Paracetamol 1000mg oral Administration Instructions To be taken 1 -3 hours prior to daratumumab infusion Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 5.Montelukast 10mg oral Administration Instructions To be taken 1-3 hours prior to daratumumab 6.Daratumumab 1800mg subcutaneous injection over 3 – 5 minutes Administration Instructions Inject the daratumumab solution for subcutaneous injection into the subcutaneous tissue of the abdomen approximately 7.5 cm to the right or left of the navel over approximately 3-5 minutes. Do not inject daratumumab solution for subcutaneous injection at other sites of the body as no data are available. Injection sites should be rotated for successive injections Daratumumab solution for subcutaneous injection should never be injected into areas where the skin is red, bruised, tender, hard or areas where there are scars. Pause or slow down delivery rate if the patient experiences pain. In the event pain is not alleviated by slowing down the injection, a second injection site may be chosen on the opposite side of the abdomen to deliver the remainder of the dose. During treatment with daratumumab solution for subcutaneous injection, do not administer other medicinal products for subcutaneous use at the same site as daratumumab. 7.Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions Version 1 (October 2023) Page 12 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone 8.Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 9.Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 10.Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions Cycle 1 Days 8, 15, 22 11.Warning – Check if Antihistamine Taken Administration Instructions Ensure the patient has taken the antihistamine premedication. If not please administer one of the following according to local formulary choice; To be taken 1 -3 hours prior to daratumumab infusion Chlorphenamine 4mg Oral Loratadine 10mg Oral Cetirizine 10mg Oral Fexofenadine 120mg Oral Acrivastine 8mg Oral 12.Warning – Check if the Dexamethasone Taken Administration Instructions Ensure the patient has taken the dexamethasone premedication. If not please administer dexamethasone 20mg oral or intravenous if the patient is unable to tolerate the oral dose. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 13.Warning – Check if the Paracetamol Taken Administration Instructions Please check if the patient has taken paracetamol. If not please administer paracetamol 1000mg. The maximum dose is 4000mg/24 hours 14.Montelukast 10mg oral Administration Instructions To be taken 1-3 hours prior to daratumumab 15.Daratumumab 1800mg subcutaneous injection over 3 – 5 minutes Administration Instructions Inject the daratumumab solution for subcutaneous injection into the subcutaneous tissue of the abdomen approximately 7.5 cm to the right or left of the navel over approximately 3-5 minutes. Do not inject daratumumab solution for subcutaneous injection at other sites of the body as no data are available. Injection sites should be rotated for successive injections Daratumumab solution for subcutaneous injection should never be injected into areas where the skin is red, bruised, tender, hard or areas where there are scars. Pause or slow down delivery rate if the patient experiences pain. In the event pain is not alleviated by slowing down the injection, a second injection site may be chosen on the opposite side of the abdomen to deliver the remainder of the dose. During treatment with daratumumab solution for subcutaneous injection, do not administer other medicinal products for subcutaneous use at the same site as daratumumab. 16.Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 17.Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 18.Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Version 1 (October 2023) Page 13 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 19.Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions Cycle 1 Take home medicines (day 1 only) 20.Warning – Pregnancy Prevention Programme Administration Instructions Lenalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients 21.Dexamethasone 20mg on days 2, 8, 9, 15, 16, 22 and 23 oral Administration Information Reduce dose to 10mg in patients over 75 years old Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 22.Dexamethasone 20mg on day 1 of the next cycle Take in the morning prior to daratumumab injection Note to pharmacy; dispense for day 1 of the next cycle 23.Lenalidomide 25mg once a day for 21 days from Day 1 to 21 of cycle oral Administration Instructions Lenalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients. Oral chemotherapy. Take at night to avoid daytime drowsiness. To start at 25mg and adjust the dose according to toxicity and patient’s tolerance 24.Allopurinol 300mg once a day for 7 days oral Administration information Take in the morning with food and plenty of water. This should be supplied for the first cycle only. 25.Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 26.Levofloxacin 500mg once a day for 84 days oral Administration Instructions Please supply 12 weeks on cycle 1 only 27.Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice 28.Fluconazole 100mg once a day oral Administration information Prescribe if recurrent oral candidiasis. 29.Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - Esomeprazole 20mg once a day oral - Omeprazole 20mg once a day oral - Lansoprazole 15mg once a day oral - Pantoprazole 20mg once a day oral - Rabeprazole 20mg once a day oral - Cimetidine 400mg twice a day oral - Famotidine 20mg once a day oral - Nizatidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. 30.Anthistamine on the days of daratumumab administration Administration Instructions Version 1 (October 2023) Page 14 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone Take on the day of daratumumab administration. To be taken 1 -3 hours prior to daratumumab infusion Please supply 1 x OP. This is to cover all cycles. To be supplied as per local formulary choice - Chlorphenamine 4mg Oral - Loratadine 10mg Oral - Cetirizine 10mg Oral - Fexofenadine 120mg Oral - Acrivastine 8mg Oral 31.Paracetamol 1000mg oral on the days of daratumumab administration Administration Instructions Take 1000mg prior to daratumumab administration. To be taken 1 -3 hours prior to daratumumab infusion Please supply 1 x 100 x 500mg. This is to cover all cycles 32.Thromboprophylaxis according to local formulary choice; Administration Instructions The choice of thromboprophylaxis is dependent on local formulary choice and may include; - Dalteparin 5000units once a day subcutaneous injection - Enoxaparin 40mg once a day subcutaneous injection - Heparin 5000units twice a day subcutaneous injection - Apixaban 2.5mg twice a day oral (unlicensed use) - Aspirin 75mg once daily (patients with no or one risk factor) Please supply 28 days or nearest original pack size. Cycles 2 days 1, 8, 15, 22 33.Warning – Check if Antihistamine Taken Administration Instructions Ensure the patient has taken the antihistamine premedication. If not please administer one of the following according to local formulary choice; - Chlorphenamine 4mg Oral - Loratadine 10mg Oral - Cetirizine 10mg Oral - Fexofenadine 120mg Oral - Acrivastine 8mg Oral 34.Warning – Check if the Dexamethasone Taken Administration Instructions Ensure the patient has taken the dexamethasone premedication. If not please administer dexamethasone 20mg oral or intravenous if the patient is unable to tolerate the oral dose. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 35.Warning – Check if the Paracetamol Taken Administration Instructions Please check if the patient has taken paracetamol. If not please administer paracetamol 1000mg. The maximum dose is 4000mg/24 hours 36.Daratumumab 1800mg subcutaneous injection over 3 – 5 minutes Administration Instructions Inject the daratumumab solution for subcutaneous injection into the subcutaneous tissue of the abdomen approximately 7.5 cm to the right or left of the navel over approximately 3-5 minutes. Do not inject daratumumab solution for subcutaneous injection at other sites of the body as no data are available. Injection sites should be rotated for successive injections Daratumumab solution for subcutaneous injection should never be injected into areas where the skin is red, bruised, tender, hard or areas where there are scars. Pause or slow down delivery rate if the patient experiences pain. In the event pain is not alleviated by slowing down the injection, a second injection site may be chosen on the opposite side of the abdomen to deliver the remainder of the dose. During treatment with daratumumab solution for subcutaneous injection, do not administer other medicinal products for subcutaneous use at the same site as daratumumab. 37.Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions Version 1 (October 2023) Page 15 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone 38.Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 39.Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 40.Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions. Cycles 2 Take home medicines (day 1 only) 41.Warning – Pregnancy Prevention Programme Administration Instructions Thalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients. 42.Dexamethasone 20mg on days 2, 8, 9, 15, 16, 22 and 23 oral Administration Information Reduce dose to 10mg in patients over 75 years old. Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 43.Dexamethasone 20mg on day 1 of the next cycle Take in the morning prior to daratumumab injection. Reduce dose to 10mg in patients over 75 years old. Note to pharmacy; dispense for day 1 of the next cycle. 44.Lenalidomide 25mg once a day for 21 days from Day 1 to 21 of cycle oral Administration Instructions Lenalidomide is associated with a pregnancy prevention programme. Please ensure this is Lenalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients. Oral chemotherapy. Take at night to avoid daytime drowsiness. To start at 25mg and adjust the dose according to toxicity and patient’s tolerance. 45.Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 46.Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 47.Fluconazole 100mg once a day for 28 days oral Administration Instructions 48.Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - Esomeprazole 20mg once a day oral - Omeprazole 20mg once a day oral - Lansoprazole 15mg once a day oral - Pantoprazole 20mg once a day oral - Rabeprazole 20mg once a day oral - Cimetidine 400mg twice a day oral - Famotidine 20mg once a day oral - Nizatidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. 49.Thromboprophylaxis according to local formulary choice; Administration Instructions The choice of thromboprophylaxis is dependent on local formulary choice and may include; - Dalteparin 5000units once a day subcutaneous injection - Enoxaparin 40mg once a day subcutaneous injection Version 1 (October 2023) Page 16 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone - Heparin 5000units twice a day subcutaneous injection - Apixaban 2.5mg twice a day oral (unlicensed use) - Aspirin 75mg once daily (patients with no or one risk factor) Please supply 28 days or nearest original pack size. Cycles 3 to 6 day 1 and 15 50.Warning – Check if Antihistamine Taken Administration Instructions Ensure the patient has taken the antihistamine premedication. If not please administer one of the following according to local formulary choice; Chlorphenamine 4mg Oral Loratadine 10mg Oral Cetirizine 10mg Oral Fexofenadine 120mg Oral Acrivastine 8mg Oral 51.Warning – Check if the Dexamethasone Taken Administration Instructions Ensure the patient has taken the dexamethasone premedication. If not please administer dexamethasone 20mg oral or intravenous if the patient is unable to tolerate the oral dose. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 52.Warning – Check if the Paracetamol Taken Administration Instructions Please check if the patient has taken paracetamol. If not please administer paracetamol 1000mg. The maximum dose is 4000mg/24 hours 53.Daratumumab 1800mg subcutaneous injection over 3 – 5 minutes Administration Instructions Inject the daratumumab solution for subcutaneous injection into the subcutaneous tissue of the abdomen approximately 7.5 cm to the right or left of the navel over approximately 3-5 minutes. Do not inject daratumumab solution for subcutaneous injection at other sites of the body as no data are available. Injection sites should be rotated for successive injections. Daratumumab solution for subcutaneous injection should never be injected into areas where the skin is red, bruised, tender, hard or areas where there are scars. Pause or slow down delivery rate if the patient experiences pain. In the event pain is not alleviated by slowing down the injection, a second injection site may be chosen on the opposite side of the abdomen to deliver the remainder of the dose. During treatment with daratumumab solution for subcutaneous injection, do not administer other medicinal products for subcutaneous use at the same site as daratumumab. 54.Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 55.Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 56.Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 57.Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions Cycles 3,4,5 Take home medicines (day 1 only) 58.Warning – Pregnancy Prevention Programme Administration Instructions Thalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients Version 1 (October 2023) Page 17 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone 59.Dexamethasone 20mg on days 2, 15 and 16 oral Administration Information Reduce dose to 10mg in patients over 75 years old Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 60.Dexamethasone 20mg on day 1 of the next cycle Take in the morning prior to daratumumab injection. Reduce dose to 10mg in patients over 75 years old. Note to pharmacy; dispense for day 1 of the next cycle 61.Lenalidomide 25mg once a day for 21 days from Day 1 to 21 of cycle oral Administration Instructions Lenalidomide is associated with a pregnancy prevention programme. Please ensure this is Lenalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients. Oral chemotherapy. Take at night to avoid daytime drowsiness. To start at 25mg and adjust the dose according to toxicity and patient’s tolerance. 62.Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 63.Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 64.Fluconazole 100mg once a day for 28 days oral Administration Instructions 65.Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. 66.Thromboprophylaxis according to local formulary choice; Administration Instructions The choice of thromboprophylaxis is dependent on local formulary choice and may include; - dalteparin 5000units once a day subcutaneous injection - enoxaparin 40mg once a day subcutaneous injection - heparin 5000units twice a day subcutaneous injection - Apixaban 2.5mg twice a day oral (unlicensed use) - Aspirin 75mg once daily (patients with no or one risk factor) Please supply 28 days or nearest original pack size. Cycle 6 Take home medicines (day 1 only) 67.Warning – Pregnancy Prevention Programme Administration Instructions Thalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients 68.Dexamethasone 20mg on days 2, 15 and 16 oral Administration Information Reduce dose to 10mg in patients over 75 years old Version 1 (October 2023) Page 18 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 69.Dexamethasone 20mg on day 1 of the next cycle Administration Information Reduce dose to 10mg in patients over 75 years old Take in the morning with or after food. Please dispense on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 70.Lenalidomide 25mg once a day for 21 days from Day 1 to 21 of cycle oral Administration Instructions Lenalidomide is associated with a pregnancy prevention programme. Please ensure this is Lenalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients. Oral chemotherapy. Take at night to avoid daytime drowsiness. To start at 25mg and adjust the dose according to toxicity and patient’s tolerance. 71.Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 72.Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 73.Fluconazole 100mg once a day for 28 days oral Administration Instructions 74.Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. 75.Thromboprophylaxis according to local formulary choice; Administration Instructions The choice of thromboprophylaxis is dependent on local formulary choice and may include; - dalteparin 5000units once a day subcutaneous injection - enoxaparin 40mg once a day subcutaneous injection - heparin 5000units twice a day subcutaneous injection - Apixaban 2.5mg twice a day oral (unlicensed use) - Aspirin 75mg once daily (patients with no or one risk factor) Please supply 28 days or nearest original pack size. Cycles 7 and further cycles day 1 76.Warning – Check if Antihistamine Taken Administration Instructions Ensure the patient has taken the antihistamine premedication. If not please administer one of the following according to local formulary choice; Chlorphenamine 4mg Oral Loratadine 10mg Oral Cetirizine 10mg Oral Fexofenadine 120mg Oral Version 1 (October 2023) Page 19 of 22 Myeloma –DRD-Daratumumab-Lenalidomide-Dexamethasone Acrivastine 8mg Oral 77.Warning – Check if the Dexamethasone Taken Administration Instructions Ensure the patient has taken the dexamethasone premedication. If not please administer dexamethasone 20mg oral or intravenous if the patient is unable to tolerate the oral dose. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 78.Warning – Check if the Paracetamol Taken Administration Instructions Please check if the patient has taken paracetamol. If not please administer paracetamol 1000mg. The maximum dose is 4000mg/24 hours 79.Daratumumab 1800mg subcutaneous injection over 3 – 5 minutes Administration Instructions Inject the daratumumab solution for subcutaneous injection into the subcutaneous tissue of the abdomen approximately 7.5 cm to the right or left of the navel over approximately 3-5 minutes. Do not inject daratumumab solution for subcutaneous injection at other sites of the body as no data are available. Injection sites should be rotated for successive injections. Daratumumab solution for subcutaneous injection should never be injected into areas where the skin is red, bruised, tender, hard or areas where there are scars. Pause or slow down delivery rate if the patient experiences pain. In the event pain is not alleviated by slowing down the injection, a second injection site may be chosen on the opposite side of the abdomen to deliver the remainder of the dose. During treatment with daratumumab solution for subcutaneous injection, do not administer other medicinal products for subcutaneous use at the same site as daratumumab. 80.Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 81.Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 82.Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is
Url: /Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Myeloma/DRD-Daratumumab-Lenalidomide-Dexamethasone.pdf

Annual ward staffing review January 2025

Description: [5.15] Report to the Trust Board of Directors, 7th January 2025 Title: Ward Staffing Nursing Establishment Review July 2024 – October 2024 Sponsor: Gail Byrne, Chief Nursing Officer Author: Rosemary Chable, Head of Nursing for Education, Practice and Staffing Purpose (type an ‘x’ in the appropriate box(es)) (Re)Assurance Approval Ratification Information X Strategic Theme (type an ‘x’ in the appropriate box(es)) Outstanding patient Pioneering research World class people outcomes, safety and innovation and experience Integrated networks and collaboration Foundations for the future X X Executive Summary: a) The report details the methodology, findings, risk assessment and recommendations arising from the ward staffing review undertaken from July 2024 – October 2024. Recommendations in this report link to the statutory responsibilities arising from the National Quality Board (2016) expectations on ensuring safe, sustainable, and productive staffing, the NHS Improvement Developing Workforce Safeguards guidance (2018) and the Nursing Workforce Standards (RCN May 2021) assessed as part of CQC ‘safe’ and ‘well-led’ domain. The report outlines UHS progress in meeting the 38 recommendations included in the NICE guideline (2014) on safe staffing for in-patient wards and provides an update on the action – plan to achieve the recommendations in the national staffing levels guidance published by the National Quality Board in July 2016 (a key requirement of the NHSI ‘Developing workforce safeguards’ guidance (October 2018). b) To note findings of this annual ward establishment review and the Trust position in relation to adherence to the monitored metrics on nurse staffing levels, specifically: Overall, the staffing establishments remain appropriate and within recommended guidelines. There are some key exceptions where acuity and dependency levels and growing demand continue to outstrip the nursing ratios, coupled with the impact of ward reconfigurations – recommendations for uplifts in these areas will be put forward by the Divisions as part of the annual budget setting process.  UHS nursing establishments are set to achieve a range of 1:1 to 1:9 registered nurse to patient ratio in most areas during the day with the majority (43) set between 1:4 to 1:8. Differences relate to specialty and overall staffing model.  The majority of wards (32) are staffed at between 50:50 and 80:20 registered/unregistered ratio or above. Those wards with lower ratios (21 wards) are linked to the systematic and evaluated implementation of trained band 4 staff where appropriate and those with higher ratios (2) are both higher intensity care areas requiring a higher registered skill. 33 wards (down from 35 last year but remaining up significantly from 25 in 2019) are below the 60:40 ratio.  Planned total Care Hours Per Patient Day (CHPPD) range from 4.2 – 19.2 and average at 7.7  High levels of enhanced care demand, a reduced skill-mix and impact of financial controls have been highlighted as ongoing challenges for mitigation to ensure safe staffing. 1 The paper is presented for DISCUSSION. c) The report is presented in full to Trust Board as an expectation of the National Quality Board guidance on staffing which requires presentation and discussion at open board on all aspects of the staffing reviews. Contents: Paper; Appendix 1: National Quality Board (NQB Expectations for safe staffing Safe, Sustainable, and productive staffing; Appendix 2: NQB Safe Staffing Recommendations – UHS action plan; Appendix 3: NICE Guideline 1: Safe Staffing for nursing in adult inpatient wards in acute hospital - UHS action plan; Appendix 4: Ward by Ward staffing review metrics spreadsheet; Appendix 5: Specific Divisional issues emerging; Appendix 6: RCN Workforce Standards Risk(s): 1b – Due to the current challenges we fail to provide patients and families/carers with a highquality experience of care and positive patient outcomes. 3a – We are unable to meet current and planned service requirements due to the unavailability of staff to fulfil key roles. Equality Impact Consideration: NO 2 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 2.0 2.1 2.1.1 2.1.2 Introduction or Background The purpose of this paper is to report on the outcomes of the review of ward staffing nursing establishments undertaken from July 2024 – October 2024. This 6-monthly review forms part of the Trust approach to the systematic review of staffing resources to ensure safe staffing levels effectively meet patient care needs. This paper focuses specifically on a review of nursing levels for in-patient ward areas. Areas such as maternity, critical care, theatres and the emergency department are reviewed separately. Divisional ‘light touch’ 6 monthly staffing reviews took place in March/April 2024 for all 4 clinical divisions and were reported to their relevant divisional boards and Nursing and Midwifery Staffing Review Group. Emergent themes have been incorporated into this review. The ward staffing review this year has taken place against the backdrop of financial recovery measures, some of which came into effect in Q4 of 2023/24 after the last annual staffing review with increasing measures being introduced in 2024/25. Discussions at the staffing review meetings focussed on any impact arising from the close monitoring and management of establishment levels and any mitigations/adjustments needed to continue to assure the delivery of safe care. It should also be noted that there were some key ward reconfigurations and refurbishments, some ward moves and a new ward opening since the last annual review and these areas have now been fully included in the annual cycle. The report also includes an update on the NICE clinical guideline 1 – Safe Staffing for nursing in adult inpatient wards in acute hospitals, issued in July 2014 and details progress with the action plan for adopting this guideline within UHS. This report fulfils expectation 1 and 2 of the National Quality Board requirements for Trusts in relation to safe nurse staffing and fulfils a number of the requirements outlined in the NHS Improvement ‘Developing Workforce Safeguards’ guidance (October 2018) which sets out to support providers to deliver high quality care through safe and effective staffing. This review also meets standards outlined in the RCN Nursing Workforce Standards (May 2021). Organisations are expected to be compliant with the recommendations in these reports and are subject to review on this as part of the CQC inspection programme under both the ‘safe’ and ‘well led’ domains. Analysis and Discussion Ward staffing review methodology In 2006 UHS established a systematic, evidence based and triangulated methodological approach to reviewing ward staffing levels on an annual basis linked to budget setting and to staffing requirements arising from any developments planned in-year. This was aimed to provide safe, competent and fit for purpose staffing to deliver efficient, effective and high-quality care and has resulted in consistent year-onyear review of the nursing workforce matched by increased investment where required. Following the National Quality Board expectations in 2014 and the refresh in 2016, a full review is now undertaken annually (with a light touch review at 6 months reporting to Divisional boards to ensure ongoing quality) with annual reporting to Trust Board in October/November. 3 2.1.3 The approach utilises the following methodologies:  Shelford Safer Nursing Care Tool Acuity/Dependency staffing multiplier (A nationally validated tool reviewed in 2013 - previously AUKUH acuity tool). Now incorporated into the Healthroster Safecare system  Care Hours Per Patient Day (CHPPD)  Professional Judgement  Peer group validation  Benchmarking and review of national guidance including Model Health System data  Review of eRostering data  Review of ward quality metrics 2.2 2.2.1 2.2.2 National guidance In 2013 as part of the national response to the Francis enquiry, the National Quality Board published a guide to nursing, midwifery and care staffing capacity and capability (2013) ‘How to ensure the right people, with the right skills, are in the right place at the right time.’ This guidance was refreshed, broadened to all staff, and reissued in July 2016 to include the need to focus on safe, sustainable and productive staffing. The NQB further reviewed this document and issued an updated recommendations brief in July 2017. The expectations outlined in this guide are presented in Appendix 1. These expectations are fulfilled in part by this review and the detailed action plan (Appendix 2) has been updated with progress towards achieving compliance with the 37 recommendations that make up the 3 over-arching expectations. The latest 4 monthly review of the action plan (November 2024) shows maintenance of compliance levels despite the ongoing activity and financial challenges. UHS remaining compliant with 35 of the 37 recommendations. The following 2 outstanding areas are progressing but require further action before being signed off: Allocated time for the supervision of students and learners: Staffing establishments take account of the need to allow clinical staff the time to undertake mandatory training and continuous professional development, meet revalidation requirements, and fulfil teaching, mentorship and supervision roles, including the support of preregistration and undergraduate students. Whilst there is some allowance within the 23% headroom, requirements for supervision are growing with revised initiatives around preceptorship, staff wellbeing and student supervision. Learner numbers (students, international and apprentices, preceptees) are increasing with limited additional supervisory support available. It is also important to note that the Ward Leader Supervisory allowance was put on hold in Q4 2023/24 and reinstated slowly from Q1 2024/25 as part of the trust recovery plan. This impacted short term on some of the supervision and support available to students and learners. Equality and diversity: The organisation has clear plans to promote equality and diversity and has leadership that closely resembles the communities it serves. The research outlined in the NHS provider roadmap42 demonstrates the scale and persistence of discrimination at a time when the evidence demonstrates the links between staff satisfaction and patient outcomes. Ongoing action through Equality & Diversity Group which is reported to Board separately. 4 2.2.3 2.2.4 2.2.5 2.2.6 2.2.7 2.3 2.3.1 In July 2014 NICE published Clinical Guideline 1: Safe Staffing for nursing in adult inpatient wards in acute hospitals. This guideline is made up of 38 recommendations. A detailed action plan was developed within UHS and is reviewed 4 monthly by the Nursing and Midwifery Staffing review group. The current assessment (November 2024) shows UHS has maintained compliance in 37 of the 38 recommendations. The 1 remaining recommendation is: Escalation actions taken to address deficits on one ward should not compromise another. Management of trustwide staffing deficits and thrice daily reviews of staffing via the staffing hub, as well as an improved recruitment situation, have minimised the risk of this. The close management and maintenance of minimal staffing levels, however, does not enable assurance that wards are not compromised by staff movements in extremis. The ongoing action plan is included at Appendix 3 detailing the recommendations and the UHS compliance position and actions in progress. In October 2018 NHS Improvement published ‘Developing Workforce Safeguards’ guidance which sets out to support providers to deliver high quality care through safe and effective staffing. It includes many of the actions identified in both the NICE guidance and the National Quality Board recommendations broadened to all staff groups. In May 2021 the Royal College of Nursing published their Nursing Workforce Standards (Appendix 6), developed as part of their safe staffing campaigns. The standards summarise the expectations in other national guidance and reiterates the importance of the Chief Nurse being responsible for setting nurse staffing levels based on service demand and user needs and the requirement to report directly to the Trustboard. Self-assessment undertaken by the Nursing and Midwifery Staffing Review Group (NMSRG) show UHS remains compliant with these standards. In October 2024 the RCN launched a review of these standards which are expected to be published at the end of the year. In light of this imminent review NMSRG have refreshed the self-assessment and confirmed that UHS remains compliant with the standards. In September 2022 a key research study was published (Zaranko B, Sanford NJ, Kelly E et al. BMJ Quality and Safety Epub) which highlights the link between higher registered nurse numbers and seniority and improved patient outcomes. Additionally in August 2024 an additional follow-up article (Griffiths, P; Saville C; Ball, J JAMA Network open) identified that substitution of registered gaps with temporary staff does not necessarily significantly lower the risks for patients. In late 2023 NIHR published an evidence based Professional Judgement Framework to support the application of professional judgement in nurse staffing reviews. Rosemary Chable and Natasha Watts from UHSFT were contributors to this guidance and are acknowledged in the authorship. This framework has been used as the basis for professional judgement throughout the staffing reviews. 6 monthly Ward Staffing review July 2024 – October 2024 – Outcomes The 6 monthly review was carried out from August 2024 – October 2024 with initial review meetings taking place with each Division (attended by DHN, Matrons, Ward Leaders, Finance representatives, workforce representatives and facilitated by the Head of Nursing for Education, Practice and Staffing). The same triangulated methodology was used as in previous reviews. An update on the latest guidance and reporting requirements in relation to staffing were also included in the divisional review meetings. 5 2.3.2 2.3.3 2.3.4 2.3.5 2.3.5.1 2.3.5.2 2.3.5.3 2.3.5.4 The detailed spreadsheet with ward-by-ward findings is included at Appendix 4. This provides information on the current establishment data broken down by shift and assessing against registered/unregistered ratios; CHPPD; nurse to patient ratios by registered and total nurse staffing and acuity information from Safecare where appropriate. It should be noted that a number of wards continue to be regularly reconfigured in response to the changing capacity and service situation, including new ward build and ward moves. A number of rostering template reviews were therefore instigated as a result of the review discussions so some figures may have changed for individual wards since the review. The staffing hub which was established in April 2020 to co-ordinate and oversee the real-time nurse staffing levels across the hospital in support of the clinical site function has continued to operate and adapt. It now maintains a stronger role in the daily deployment of staff and the ongoing management of bank/agency bookings and is having a measurable impact on the reduction in high-cost agency bookings. This is particularly evident in reviewing the deployment of bank and agency support for enhanced care. The hub activity is led by a daily designated staffing matron who takes responsibility for leading the continuous review and reassignment of the nurse staffing resource throughout the day. Nurse to patient ratios by registered and total nursing The ward establishments across UHS allow for registered nurse to patient ratios during the day to range from 1:1 (Piam Brown – Children) to 1:9 (Bassett, D6, D7 G6, G8, G9, E7 and E12) depending on specialty and overall staffing model. This is a further slight increase in the number of wards with lower RN: patient ratios (up from 4 wards to 8 wards with all areas in medicine) and this will require ongoing monitoring to ensure there is not further drift. The average level is set to achieve 1:4 to 1:8 registered nurse to patient ratio in most areas during the day (43 wards, previously 47) with 42 wards set between 1:4 to 1:7 (up from 38). Exceptions are where there has previously been a planned model of trained band 4 staff to mitigate recruitment challenges and is particularly evident in Medicine and Medicine for older people. The areas on or above 1:7 (22 wards) include the medicine wards, Medicine for Older People wards, some Trauma and Orthopaedic wards, including Brooke and the Acute Stroke Unit. These areas include a higher ratio of band 2 to 4 staff creating a total nurse to patient ratio of 1:3 – 1:4. It should be noted that the ratio of patients to registered nurse can regularly increase when wards are not fully established and these wards with lower RN to patient ratios are working on their minimum safe levels. Planned staffing ratios at night require constant oversight to ensure the model is sufficient to provide the required support for patients out of hours.  In areas that are working on lower staffing ratios, managing the workload at night has again emerged as an area that still requires action in a number of ward areas.  Wards are piloting different twilight shift patterns (within existing budget) to continue to support the demands at night.  Rising acuity of patients, more therapeutic activity taking place overnight and the impact of more geographically spread clinical areas has increased the pressure on the staffing resource at night. This also highlights the importance of supernumerary bleep-holders in supporting the ward areas 6 2.3.5.5 There are now 3 in-patient ward areas with ratios of 1:11 (RN to patient) at night (the same level as the previous year). These are E3(G), Acute Surgical Assessment and F7 this is offset by a total nurse to patient ratio of 1:5 and 1:6 with the utilisation of support staff. 2.3.6 2.3.6.1 2.3.6.2 2.3.6.3 2.3.6.4 2.3.6.5 2.3.6.6 2.3.6.7 Registered to unregistered ratios UHS ward areas were reviewed against the benchmark of 60:40 registered to unregistered ratios as the level to which ward establishments should ideally not fall below unless planned as the model of care. 15 wards are now rostered at between 60:40 and 70:30. This is an increase of 1 ward on last year when there had been a reduction of 5 wards. 32 wards (an improvement on the 35 in the previous year but still remaining up significantly from 25 in 2019) are below the 60:40 ratio. These wards are utilising band 4 staff as a key contribution to the model of care and are areas where there is a wider multidisciplinary team contributing to care (e.g., MOP, T & O, Medicine, Acute Stroke). It should be noted however that this reducing trend needs to be kept under close review against other metrics to ensure safe, quality care can be provided within the establishments. As highlighted previously, recent research highlights the impact on patient outcomes in areas with reduced registered nurse cover. 8 wards (1 more than 2023) are above the 70:30 ratio reflecting the increased specialism of our regional specialties where the intensity of the patient needs requires a higher ratio of registered staff (Child Health, CV&T, Neurosciences, and Cancer Care areas). The support of band 4 roles continues to be designed in as part of a model of care in a number of areas linked to the further development of apprenticeship opportunities. This has also provided a role in which to appoint the emerging cohorts of nursing associates who have qualified and registered with the NMC from January 2019 onwards. In many areas where the acuity and intensity of patients has increased, and treatment and medication regimes are complex, further reduction in the overall skill-mix of registered to unregistered staff is not appropriate to maintain safe staffing levels and ensure adequate supervision. Additionally, in some cases a band 4 model was used to mitigate ongoing gaps in registered roles – this was particularly notable in Medicine for Older People. As recruitment for registered nurses improves these areas will be reviewing the overall required skill mix model. Focus will continue on reviewing the overall registered to unregistered ratios to ensure reductions are linked to planned model of care changes and are accompanied by appropriate quality impact assessment and evaluation. The current review of band 2/3 banding linked to national job assimilation will not have an impact on the overall registered to unregistered ratios but will have a financial impact on the establishments where uplift results. It is important to note that this will need to be managed without reducing the overall availability of unregistered nursing hours in order to maintain staffing levels. 2.3.7 Assessment against the Safer Nursing Care Tool (acuity/dependency model)  The Safer Nursing Care Tool (acuity/dependency model) has been used to model required staffing based on the national recommended nurse to patient ratios for each category of patient in all the areas. This is integrated into the health roster system as part of the safe-care tool and provides information on acuity/dependency levels and corresponding staffing levels on a real-time basis converted into recommended care hours per patient day. Where the predicted levels differ from established numbers, professional judgement has been used to 7 assure that the levels set are appropriate for the speciality and number of beds. During the review period, a Trust-wide rollout of a new version of the software took place which has seen a total refresh of the use and application of the safer nursing care tool to ensure this is being used consistently across the organisation. There is also ongoing education and support work taking place to ensure all areas are using the tool in line with the recommendations to ensure consistency. 2.3.8 Care Hours Per Patient Day 2.3.8.1 Planned total Care Hours Per Patient Day (CHPPD) range from 4.2 (G5) rising to 19.2 (Piam Brown) and average at 7.7. The average is slightly lower than the previous year and there are a higher number of wards in the lower range. This will be linked to small bed increases in ward areas that have not been accompanied by staffing increases. 2.3.8.2 Planned Registered care hours per patient day range from 1.9 (G5) rising to 14.5 (Piam Brown) and average at 4.5. This average is slightly lower this year. 2.3.8.3 Planned Unregistered care hours per patient day range from 1.3 (C6 TYA) – 8.7 (G2 Neuro) and average at 3.2. This average is slightly lower than last year. 2.3.8.4 Actual CHPPD fluctuate significantly across the year and are strongly linked to patient numbers and changes in patient acuity. For example, increased staffing for patients who require enhanced care will increase the overall CHPPD numbers attributed to a ward. An aggregated Trust-wide average, whilst useful to review month by month and annually for a trend, are less meaningful than the granular review of each ward CHPPD. 2.3.9 Allowance for additional headroom requirements and supervisory ward leader model 2.3.9.1 All areas have 23% funding allocated to allow for additional headroom requirements arising from non-direct care time. It is recognised that in a number of areas this percentage is too low to cover all of the indirect requirements in an area, particularly related to speciality and supervisory and training needs. There remains significant pressure on maintaining staffing within the allowed headroom. This is due to high training levels (resulting from the more junior workforce) and maternity/paternity levels that consistently exceed the allowance. 2.3.9.2 New national initiatives and requirements of the NHS contract such as the implementation of Professional Nurse Advocacy for all staff and Preceptorship support for all new registrants has further increased the pressure on this set level of headroom. 2.3.9.3 A discussion around management of headroom was included in each of the ward staffing reviews which took place with clear actions for the ward leaders to implement. 2.3.9.4 UHS has an established Ward Leader Supervisory model which means the Ward Leader is not included in the established numbers required to deliver safe care per shift. This enables them to focus more time on supervising and leading the ward team whilst supporting clinical care. This proved particularly important during recent years with developing the junior workforce. 2.3.9.5 In Q4 2023/24 and Q1 24/25 this model was paused as part of the financial recovery plan and Ward Leaders were rostered directly to support shifts. This impacted a range of indicators including appraisal completion, sickness reviews, roster management and learner development. In Q2 this was reinstated as part of the workforce plan for nursing and key metrics have again improved. The model is used flexibly whilst the priority is always to ensure safe staffing levels on the wards. Ward 8 Leaders clearly articulated the personal and professional impact of this pause during the discussions at the review meetings. 2.3.10 Specific Divisional issues emerging Specific Divisional issues highlighted in the review are contained in Appendix 5. 2.4 Trust wide risks and issues considered in the review 2.4.1 Establishment monitoring and controls in line with financial recovery The staffing reviews took place against the backdrop of ongoing financial recovery. During the review period inpatient areas have been working to 97% of establishments (with identified exceptions) as a control measure and this is being monitored weekly to ensure any impact on quality indicators and staff wellbeing are flagged and responded to in a timely way to ensure safe staffing in line with NQB standards. Issues arising from these measures were openly discussed at the staffing reviews. 2.4.2 Increasing patient acuity/dependency The ongoing development of our defining services continues to result in an evidenced increase in the complexity, acuity and dependency of the patients cared for in our general ward beds, also linked to reducing length of stay. COVID-19 has had a significant impact as our patients are definitely presenting with a higher level of both acuity and dependency. Information on the acuity and dependency of our patients is available via the ‘Safe Care’ functionality in health roster and is used in real time as part of our daily staffing meetings. The information is also used at the 6 monthly reviews as part of the professional judgment assessment. 2.4.3 Increasing enhanced care needs Trust wide we have continued to see an increase in the complexity of patients particularly in relation to mental health needs including dementia and patients remaining in the acute settings for prolonged lengths of time whilst awaiting appropriate placements. We have also seen a significant rise in the episodes of violence and aggression experienced in our clinical areas which creates additional needs for staffing support. This continues to have an impact on the ability to support the additional enhanced care needs that arise for these groups of patients particularly across key specialties (MOP, Medicine, Child Health, Neurosciences, T & O and latterly Surgery). Division B retain the Trustwide overview for enhanced care, specifically mental health support, and provide an advice service, supporting clinical areas in their decision making around the need for additional support. Divisions have then developed enhanced care bays on wards and/or a local pool of staff to deploy to support enhanced care needs. Ward leaders report that this has made a major difference to the management of patients with these enhanced needs and has reduced the reliance on last minute agency to support. The numbers however remain unpredictable and are therefore managed in real-time as part of overall considerations around safe staffing. The management of additional enhanced care needs extends beyond the definition of patients requiring formal mental health support. Increased numbers of patients with 9 challenging behaviour or needing 1:1 presence brings additional pressures to ward establishments but are necessary to keep the environment safe for all patients. Through the work completed in agreeing and setting an affordable workforce level for 24/25 there was recognition and agreement to fund enhanced care based on 2023/24 M10 position, as an addition to establishments. This has had a positive impact and has resulted in a reduction in usage due to the controls in place and leadership/oversight from the matrons. During 24/25 the staffing hub has been co-ordinating the requests for additional staff with additional mental health needs specifically linked to the mental health support team. This has shown key reductions in the use of registered mental health staff and tangible financial savings but despite these efforts, demand has continued to outstrip supply. 2.4.3 Supervising and supporting the junior workforce The professional judgement discussions with all the Ward Leaders again highlighted the additional challenges posed to the staffing models of appropriately supervising and supporting the increasing range of learners having placements on the ward areas. This includes the ability to meet the supervisory standards with an increasingly junior workforce. New national guidance was issued in October 2022 and implemented within UHS during 2023 with additional requirements in relation to the provision of preceptorship for all staff new to registration. Protected time for both preceptors and preceptees is now an expectation for organisations. The robust retention and recruitment strategies across the Trust and the strong vision to ‘grow our own’ nurses for the future means that wards continue to support a range of learners including undergraduate students, trainee nursing associates, nurse degree apprentices, Return to Practice students, newly registered staff undergoing preceptorship and internationally educated nurses awaiting registration. Education teams across the trust have proved key to supporting the development and learning into the wards and particularly in continuing to train and support learners to full registration and into preceptorship. The capacity and capability within the education and support teams needs to be further reviewed for 25/26 and beyond to ensure they can continue to support the further increase in numbers which will be required for UHS to meet the challenging workforce targets set in the national plan - with nursing student placements alone set to increase by up to 230% in the southeast over the coming years. 2.4.4 Benchmarking using the Model Health System UHSFT provides data monthly to the national Model Hospital System (MHS) detailing the actual CHPPD provided (based on patient numbers) for all clinical areas including critical care. During 2024 the uploads to this system from UHS have been resubmitted following some data anomalies over the summer. It is unclear whether all of the corresponding graphs and information have been amended following this change. Direct comparison of ward areas or specialty is no longer available via the benchmarking system however an overall average of total CHPPD is available to review via peer group and this is used as part of the staffing review. Hospitals with a high volume of critical care beds (providing 1:1 care) will have a 10 higher CHPPD. Table 1 Organisation/Group Total CHPPD Registered CHPPD Unregistered CHPPD UHS excl. Critical Care 8.7 4.8 3.9 UHS with Critical Care 10.5 6.7 3.8 Shelford Group 9.8 6.7 3.2 MHS Peer Group 9.56 5.7 3.4 Region 8.9 5.6 3.3 National 8.7 5.1 3.5 All data submissions (registered and unregistered) are averaged so will not necessarily equal the total CHPPD) Data is from the MHS August 2024 (latest figure) and includes nursing and midwifery and ward AHP staffing. and the UHS excluding critical care is UHS reporting Sept 2024 figure from People Report just for nursing. 2.4.5 Review of quality metrics and staffing incidents The NICE guidance outlines some key quality metrics that should be considered as part of the staffing reviews. The safety metrics defined are patient falls, pressure ulcers and medicine administration errors. These metrics, along with a range of other UHS defined quality indicators are already monitored through our internal clinical quality dashboard and are discussed ward by ward as part of the professional judgement methodology in the reviews. In addition, there is ongoing review of red flags raised as part of the adverse event reporting system and on ‘safecare’. 3.0 Conclusion 3.1 A robust ward staffing establishment review was undertaken using a mixed methodology of approaches and in line with recommendations from the National Quality Board, NICE guidance, and the RCN Nursing Workforce Standards 3.2 Overall the staffing establishments remain appropriate and within recommended guidelines. There are some key exceptions where acuity and dependency levels and growing demand continue to outstrip the nursing ratios, coupled with the impact of ward reconfigurations – recommendations for uplifts in these areas will be put forward by the Divisions as part of the annual budget setting process. 4.0 Recommendations 4.1 To discuss the report at Trust Executive Committee and Trust Board as an ongoing requirement of the National Quality Board and developing workforce safeguards guidance around safe staffing assurance. 4.2 To note findings of this annual ward establishment review and the Trust position in relation to adherence to the monitored metrics on nurse staffing levels. 4.3 To note the ongoing progress in UHS compliance with the guidance from the National Quality Board on safe, sustainable, and productive staffing. 4.4 To note the ongoing progress in UHS compliance with the NICE guideline on safe staffing for nursing in adult inpatient wards. 4.5 To note and acknowledge the ongoing risks and challenges of matching actual staffing to established staffing levels and to agree the continuous monitoring of this with the introduction of any additional financial recovery measures. 11 4.6 To support the continued Trust wide commitment and momentum on actions to fill clinical nursing vacancies and further reduce the reliance on high-cost agency against the backdrop of rising acuity and emergency and elective recovery. 4.7 Systematic ward staffing reviews to be reported to board annually, with 6 monthly light touch reviews reported through Divisional Boards. Next full staffing review to be presented to Trust Board in November 2025. 5.0 Appendices Appendix 1: National Quality Board (NQB Expectations for safe staffing Safe, Sustainable, and productive staffing Appendix 2: NQB Safe Staffing Recommendations – UHS action plan Appendix 3: NICE Guideline 1: Safe Staffing for nursing in adult inpatient wards in acute hospital - UHS action plan Appendix 4: Ward by Ward staffing review metrics spreadsheet Appendix 5: Specific Divisional issues emerging Appendix 6: RCN Workforce Standards 12 Appendix 1 National Quality Board Expectations for safe staffing - Safe, Sustainable, and productive staffing (July 2016) Expectation 1: Right staff  Boards should ensure there is sufficient and sustainable staffing capacity and capability to provide safe and effective care to patients at all times, across all care settings in NHS provider organisations.  Boards should ensure there is an annual strategic staffing review, with evidence that this is developed using a triangulated approach (i.e., the use of evidence-based tools, professional judgement, and comparison with peers), which takes account of all healthcare professional groups and is in line with financial plans.  This should be followed with a comprehensive staffing report to the board after six months to ensure workforce plans are still appropriate.  There should also be a review following any service change or where quality or workforce concerns are identified.  Safe staffing is a fundamental part of good quality care, and CQC will therefore always include a focus on staffing in the inspection frameworks for NHS provider organisations.  Commissioners should actively seek to assure themselves that providers have sufficient care staffing capacity and capability, and to monitor outcomes and quality standards, using information that providers supply under the NHS Standard Contract. Expectation 2: Right skills  Boards should ensure clinical leaders and managers are appropriately developed and supported to deliver high quality, efficient services, and there is a staffing resource that reflects a multi professional team approach.  Decisions about staffing should be based on delivering safe, sustainable, and productive services.  Clinical leaders should use the competencies of the existing workforce to the full, further developing and introducing new roles as appropriate to their skills and expertise, where there is an identified need or skills gap. Expectation 3: Right place and time  Boards should ensure staff are deployed in ways that ensure patients receive the right care, first time, in the right setting. This will include effective management and rostering of staff with clear escalation policies, from local service delivery to reporting at board, if concerns arise.  Directors of nursing, medical directors, directors of finance and directors of workforce should take a collective leadership role in ensuring clinical workforce planning forecasts reflect the organisation’s service vision and plan, while supporting the development of a flexible workforce able to respond effectively to future patient care needs and expectations. 13 Appendix 2 Expectation 1: Right staff NATIONAL QUALITY BOARD - JULY 2016 Supporting NHS Providers to deliver the right staff with the right skills, in the right place at the right time - safe sustainable and productive staffing - NURSING & MIDWIFERY Assessed UHS rating Descriptor No. Recommendation Current measures in place (November 2024) C = compliant Boards should ensure there is sufficient A = Actions required and sustainable staffing capacity and 1.1 Evidence-based workforce planning capability to provide safe and effective Triangulated approach to care to patients at all times, across all care settings in NHS provider organisations. Boards should ensure there is an annual 1.1.1 strategic staffing review, with evidence that this is developed using a triangulated approach (i.e. the use of evidence-based The organisation uses evidence-based guidance such as that produced by NICE, Royal Colleges and other national bodies to inform workforce planning, within the wider triangulated approach in this NQB resource (see Appendix 4 for list of evidence-based guidance for nursing and midwifery care staffing). staffing establishments well embedded. Shelford SNCT used and embedded in 'safecare' as part of eRostering. NICE guidance systematically reviewed 3 x per year. C tools, professional judgement and comparison with peers), which takes The organisation uses workforce tools in accordance with their account of all healthcare professional groups and is in line with financial plans. 1.1.2 guidance and does not permit local modifications, to maintain the All tools used as reliability and validity of the tool and allow benchmarking with recommended. C This should be followed with a peers. comprehensive staffing report to the board after six months to ensure Workforce plans contain sufficient provision for planned and 23% included in all direct care in-patient areas. workforce plans are still appropriate. 1.1.3 unplanned leave, e.g. sickness, parental leave, annual leave, Compliance monitored as C There should also be a review following training and supervision requirements. part of healthroster reporting any service change or where quality or suite workforce concerns are identified. Safe staffing is a fundamental part of 1.2 Professional judgement good quality care, and CQC will therefore always include a focus on staffing in the inspection frameworks for NHS provider organisations. Commissioners should actively seek to assure themselves that providers have sufficient care staffing capacity and 1.2.1 Clinical and managerial professional judgement and scrutiny are a crucial element of workforce planning and are used to interpret the results from evidence-based tools, taking account of the local context and patient needs. This element of a triangulated approach is key to bringing together the outcomes from evidencebased tools alongside comparisons with peers in a meaningful way. 6 monthly staffing reviews include face to face meetings with Corporate Nursing Team/DHN/Matron/ward leaders as well as workforce systems and finance. Professional judgement key part of the reviews. C capability, and to monitor outcomes and quality standards, using information that providers supply under the NHS Standard Contract. 1.2.2 Professional judgement and knowledge are used to inform the skill mix of staff. They are also used at all levels to inform real-time decisions about staffing taken to reflect changes in case mix, acuity/dependency and activity. As above. Professional judgement also used as part of the daily staffing review meetings through site control. C Identified actions required and notes on compliance Timescale Continue with current approach and strengthen with the use of CHPPD and safecare complete Need to ensure there is corporate rigour on adapting SNCT while rolling out 'safecare'. Monitor the impact on the inclusion of 'enhanced care' scoring. Participate in the national NIHR research Ongoing compliance monitored as part of healthroster reporting suite. Increased headroom requirement due to COVID-19 complete complete Continue with current approach and strengthen with the use of CHPPD and safecare complete Continue with current approach. Professional judgement remains the ultimate measure of safe staffing. Key part of the staffing hub set-up during COVID-19 complete 1.3 Compare staffing with peers Lead Head of Nursing staffing/DMT Head of Nursing staffing/DMT DoF/Chief Nurse Head of Nursing staffing/DMT Head of Nursing staffing/DMT/site team 1.3.1 Previous ad hoc The organisation compares local staffing with staffing provided by peers, where appropriate peer groups exist, taking account of any underlying differences. benchmarking included through AUKUH network and targeted at specific services under development. Need to strengthen and formalise C Build on the current benchmarking capabilities included in the Model Hospital and N&M Dashboard. Continue to utlise the 'civil eyes' data for child health. Work with eRoster provider to introduce reporting that includes benchmarking data complete Head of Nursing staffing/workforce systems team 1.3.2 1.3.3 The organisation reviews comparative data on actual staffing alongside data that provides context for differences in staffing requirements, such as case mix (e.g. length of stay, occupancy rates, caseload), patient movement (admissions, discharges and transfers), ward design, and patient acuity and dependency. The organisation has an agreed local quality dashboard that triangulates comparative data on staffing and skill mix with other efficiency and quality metrics: e.g. for acute inpatients, the model hospital dashboard will include CHPPD. All considered as part of the systematic staffing reviews Clinical Quality Dashboard (CQD) includes all staffing and quality metrics. Used as part of the systematic clinical accreditation scheme reviews Model hospital benchmarking now C being used routinely. All services benchmark with other areas where complete Head of Nursing staffing/DMT appropriate C Build the model hospital work into the CQD complete Head of Quality and Clinical Assurance Appendix 2 Boards should ensure clinical leaders and managers are appropriately developed 2.1 Mandatory training, development and education and supported to deliver high quality, efficient services, and there is a staffing resource that reflects a multiprofessional 2.1.1 Frontline clinical leaders and managers are empowered and have the necessary skills to make judgements about staffing and assess their impact, using the triangulated approach outlined in team approach. Decisions about staffing this document. should be based on delivering safe, sustainable and productive services. Clinical leaders should use the competencies of the existing workforce to the full, further developing and introducing new roles as appropriate to their skills and expertise, where there is an identified need or skills gap. All frontline leaders skilled to manage staffing agenda. Included in competencies for ward leaders 2.1.2 Staffing establishments take account of the need to allow clinical staff the time to undertake mandatory training and continuous professional development, meet revalidation requirements, and fulfil teaching, mentorship and supervision roles, including the support of preregistration and undergraduate students. 23% headroom allowance and provision of supervisory ward leader role covers most aspects of time identified but not fully assured around adequate time for supervision of all learners. Backfill provided for some roles in development degree apprenticeships but does not cover release for all staff C Continue to maintain competence, skills and knowledge through master classes and staffing review meetings complete Head of Nursing staffing/DMT 23% headroom is included in all nursing establishments as well as an allowance in all areas for the Ward Leader to be supervisory. A number of additional requirements e.g. increased student numbers and supervision, increased numbers of junior staff needing more supernumerary training time and A professional nurse advocacy have led Unable to to the 23% allocation falling short of identify an the needs in a number of areas. expected date This is particarly notable in critical for compliance. care and ED where the training needs Mitigations in outstrip the provision in the 23% place Head of Nursing staffing/DHN's/Divisional Education Leads/Education Quality Lead headroom. Important to note that the Ward Leader Supervisory allowance was put on hold in Q4 2023/24 and reinstated slowly from Q1 2024/25 as part of the trust recovery plan. This impacted short term on some of the non-direct activities and KPI's eg appraisal rates/progression/HR actions 2.1.3 Those with line management responsibilities ensure that staff are All expectations clearly managed effectively, with clear objectives, constructive appraisals, included in JD and annual and support to revalidate and maintain professional registration. objectives for line managers C Monitored as part of ongoing HR key performance metrics complete Associate Director of People/DMT 2.1.4 The organisation analyses training needs and uses this analysis to Annual training needs help identify, build and maximise the skills of staff. This forms part analysis process well of the organisation’s training and development strategy, which embedded within the annual also aligns with Health Education England’s quality framework. cycle for the trust C Continue with current approach with review in 2020 to further streamline priorities to staffing needs and match to changed CPD arrangements . complete Divisional Education Leads/Education Quality Lead/DMT 2.1.5 The organisation develops its staff’s skills, underpinned by Comprehensive training knowledge and understanding of public health and prevention, and programmes in place to supports behavioural change work with patients, including self- equip staff with required care, wellbeing and an ethos of patients as partners in their care. skills C Monitored through ongoing evaluation complete Director of TD&W/Divisional Education Leads//DMT 2.1.6 2.1.7 The workforce has the right competencies to support new models of care. Staff receive appropriate education and training to enable them to work more effectively in different care settings and in different ways. The organisation makes realistic assessments of the time commitment required to undertake the necessary education and training to support changes in models of care. Comprehensive training programmes in place to equip staff with required skills The organisation recognises that delivery of high quality care depends upon strong and clear clinical leadership and well-led and motivated staff. The organisation allocates significant time for team leaders, professional leads and lead sisters/charge nurses/ward managers to discharge their supervisory responsibilities and have sufficient time to coordinate activity in the care environment, manage and support staff, and ensure 100% Supervisory ward leader time provided in all inpatient direct care areas. Clinical leaders programme in place standards are maintained. C Monitored through ongoing evaluation complete Director of TD&W/Divisional Education Leads//DMT Continue to review % of time Head of Nursing - C achieved as supervisory linked to complete staffing/DMT/workforce ongoing vacancy position systems 2.2 Working as a multiprofessional team 2.2.1 The organisation demonstrates a commitment to investing in new roles and skill mix that will enable nursing and midwifery staff to spend more time using their specialist training to focus on clinical duties and decisions about patient care. The organisation recognises the unique contribution of nurses, Range of new roles developed and evaluated within the organisation. Extended scope policies in place to support. Further strengthen the trustwide Director of C approach to service by service complete TD&W/Divisional workforce development Education Leads//DMT midwives and all care professionals in the wider workforce. Multiprofessional approach to 2.2.2 Professio
Url: /Media/UHS-website-2019/Docs/About-the-Trust/performance/TB-6-monthly-staffing-review-report.pdf

Trastuzumab Main

Description: Chemotherapy Protocol GASTROINTESTINAL (UPPER) CANCER TRASTUZUMAB (21 day-Maintenance) Regimen • GI (upper) – Trastuzumab (21 day-Maintenance) Indication • Trastuzumab, in combination with capecitabine and cisplatin or cisplatin and fluorouracil, is recommended as an option for the treatment of people with human epidermal growth factor receptor 2 (HER2) positive metastatic adenocarcinoma of the stomach or gastro-oesophageal junction who have not received prior treatment for their metastatic disease and who have tumours expressing high levels of HER2 • WHO performance status 0, 1, 2 Toxicity Drug Trastuzumab Adverse Effect Cardio toxicity, acute respiratory distress syndrome, infusion related effects The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Monitoring Regimen • HER2 status before initiating therapy • Cardiac function must be assessed prior to starting trastuzumab. Thereafter in the adjuvant setting it should be assessed every 12 weeks unless there is clinical evidence of cardiac failure. In the metastatic setting cardiac function should be assessed every 12 weeks for 24 weeks then every 24 weeks thereafter, again, unless there is clinical evidence suggestive of cardiac failure • Blood pressure prior to each trastuzumab administration • FBC, U&Es and LFTs every 12 weeks in conjunction with cardiac monitoring Dose Modifications No dose modifications for haematological toxicity are necessary for trastuzumab. If treatment with trastuzumab is not tolerated it should be stopped. Version 1.1 (July 2014) Page 1 of 6 GI (upper) –Trastuzumab (21 day-Maintenance) Please discuss all dose reductions / delays with the relevant consultant before prescribing if appropriate. The approach may be different depending on the clinical circumstances. The following is a general guide only. Liver Impairment Drug Trastuzumab Dose (% of original dose) No dose adjustment necessary Kidney Impairment Drug Trastuzumab Dose (% of original dose) No dose adjustment necessary Cardiac The LVEF should be forty or above before starting cycle one of trastuzumab. Subsequent Echocardiograms The flow chart below describes the process to be followed if there is an asymptomatic decline in LVEF during trastuzumab treatment. Version 1.1 (July 2014) Page 2 of 6 GI (upper) –Trastuzumab (21 day-Maintenance) In general patients who develop symptomatic cardiac dysfunction should have trastuzumab discontinued, be commenced on ACE inhibitor therapy and be referred to a cardiologist. Further treatment should be discussed with the relevant oncology consultant. Version 1.2 (July 2024) Page 3 of 6 GI (upper) –Trastuzumab (21 day-Maintenance) Regimen 21 day cycle until disease progression or intolerance (6 cycles will be set in Aria) Drug Dose Trastuzumab 6mg/kg Days 1 Route Intravenous Infusion in 250ml sodium chloride 0.9% over a minimum of 30 minutes Dose Information • Trastuzumab will be dose banded in accordance with national dose bands (21mg/ml) • If the patient misses a dose of trastuzumab by fourteen days or less, then the usual maintenance dose of 6mg/kg should be given as soon as possible. Do not wait until the next planned cycle. Subsequent maintenance doses should be given according to the previous schedule • If the patient misses a dose of trastuzumab by more than fourteen days, a reloading dose of 8mg/kg should be given over 90 minutes. Subsequent maintenance doses should then be given every 21 days from that point Administration Information • Trastuzumab is associated with hypersensitivity reactions. Patients should be observed for six hours following the start of the first infusion of trastuzumab and for two hours following the start of subsequent infusions. If the patient has tolerated the first two infusions with no infusion related effects consideration can be given to reducing this observation period further Extravasation • Trastuzumab - neutral Additional Therapy For treatment of trastuzumab infusion reactions ‘once only when required’ doses of the following should be prescribed; - chlorphenamine 10mg intravenous - hydrocortisone 100mg intravenous - paracetamol 1000mg oral Coding • Procurement – X71.3 • Delivery – X72.3 References 1. Bang YJ, Van Custem E, Fevereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for the treatment of HER2 positive advanced gastric or gastro-oesophageal junction cancer (TOGA): a phase 3, open label, randomised, controlled clinical trial. Lancet 2010; 376 (9742): 687-697. Version 1.2 (July 2024) Page 4 of 6 GI (upper) –Trastuzumab (21 day-Maintenance) 2. National Institute for Health and Clinical Excellence (2010). NICE Technology Appraisal Guidance 208. Trastuzumab for the treatment of HER2-positive metastatic gastric cancer. DOH: London. REGIMEN SUMMARY Trastuzumab (21day-Maintenance) Day One 1. Trastuzumab 6mg/kg intravenous infusion in 250ml sodium chloride 0.9% over 30 minutes 2. Chlorphenamine 10mg intravenous when required for infusion related reactions 3. Hydrocortisone 100mg intravenous when required for infusion related reactions 4. Paracetamol 1000mg oral when required for infusion related reactions Version 1.2 (July 2024) Page 5 of 6 GI (upper) –Trastuzumab (21 day-Maintenance) DOCUMENT CONTROL Version Date Amendment 1.2 July 2024 Trastuzumab updated with national dose banding 1.1 July 2014 Header changed Disclaimer added Tabulation used throughout Bolus removed from supportive therapies OPCS codes updated 1 Feb 2012 None Written By Alexandra Pritchard Pharmacist Dr Debbie Wright Pharmacist Dr Debbie Wright Pharmacist Approved By Nanda Basker Pharmacist Donna Kimber Pharmacy Technician Dr Tim Iveson Consultant Medical Oncologist Version 1.2 (July 2024) Page 6 of 6 GI (upper) –Trastuzumab (21 day-Maintenance)
Url: /Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Upper-gastro-intestinal/TrastuzumabMainVer1.2.pdf

My Medical Record - patient information

Description: Guide to My Medical record, manage your health on line, MMR
Url: /Media/UHS-website-2019/Patientinformation/Visitinghospital/My-medical-record-1634-PIL.pdf

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