Guidelines for the administration of Rituximab

Transcription

1 the administration of 1. Introduction Administration of the anti-cd20 monoclonal antibody is associated with severe hypersensitivity reactions, potentially life threatening cytokine release syndrome, and more rarely anaphylaxis 1. The risk of infusion reactions is greatest during the first exposure to, and the severity of reaction becomes less with subsequent cycles. In order to reduce the likelihood of reactions occurring, whilst minimising treatment time for the patient, the following guidelines should be followed. 2. Infusion rates 2.1 For first infusions where the dose of is given as a single infusion The initial infusion is 50mg/hr for the first 90 minutes. Thereafter the rate should be increased in increments of 50mg/hr at 30 minute intervals. The maximum rate should not exceed 300mg/hr. The rate calculator should be used to generate the correct infusion volumes, using the First Infusion rate table. NB the maximum rate of 300mg/hr is lower than the maximum rate in the SPC for, however this lower infusion rate matches rates used in some clinical trials 1, and is adopted here as a more cautious approach to avoid infusion reactions. 2.2 For first infusion where the dose of is split into two doses on consecutive days Day 1 The initial infusion is of 100mg in 100ml 0.9% sodium chloride over 4 hours (i.e. a rate of 25mg/hr) The rate calculator should not be used for this infusion REVIEWED BY A. BRYAN AUTHORISED BY: Dr J Addada PAGE 1 of 9

2 Day 2 The remainder of the dose should be given as for first infusions above (i.e 50mg/hr for 90 minutes, followed by increasing rates at 50mg/hr increments at 30 minutes intervals, up to a maximum rate of 300mg/hr). The rate calculator should be used to generate the correct infusion volumes for Day 2 only, using the First Infusion rate table. 2.3 Subsequent infusions After the first infusion, subsequent infusions can be given at either the Licensed Rate or the Rapid Rate depending on: The treatment regimen being given, and/or the condition being treated (Section 4) Whether the patient had a reaction to the first infusion (Sections 4, 5 and Appendix). 2.4 Licensed Rate The initial rate is 100mg/hr over 30 minutes. Subsequently the infusion should be increased in increments of 50mg/hr at 30 minute intervals. The maximum rate should not exceed 400mg/hr. The rate calculator should be used to generate the correct infusion volumes using the Licensed Rate table. 2.5 Rapid Rate The initial rate is 20% of the total dose of over the first 30 minutes. The remainder of the infusion (i.e 80% of the dose) should be given over 60 minutes. The rate calculator should be used to generate the correct infusion volumes using the Rapid Rate table. REVIEWED BY A. BRYAN AUTHORISED BY: Dr J Addada PAGE 2 of 9

3 3. Premedication 3.1 For all patients All patients should receive premedication with the following: Paracetamol 1g oral Chlorphenamine 10mg IV bolus Hydrocortisone 100mg IV bolus 3.2 Patients receiving regimens containing corticosteroids as part of their treatment (e.g. RCHOP, RCVP, REPOCH) Patients receiving regimens containing Prednisolone as part of the treatment must take their first day of corticosteroids (e.g. Prednisolone 100mg) as part of the premedication 3.3 Patients receiving regimens which do not contain corticosteroids as part of their treatment (e.g. FCR, R-Bendamustine, R-Chlorambucil) Patients receiving regimens which do not contain corticosteroids should be given additional premedication in the form of Prednisolone 100mg (or equivalent IV if unable to tolerate oral medication) prior to their first dose of (or both days if having a split dose). This additional premedication can be omitted with subsequent cycles (i.e. from cycle 2 onwards) provided the patient has not had a severe reaction (Grade 2 or above) to the first infusion. Premedication must be given at least 30 minutes prior to commencing the infusion. REVIEWED BY A. BRYAN AUTHORISED BY: Dr J Addada PAGE 3 of 9

4 4. Infusion guidelines for specific regimens 4.1 Patients receiving regimens which do not include high dose corticosteroids as part of the treatment Patients having these regimes are more likely to have severe infusion reactions with the first cycle of. To avoid severe reactions the first cycle of will be given either as a split dose (Sect 4.1.1) or a single dose (Sect 4.1.2) depending on the presence of risk factors outlined below Split dose Patients with CLL and WBC>25x10 9, or CLL or low grade NHL with bulky disease, lymphoplasmacytic lymphoma or other risk factors for severe infusion reaction should always be given split dose for cycle 1 of chemotherapy. Day 1: 100mg in 100mls 0.9% Sodium chloride, given over 4 hours (i.e 25mg/hr). Do not use the rate calculator. Day 2: the remainder of the dose, given via the First Infusion rate using the rate calculator (see Appendix). Cycle 2 should be given at the licensed rate, unless the patient has had a severe infusion reaction (Grade 2 or more) to cycle 1, in which case cycle 2 should be given at the first infusion rate. Cycle 3 onwards may be given at the rapid rate provided the patient has previously tolerated an infusion at the licensed rate Single dose Cycle 1 should be given at the first infusion rate Cycle 2 should be given at the licensed rate, unless the patient has had a severe infusion reaction (Grade 2 or more) to cycle 1, in which case cycle 2 should be given at the first infusion rate. Cycle 3 onwards may be given at the rapid rate provided the patient has previously tolerated an infusion at the licensed rate. REVIEWED BY A. BRYAN AUTHORISED BY: Dr J Addada PAGE 4 of 9

5 4.2 Patients receiving chemotherapy containing corticosteroids Some patients receiving chemotherapy containing corticosteroids have risk factors for severe infusion reaction (e.g. very bulky disease, low grade NHL, high WCC, very high grade NHL). Patients with risk factors for severe infusion reaction should be given split dose, otherwise single dose may be given Split dose Day 1: 100mg in 100mls 0.9% Sodium chloride, given over 4 hours (i.e 25mg/hr). Do not use the rate calculator. Day 2: the remainder of the dose, given via the first Infusion rate using the rate calculator (see Appendix). Cycle 2 may be given at the rapid rate, unless the patient has had a severe infusion reaction (Grade 2 or more) to cycle 1, in which case cycle 2 should be given at the licensed rate. Cycle 3 onwards may be given at the rapid rate provided the patient has previously tolerated an infusion at the licensed rate Single dose Cycle 1 should be given at the first infusion rate Cycle 2 should be given at the rapid rate, unless the patient has had a severe infusion reaction (Grade 2 or more) to cycle 1, in which case cycle 2 should be given at the licensed rate. Cycle 3 onwards may be given at the rapid rate provided the patient has previously tolerated an infusion at the licensed rate. REVIEWED BY A. BRYAN AUTHORISED BY: Dr J Addada PAGE 5 of 9

6 5. Infusion reactions Vital signs (temperature, blood pressure, pulse and respirations) should be measured every 15 minutes during the first hour of the infusion, or until stable. Thereafter vital signs should be measured hourly until the end of the infusion. Toxicities related to infusion should be measured using the criteria in Table 1. If an infusion reaction of Grade 2 or greater occurs: o Stop the infusion o Contact the doctor o If severe rigor is occurring, Pethidine 25mg IV slow bolus should be administered without waiting for the doctor to arrive. o Once the reaction has subsided, the infusion may be started at half the rate that was being given prior to the reaction. o Patients may need to continue at the highest rate tolerated, rather than increasing the rate further. 5.1 Subsequent infusions If a patient is unable to tolerate infusion at a particular rate (e.g rapid rate) without a Grade 2 or greater reaction, subsequent infusions should be given at the fastest tolerated rate. REVIEWED BY A. BRYAN AUTHORISED BY: Dr J Addada PAGE 6 of 9

7 5.2 Table 1 Adverse event Allergic reaction/hypersensitivity Cytokine release syndrome/acute infusion reaction Grade Rash: flushing; Anaphylaxis Death urticaria; dyspnoea; drug fever 38 C Transient flushing or rash, fever <38 C Mild reaction: infusion interruption or other intervention not indicated Requires therapy or infusion interruption but responds promptly to symptomatic treatment (e.g.antihistamines, IV fluids); prophylactic medications indicated for 24 hrs Symptomatic bronchospasm, with or without urticaria; parenteral medications indicated; allergy related oedema/angioedema; hypotension Prolonged recurrence of symptoms following initial improvement; hospitalisation required for other clinical sequelae Life threatening; pressor or ventilatory support indicated Death REVIEWED BY A. BRYAN AUTHORISED BY: Dr J Addada PAGE 7 of 9

8 6. Using the infusion rate calculator The appropriate rate calculator for the regime and cycle should be generated in clinic and attached to the prescription by the nurse generating the prescription. In addition the rate specified should be annotated on the prescription. The rate calculator should be signed and dated by the nurse generating the prescription or the doctor signing the prescription. The volume of the infusion should be given as 550mls for all doses of from 500mg to 900mg inclusive. Doses above and below these values should be discussed with pharmacy. Nurses administering infusions should note that the actual volume of in the infusion bags may differ from 550ml. This difference should be ignored. 7. References 1. Ball, D. (2009) Guidance on the administration of infusions, North London Cancer Network, 2. Roche (2012) SPC Mabthera REVIEWED BY A. BRYAN AUTHORISED BY: Dr J Addada PAGE 8 of 9

9 Appendix: Infusion Rate Algorithm CYCLE 1 Split dose Day 1 100mg over 4hrs Does patient have WCC>25, bulky disease or other risk factors Single dose 1 st infusion rate Day 2 Remainder 1 st infusion rate CYCLE 2 Grade 2 infusion reaction to cycle 1? Licensed rate Is patient on non steroid containing regimen? Rapid rate Is patient on non steroid containing regimen? CYCLE 3 Licensed rate Grade 2 infusion reaction to cycle 2? Rapid rate Grade 2 infusion reaction to cycle 3? Grade 2 infusion reaction to cycle 3? Continue at First rate Continue at Licensed rate Continue at Rapid rate REVIEWED BY A. BRYAN AUTHORISED BY: Dr J Addada PAGE 9 of 9