Obinutuzumab infusion
Prior to administration:
- check baseline observations
- check for previous adverse events with drug infusions
- verify premedication has been taken. If not, administer 60 minutes prior to obinutuzumab administration:
- paracetamol 1000 mg orally AND
- loratadine 10 mg orally (or similar antihistamine)
- dexamethasone 20 mg IV
Note: The incidence of infusion related reactions was 65% with the first 1000 mg, subsequent infusions was 3% with the second 1000 mg dose and 1% thereafter.
Initial infusion:
- administer obinutuzumab at 25 mg/hr over 4 hours (do not increase the infusion rate)
- perform baseline observations and repeat every 30 minutes
- flush with ~ 100 mL of sodium chloride 0.9%
Hypotension may occur during obinutuzumab infusion. Consider withholding antihypertensive medication for 12 hours before, during, and for one hour after each infusion (if appropriate).
If an infusion reaction occurs, temporarily discontinue the infusion and notify medical officer, on resolution of symptoms, (after 60 minutes) recommence the infusion at half the previous rate. If the patient dose not experience any further IRR symptoms the dose may be increased to 25 mg/hr. DO NOT INCREASE FURTHER.
Note: If patients can tolerate the first 100 mg infusion at a rate of 25 mg/hr over 4 hours, it is possible to continue to infuse the remaining 900 mg of the dose on day 1. A total time of at least 8 hours will be required.
Day 2 (or day 1 continued)
Note: If an adverse event was experienced with initial infusion (cycle 1, day 1 or 2) recommence infusion at the same rate as initial infusion.
If no adverse event experienced with initial infusion:
- administer obinutuzumab at 50 mg/hr
- increase rate by 50 mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr if observations are stable
- perform baseline observations and repeat at each rate increase
- flush with ~ 100 mL of sodium chloride 0.9%
If a patient experiences any grade infusion related reaction during infusion, adjust the infusion as outlined below:
Grade 4 (life threatening)
- stop infusion and permanently discontinue therapy
Grade 3 (severe)
- temporarily interrupt infusion and treat symptoms
- upon resolution of symptoms, restart the infusion at no more than half the previous rate (the rate being used at the time that the IRR occurred)
- if patient does not experience any further IRR symptoms, infusion rate escalation may resume at the increments and intervals as appropriate for the treatment dose. (if not tolerated, use a rate of 25 mg/hr.
- the day 1 infusion rate may be recommenced to 25 mg/hr after 60 minutes, but not increased further
- stop infusion and permanently discontinue therapy if patients experience a second occurrence of a grade 3 IRR
Grade 1-2 (mild to moderate)
- reduce infusion rate and treat symptoms
- upon resolution of symptoms, continue infusion
- if patient dose not experience any IRR symptoms, infusion rate escalation may resume at the increments and intervals as appropriate for the treatment dose.
- the day 1 infusion rate may be increased back to 25 mg/hr after 60 minutes, but not increased further