OBIN(MNT)

REPEAT EVERY 2 MONTHS           

Until disease progression or for up to 2 years (maximum 12 doses), whichever occurs first.

Other Supportive Care:

Patients at risk for tumour lysis syndrome should receive adequate hydration and uricostatics or alternative starting 12 to 24 hours prior to infusion.

Consider withholding antihypertensives (if applicable) 12 hours prior to infusion, during infusion and for the first hour after drug administration, and withholding concomitant medications that increase bleeding risk, especially in the first induction cycle.

Patients with neutropenia should receive antimicrobial prophylaxis; consider use of G-CSF, antiviral and antifungal prophylaxis.

Premedications (prophylaxis for infusion reactions):

*e.g. 80 mg methylprednisolone or 20 mg dexamethasone. Hydrocortisone is not recommended as it has not been effective in reducing IR rates.

**e.g. 1000 mg acetaminophen

***e.g. 50 mg diphenhydramine

Doses should be modified according to the protocol by which the patient is being treated. 

No dose reductions are recommended for obinutuzumab. The infusion may be discontinued, held or its rate reduced as described in Table 1 & 2. 

Table 1:

_{*Missed doses may be administered later at physician discretion; the planned treatment interval should then be maintained between doses.}

_{**Hold up to 4 weeks. Before retreatment, major organ toxicities should recover to ≤ grade 1 (or as specified in table 2), platelets ≥ 100 x 10⁹/L and ANC ≥ 1.5 x 10⁹/L.}

Table 2: Management of Infusion-related reactions:

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.

Safety and efficacy have not been established in patients with hepatic impairment.

Patients who have a creatinine clearance < 50mL/min in the pivotal study experienced more serious adverse events, including fatal ones than those with creatinine ≥ 50 mL/min.

No dose adjustment is required.  NHL patients ≥ 65 years of age experienced more serious adverse effects than younger patients. No efficacy differences were observed between older and younger patients.

Refer to oBINutuzumab drug monograph(s) for additional details of adverse effects

Refer to oBINutuzumab drug monograph(s) for additional details

• No clinical drug interaction studies have been conducted with obinutuzumab.
• Consider withholding antihypertensives (if applicable) 12 hours prior to obintuzumab infusion, during infusion and for the first hour after drug administration, and withholding concomitant medications that increase bleeding risk, especially in the first cycle.
• Use with caution and monitor closely for infections when given with other immunosuppressive drugs.

Refer to oBINutuzumab drug monograph(s) for additional details

Administration

• Obinutuzumab should be administered only as an IV infusion through a dedicated line.  Do not administer as an IV push or bolus.
• Withdraw required amount of diluent from vial and dilute in 250 ml PVC or non-PVC polyolefin bags containing 0.9% sodium chloride. See product monograph for details.
• Gently invert the IV bag to mix. Do not shake.
• If a planned dose is missed, it should be administered as soon as possible; do not wait until the next planned dose. The planned treatment interval should then be maintained between doses.
• Compatible with sodium chloride 0.9%. Do not mix with other IV solutions.
• Also compatible with the following IV bags and sets:
  • polyethylene, polypropylene bags
  • PVC, polyurethane or polyethylene infusion sets
  • polyetherurethane catheters
  • optional inline filters with polyethersulfon product contact surfaces
  • 3-way stopcock infusion aid made from polycarbonate

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.

Contraindications

• Patients who have a hypersensitivity to this drug or any of its components

Precautions

• Obinutuzumab should not be given to patients with an active infection.
• Avoid live vaccines during treatment and until B-cell recovery. Following vaccination, do not start obinutuzumab until protective antibody titres have been reached.
• Use with extreme caution in patients who are positive for hepatitis.
• Use with caution in patients with a history of recurring or chronic infections
• Patients with a history of cardiovascular or respiratory disease should be monitored closely during and after infusions. Use caution when hydrating patients with history of cardiovascular disease, to prevent fluid overload
• Patients at acute risk of hypertensive crisis should be assessed for the risk vs benefit of withholding anti-hypertensives. If deemed clinically appropriate, hold antihypertensive medications for 12 hours prior to, during, and for the first hour after obinutuzumab infusion.

Pregnancy/Lactation:

• Obinutuzumab is not recommended for use in pregnancy.  Adequate contraception should be used by both sexes during treatment, and for at least 18 months after the last dose. In case of exposure during pregnancy, newborns should be monitored for B-cell depletion and live vaccines postponed until B cell recovery.
• Breastfeeding is not recommended during treatment and for at least 18 months after the last dose.

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

Obinutuzumab drug monograph, Cancer Care Ontario.

Cheson BD, Chua N, Mayer J, et al.  Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study.  J Clin Oncol. 2018 Aug 1;36(22):2259-66.