Columvi Dosage/Direction for Use

Important Dosing Information: Administer only as an intravenous infusion through a dedicated infusion line that includes a sterile 0.2-micron in-line filter.
COLUMVI should only be administered by a healthcare professional with immediate access to appropriate medical support, including supportive medications to manage severe CRS [see Dosage Modifications for Adverse Reactions as follows].
Ensure adequate hydration before administering COLUMVI.
Premedicate before each dose [see Recommended Premedication and Prophylactic Medications as follows].
Following pretreatment with obinutuzumab, administer COLUMVI according to the step-up dosing schedule in Table 3 with appropriate premedication, including dexamethasone, to reduce the incidence and severity of CRS [see Recommended Premedication and Prophylactic Medications as follows].
Due to the risk of CRS, patients should be hospitalized during and for 24 hours after completion of infusion of step-up dose 1 (2.5 mg on Cycle 1 Day 8) [see Recommended Dosage as follows and Cytokine Release Syndrome under Precautions].
Patients who experienced any grade CRS during step-up dose 1 should be hospitalized during and for 24 hours after completion of step-up dose 2 (10 mg on Cycle 1 Day 15). CRS with step-up dose 2 can occur in patients who did not experience CRS with step-up dose 1 [see Recommended Dosage as follows and Cytokine Release Syndrome under Precautions].
For subsequent doses, patients who experienced Grade ≥ 2 CRS with their previous infusion should be hospitalized during and for 24 hours after the completion of the next COLUMVI infusion.
Recommended Dosage: Pretreatment with Obinutuzumab: Pretreat all patients with a single 1,000 mg dose of obinutuzumab administered as an intravenous infusion on Cycle 1 Day 1, 7 days prior to initiation of COLUMVI (see Table 3) to deplete the circulating and lymphoid tissue B cells.
Obinutuzumab should be administered as an intravenous infusion at 50 mg/hour. The rate of infusion can be escalated in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour. Refer to the obinutuzumab prescribing information for complete dosing information.
COLUMVI Step-up Dose Schedule: COLUMVI dosing begins with a step-up dose schedule. Following completion of pretreatment with obinutuzumab on Cycle 1 Day 1, administer COLUMVI as an intravenous infusion according to the step-up dose schedule in Table 3. Administer premedications for each dose of COLUMVI as described in Table 5 [see Recommended Premedication and Prophylactic Medications as follows].

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Continue COLUMVI for a maximum of 12 cycles (inclusive of Cycle 1 step-up dosing) or until disease progression or unacceptable toxicity, whichever occurs first.
Monitoring for Cytokine Release Syndrome [see Cytokine Release Syndrome under Precautions]: Administer the COLUMVI infusions intravenously in a healthcare setting with immediate access to medical support to manage CRS, including severe CRS.
For the first COLUMVI step-up dose (2.5 mg on Cycle 1 Day 8), patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion.
Patients who experienced any grade CRS during step-up dose 1 should be hospitalized during and for 24 hours after completion of step-up dose 2 (10 mg on Cycle 1 Day 15). CRS with step-up dose 2 can occur in patients who did not experience CRS with step-up dose 1.
For subsequent infusions (30 mg on Day 1 of Cycle 2 or subsequent cycles), patients who experienced Grade ≥ 2 CRS with their previous infusion should be hospitalized during and for 24 hours after completion of the next COLUMVI infusion.
For monitoring after delayed or missed doses of COLUMVI, follow the recommendations in Table 4.
Delayed or Missed Doses: If a dose of COLUMVI is delayed, restart therapy based on the recommendations made in Table 4, then resume the treatment schedule accordingly.
For repeat of the 2.5 mg dose patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion. For the repeat of the 10 mg dose, patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion if any grade CRS occurred during the most recent 2.5 mg dose. (See Table 4.)

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Recommended Premedication and Prophylactic Medications: Premedication: Administer the following premedications to reduce the risk of CRS and infusion-related reactions [see Cytokine Release Syndrome under Precautions]. (See Table 5.)

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Tumor Lysis Syndrome Prophylaxis: Before starting COLUMVI, administer anti-hyperuricemics to patients at risk of tumor lysis syndrome, ensure adequate hydration status, and monitor as appropriate [see Clinical Trials Experience under Adverse Reactions].
Antiviral Prophylaxis: Before starting COLUMVI, consider initiation of antiviral prophylaxis to prevent herpes virus reactivation. Consider prophylaxis for cytomegalovirus infection in patients at increased risk [see Serious Infections under Precautions].
Pneumocystis jirovecii Pneumonia (PJP): Consider PJP prophylaxis prior to starting COLUMVI in patients at increased risk [see Serious Infections under Precautions].
Dosage Modifications for Adverse Reactions: No dosage reduction for COLUMVI is recommended.
Cytokine Release Syndrome: Identify CRS based on clinical presentation [see Cytokine Release Syndrome under Precautions]. Evaluate for and treat other causes of fever, hypoxia, and hypotension.
If CRS is suspected, withhold COLUMVI and manage according to the recommendations in Table 6 and current practice guidelines. Administer supportive care for CRS, which may include intensive care for severe or life-threatening cases. (See Table 6.)

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Neurologic Toxicity, Including ICANS: Management recommendations for neurologic toxicity, including ICANS, is summarized in Table 7. At the first sign of neurologic toxicity, including ICANS, consider neurology evaluation and withholding COLUMVI based on the type and severity of neurotoxicity. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care. (See Table 7.)

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Other Adverse Reactions: See Table 8.

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Preparation and Administration: Preparation: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. COLUMVI is a colorless clear solution. Discard the vial if the solution is cloudy, discolored, or contains visible particles.
Use aseptic technique when preparing the COLUMVI diluted solution for intravenous infusion.
Determine the dose, total volume of COLUMVI solution, and the number of COLUMVI vials needed (see Table 9).
Dilution: Withdraw the volume of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection from the infusion bag according to Table 9 and discard.
Withdraw the required volume of COLUMVI from vial(s) using a sterile needle and syringe and dilute into the infusion bag of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection according to Table 9 to a final concentration of 0.1 mg/mL to 0.6 mg/mL. Discard any unused portion left in the vial. (See Table 9.)

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Gently invert infusion bag to mix the solution, in order to avoid excessive foaming. Do not shake.
Immediately use diluted COLUMVI solution. If not used immediately, the diluted solution can be stored: Refrigerated at 2°C to 8°C (36°F to 46°F) for up to 64 hours; or At room temperature up to 25°C (77°F) for up to 4 hours; Do not freeze the diluted infusion solution; Discard diluted infusion solution if storage time exceeds these limits.
COLUMVI diluted with 0.9% Sodium Chloride Injection is compatible with intravenous infusion bags composed of polyvinyl chloride (PVC), polyethylene (PE), polypropylene (PP) or non-PVC polyolefin. When diluted with 0.45% Sodium Chloride Injection, COLUMVI is compatible with intravenous infusion bags composed of PVC.
No incompatibilities have been observed with infusion sets with product-contacting surfaces of polyurethane (PUR), PVC, or PE, and in-line filter membranes composed of polyethersulfone (PES) or polysulfone.
COLUMVI Administration: Administer COLUMVI as an intravenous infusion only through a dedicated infusion line that includes a sterile 0.2-micron in-line filter.
See Table 3 for duration of infusion. The maximum time for the administration of the diluted infusion solution may be extended up to 8 hours (see Table 6).
Do not mix COLUMVI with other drugs.