June 25, 2016
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Gazyva

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Gazyva

Indications
Dosage
How Supplied

INDICATIONS

Chronic Lymphocytic Leukemia

GAZYVA, in combination with chlorambucil, is indicated for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL) [see Clinical Studies].

Follicular Lymphoma

GAZYVA, in combination with bendamustine followed by GAZYVA monotherapy, is indicated for the treatment of patients with follicular lymphoma (FL) who relapsed after, or are refractory to, a rituximab-containing regimen [see Clinical Studies].

DOSAGE AND ADMINISTRATION

Recommended Dosage Regimen

  • Premedicate before each infusion [see Recommended Premedication below].
  • Provide prophylactic hydration and anti-hyperuricemics to patients at high risk of tumor lysis syndrome [seeRecommended Premedication below and WARNINGS AND PRECAUTIONS].
  • Administer only as an intravenous infusion through a dedicated line [see Preparation and Administration below].
  • Do not administer as an intravenous push or bolus.
  • Monitor blood counts at regular intervals.
  • GAZYVA should only be administered by a healthcare professional with appropriate medical support to manage severe infusion reactions that can be fatal if they occur [see WARNINGS AND PRECAUTIONS].

Chronic Lymphocytic Leukemia

Each dose of GAZYVA is 1000 mg, administered intravenously, with the exception of the first infusions in Cycle 1, which are administered on day 1 (100 mg) and day 2 (900 mg).

Table 1 : Dose of GAZYVA to Be Administered During 6 Treatment Cycles, Each of 28 days Duration, for Patients with CLL

Day of treatment cycle Dose of GAZYVA Rate of infusion (in the absence of infusion reactions/hypersensitivity during previous infusions)
Cycle 1 (loading doses) Day 1 100 mg Administer at 25 mg/hr over 4 hours. Do not increase the infusion rate.
Day 2 900 mg Administer at 50 mg/hr. The rate of the infusion can be escalated in increments of 50 mg/hr every 30 minutes to a maximum rate of 400 mg/hr.
Day 8 1000 mg If no infusion reaction occurred during the previous infusion and the final infusion rate was 100 mg/hr or faster, infusions can be started at a rate of 100 mg/hr and increased by 100 mg/hr increments every 30 minutes to a maximum of 400 mg/hr.
Day 15 1000 mg
Cycles 2-6 Day 1 1000 mg

If a planned dose of GAZYVA is missed, administer the missed dose as soon as possible and adjust dosing schedule accordingly. If appropriate, patients who do not complete the Day 1 Cycle 1 dose may proceed to the Day 2 Cycle 1 dose.

Follicular Lymphoma

Each dose of GAZYVA is 1000 mg administered intravenously according to Table 2. Patients who achieve stable disease, complete response, or partial response to the initial 6 cycles of GAZYVA treatment in combination with bendamustine should continue on GAZYVA 1000 mg as monotherapy for two years.

Table 2 : Dose of GAZYVA to Be Administered During 6 Treatment Cycles, Each of 28 days Duration, Followed by GAZYVA Monotherapy for Patients with FL

Day of treatment cycle Dose of GAZYVA Rate of infusion (in the absence of infusion reactions/hypersensitivity during previous infusions)
Cycle 1 (loading doses) Day 1 1000 mg Administer at 50 mg/hr. The rate of the infusion can be escalated in 50 mg/hr increments every 30 minutes to a maximum of 400 mg/hr.
Day 8 1000 mg If no infusion reaction occurred during the previous infusion and the final infusion rate was 100 mg/hr or faster, infusions can be started at a rate of 100 mg/hr and increased by 100 mg/hr increments every 30 minutes to a maximum of 400 mg/hr.
Day 15 1000 mg
Cycles 2-6 Day 1 1000 mg
Monotherapy Every two months for two years 1000 mg

If a planned dose of GAZYVA is missed, administer the missed dose as soon as possible. During GAZYVA and bendamustine treatment, adjust the dosing schedule accordingly. During monotherapy, maintain the original dosing schedule for subsequent doses.

Management Of Infusion Reactions In CLL And FL Patients
  • If a patient with CLL or FL experiences an infusion reaction of any grade during infusion, adjust the infusion as follows [see WARNINGS AND PRECAUTIONS]:
  • Grade 4 (life-threatening): Stop infusion immediately and permanently discontinue GAZYVA therapy.
  • Grade 3 (severe): Interrupt infusion and manage symptoms. Upon resolution of symptoms, consider restarting GAZYVA infusion at no more than half the previous rate (the rate being used at the time that the infusion reaction occurred) and, if patient does not experience any further infusion reaction symptoms, infusion rate escalation may resume at the increments and intervals as appropriate for the treatment cycle dose. Permanently discontinue treatment if patients experience a Grade 3 infusion-related symptom at rechallenge.
    • For CLL patients only, the Day 1 infusion rate may be increased back up to 25 mg/hr after 1 hour but not increased further.
  • Grade 1–2 (mild to moderate): Reduce infusion rate or interrupt infusion and treat symptoms. Upon resolution of symptoms, continue or resume infusion and, if patient does not experience any further infusion reaction symptoms, infusion rate escalation may resume at the increments and intervals as appropriate for the treatment cycle dose.
    • For CLL patients only, the Day 1 infusion rate may be increased back up to 25 mg/hr after 1 hour but not increased further.

Recommended Premedication

Infusion Reactions

Premedication to reduce the risk of infusion reactions is outlined in Table 3 [see WARNINGS AND PRECAUTIONS].

Hypotension may occur during GAZYVA intravenous infusions. Consider withholding antihypertensive treatments for 12 hours prior to and throughout each GAZYVA infusion and for the first hour after administration [see WARNINGS AND PRECAUTIONS].

Tumor Lysis Syndrome

Patients with high tumor burden, high circulating absolute lymphocyte counts (greater than 25 x 109/L) or renal impairment are considered at risk of tumor lysis syndrome and should receive prophylaxis. Premedicate with anti-hyperuricemics (e.g., allopurinol or rasburicase) and ensure adequate hydration prior to start of GAZYVA therapy. Continue prophylaxis prior to each subsequent GAZYVA infusion, as needed [see WARNINGS AND PRECAUTIONS].

Table 3 : Premedication for GAZYVA Infusion to Reduce Infusion-Related Reactions (IRR)

Day of Treatment Cycle Patients requiring premedication Premedication Administration
Cycle 1: CLL Day 1, Day 2 FL Day 1 All patients Intravenous glucocorticoid: 20 mg dexamethasone or 80 mg methylprednisolone1 Completed at least 1 hour prior to GAZYVA infusion.
650-1000 mg acetaminophen anti-histamine (e.g., 50 mg diphenhydramine) At least 30 minutes before GAZYVA infusion.
All subsequent infusions All patients 650-1000 mg acetaminophen At least 30 minutes before GAZYVA infusion.
Patients with an IRR (Grade 1-2) with the previous infusion 650-1000 mg acetaminophen anti-histamine (e.g., 50 mg diphenhydramine) At least 30 minutes before GAZYVA infusion.
Patients with a Grade 3 IRR with the previous infusion OR with a lymphocyte count > 25 x 109 /L prior to next treatment Intravenous glucocorticoid: 20 mg dexamethasone or 80 mg methylprednisolone1 Completed at least 1 hour prior to GAZYVA infusion.
650-1000 mg acetaminophen anti-histamine (e.g., 50 mg diphenhydramine) At least 30 minutes before GAZYVA infusion.
1Hydrocortisone is not recommended as it has not been effective in reducing the rate of infusion reactions.

Antimicrobial Prophylaxis

Patients with Grade 3 to 4 neutropenia lasting more than one week are strongly recommended to receive antimicrobial prophylaxis until resolution of neutropenia to Grade 1 or 2. Antiviral and antifungal prophylaxis should be considered.

Treatment Interruption For Toxicity

Consider treatment interruption if patients experience an infection, Grade 3 or 4 cytopenia, or a ≥ Grade 2 non-hematologic toxicity.

Preparation And Administration

Preparation

Prepare the solution for infusion, using aseptic technique, as follows:

  • Inspect visually for any particulate matter and discoloration prior to administration.
  • Dilute into a 0.9% sodium chloride PVC or non-PVC polyolefin infusion bag. Do not use other diluents such as dextrose (5%).
Chronic Lymphocytic Leukemia
  • Preparation of solution for infusion on day 1 (100 mg) and day 2 (900 mg) of Cycle 1:
    • Withdraw 40 mL of GAZYVA solution from the vial.
    • Dilute 4 mL (100 mg) of GAZYVA into a 100 mL 0.9% sodium chloride infusion bag for immediate administration.
    • Dilute the remaining 36 mL (900 mg) into a 250 mL 0.9% sodium chloride infusion bag at the same time for use on day 2 and store at 2°C to 8°C (36°F to 46°F) for up to 24 hours. After allowing the diluted bag to come to room temperature, use immediately.
    • Clearly label each infusion bag.
  • Preparation of solution for infusion on day 8 and 15 of Cycle 1 and day 1 Cycles 2–6:
    • Withdraw 40 mL of GAZYVA solution from the vial.
    • Dilute 40 mL (1000 mg) into a 250 mL 0.9% sodium chloride infusion bag.
Follicular Lymphoma
  • Preparation of solution for infusion:
    • Withdraw 40 mL of GAZYVA solution from the vial.
    • Dilute 40 mL (1000 mg) into a 250 mL 0.9% sodium chloride infusion bag.
  • Mix diluted solution by gentle inversion. Do not shake or freeze.
  • For microbiological stability, the diluted GAZYVA infusion solution should be used immediately. Dilute under appropriate aseptic conditions. If not used immediately, the solution may be stored in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours prior to use.

The product can be administered at a final concentration of 0.4 mg/mL to 4 mg/mL.

Administration for CLL and FL Patients
  • Administer as an intravenous infusion only.
  • Do not administer as an intravenous push or bolus.
  • Do not mix GAZYVA with other drugs.
  • No incompatibilities between GAZYVA and polyvinylchloride (PVC) or non-PVC polyolefin bags and administration sets have been observed [see HOW SUPPLIED/Storage and Handling].

HOW SUPPLIED

Dosage Forms And Strengths

1000 mg/40 mL (25 mg/mL) single-dose vial.

Storage And Handling

Storage

GAZYVA 1000 mg/40 mL (25 mg/mL) single-dose vials containing preservative-free solution (NDC 50242-070-01) are stable at 2°C to 8°C (36°F to 46°F). Do not use beyond expiration date stamped on carton. Protect GAZYVA vials from light. DO NOT FREEZE. DO NOT SHAKE.

For the diluted product, chemical and physical stability have been demonstrated in 0.9% NaCl at concentrations of 0.4 mg/mL to 20 mg/mL for 24 hours at 2°C to 8°C (36°F to 46°F) followed by 48 hours (including infusion time) at room temperature ( ≤ 30°C/86°F). GAZYVA does not contain antimicrobial preservatives. Therefore, care must be taken to ensure that the solution for infusion is not microbiologically compromised during preparation. The solution for infusion should be used immediately. If not used immediately, the prepared solution may be stored up to 24 hours at 2 to 8°C. No incompatibilities between GAZYVA and polyvinyl chloride or polyolefin infusion materials have been observed in concentration ranges from 0.4 mg/mL to 20.0 mg/mL after dilution of GAZYVA with 0.9% sodium chloride.

Manufactured by: Genentech, Inc. A Member of the Roche Group South San Francisco, CA 94080-4990. Revised: Feb 2016

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 3/7/2016

Indications
Dosage
How Supplied

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