"The U.S. Food and Drug Administration today approved Gazyva (obinutuzumab) for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia (CLL).
CLL is a blood and bone ma"...
Previously Untreated Chronic Lymphocytic Leukemia
ARZERRA (ofatumumab) is indicated, in combination with chlorambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate [see Clinical Studies].
Extended Treatment In CLL
DOSAGE AND ADMINISTRATION
Recommended Dosage Regimen
- Dilute and administer as an intravenous infusion according to the following schedules.
- Do not administer as an intravenous push or bolus or as a subcutaneous injection.
- Pre-medicate before each infusion [see Premedication].
Previously Untreated CLL: The recommended dosage and schedule is:
- 300 mg on Day 1 followed 1 week later by 1,000 mg on Day 8 (Cycle 1) followed by
- 1,000 mg on Day 1 of subsequent 28-day cycles for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Extended Treatment in CLL: The recommended dosage and schedule as single-agent extended treatment in CLL is:
- 300 mg on Day 1, followed by
- 1,000 mg 1 week later on Day 8, followed by
- 1,000 mg 7 weeks later and every 8 weeks thereafter for up to a maximum of 2 years.
Refractory CLL: The recommended dosage and schedule is 12 doses administered as follows:
- 300 mg initial dose on Day 1, followed 1 week later by
- 2,000 mg weekly for 7 doses (Infusions 2 through 8), followed 4 weeks later by
- 2,000 mg every 4 weeks for 4 doses (Infusions 9 through 12).
Prepare all doses in 1,000 mL of 0.9% Sodium Chloride Injection, USP [see Preparation and Administration].
Previously Untreated CLL and Extended Treatment in CLL:
- For initial 300-mg dose: Initiate infusion at a rate of 3.6 mg/hour (12 mL/hour).
- For subsequent infusions of 1,000 mg: Initiate infusion at a rate of 25 mg/hour (25 mL/hour). Initiate infusion at a rate of 12 mg/hour if a Grade 3 or greater infusion-related adverse event was experienced during the previous infusion.
In the absence of an infusion-related adverse event, the rate of infusion may be increased every 30 minutes (Table 1). Do not exceed the infusion rates in Table 1.
Table 1: Infusion Rates for
ARZERRA in Previously Untreated CLL and Extended Treatment in CLL
|Interval After Start of Infusion (min)||Initial 300 mg Dosea (mL/hour)||Subsequent Infusionsb (mL/hour)|
|aInitial 300 mg: median durations of infusions = 4.8 to 5.2
bSubsequent infusions of 1,000 mg: median durations of infusions = 4.2 to 4.4 hours.
- Infusion 1 (300-mg dose): Initiate infusion at a rate of 3.6 mg/hour (12 mL/hour).
- Infusion 2 (2,000-mg dose): Initiate infusion at a rate of 24 mg/hour (12 mL/hour).
- Infusions 3 through 12 (2,000-mg doses): Initiate infusion at a rate of 50 mg/hour (25 mL/hour).
In the absence of an infusion-related adverse event, the rate of infusion may be increased every 30 minutes (Table 2). Do not exceed the infusion rates in Table 2.
Table 2: Infusion Rates for
ARZERRA in Refractory CLL
|Interval after Start of Infusion (min)||Infusions 1 and 2a (mL/hour)||Subsequent Infusions b (mL/hour)|
|aInfusions 1 and 2 (300 mg and 2,000 mg): median duration of
infusions = 6.8 hours.
bSubsequent infusions of 2,000 mg: median durations of infusions = 4.2 to 4.4 hours.
Infusion Rate Dose Modification For Infusion Reactions
- Interrupt infusion for infusion reactions of any severity [see WARNINGS AND PRECAUTIONS]. Treatment can be resumed at the discretion of the treating physician. The following infusion rate modifications can be used as a guide.
- If the infusion reaction resolves or remains less than or
equal to Grade 2, resume infusion with the following modifications according to
the initial Grade of the infusion reaction.
- Grade 1 or 2: Infuse at one-half of the previous infusion rate.
- Grade 3 or 4: Infuse at a rate of 12 mL/hour.
- After resuming the infusion, the infusion rate may be increased according to Tables 1 and 2 above, based on patient tolerance.
- Consider permanent discontinuation of ARZERRA if the severity of the infusion reaction does not resolve to less than or equal to Grade 2 despite adequate clinical intervention.
- Permanently discontinue therapy for patients who develop an anaphylactic reaction to ARZERRA.
Patients should receive all of the following premedication agents 30 minutes to 2 hours prior to each infusion of ARZERRA. See Table 3 for pre-medication schedule prior to each infusion.
Table 3: Premedication Schedule for ARZERRA
|Infusion Number||Previously Untreated CLL or Extended Treatment in CLL||Refractory CLL|
|1 and 2||3 and beyonda||1, 2, and 9||3 to 8||10 to 12|
|Intravenous corticosteroid (prednisolone or equivalent)||50 mg||0-50 mgb||100 mg||0-100 mgb||50-100 mgc|
|Oral acetaminophen||1,000 mg|
|Oral or intravenous antihistamine||Diphenhydramine 50 mg or cetirizine 10 mg (or equivalent)|
|aUp to 13 infusions in previously untreated CLL; up to 14
infusions in extended treatment in CLL.
b Corticosteroid may be reduced or omitted for subsequent infusions if a Grade 3 or greater infusion-related adverse event did not occur with the preceding infusion(s).
cPrednisolone may be given at reduced dose of 50 mg to 100 mg (or equivalent) if a Grade 3 or greater infusion-related adverse event did not occur with Infusion 9.
Preparation And Administration
- Do not shake product.
- Inspect parenteral drug products visually for particulate matter and discoloration prior to administration. ARZERRA should be a clear to opalescent, colorless solution. The solution should not be used if discolored or cloudy, or if foreign particulate matter is present.
Preparation of Solution
- 300-mg dose: Withdraw and discard 15 mL from a 1,000-mL bag of 0.9% Sodium Chloride Injection, USP. Withdraw 5 mL from each of 3 single-use 100-mg vials of ARZERRA and add to the bag. Mix diluted solution by gentle inversion.
- 1,000-mg dose: Withdraw and discard 50 mL from a 1,000-mL bag of 0.9% Sodium Chloride Injection, USP. Withdraw 50 mL from 1 single-use 1,000-mg vial of ARZERRA and add to the bag. Mix diluted solution by gentle inversion.
- 2,000-mg dose: Withdraw and discard 100 mL from a 1,000-mL bag of 0.9% Sodium Chloride Injection, USP. Withdraw 50 mL from each of 2 single-use 1,000-mg vials of ARZERRA and add to the bag. Mix diluted solution by gentle inversion.
- Store diluted solution between 2° to 8°C (36° to 46°F).
- No incompatibilities between ARZERRA and polyvinylchloride or polyolefin bags and administration sets have been observed.
- Do not mix ARZERRA with, or administer as an infusion with, other medicinal products.
- Administer using an infusion pump and an administration set.
- Flush the intravenous line with 0.9% Sodium Chloride Injection, USP before and after each dose.
- Start infusion within 12 hours of preparation.
- Discard prepared solution after 24 hours.
Dosage Forms And Strengths
- 100 mg/5 mL single-use vial for intravenous infusion.
- 1,000 mg/50 mL single-use vial for intravenous infusion.
Storage And Handling
ARZERRA (ofatumumab) is a sterile, clear to opalescent, colorless, preservative-free liquid concentrate (20 mg/mL) for dilution and intravenous administration provided in single-use glass vials with a rubber stopper (not made with natural rubber latex) and an aluminum overseal. Each vial contains either 100 mg ofatumumab in 5 mL of solution or 1,000 mg ofatumumab in 50 mL of solution.
ARZERRA is available as follows:
|3 single-use 100 mg/5 mL vials||Vial: NDC 0078-0669-61|
|Carton of 3 vials: NDC 0078-0669-13|
|1 single-use 1,000 mg/50 mL vial||Vial and Carton: NDC 0078-0690-61|
Store ARZERRA refrigerated between 2° to 8°C (36° to 46°F). Do not freeze. Vials should be protected from light.
Manufactured by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 US License 1244 At Glaxo Group Ltd Brentford, Middlesex, UK. Jan 2016This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 1/27/2016
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