ARZERRA

ARZERRA- ofatumumab injection, solution
Novartis Pharmaceuticals Corporation

WARNING: HEPATITIS B VIRUS REACTIVATION AND PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

  • Hepatitis B Virus (HBV) reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including ARZERRA® , in some cases resulting in fulminant hepatitis, hepatic failure, and death [see Warnings and Precautions (5.2)].
  • Progressive Multifocal Leukoencephalopathy (PML) resulting in death can occur in patients receiving CD20-directed cytolytic antibodies, including ARZERRA [see Warnings and Precautions (5.4)].

1 INDICATIONS AND USAGE

Chronic Lymphocytic Leukemia (CLL)

ARZERRA (ofatumumab) is indicated:

  • in combination with chlorambucil, for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate [see Clinical Studies (14.1)]
  • in combination with fludarabine and cyclophosphamide for the treatment of patients with relapsed CLL [see Clinical Studies (14.2)]
  • for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL [see Clinical Studies (14.3)]
  • for the treatment of patients with CLL refractory to fludarabine and alemtuzumab [see Clinical Studies (14.4)]

2 DOSAGE AND ADMINISTRATION

2.1 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 Dosage and Administration (2.4)].

Previously Untreated CLL:

The recommended dosage and schedule in combination with chlorambucil 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.

Relapsed CLL:

The recommended dosage and schedule in combination with fludarabine and cyclophosphamide 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 maximum of 6 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).

2.2 Administration

Administer ARZERRA in an environment where facilities to adequately monitor and treat infusion reactions are available [see Warnings and Precautions (5.1)].

Prepare all doses in 1,000 mL of 0.9% Sodium Chloride Injection, USP [see Dosage and Administration (2.5)].

Previously Untreated CLL, Relapsed 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, Relapsed CLL, and Extended Treatment in CLL
a Initial 300 mg: median durations of infusions = 4.8 to 5.2 hours. b Subsequent infusions of 1,000 mg: median durations of infusions = 4.2 to 4.4 hours.

Interval After

Start of Infusion (min)

Initial 300 mg Dosea

(mL/hour)

Subsequent Infusionsb

(mL/hour)

0-30

12

25

31-60

25

50

61-90

50

100

91-120

100

200

121-150

200

400

151-180

300

400

>180

400

400

Refractory CLL:

  • 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
a Infusions 1 and 2 (300 mg and 2,000 mg): median duration of infusions = 6.8 hours. b Subsequent infusions of 2,000 mg: median durations of infusions = 4.2 to 4.4 hours.

Interval after Start of Infusion (min)

Infusions 1 and 2a

(mL/hour)

Subsequent Infusions b

(mL/hour)

0-30

12

25

31-60

25

50

61-90

50

100

91-120

100

200

>120

200

400

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