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Ofatumumab

FDA Drug Information • Also known as: Arzerra, Kesimpta

Brand Names
Arzerra, Kesimpta
Drug Class
CD20-directed Cytolytic Antibody [EPC]
Route
INTRAVENOUS
Dosage Form
INJECTION, SOLUTION
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

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)] . WARNING: HEPATITIS B VIRUS REACTIVATION AND PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY See full prescribing information for complete boxed warning. Hepatitis B Virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death. ( 5.2 ) Progressive Multifocal Leukoencephalopathy (PML) resulting in death. ( 5.4 )

Description

11 DESCRIPTION ARZERRA (ofatumumab) is an IgG1κ human monoclonal antibody with a molecular weight of approximately 149 kDa. The antibody was generated via transgenic mouse and hybridoma technology and is produced in a recombinant murine cell line (NS0) using standard mammalian cell cultivation and purification technologies. ARZERRA is a sterile, clear to opalescent, colorless, preservative-free liquid concentrate for intravenous administration. ARZERRA is supplied at a concentration of 20 mg/mL in single-use vials. Each single-use vial contains either 100 mg ofatumumab in 5 mL of solution or 1,000 mg ofatumumab in 50 mL of solution. Inactive ingredients include: 10 mg/mL arginine, diluted hydrochloric acid, 0.019 mg/mL edetate disodium, 0.2 mg/mL polysorbate 80, 6.8 mg/mL sodium acetate, 2.98 mg/mL sodium chloride, and Water for Injection, USP. The pH is 5.5.

What Is Ofatumumab Used For?

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)] ARZERRA (ofatumumab) is a CD20-directed cytolytic monoclonal antibody indicated for the treatment of chronic lymphocytic leukemia (CLL) ( 1 ): in combination with chlorambucil, for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate. in combination with fludarabine and cyclophosphamide for the treatment of patients with relapsed CLL. for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. for the treatment of patients with CLL refractory to fludarabine and alemtuzumab.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Dilute and administer as an intravenous infusion. Do not administer subcutaneously or as an intravenous push or bolus. ( 2.1 ) Previously untreated CLL in combination with chlorambucil recommended dosage and schedule is: 300 mg on Day 1 followed by 1,000 mg on Day 8 (Cycle 1) 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. ( 2.1 ) Relapsed CLL in combination with fludarabine and cyclophosphamide recommended dosage and schedule is: 300 mg on Day 1 followed by 1,000 mg on Day 8 (Cycle 1) 1,000 mg on Day 1 of subsequent 28-day cycles for a maximum of 6 cycles ( 2.1 ) Extended treatment in CLL recommended dosage and schedule 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. ( 2.1 ) Refractory CLL recommended dosage and schedule is: 300 mg initial dose, followed 1 week later by 2,000 mg weekly for 7 doses, followed 4 weeks later by 2,000 mg every 4 weeks for 4 doses. ( 2.1 ) Administer where facilities to adequately monitor and treat infusion reactions are available. ( 2.2 ) Pre-medicate with acetaminophen, antihistamine, and corticosteroid. ( 2.4 ) 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Infusion Reactions [see Warnings and Precautions (5.1)] Hepatitis B Virus Reactivation [see Warnings and Precautions (5.2)] Hepatitis B Virus Infection [see Warnings and Precautions (5.3)] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.4)] Tumor Lysis Syndrome [see Warnings and Precautions (5.5)] Cytopenias [see Warnings and Precautions (5.6)] Previously Untreated CLL: Common adverse reactions (≥10%) were infusion reactions and neutropenia. ( 6 ) Relapsed CLL: Common adverse reactions (>10%) were infusion reactions, neutropenia, leukopenia and febrile neutropenia. ( 6 ) Extended Treatment in CLL: Common adverse reactions (≥10%) were infusion reactions, neutropenia, and upper respiratory tract infection. ( 6 ) Refractory CLL: Common adverse reactions (≥10%) were neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Previously Untreated CLL: The safety of ARZERRA was evaluated in an open-label, parallel-arm, randomized trial (Study 1) in 444 patients with previously untreated CLL. Patients were randomized to receive either ARZERRA as an intravenous infusion every 28 days in combination with chlorambucil (n = 217) or chlorambucil as a single agent (n = 227). In both arms, patients received chlorambucil 10 mg/m 2 orally on Days 1 to 7 every 28 days. The infusion schedule for ARZERRA was 300 mg administered on Cycle 1 Day 1, 1,000 mg administered on Cycle 1 Day 8, and 1,000 mg administered on Day 1 of subsequent 28-day cycles. The median number of cycles of ARZERRA completed was 6. The most common adverse reactions (≥10%) were infusion reactions and neutropenia (Table 4). The data described in Table 4 include relevant adverse reactions occurring up to 60 days after the last dose of study medication; Table 5 includes relevant hematologic laboratory abnormalities. Table 4. Adverse Reactions with ≥5% Incidence in Patients Receiving ARZERRA plus Chlorambucil and Also ≥2% More than Patients Receiving Chlorambucil a Includes events which occurred on the day of an infusion or within 24 hours of the end of an infusion and resulted in an interruption or discontinuation of treatment. Infusion reactions may include, but are not limited to, chills, dyspnea, flushing, hypotension, nausea, pain, pruritus, pyrexia, rash, and urticaria. b Includes oral herpes, herpes, herpes virus infection, genital herpes, and herpes simplex. Adverse Reactions ARZERRA plus Chlorambucil (N = 217) Chlorambucil (N = 227) All Grades % Grade ≥3 % All Grades % Grade ≥3 % Infusion reactions a 67 10 0 0 Neutropenia 27 26 18 14 Asthenia 8 <1 5 0 Headache 7 <1 3 0 Leukopenia 6 3 2 <1 Herpes simplex b 6 0 4 <1 Lower respiratory tract infection 5 1 3 <1 Arthralgia 5 <1 3 0 Upper abdominal pain 5 0 3 0 Table 5. Post-baseline Hematologic Laboratory Abnormalities Occurring with ≥5% Incidence in Patients Receiving ARZERRA plus Chlorambucil and Also ≥2% More than Patients Receiving Chlorambucil Investigations ARZERRA plus Chlorambucil (N = 217) Chlorambucil (N = 227) All Grades % Grade ≥3 % All Grades % Grade ≥3 % Leukopenia 67 23 28 4 Neutropenia 66 29 56 24 Lymphopenia 52 29 20 7 Infusion Reactions: Overall, 67% of patients who received ARZERRA in combination with chlorambucil experienced one or more symptoms of infusion reactions (10% were Grade 3 or greater; none were fatal). Infusion...

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary ARZERRA may cause fetal B-cell depletion based on findings from animal studies and the drug’s mechanism of action [see Clinical Pharmacology (12.1)] . There are no data on ARZERRA use in pregnant women to inform a drug-associated risk. However, there are clinical considerations [see Clinical Considerations] . No teratogenicity was observed in animal reproduction studies with administration of ARZERRA to pregnant monkeys during organogenesis at doses 0.3 and 2.4 times the maximum recommended human dose (MRHD) of 2000 mg based on monkey geometric mean AUC inf of 213 mg.h/mL and 1646 mg.h/mL, respectively. However, ofatumumab caused depletion of maternal circulating B-cells, depletion of peripheral and splenic fetal B-cells, and decreased fetal spleen weights [see Data] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies, respectively. Clinical Considerations Fetal/neonatal adverse reactions ARZERRA may cause fetal B-cell depletion [see Data] . Avoid administering live vaccines to neonates and infants exposed to ARZERRA in utero until B-cell recovery occurs [see Warnings and Precautions (5.7) and Clinical Pharmacology (12.2)] . Data Animal Data In an embryo-fetal development study, pregnant cynomolgus monkeys received 20 or 100 mg/kg/day of ofatumumab intravenously (30 minute infusion) once weekly during the period of organogenesis [Gestation Days (GD) 20 to 50] with systemic exposure throughout pregnancy due to the long half-life as drug was detected in maternal serum on GD 100 (early fetal period of development). At the end of organogenesis on GD 48, the exposure in pregnant monkeys receiving ofatumumab 20 and 100 mg/kg/day was approximately 0.3 and 2.4 times the human exposure after the 8 th infusion of the MRHD of...

How Supplied

16 HOW SUPPLIED/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: Carton Contents NDC 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.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.