ofatumumab (Rx)

>10%

Neutropenia

Pneumonia

Pyrexia

Cough

Diarrhea

Anemia

Fatigue

Dyspnea

Rash

Nausea

Bronchitis

Upper respiratory tract infections

<10%

Infusion reaction/complication

Cytopenias

Infection (pneumonia, sepsis)

Progressive multifocal leukoencephalopathy

Hepatitis B reactivation

Intestinal obstruction

Contraindications

Hypersensitivity

Cautions

Increased susceptibility to infection

May increase risk for progressive multifocal leukoencephalopathy (PML)

Fulminant and fatal hepatitis B infection and reactivation reported following treatment; closely monitor HBV carriers for clinical and laboratory signs of active HBV infection during treatment and for 6-12 months following last infusion

Infusion reaction may occur, monitor closely

Neutropenia

Thrombocytopenia

Intestinal obstruction of small intestine

Tumor lysis syndrome (TLS) reported, including the need for hospitalization; patients with high tumor burden and/or high circulating lymphocyte counts (>25 x 10^9/L) are at greater risk; consider TSL prophylaxis with antihyperuricemics and hydration beginning 12-24 hr before infusion

Do not administer live virus vaccines (inability to generate immune response)

Pregnancy Category: C

Lactation: unknown whether distributed in breast milk; published data suggest neonate/infant does not ingest substantial amount of these maternal antibodies from breast milk, although caution is warranted

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Anti-CD20 human monoclonal antibody that inhibits B-cell activation in early stages

Pharmacokinetics

Half-Life: 14 days (mean between 4th-12th infusions)

Cmax: 63 mcg/mL (after 1st dose); 1482 mcg/mL (after 8th dose); 881 mcg/mL (after 12th dose)

Vdss: 3.2 L (after 1st dose); 5.1 L (after 8th dose); 4.7 L after 12th dose

Clearance: 0.01 L/hr (mean clearance between 4th-12th infusions)

IV Compatibilities

Solution: 0.9% NaCl

IV Preparation

Do NOT shake product

IV infusion: Prepare all doses in 1000-mL polyolefin bag of 0.9% NaCl

300 mg dose: Withdraw and discard 15 mL from 1000 mL 0.9% NaCl; add measured dose to IV bag; yields 300 mg/L = 0.3 mg/mL

1,000 mg dose: Withdraw and discard 50 mL from 1000 mL 0.9% NaCl; add measured dose to IV bag; yields 1,000 mg/L = 1 mg/mL

2000 mg dose: Withdraw and discard 100 mL from 1000 mL 0.9% NaCl; add measured dose to IV bag; yields 2000 mg/L = 2 mg/mL

IV Administration

Premedicate with corticosteroid, analgesic, and antihistamine before each infusion to avoid infusion-related reactions

Administer by slow IV infusion and use in-line filter supplied with product via volumetric infusion pump; do NOT administer as IV push or bolus

Previously untreated and extended treatment CLL

• For initial 300 mg dose: Initiate IV infusion at rate of 3.6 mg/hr (12 mL/hr)
• For subsequent 1,000 mg doses: Initiate IV infusion at rate of 25 mg/hr (25 mL/hr); initiate infusion at a rate of 12 mg/hr if a ≥grade 3 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 by 12-25 mL/hr; not to exceed 400 mL/hr

Refractory CLL

• Dose 1 (300 mg dose): Initiate IV infusion at rate of 3.6 mg/hr (12 mL/hr)
• Dose 2 (2,000 mg dose): Initiate IV infusion at a rate of 24 mg/hr (12 mL/hr)
• Doses 3-12 (2,000 mg dose): Initiate IV infusion at a rate of 50 mg/hr (25 mL/hr)
• In the absence of an infusion-related adverse event, the rate of infusion may be increased every 30 minutes by 12-25 mL/hr; not to exceed 200 mL/hr for doses 1-2, and 400 mL/hr for doses 3-12

Storage

Store undiluted vials refrigerated (between 36-46 degrees F); protect from light

Store diluted solution refrigerated (between 36-46 degrees F)

Start infusion within 12 hr of preparation

Discard prepared solution after 24 hr