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

Progressive multifocal leukoencephalopathy (PML) resulting in death has occurred with therapy; consider PML in any patient with new-onset of or changes in pre-existing neurological signs or symptoms; if PML is suspected, discontinue therapy and initiate evaluation for PML including neurology consultation

The safety of immunization with live viral vaccines during or following administration of the drug has not been studied; do not administer live viral vaccines to patients who have recently received the drug; the ability to generate an immune response to any vaccine following administration of the drug has not been studied

Tumor lysis syndrome

• Tumor lysis syndrome (TLS), including the need for hospitalization, reported; patients with high tumor burden and/or high circulating lymphocyte counts (>25 x 10⁹/L) are at greater risk for developing TLS
• Consider tumor lysis prophylaxis with anti-hyperuricemics and hydration beginning 12 to 24 hours prior to infusion of the drug; for treatment of TLS, administer aggressive intravenous hydration and anti-hyperuricemic agents, correct electrolyte abnormalities, and monitor renal function

Cytopenias

• Severe cytopenias, including neutropenia, thrombocytopenia, and anemia, reported; pancytopenia, agranulocytosis, and fatal neutropenic sepsis have occurred in patients who received the drug in combination with chlorambucil
• Grade 3 or 4 late-onset neutropenia (onset at least 42 days after last treatment dose) and/or prolonged neutropenia (not resolved between 24 and 42 days after last treatment dose) reported in patients who received the drug
• Monitor complete blood counts at regular intervals during and after conclusion of therapy, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias

Infusion reactions

• The drug can cause serious, including fatal, infusion reactions manifesting as bronchospasm, dyspnea, laryngeal edema, pulmonary edema, flushing, hypertension, hypotension, syncope, cardiac events (eg, myocardial ischemia/infarction, acute coronary syndrome, arrhythmia, bradycardia), back pain, abdominal pain, pyrexia, rash, urticaria, angioedema, cytokine release syndrome, and anaphylactoid/anaphylactic reactions
• Infusion reactions occur more frequently with the first 2 infusions; these reactions may result in temporary interruption or withdrawal of treatment
• Pre-medicate with acetaminophen, an antihistamine, and a corticosteroid
• Infusion reactions may occur despite premedication; interrupt infusion with the drug for infusion reactions of any severity; institute medical management for severe infusion reactions including angina or other signs and symptoms of myocardial ischemia
• If an anaphylactic reaction occurs, immediately and permanently discontinue treatment and initiate appropriate medical treatment

Hepatitis B virus infection

• Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, has occurred; cases have been reported in patients who are hepatitis B surface antigen (HBsAg) positive and also in patients who are HBsAg negative but are hepatitis B core antibody (anti-HBc) positive
• Reactivation also has occurred in patients who appear to have resolved hepatitis B infection (ie, HBsAg negative, anti-HBc positive, and hepatitis B surface antibody [anti-HBs] positive)
• HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive.
• Reactivation of HBV replication is often followed by hepatitis, ie, increase in transaminase levels and, in severe cases, increase in bilirubin levels, liver failure, and death
• Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment; for patients who show evidence of hepatitis B infection (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy
• Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following treatment
• HBV reactivation has been reported for at least 12 months following completion of therapy. In patients who develop reactivation of HBV while receiving the drug, immediately discontinue therapy and any concomitant chemotherapy, and institute appropriate treatment
• Resumption of treatment in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing hepatitis B; insufficient data exist regarding the safety of resuming therapy in patients who develop HBV reactivation
• Fatal infection due to hepatitis B in patients who have not been previously infected reported; monitor patients for clinical and laboratory signs of hepatitis

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