Trade Names:Arzerra- Injection, solution, concentrate 20 mg/mL
Ofatumumab is an immunoglobulin G1–kappa human monoclonal antibody generated via transgenic mouse and hybridoma technology. It binds specifically to CD20, expressed on normal B lymphocytes and on B-cell chronic lymphocytic leukemia (CLL). The proposed mechanism of action is complement-dependent cytotoxicity and antibody-dependent, cell-mediated cytotoxicity.
Vd at steady state is about 1.7 to 5.1 L.
Displays dose-dependent elimination kinetics. Cl decreased substantially with repeated administration (due to depletion of B cells). Mean Cl between the 4th and 12th infusions was about 0.01 L/h and exhibited large intersubject variability with coefficient of variation greater than 50%. Mean half-life between the 4th and 12th infusions was approximately 14 days.
CrCl ranging from 33 to 287 mL/min did not have a clinically important effect on ofatumumab pharmacokinetics.Hepatic Function Impairment
No formal studies in patients with hepatic impairment have been conducted.Children
No pharmacokinetic data are available in children.Gender
Gender had a modest effect on ofatumumab pharmacokinetics (14% to 25% lower Cl and Vd in female patients compared with male patients). No dosage adjustment is recommended.Body weight
Vd and Cl increased with body weight. No dosage adjustment is recommended based on body weight.
Treatment of CLL refractory to fludarabine and alemtuzumab.
None well documented.
IV 12 doses administered as follows: 300 mg initial dose (dose 1), followed 1 week later by 2,000 mg weekly for 7 doses (doses 2 to 8), followed 4 weeks later by 2,000 mg every 4 weeks for 4 doses (doses 9 to 12).PremedicationAdults
Premedicate 30 min to 2 h prior to each dose with oral acetaminophen 1,000 mg, oral or IV antihistamine (cetirizine 10 mg or equivalent), and IV corticosteroid (prednisolone 100 mg or equivalent). Do not reduce corticosteroid dose for doses 1, 2, and 9. Corticosteroid dose may be reduced as follows for doses 3 to 8 and 10 to 12: For doses 3 to 8, gradually reduce corticosteroid dose with successive infusions if a grade 3 or greater infusion reaction did not occur with the preceding dose. For doses 10 to 12, administer prednisolone 50 to 100 mg or equivalent if a grade 3 or greater infusion reaction did not occur with dose 9.Dose ModificationAdults
IV Interrupt infusion for infusion reactions of any severity. For grade 1, 2, or 3 infusion reaction, if the infusion reaction resolves or remains grade 2 or less, resume infusion with the following modifications according to the initial grade of the infusion reaction. For grade 1 or 2, infuse at one-half of the previous infusion rate. For grade 3, infuse at a rate of 12 mL/h. After resuming the infusion, the infusion rate may be increased based on patient tolerance. For grade 4 infusion reactions, do not resume the infusion.
Store vials in refrigerator (36° to 46°F). Do not freeze. Vials should be protected from light. Discard prepared solution after 24 h.
Do not administer live viral vaccines to patients who have recently received ofatumumab. The safety of immunization and the ability to generate an immune response with live viral vaccines during or following ofatumumab administration have not been studied.
None well documented.
Peripheral edema (9%); hypertension (8%); tachycardia (7%); hypotension (5%).
Pyrexia (25%); fatigue (15%); insomnia (10%); headache (7%).
Rash (17%); urticaria (8%); hyperhidrosis (5%).
Diarrhea (19%); nausea (12%).
Neutropenia (42%); anemia (16%).
Back pain (12%); muscle spasms (5%).
Pneumonia (25%); bronchitis, cough, dyspnea (19%); upper respiratory tract infection (11%); nasopharyngitis (8%); sinusitis (5%).
Infection (70%); infusion reactions (44%); chills, sepsis (10%); herpes zoster infection (7%).
Monitor CBC periodically. Closely monitor carriers of hepatitis B for clinical and laboratory signs of active hepatitis B virus infection during and for 6 to 12 mo following the last infusion.
Category C .
Safety and efficacy not established.
Clinical studies did not include enough subjects 65 years of age and older to determine whether they respond differently than younger subjects.
Prolonged severe neutropenia and thrombocytopenia may occur.
May occur. Discontinue if viral hepatitis or reactivation of viral hepatitis occurs, and institute appropriate treatment.
Do not immunize patients who recently received ofatumumab with live viral vaccines.
Serious infusion reactions may occur. Premedicate with acetaminophen, an antihistamine, and a corticosteroid. Interrupt infusion for infusion reactions of any severity and institute medical management as needed.
May occur. Perform a diagnostic evaluation if obstruction is suspected.
May occur. Monitor for new or changes in neurological signs or symptoms. Discontinue ofatumumab if PML is suspected and initiate evaluation for PML.
No data available regarding overdosage.
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