Class: Monoclonal antibody
- 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.
Special PopulationsRenal Function Impairment
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.
Indications and Usage
Treatment of CLL refractory to fludarabine and alemtuzumab.
None well documented.
Dosage and AdministrationCLL
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).Premedication
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 Modification
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.
- For IV infusion only. Do not administer as an IV push or bolus. Do not shake vial prior to use.
- Do not mix ofatumumab with, or administer as an infusion with, other medicinal products.
- Administer using an infusion pump, the in-line filter provided with the product, and polyvinyl chloride administration sets.
- Premedicate before each infusion.
- Start infusion within 12 h of preparation.
- Initial infusion rates: For dose 1: Initiate infusion at a rate of 3.6 mg/h (12 mL/h). For dose 2: Initiate infusion at a rate of 24 mg/h (12 mL/h). For doses 3 to 12: Initiate infusion at a rate of 50 mg/h (25 mL/h).
- In the absence of infusional toxicity, the rate of infusion may be increased every 30 min. Do not exceed the following infusion rates: For infusions within 0 to 30 min of initial infusion: dose 1 is 12 mL/h, dose 2 is 12 mL/h, doses 3 to 12 is 25 mL/h. For infusions within 31 to 60 min of initial infusion: dose 1 is 25 mL/h, dose 2 is 25 mL/h, doses 3 to 12 is 50 mL/h. For infusions within 61 to 90 min of initial infusion: dose 1 is 50 mL/h, dose 2 is 50 mL/h, doses 3 to 12 is 100 mL/h. For infusions within 91 to 120 min of initial infusion: dose 1 is 100 mL/h, dose 2 is 100 mL/h, doses 3 to 12 is 200 mL/h. For infusions after 120 min of initial infusion: dose 1 is 200 mL/h, dose 2 is 200 mL/h, doses 3 to 12 is 400 mL/h.
- Flush the IV line with sodium chloride 0.9% injection before and after each dose.
- Ofatumumab should be a colorless solution and may contain a small amount of visible translucent-to-white, amorphous ofatumumab particles. Do not use if solution is discolored, cloudy, or contains foreign particulate matter.
- Discard any unused solution. Do not save unused solution for future use.
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.
Laboratory Test Interactions
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.
Hepatitis B reactivation, including fulminant hepatitis and death
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.
Progressive multifocal leukoencephalopathy (PML)
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.
- Advise patient that additional medications to prevent infections and infusion-related reactions may be prescribed and to take exactly as instructed.
- Advise patients to contact a health care provider for any of the following: signs and symptoms of infusion reactions, including fever, chills, rash, or breathing problems within 24 h of infusion; bleeding, easy bruising, petechiae, pallor, worsening weakness, or fatigue; signs of infections, including fever and cough; new neurological symptoms, such as confusion, dizziness, loss of balance, difficulty talking or walking, or vision problems; symptoms of hepatitis, including worsening fatigue or yellow discoloration of the skin or eyes; or new or worsening abdominal pain or nausea.
- Advise patient of the need for periodic monitoring of CBC.
- Caution patient not to receive live viral vaccines during treatment.
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