ARZERRA
Clinical safety rating
cautionComprehensive clinical and safety monograph for ARZERRA (ARZERRA).
Comprehensive clinical and safety monograph for ARZERRA (ARZERRA).
Treatment of chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumabTreatment of previously untreated CLL in combination with chlorambucilTreatment of relapsed CLL in combination with fludarabine and cyclophosphamide
Nausea, Diarrhea, Breathlessness, Cough, Flushing of skin, Low energy, Skin rash
Ofatumumab is a fully human monoclonal antibody that binds specifically to the CD20 molecule on B lymphocytes, resulting in complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) of CD20+ cells.
| Metabolism | Ofatumumab is a monoclonal antibody; metabolism is not through typical cytochrome P450 pathways. Clearance involves catabolism to peptides and amino acids. |
| Excretion | Arzerra (ofatumumab) is eliminated primarily via the reticuloendothelial system and catabolism; renal excretion is minimal (<1% of dose as intact antibody). Biliary/fecal excretion has not been characterized, but as a monoclonal antibody, it is not significantly excreted in urine or feces. |
| Half-life | Mean terminal elimination half-life after first dose is approximately 14 days (range 7–21 days) and increases with repeated dosing due to target-mediated clearance saturation; at steady state, half-life is ~24 days. |
| Protein binding | As a monoclonal antibody, ofatumumab does not bind to plasma proteins; protein binding is negligible. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 2.5–4.5 L, approximating plasma volume; does not distribute extensively into tissues (not reported in L/kg, but typical for IgG1 monoclonal antibodies ~0.1–0.2 L/kg). |
| Bioavailability | Subcutaneous: ~60–70% absolute bioavailability; intravenous: 100%. |
| Onset of Action | Subcutaneous: Time to maximal B-cell depletion (clinical effect) occurs within 1 week; median time to achieve complete depletion is 7 days. |
| Duration of Action | Duration of B-cell depletion is prolonged; B-cell counts return to baseline within 12 months after discontinuation, with median time to recovery ~9 months. |
| Molecular Weight | Approximately 149,000 Da (149 kDa) |
| Action Class | CD 20 Inhibitor |
ARZERRA (ofatumumab) for chronic lymphocytic leukemia (CLL): Initial dose 300 mg IV, then 1 week later 2000 mg IV weekly for 6 doses, then 2000 mg IV every 4 weeks for up to 4 additional doses. For relapsed CLL: 300 mg IV followed by 1000 mg IV on day 8, then 1000 mg IV on day 15 and day 22 of cycle 1, then 1000 mg IV on day 1 of cycles 2-6 (28-day cycles). Premedicate with acetaminophen, antihistamine, and corticosteroid.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or hemodialysis; use with caution. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe hepatic impairment (Child-Pugh B or C); use with caution. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established; no recommended dosing. |
| Geriatric use | No specific dose adjustment required for elderly patients. Clinical studies included patients ≥65 years; overall efficacy and safety similar to younger adults, but higher incidence of serious infections and cardiac events observed. |
| 1st trimester | No adequate studies in pregnant women. Based on mechanism of action, there is a potential risk of fetal B-cell depletion. Should only be used if clearly needed. |
| 2nd trimester | Same as T1. Human IgG molecules are known to cross the placenta with increasing transfer as pregnancy progresses. Potential for fetal B-cell depletion and immunosuppression. |
| 3rd trimester | IgG crosses the placenta most actively in the third trimester. Use is generally not recommended due to possible neonatal B-cell depletion and immune suppression. |
Clinical note
Comprehensive clinical and safety monograph for ARZERRA (ARZERRA).
| Placental transfer | Ofatumumab is a monoclonal antibody (IgG1). Active placental transfer occurs via FcRn receptors, increasing across gestation, especially in the third trimester. |
| Breastfeeding | It is not known whether ofatumumab is excreted in human milk. However, human IgG is present in breast milk. Potential for infant absorption is minimal due to gastrointestinal breakdown, but risk of B-cell depletion cannot be excluded. Use caution and consider the benefits of breastfeeding vs. therapy. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | ARZERRA (ofatumumab) is a human monoclonal antibody. IgG molecules cross the placenta increasingly after the first trimester. Based on its mechanism of action (B-cell depletion), there is a potential risk of fetal B-cell lymphocytopenia and impaired immune response. Data from animal studies are insufficient. The drug should be avoided during pregnancy unless the benefit clearly outweighs the risk. |
| Fetal Monitoring | Monitor maternal complete blood counts, liver function tests, and signs of infection. For the fetus, consider monitoring for B-cell lymphocytopenia and immunoglobulin levels after birth if exposure occurred in the second or third trimester. |
| Fertility Effects | No human data on fertility effects. In animal studies, no impairment of male or female fertility was observed. |
■ FDA Black Box Warning
Hepatitis B virus (HBV) reactivation can occur with ofatumumab, leading to fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before initiation. Monitor HBV carriers during and after treatment.
| Serious Effects |
Known hypersensitivity to ofatumumab or any excipientsSevere active hepatitis B infection
| Precautions | Infusion reactions (including anaphylaxis), prolonged cytopenias, progressive multifocal leukoencephalopathy (PML), intestinal obstruction, tumor lysis syndrome, and infections including hepatitis B reactivation. |
| Food/Dietary | No known food interactions. Take with or without food. |
| Clinical Pearls | ARZERRA (ofatumumab) is a monoclonal antibody targeting CD20 used in relapsing multiple sclerosis. First dose reactions are common; premedicate with corticosteroids, antihistamines, and antipyretics. Monitor for infections, especially hepatitis B reactivation. Contraindicated in active hepatitis B. Administer as subcutaneous injection; injection site reactions frequent. Live vaccines contraindicated during and after treatment until immune reconstitution. |
| Patient Advice | Report any signs of infection (fever, chills, cough, painful urination) promptly. · Inform your doctor of any history of hepatitis B infection. · You will receive premedication before the first dose to reduce allergic reactions. · Do not receive live vaccines during treatment or until your doctor confirms immune recovery. · Common side effects include injection site reactions, headache, and fever. · ARZERRA is given as an injection under the skin; rotation of injection sites is recommended. |
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