KESIMPTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KESIMPTA (KESIMPTA).
KESIMPTA (ofatumumab) is a fully human anti-CD20 monoclonal antibody that selectively binds to the CD20 antigen on B lymphocytes, leading to B-cell lysis via complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). This results in depletion of circulating B cells, reducing inflammatory demyelination in multiple sclerosis.
| Metabolism | Ofatumumab is degraded into small peptides and amino acids via general protein catabolic pathways; not metabolized by cytochrome P450 enzymes. |
| Excretion | Primarily degraded into small peptides and amino acids; not excreted renally or fecally as intact drug. Elimination pathways not fully characterized due to monoclonal antibody catabolism. |
| Half-life | 16 days (range 13–20 days) with linear pharmacokinetics; supports every 4-week dosing. |
| Protein binding | <90% (primarily to endogenous immunoglobulins); specific binding proteins not identified. |
| Volume of Distribution | 3.1 L/kg (central compartment); indicates distribution primarily within plasma and interstitial space, limited tissue penetration. |
| Bioavailability | Subcutaneous: ~40% (absolute bioavailability not determined; relative to IV administration). |
| Onset of Action | Subcutaneous: Reduction in MRI lesions observed as early as 4 weeks; clinical benefit in relapses seen by 3 months. |
| Duration of Action | Pharmacodynamic effects (CD20+ B-cell depletion) persist for 6–12 months after discontinuation; clinical effect lasts through dosing interval. |
20 mg administered subcutaneously once monthly after a loading dose of 20 mg on Days 0, 7, and 14.
| Dosage form | SOLUTION |
| Renal impairment | No dosage adjustment required in patients with mild to moderate renal impairment. Not recommended in severe renal impairment (GFR <30 mL/min) due to lack of data. |
| Liver impairment | No dosage adjustment required in patients with mild hepatic impairment (Child-Pugh class A). Not recommended in moderate to severe hepatic impairment (Child-Pugh class B or C) due to lack of data. |
| Pediatric use | Safety and efficacy have not been established in pediatric patients. Use is not recommended. |
| Geriatric use | No specific dose adjustment is required. Clinical studies included a limited number of patients aged 65 and older. Caution is advised due to higher prevalence of infections and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KESIMPTA (KESIMPTA).
| Breastfeeding | Ofatumumab is present in human milk at low levels due to its large size. M/P ratio not established. Likely low oral bioavailability in infants, but may result in B-cell depletion. Breastfeeding during treatment is not recommended due to potential adverse effects. Consider discontinuing breastfeeding or drug based on importance to mother. |
| Teratogenic Risk | Ofatumumab (KESIMPTA) is a monoclonal antibody (IgG1) that crosses the placenta. For first trimester: limited data, but IgG antibodies are not actively transported until after 13 weeks; theoretical risk is low. Second and third trimesters: active transport increases fetal exposure. Potential risks include B-cell depletion and lymphopenia in neonates. Avoid use during pregnancy unless benefit outweighs risk; pregnancy testing recommended before initiation. |
■ FDA Black Box Warning
None
| Serious Effects |
["Active hepatitis B virus infection","History of life-threatening hypersensitivity to ofatumumab or any excipient"]
| Precautions | ["Hepatitis B virus (HBV) reactivation: screen for HBV before initiation; do not use in active HBV.","Progressive multifocal leukoencephalopathy (PML): monitor for new or worsening neurological symptoms.","Infections: increased risk, including serious bacterial, viral, and fungal infections; consider delaying vaccination during treatment.","Immunoglobulin levels: monitor; consider discontinuation if low and serious infections occur.","Fetal harm: can cause B-cell depletion and transient hypotension in neonates; avoid live vaccines in infants.","Herpes simplex and varicella-zoster virus reactivation: monitor and treat appropriately."] |
| Food/Dietary | No specific food interactions reported. |
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| Fetal Monitoring | Monitor complete blood count (CBC) with differential before and during treatment for lymphopenia. Screening for hepatitis B virus (HBV) before initiation. During pregnancy, monitor fetal growth via ultrasound. Neonates should be evaluated for B-cell counts and immunoglobulin levels after exposure. |
| Fertility Effects | No formal fertility studies in humans. In animal studies, no adverse effects on male or female fertility at doses up to 100 mg/kg (human equivalent ~16 mg/kg). However, B-cell depletion may theoretically affect reproductive function; limited clinical data. |
| Clinical Pearls | Administer subcutaneously in the abdomen, thigh, or upper arm. Do not administer intramuscularly. Premedicate with corticosteroids, antihistamines, and antipyretics to reduce infusion-related reactions. Disseminated herpes zoster cases have been reported; consider herpes zoster vaccination prior to initiation. Live vaccines contraindicated. Monitor for hepatitis B reactivation; screen before starting. Severe increases in transaminases and bilirubin have been reported; monitor liver enzymes. Obtain baseline CBC and LFTs. Contraindicated in active HBV infection. Administer first three doses weekly, then every 28 days. Pregnancy registry available. |
| Patient Advice | You will receive a starter pack of injections weekly for 3 weeks, then every 28 days thereafter. · Common side effects include injection site reactions (redness, swelling, pain) and upper respiratory tract infections. · Call your doctor immediately if you develop signs of herpes zoster (shingles) like painful skin blisters. · Do not receive live vaccines during treatment and for at least 4 weeks after your last dose. · Before starting therapy, you will be screened for hepatitis B infection. · If you are pregnant or plan to become pregnant, enroll in the pregnancy registry by calling 1-866-626-2958. · Store KESIMPTA in the refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. · Do not shake the prefilled syringe. · If you miss a dose, contact your healthcare provider for instructions. |