KESIMPTA
Clinical safety rating
cautionComprehensive clinical and safety monograph for KESIMPTA (KESIMPTA).
Comprehensive clinical and safety monograph for KESIMPTA (KESIMPTA).
Relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
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. |
| Molecular Weight | ~149 kDa |
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 | Limited human data; based on mechanism, IgG antibodies cross placenta increasingly after first trimester. Use only if clearly needed. |
| 2nd trimester | IgG transport increases; potential fetal B-cell depletion. Avoid unless benefit outweighs risk. |
| 3rd trimester | IgG transport highest; may cause fetal B-cell depletion and hematologic effects. Avoid in third trimester unless essential. |
Clinical note
Comprehensive clinical and safety monograph for KESIMPTA (KESIMPTA).
| Placental transfer | Monoclonal antibody of IgG1 subtype; known to cross placenta, with increasing transfer as pregnancy progresses, especially in second and third trimesters. |
| Breastfeeding | Present in human milk; unknown effects on breastfed infant. Consider developmental and health benefits of breastfeeding, mother's clinical need, and potential adverse effects on infant. |
| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Active hepatitis B infection
| 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. |
| 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. |
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