KEVZARA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KEVZARA (KEVZARA).
Interleukin-6 (IL-6) receptor antagonist; sarilumab binds specifically to both soluble and membrane-bound IL-6 receptors, inhibiting IL-6-mediated signaling through gp130 and STAT3.
| Metabolism | Metabolized by cytochrome P450 enzymes, primarily CYP3A4, with minor contributions from CYP2C8 and CYP2D6. |
| Excretion | Primarily eliminated via reticuloendothelial system catabolism. No significant renal or biliary excretion; <1% excreted unchanged in urine or feces. |
| Half-life | Terminal elimination half-life ~21-22 days, supporting subcutaneous dosing every 2 weeks. |
| Protein binding | ~99% bound, primarily to soluble IL-6 receptor and to a lesser extent to other plasma proteins. |
| Volume of Distribution | Vd ~5.5 L (0.08 L/kg based on 70 kg), indicating limited extravascular distribution, consistent with a monoclonal antibody. |
| Bioavailability | Subcutaneous: 80% absolute bioavailability. |
| Onset of Action | Subcutaneous: Clinical effect observed as early as 2 weeks, with maximal response by 12-16 weeks. |
| Duration of Action | Duration ~28 days after subcutaneous injection, with sustained suppression of IL-6 signaling through the dosing interval. |
200 mg subcutaneously once weekly.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | No dose adjustment required in mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Not studied in severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; limited data in patients ≥65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KEVZARA (KEVZARA).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Large IgG molecules are excreted in breast milk in limited amounts; however, systemic absorption by infant is low. Caution is advised; consider developmental and health benefits of breastfeeding along with mother's need for treatment. |
| Teratogenic Risk | KEVZARA (sarilumab) is a human monoclonal antibody against IL-6 receptor. Based on its mechanism, placental transfer occurs in the second and third trimesters. No adequate human data; animal studies showed increased fetal loss and skeletal abnormalities at high doses. Avoid use in pregnancy unless benefit outweighs risk. First trimester: minimal IgG transfer; theoretical risk remains. Second/third trimester: increased fetal exposure; may cause immunosuppression in the neonate. |
■ FDA Black Box Warning
Risk of serious infections including tuberculosis, invasive fungal infections, and other opportunistic pathogens; test for latent TB prior to therapy.
| Serious Effects |
["Known hypersensitivity to sarilumab or any excipient","Active serious infections"]
| Precautions | ["Serious infections (including tuberculosis, bacterial, fungal, viral)","Neutropenia, thrombocytopenia, and elevated liver enzymes","Gastrointestinal perforation risk (especially in patients with diverticulitis)","Hypersensitivity reactions (including anaphylaxis)","Vaccination status; avoid live vaccines during therapy"] |
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| Fetal Monitoring | Monitor for maternal infections due to immunosuppression. Assess fetal growth and development via ultrasound if exposure occurs in second/third trimester. Neonatal vigilance for signs of immunosuppression (e.g., infection) after in utero exposure. |
| Fertility Effects | IL-6 inhibition may affect female fertility as IL-6 is involved in follicular development and ovulation. Animal studies showed impaired fertility at high doses. The effect on human fertility is unknown; consider reproductive plans prior to treatment. |