KEVZARA
Clinical safety rating
cautionComprehensive clinical and safety monograph for KEVZARA (KEVZARA).
Comprehensive clinical and safety monograph for KEVZARA (KEVZARA).
Treatment of moderately to severely active rheumatoid arthritis in adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs)Treatment of polymyalgia rheumatica in adults inadequately responsive to corticosteroids
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. |
| Molecular Weight | 150000 |
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 | Limited human data; based on animal studies, there is a potential risk of fetal harm due to inhibition of IL-6 signaling, which is involved in normal fetal development. Use only if clearly needed. |
| 2nd trimester | Same as T1; avoid unless benefit outweighs risk. Consider alternative therapies. |
| 3rd trimester | Same as T1; may affect neonatal immune responses. Avoid use unless absolutely necessary. |
Clinical note
Comprehensive clinical and safety monograph for KEVZARA (KEVZARA).
| Placental transfer | Human IgG monoclonal antibodies are known to cross the placental barrier; transfer increases as pregnancy progresses, especially in third trimester. No specific data for sarilumab but expected to cross. |
| Breastfeeding | It is unknown if sarilumab is excreted in human milk. Given the potential for adverse reactions in breastfed infants, decide whether to discontinue breastfeeding or discontinue drug, taking into account importance of drug to mother. |
| Lactation Rating | L4 |
| 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. |
| 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. |
■ 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 |
Hypersensitivity to sarilumab or any excipients
| 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 |
| Food/Dietary | No known food interactions. May be taken without regard to meals. |
| Clinical Pearls | Administer subcutaneously once weekly; do not administer with live vaccines; monitor for neutropenia, thrombocytopenia, elevated transaminases; risk of serious infections; preferentially use biologic-naive patients; onset of action may take several weeks. |
| Patient Advice | Inject exactly as prescribed once weekly, on the same day each week. · Seek medical help immediately if signs of serious infection, allergic reaction, or blood clot occur. · Do not receive live vaccines during treatment. · Store in refrigerator (2°C-8°C); do not freeze or shake. · Report any new or worsening symptoms to your healthcare provider. |
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