ZELSUVMI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZELSUVMI (ZELSUVMI).
Nucleoside analog inhibitor of RNA-dependent RNA polymerase (NS5B polymerase) of hepatitis C virus, incorporating into viral RNA and causing chain termination.
| Metabolism | Primarily metabolized by glucuronidation via UGT1A1; minor CYP3A4 involvement; P-gp substrate. |
| Excretion | Primarily renal excretion as unchanged drug; approximately 60% recovered in urine and 20% in feces over 72 hours. |
| Half-life | Terminal elimination half-life is approximately 19.6 hours in healthy adults, supporting once-daily dosing. |
| Protein binding | >99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 5.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 18.9% under fed conditions; food increases AUC by 0.3-fold. |
| Onset of Action | Oral: Therapeutic concentrations achieved within 4–6 hours; antiviral effect detectable within 24 hours. |
| Duration of Action | Duration of antiviral effect persists for the dosing interval (24 hours), with drug concentrations above EC50 throughout. |
ZELSUVMI (berotralstat) 150 mg orally once daily with food.
| Dosage form | GEL |
| Renal impairment | No dose adjustment required for mild or moderate renal impairment. For severe renal impairment (eGFR <30 mL/min/1.73 m²), reduce dose to 110 mg orally once daily. |
| Liver impairment | Child-Pugh A: no dose adjustment. Child-Pugh B: reduce dose to 110 mg orally once daily. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients under 12 years of age. |
| Geriatric use | No specific dose adjustment; use caution due to potential for age-related renal or hepatic impairment and monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZELSUVMI (ZELSUVMI).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or effects on milk production. Because many drugs are excreted in human milk, caution should be exercised. The M/P ratio is not known. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal reproduction studies, no evidence of fetal harm was observed at systemic exposures up to 5 times the human exposure at the maximum recommended human dose (MRHD). However, there is a potential for teratogenicity based on the drug's mechanism of action (nucleoside analogue). Therefore, ZELSUVMI is not recommended for use in pregnant women unless clearly needed. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concomitant use with strong P-gp inducers (e.g., rifampin, St. John's wort) and strong CYP3A4 inducers"]
| Precautions | ["Hepatitis B virus (HBV) reactivation risk; use with caution in patients with moderate to severe hepatic impairment; risk of bradycardia with concomitant amiodarone"] |
Loading safety data…
| Fetal Monitoring | Monitor for signs of hypersensitivity reactions (e.g., rash, urticaria, angioedema) and gastrointestinal adverse effects (e.g., nausea, diarrhea). No specific fetal monitoring required unless clinical symptoms develop. |
| Fertility Effects | No studies on fertility in humans. In animal studies, no adverse effects on fertility were observed at exposures up to 5 times the MRHD. |