LIBERVANT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LIBERVANT (LIBERVANT).
GABA-A receptor positive allosteric modulator; enhances inhibitory neurotransmission.
| Metabolism | Hepatic via CYP3A4 and CYP2C19; active metabolite N-desmethylclobazam. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 85%) and glucuronide conjugates (approximately 10%); biliary/fecal excretion accounts for less than 5%. |
| Half-life | Terminal elimination half-life is approximately 2–4 hours in patients with normal renal function; may be prolonged up to 8–12 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 92% bound to albumin. |
| Volume of Distribution | Volume of distribution is 0.15–0.3 L/kg, indicating limited extravascular distribution and confinement mainly to the central compartment. |
| Bioavailability | Not applicable for oral route (not orally administered). For intramuscular administration, bioavailability is essentially 100%. |
| Onset of Action | Intravenous: 2–5 minutes; Intramuscular: 5–10 minutes. |
| Duration of Action | Clinical effects persist for 3–6 hours after a single IV or IM dose; duration may be extended in hepatic impairment or with repeated dosing. |
0.25 mg intravenously over 2 minutes, may repeat once after 15 minutes if inadequate response; maximum total dose 0.5 mg.
| Dosage form | FILM |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation; data insufficient for specific recommendations. |
| Liver impairment | Child-Pugh Class A and B: No adjustment required. Child-Pugh Class C: Reduce dose by 50% (e.g., initial dose 0.125 mg) and monitor for prolonged sedation. |
| Pediatric use | Neonates and infants: 0.02 mg/kg/dose intravenously over 2 minutes, may repeat once after 15 minutes; maximum total dose 0.5 mg. Children >1 year: 0.03 mg/kg/dose (max 0.25 mg) intravenously, may repeat once after 15 minutes; maximum total dose 0.5 mg. |
| Geriatric use | Initial dose of 0.125 mg intravenously over 2 minutes due to increased sensitivity; may repeat once after 15 minutes; maximum total dose 0.25 mg. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LIBERVANT (LIBERVANT).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. Caution in nursing infants due to potential CNS effects. Use only if clearly needed. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no evidence of teratogenicity at clinically relevant doses. Second and third trimesters: No known increase in malformations; potential for fetal CNS depression with high maternal doses. Avoid in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
Respiratory depression: May cause life-threatening respiratory depression; use with caution in patients with pre-existing respiratory disease. Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
| Serious Effects |
Severe hepatic impairment, acute narrow-angle glaucoma, hypersensitivity to clobazam or any excipient, concurrent use with St. John's Wort.
| Precautions | Respiratory depression, sedation, dependence and withdrawal, tolerance, risk of abuse, suicidal ideation, seizures upon abrupt discontinuation, hepatic impairment, elderly patients. |
Loading safety data…
| Monitor maternal blood pressure, heart rate, and respiratory status. Fetal assessment via ultrasound for growth and amniotic fluid volume if used long-term. Avoid abrupt discontinuation near term. |
| Fertility Effects | No significant impact on fertility in animal studies. Human data limited; no known adverse effects on spermatogenesis or ovulation. |