SYMPAZAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYMPAZAN (SYMPAZAN).
SYMPAZAN (clobazam) is a benzodiazepine that potentiates GABAergic inhibition via binding to the GABA-A receptor at the benzodiazepine site, enhancing chloride ion influx and neuronal hyperpolarization.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2C19 to N-desmethylclobazam, an active metabolite. N-desmethylclobazam is further metabolized by CYP2C19. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 60-70%), with minor fecal elimination (10-15%) and metabolism. |
| Half-life | Terminal elimination half-life is approximately 20-30 minutes sublingually, prolonged to 2-3 hours in hepatic impairment. Clinical context: Short t½ necessitates repeated dosing for seizure clusters. |
| Protein binding | Approximately 90-95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd is 1-2 L/kg, indicating extensive tissue distribution beyond plasma volume. |
| Bioavailability | Sublingual and buccal: 100% bioequivalent to intravenous; intranasal: approximately 80%. |
| Onset of Action | Sublingual: 2-5 minutes; buccal: 2-5 minutes; intranasal: 3-5 minutes. Rapid onset due to high bioavailability. |
| Duration of Action | Duration is 1-2 hours for acute seizure control, with possible prolonged effect up to 6 hours. Clinical note: Short duration limits use to seizure clusters rather than maintenance. |
10-20 mg orally three times daily (maximum 60 mg/day). If switching from another benzodiazepine, use equivalent dose.
| Dosage form | FILM |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (CrCl <30 mL/min), use with caution and consider dose reduction; specific guidelines not established. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), reduce dose by 50% or administer with caution, as clobazam is extensively metabolized in the liver. |
| Pediatric use | Based on body weight: 5 mg orally once daily for <30 kg, increase to 10 mg daily after 2 weeks if needed (max 20 mg/day). For ≥30 kg, 5-10 mg once daily initially, titrate to 20 mg/day (max 40 mg/day). |
| Geriatric use | Initiate at 5 mg once daily, titrate slowly due to increased sensitivity to benzodiazepines and risk of falls. Maximum dose generally not to exceed 20 mg/day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SYMPAZAN (SYMPAZAN).
| Breastfeeding | Clobazam is excreted in breast milk. The milk-to-plasma ratio is approximately 0.3 to 0.5. Monitor infant for sedation, poor feeding, and weight gain. Avoid breastfeeding if possible. |
| Teratogenic Risk | Benzodiazepines are generally associated with increased risk of oral clefts when used in the first trimester. Use in the third trimester may cause neonatal sedation, withdrawal, or floppy infant syndrome. Specific fetal risk data for clobazam (Sympazan) are limited. |
| Fetal Monitoring |
■ FDA Black Box Warning
Concomitant use of benzodiazepines with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate.
| Serious Effects |
["Hypersensitivity to clobazam or any component of the formulation","Severe hepatic impairment (Child-Pugh Class C)"]
| Precautions | ["Respiratory depression","Sedation and somnolence","Risk of abuse, misuse, and addiction","Dependence and withdrawal reactions","Suicidal thoughts or behavior"] |
Loading safety data…
| Fetal ultrasound monitoring for growth restriction, assessment of neonatal adaptation at birth, and monitoring for signs of withdrawal or sedation in the neonate. |
| Fertility Effects | No specific studies. Benzodiazepines may cause menstrual irregularities in women; impact on fertility is unknown. |