Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ONFI vs SYMPAZAN
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
GABA-A receptor positive allosteric modulator; increases the frequency of chloride channel opening in response to GABA.
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.
Treatment of seizures associated with Lennox-Gastaut syndrome,Adjunctive therapy for other seizure types
FDA-approved for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged 2 years and older,Off-label: adjunctive therapy for other epileptic syndromes, anxiety disorders, and acute repetitive seizures
Initial: 10 mg orally twice daily; may increase by 10 mg/day after 1 week to maintenance of 20–40 mg/day in two divided doses. Maximum: 60 mg/day.
10-20 mg orally three times daily (maximum 60 mg/day). If switching from another benzodiazepine, use equivalent dose.
The terminal elimination half-life of clobazam is 36–42 hours. The active metabolite N-desmethylclobazam has a half-life of 71–82 hours. The long half-life permits once-daily dosing but also leads to slow accumulation; steady-state is achieved after 2–3 weeks.
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.
Hepatic via CYP3A4 and CYP2C19; primary metabolite N-desmethylclobazam is active.
Primarily metabolized by CYP3A4 and CYP2C19 to N-desmethylclobazam, an active metabolite. N-desmethylclobazam is further metabolized by CYP2C19.
Clobazam (ONFI) undergoes extensive hepatic metabolism. Approximately 82% of the dose is eliminated in urine (as unchanged drug and metabolites) and about 11% in feces. Unchanged clobazam accounts for <1% of urinary excretion. The major metabolite, N-desmethylclobazam, is excreted primarily renally.
Primarily renal excretion of unchanged drug (approximately 60-70%), with minor fecal elimination (10-15%) and metabolism.
Clobazam is approximately 80–90% bound to plasma proteins, primarily albumin.
Approximately 90-95% bound to albumin and alpha-1-acid glycoprotein.
The apparent volume of distribution is approximately 100 L (range 77–120 L), or roughly 1.4 L/kg. This large Vd indicates extensive tissue distribution and accumulation in fatty tissues.
Vd is 1-2 L/kg, indicating extensive tissue distribution beyond plasma volume.
Oral bioavailability is nearly complete (>90%). Clobazam is well absorbed after oral administration with only minor first-pass metabolism.
Sublingual and buccal: 100% bioequivalent to intravenous; intranasal: approximately 80%.
No specific GFR-based dose adjustments; use with caution in severe impairment (Cr Cl < 30 m L/min) due to potential for increased sedation.
No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (Cr Cl <30 m L/min), use with caution and consider dose reduction; specific guidelines not established.
Mild to moderate (Child-Pugh A/B): Initial 5 mg orally twice daily; may increase by 5 mg/day after 1 week to maximum 20 mg/day. Severe (Child-Pugh C): Not recommended.
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.
Clobazam (ONFI) for seizures: Age 2 to <6 years, body weight ≥12.5 kg: Initial 5 mg orally once daily; titrate to maintenance 5 mg twice daily. Age ≥6 years: Weight ≤30 kg: Initial 5 mg once daily; titrate to 5 mg twice daily (max 20 mg/day). Weight >30 kg: same as adult dosing. Administer with food.
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).
Elderly (≥65 years): Initial 5 mg orally twice daily; increase slowly to lowest effective maintenance due to increased sensitivity and risk of falls. Avoid doses above 20 mg/day unless clearly necessary.
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.
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant use for patients for whom alternative treatment options are inadequate.
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.
Risk of respiratory depression, especially with opioids,Sedation and somnolence,Risk of abuse and dependence,Withdrawal seizures on abrupt discontinuation,Increased risk of suicidal thoughts or behavior
Respiratory depression,Sedation and somnolence,Risk of abuse, misuse, and addiction,Dependence and withdrawal reactions,Suicidal thoughts or behavior
Hypersensitivity to clobazam or any component of formulation,Severe hepatic impairment
Hypersensitivity to clobazam or any component of the formulation,Severe hepatic impairment (Child-Pugh Class C)
Avoid grapefruit and grapefruit juice as they may increase clobazam levels. No other significant food interactions are known. CNS depressant effects may be potentiated by alcohol.
Avoid grapefruit and grapefruit juice as they may increase levels of clobazam and its active metabolite. No other significant food interactions known.
Pregnancy Category C. First trimester: increased risk of major malformations including cleft lip/palate (OR 2.0-3.0); second/third trimester: risk of neonatal withdrawal, hypotonia, poor feeding, respiratory depression, and hypothermia; consistent exposure may cause floppy infant syndrome. Late pregnancy exposure linked to neonatal benzodiazepine withdrawal syndrome.
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.
Clobazam is excreted into breast milk; M/P ratio approximately 0.5-0.6. Accumulation possible in neonates; monitor for sedation, poor feeding, apnea. Avoid if infant has impaired hepatic function or low birth weight. American Academy of Pediatrics recommends caution; use lowest effective maternal dose.
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.
Increased clearance during pregnancy (CYP3A4 induction); plasma concentrations may decrease by 30-50% in third trimester. Dose adjustments often required: monitor therapeutic response and consider dose increase by 50-100% in late pregnancy; postpartum reduce to prepregnancy dose over 1-2 weeks to avoid toxicity.
Increased clearance of clobazam in pregnancy may require dose adjustments; monitor therapeutic response and adjust accordingly.
ONFI (clobazam) is a benzodiazepine indicated for seizures associated with Lennox-Gastaut syndrome. Titrate slowly to minimize sedation. Monitor for withdrawal symptoms upon discontinuation; taper over several weeks. Not recommended for use in patients with severe hepatic impairment (Child-Pugh C). For patients on other CNS depressants, consider dose reduction. Clobazam's active metabolite, N-desmethylclobazam, has a long half-life (36-46 hours) and can accumulate, especially in poor CYP2C19 metabolizers. In such patients, consider lower doses and monitor for excessive sedation.
Clobazam oral film (SYMPAZAN) is a benzodiazepine approved for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients aged 2 years and older. It is available as a rapidly dissolving film that can be placed on the tongue. The active metabolite N-desmethylclobazam is primarily renally excreted; adjust dose in renal impairment. Avoid abrupt discontinuation due to risk of withdrawal seizures. CYP2C19 poor metabolizers have significantly higher exposure to the active metabolite; consider dose reduction. Can cause sedation, dizziness, and somnolence; monitor for respiratory depression especially with other CNS depressants. Abuse potential exists; use with caution in patients with history of substance abuse.
Take ONFI exactly as prescribed; do not stop suddenly as withdrawal seizures may occur.,Avoid alcohol and other sedatives while taking this medication due to increased risk of drowsiness and respiratory depression.,Report any unusual mood changes, depression, or suicidal thoughts to your healthcare provider.,Do not drive or operate heavy machinery until you know how ONFI affects you, as it can cause dizziness and drowsiness.,If you are pregnant, planning to become pregnant, or breastfeeding, discuss with your doctor before using ONFI.,Store at room temperature, away from moisture and heat.
Place the film on your tongue where it will dissolve quickly; do not chew or swallow it whole.,Take this medication exactly as prescribed; do not increase the dose or stop suddenly without talking to your doctor to avoid withdrawal seizures.,Avoid driving or operating heavy machinery until you know how this drug affects you, as it may cause drowsiness, dizziness, or blurred vision.,Avoid alcohol and other sedating medications while taking SYMPAZAN, as they can increase the risk of severe drowsiness and breathing problems.,Tell your doctor if you have kidney or liver disease, or if you have a history of substance abuse or depression.,If you miss a dose, take it as soon as you remember; if it is close to the next dose, skip the missed dose and continue your regular schedule. Do not double the dose.,Store the film at room temperature away from moisture and heat; keep each film in its sealed pouch until ready to use.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ONFI vs SYMPAZAN, answered by our medical review team.
ONFI is a Benzodiazepine Anticonvulsant that works by GABA-A receptor positive allosteric modulator; increases the frequency of chloride channel opening in response to GABA.. SYMPAZAN is a Benzodiazepine Anticonvulsant that works by 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.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ONFI and SYMPAZAN depend on the specific clinical indication. These are both Benzodiazepine Anticonvulsant agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of ONFI is: Initial: 10 mg orally twice daily; may increase by 10 mg/day after 1 week to maintenance of 20–40 mg/day in two divided doses. Maximum: 60 mg/day.. The standard adult dose of SYMPAZAN is: 10-20 mg orally three times daily (maximum 60 mg/day). If switching from another benzodiazepine, use equivalent dose.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between ONFI and SYMPAZAN in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. ONFI is classified as Category C. Pregnancy Category C. First trimester: increased risk of major malformations including cleft lip/palate (OR 2.0-3.0); second/third trimester: risk of neonatal withdrawal, hypotonia. SYMPAZAN is classified as Category C. 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. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.