1,5-benzodiazepine antiepileptic
Brand names: Onfi, Frisium, Sympazan
Updated · Methodology
Adjunct
Adjunct in focal epilepsy in adults and children over 6 not controlled by monotherapy. ILAE 2017 and the Spanish SEN 2024 consensus place lamotrigine, levetiracetam, and lacosamide as first-line. Clobazam is added as a third or fourth agent. Standard starting dose 5–10 mg once daily at bedtime, titrated to 20–60 mg/day. Also used in Lennox–Gastaut and Dravet syndromes in children.
ICD-10: G40.2 · ICD-11: 8A60
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Clobazam is a long-acting benzodiazepine. It is prescribed for Lennox-Gastaut syndrome and focal epilepsy ( 2018 guidelines); a short course for anxiety in adults is described in the AEMPS Ficha Técnica, but with caution. For regular use in stress and anxiety in people without epilepsy or an anxiety disorder, clobazam is not used: the risks far outweigh the benefit. Regular benzodiazepine use causes tolerance, physical dependence, abuse risk, sedation, and a severe withdrawal syndrome on abrupt discontinuation (tremor, anxiety, insomnia, and in severe cases seizures). The boxed warning for benzodiazepines flags high dependence risk and dangerous consequences when combined with opioids. If clobazam was prescribed for stress, consider seeking a second opinion.
ICD-10: F41.9 · ICD-11: 6B0Z
A 1,5-benzodiazepine – a structural variant with nitrogens at positions 1 and 5 of the imidazole ring. Binds the benzodiazepine site of GABA-A receptors and enhances inhibitory neurotransmission. Compared with classical 1,4-benzodiazepines (diazepam, lorazepam), sedation and muscle-relaxant effects are less marked while the anticonvulsant effect remains. CYP3A4-metabolized to active N-desmethylclobazam with a 71–82-hour half-life. In Spain it is widely used as an antiepileptic under the brand Noiafren.
Boxed warning
FDA boxed warning (2016): concurrent benzodiazepines and opioids carry risk of profound sedation, respiratory depression, and death. Co-prescribe only when alternatives are absent, at lowest effective doses and shortest duration.
T1 use carries a small increase in cleft lip/palate risk in some cohorts. T3 carries floppy infant syndrome and neonatal withdrawal risk. In pregnant patients with epilepsy, decisions are made with an epileptologist; therapy is not stopped without cause.
Milk concentrations are low, but the active metabolite persists in the infant. Monitor drowsiness and weight gain; if pronounced sedation occurs in the infant, switch to formula.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Verbatim lines from the interaction sections, in the language of the label
«Uso concomitante de opioides y benzodiacepinas: Se debe controlar cuidadosamente a los pacientes para monitorizar signos y síntomas de depresión respiratoria y sedación. En tal sentido, se recomienda…»AEMPS, section 4.4 · Open on CIMA
«Opioids: The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Strong or Moderate CYP2C19 Inhibitors: Dosage adjustment of clobazam oral suspension may be necessary ( 7.4 )»FDA, section 7 · Open on DailyMed
«Substratos CYP2D6: Clobazam es un inhibidor débil del CYP2D6. Puede ser necesario un ajuste de la dosis de los medicamentos metabolizados por el CYP2D6 (por ejemplo, dextrometorfano, pimozida…»AEMPS, section 4.5 · Open on CIMA
«Inhibidores CYP2C19: Los inhibidores fuertes y moderados del CYP2C19 podrían resultar en un aumento de la exposición a Ndesmetilclobazam (N-CLB), el metabolito activo de clobazam. Puede ser necesario…»AEMPS, section 4.5 · Open on CIMA
«Effect of Other Drugs on Clobazam Oral Suspension: Strong and moderate inhibitors of CYP2C19 Strong and moderate inhibitors of CYP2C19 may result in increased exposure to N-desmethylclobazam, the…»FDA, section 7 · Open on DailyMed
«Inhibidores CYP2C19: Los inhibidores fuertes y moderados del CYP2C19 podrían resultar en un aumento de la exposición a Ndesmetilclobazam (N-CLB), el metabolito activo de clobazam. Puede ser necesario…»AEMPS, section 4.5 · Open on CIMA
«Effect of Other Drugs on Clobazam Oral Suspension: Strong and moderate inhibitors of CYP2C19 Strong and moderate inhibitors of CYP2C19 may result in increased exposure to N-desmethylclobazam, the…»FDA, section 7 · Open on DailyMed
«Inhibidores CYP2C19: Los inhibidores fuertes y moderados del CYP2C19 podrían resultar en un aumento de la exposición a Ndesmetilclobazam (N-CLB), el metabolito activo de clobazam. Puede ser necesario…»AEMPS, section 4.5 · Open on CIMA
«Substratos CYP2D6: Clobazam es un inhibidor débil del CYP2D6. Puede ser necesario un ajuste de la dosis de los medicamentos metabolizados por el CYP2D6 (por ejemplo, dextrometorfano, pimozida…»AEMPS, section 4.5 · Open on CIMA
«Inhibidores CYP2C19: Los inhibidores fuertes y moderados del CYP2C19 podrían resultar en un aumento de la exposición a Ndesmetilclobazam (N-CLB), el metabolito activo de clobazam. Puede ser necesario…»AEMPS, section 4.5 · Open on CIMA
«Effect of Other Drugs on Clobazam Oral Suspension: Strong and moderate inhibitors of CYP2C19 Strong and moderate inhibitors of CYP2C19 may result in increased exposure to N-desmethylclobazam, the…»FDA, section 7 · Open on DailyMed
«Substratos CYP2D6: Clobazam es un inhibidor débil del CYP2D6. Puede ser necesario un ajuste de la dosis de los medicamentos metabolizados por el CYP2D6 (por ejemplo, dextrometorfano, pimozida…»AEMPS, section 4.5 · Open on CIMA
«Substratos CYP2D6: Clobazam es un inhibidor débil del CYP2D6. Puede ser necesario un ajuste de la dosis de los medicamentos metabolizados por el CYP2D6 (por ejemplo, dextrometorfano, pimozida…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos depresores del sistema nervioso central: Se puede producir una potenciación del efecto depresor, especialmente cuando se administran altas dosis de clobazam concomitantemente con…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos depresores del sistema nervioso central: Se puede producir una potenciación del efecto depresor, especialmente cuando se administran altas dosis de clobazam concomitantemente con…»AEMPS, section 4.5 · Open on CIMA
«Anticonvulsivantes: La carbamazepina y la fenitoína pueden provocar un incremento de la conversión metabólica del clobazam a su metabolito activo N-desmetilclobazam.»AEMPS, section 4.5 · Open on CIMA
«Effect of Clobazam Oral Suspension on Other Drugs: Hormonal Contraceptives Clobazam oral suspension is a weak CYP3A4 inducer. As some hormonal contraceptives are metabolized by CYP3A4, their…»FDA, section 7 · Open on DailyMed
«Inhibidores de la enzima citocromo P-450: El tratamiento simultáneo con medicamentos que inhiben el sistema enzimático citocromo P-450 (monooxigenasa) (por ejemplo, la cimetidina y el antibiótico…»AEMPS, section 4.5 · Open on CIMA
«Effect of Clobazam Oral Suspension on Other Drugs: Hormonal Contraceptives Clobazam oral suspension is a weak CYP3A4 inducer. As some hormonal contraceptives are metabolized by CYP3A4, their…»FDA, section 7 · Open on DailyMed
«Medicamentos depresores del sistema nervioso central: Se puede producir una potenciación del efecto depresor, especialmente cuando se administran altas dosis de clobazam concomitantemente con…»AEMPS, section 4.5 · Open on CIMA
«Anticonvulsivantes: Si se administra clobazam simultáneamente con anticonvulsivantes (p.ej., fenitoína, ácido valproico) pueden elevarse los niveles plasmáticos de estos medicamentos. Si la dosis de…»AEMPS, section 4.5 · Open on CIMA
«Relajantes musculares: La administración de clobazam puede aumentar los efectos de los relajantes musculares, analgésicos y del óxido nitroso.»AEMPS, section 4.5 · Open on CIMA
«Anticonvulsivantes: Si se administra clobazam simultáneamente con anticonvulsivantes (p.ej., fenitoína, ácido valproico) pueden elevarse los niveles plasmáticos de estos medicamentos. Si la dosis de…»AEMPS, section 4.5 · Open on CIMA
«CYP2C19 Substrates: Eslicarbazepine acetate can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and…»FDA, section 7 · Open on DailyMed
«Fármacos que pueden disminuir los niveles plasmáticos de carbamazepina: Antiepilépticos: clobazam, lamotrigina, eslicarbazepina, tiagabina, topiramato, clonazepam, etosuximida, primidona, ácido…»AEMPS, section 4.5 · Open on CIMA
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Clobazam is evaluated for the following indications with varying evidence strength: Focal epilepsy (evidence tier B), Stress and anxiety (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Clobazam (≥ 1 in 100): Drowsiness, Drooling, especially in older patients, Ataxia, Constipation, Irritability, Insomnia (paradoxical). See the Safety section for uncommon and serious reactions.
T1 use carries a small increase in cleft lip/palate risk in some cohorts. T3 carries floppy infant syndrome and neonatal withdrawal risk. In pregnant patients with epilepsy, decisions are made with an epileptologist; therapy is not stopped without cause.
Milk concentrations are low, but the active metabolite persists in the infant. Monitor drowsiness and weight gain; if pronounced sedation occurs in the infant, switch to formula.
Clobazam is contraindicated in: Benzodiazepine hypersensitivity; Severe respiratory failure; Severe hepatic impairment; Myasthenia gravis; Untreated obstructive sleep apnea. Full list in the Safety section.
FDA boxed warning (2016): concurrent benzodiazepines and opioids carry risk of profound sedation, respiratory depression, and death. Co-prescribe only when alternatives are absent, at lowest effective doses and shortest duration.
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