Brand names: Onfi, Sympazan
Drug class: Benzodiazepines

Medically reviewed by Drugs.com on Jun 10, 2025. Written by ASHP.

Introduction

Anticonvulsant that also demonstrates anxiolytic properties; a 1,5-benzodiazepine.^{1 2 3 6 7 9 14 19 34 36 44}

Uses for Clobazam

Seizure Disorders

Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients ≥2 years of age.^{1 2 3 5 6 9 17 19 22 36 49} Designated an orphan drug by FDA for use in this condition.^{5 9 19}

Also has been used as adjunctive therapy in many other seizure disorders, sometimes refractory, including partial, generalized, and myoclonic seizures^{† [off-label]}.^{6 13 14 23 24 25 26 41 44} Has been used with some success in partial onset seizures; additional studies needed to more clearly determine role in the adjunctive treatment of other refractory seizure disorders.^{14 24}

Has been used in the treatment of seizures associated with Dravet syndrome^{† [off-label]}.^{310 311 312 314} Although evidence from controlled studies limited,^{311 314 315} considered a first-line therapy for this condition.^{310 311 312 314}

Anxiety Disorders

Has been used for short-term (2–4 weeks) treatment of anxiety disorders^{† [off-label]} in some countries outside the US.^{6 13 36 42 44} Currently not FDA-labeled for the treatment of anxiety disorders in the US.¹

Clobazam Dosage and Administration

General

Pretreatment Screening

• Assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool) prior to and throughout treatment.¹ Use of clobazam, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of clobazam.^{1 49}

Patient Monitoring

• Monitor for signs and symptoms of abuse, misuse, and addiction.^{1 49}

• Monitor for somnolence and sedation, particularly during concomitant use of other CNS depressants (e.g., alcohol, opiate agonists, tricyclic antidepressants [TCAs], sedating antihistamines, other benzodiazepines).^{1 49}

• Closely monitor for emergence or worsening of suicidal thoughts or behavior or depression^{1 49} .

• Closely monitor patients for signs or symptoms of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), especially during the first 8 weeks of treatment initiation or when re-introducing therapy.^{1 49}

Dispensing and Administration Precautions

• The ISMP includes cloBAZam and clonazePAM on the ISMP List of Confused Drug Names, and recommends special safeguards to ensure the accuracy of prescriptions for these drugs.¹⁰

• The 2023 American Geriatrics Society (AGS) Beers Criteria for Potentially Inappropriate Medication (PIM) Use in Older Adults includes clobazam on the list of PIMs that are best avoided by older adults in most circumstances or under specific situations, such as certain diseases, conditions, or care settings.⁹⁹⁹ The criteria are intended to apply to adults 65 years of age and older in all ambulatory, acute, and institutional settings of care, except hospice and end-of-life care settings.⁹⁹⁹ The Beers Criteria Expert Panel recommends that use of benzodiazepines be avoided in such patients because of increased sensitivity, decreased metabolism of long-acting agents, risk of cognitive impairment, and risk of physical dependence with continued use.⁹⁹⁹ These drugs may be appropriate in certain situations (e.g., seizure disorders, rapid eye movement sleep behavior disorder, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, periprocedural anesthesia).⁹⁹⁹

Administration

Oral Administration

Administer orally as tablets, oral suspension, or oral film.^{1 49} Administer daily dosages >5 mg in divided doses twice daily; may administer 5-mg daily dosage as a single daily dose.^{1 19 49}

May administer with or without food.¹

Tablets

Administer tablets whole, broken in half, or crushed and mixed in applesauce.¹

Oral Suspension

Shake oral suspension well prior to administration.¹ Administer using bottle adapter and calibrated oral dosing syringe supplied by manufacturer.¹ Firmly insert bottle adapter into neck of bottle before first use and keep in place for duration of use (up to 90 days).¹ To dispense dose, insert oral dosing syringe into adapter, then invert bottle and withdraw appropriate dose into syringe.¹ Administer dose slowly and directly into corner of patient's mouth.¹

Oral Film

Place oral film on the surface of tongue and allow to dissolve completely.^{49 50} Do not administer with liquids.⁴⁹ As film dissolves, swallow saliva in a normal manner; avoid chewing, spitting, or talking.⁴⁹ Only one oral film should be taken at a time; if a second film is needed to complete the dose, take after first film has completely dissolved.⁴⁹

Dosage

Pediatric Patients

Seizure Disorders

Adjunctive Therapy in Lennox-Gastaut Syndrome

Oral

Individualize dosage based on patient response and tolerability.^{1 49} Although all recommended dosages have demonstrated efficacy, efficacy is dose related;^{1 2 3 13 49} titrate to maximum tolerability until adequate seizure control attained.¹³ Increase dosage no more frequently than once a week to allow sufficient time for steady-state concentrations to be achieved at each dosage level.^{1 49}

Children ≥2 years of age weighing ≤30 kg: Initially, 5 mg daily as a single daily dose.^{1 49} May increase to 10 mg daily (in 2 divided doses) after 7 days, and to recommended maximum of 20 mg daily (in 2 divided doses) after an additional 7 days if clinically indicated and tolerated.^{1 49}

Children ≥2 years of age weighing >30 kg: Initially, 10 mg daily in 2 divided doses.^{1 49} May increase to 20 mg daily (in 2 divided doses) after 7 days, and to recommended maximum of 40 mg daily (in 2 divided doses) after an additional 7 days if clinically indicated and tolerated.^{1 49}

Reduce dosage gradually (by decreasing total daily dosage by 5–10 mg at weekly intervals) when discontinuing therapy.^{1 49}

Seizures Associated with Dravet Syndrome† [off-label]

Oral

Initial dosages of 0.2–0.3 mg/kg daily (in 2 divided doses) with target daily dosages of 0.5–2 mg/kg (in 2 divided doses) have been used.^{311 314}

Adults

Seizure Disorders

Adjunctive Therapy in Lennox-Gastaut Syndrome

Oral

Individualize dosage based on patient response and tolerability.^{1 49} Although all recommended dosages have demonstrated efficacy, efficacy is dose related;^{1 2 3 13 49} titrate to maximum tolerability until adequate seizure control attained.¹³ Increase dosage no more frequently than once a week to allow sufficient time for steady-state concentrations to be achieved at each dosage level.^{1 49}

Patients weighing ≤30 kg: Initially, 5 mg daily as a single daily dose.^{1 49} May increase to 10 mg daily (in 2 divided doses) after 7 days, and to recommended maximum of 20 mg daily (in 2 divided doses) after an additional 7 days if clinically indicated and tolerated.^{1 49}

Patients weighing >30 kg: Initially, 10 mg daily in 2 divided doses.^{1 49} May increase to 20 mg daily (in 2 divided doses) after 7 days, and to recommended maximum of 40 mg daily (in 2 divided doses) after an additional 7 days if clinically indicated and tolerated.^{1 49}

Reduce dosage gradually (by decreasing total daily dosage by 5–10 mg at weekly intervals) when discontinuing therapy.^{1 49}

Seizures Associated with Dravet Syndrome† [off-label]

Oral

Initial dosages of 0.2–0.3 mg/kg daily (in 2 divided doses) with target daily dosages of 0.5–2 mg/kg (in 2 divided doses) have been used.^{311 314}

Anxiety Disorders†

Short-term Treatment of Severe, Disabling, or Intolerable Anxiety†

Oral

Usual dosage: 20–30 mg daily in divided doses or as a single dose in the evening.⁴⁴ Dosages of up to 60 mg daily have been used for severe anxiety in hospitalized patients.⁴⁴

Special Populations

Hepatic Impairment

Adjunctive Therapy in Lennox-Gastaut Syndrome

Limited pharmacokinetic data; titrate dosage slowly.^{1 49}

Mild to moderate hepatic impairment (Child-Pugh class A or B): Initially, 5 mg daily regardless of body weight.^{1 49} Subsequently titrate dosage according to weight, but to half of the usual recommended dosage as tolerated.^{1 49} May initiate an additional titration to maximum dosage of 20 mg daily (in patients weighing ≤30 kg) or 40 mg daily (in patients weighing >30 kg) at 3 weeks if necessary and based on clinical response.^{1 49}

Severe hepatic impairment (Child-Pugh class C): Data currently insufficient to make dosage recommendations.^{1 49}

Renal Impairment

Adjunctive Therapy in Lennox-Gastaut Syndrome

Mild or moderate renal impairment (Cl_cr 30–80 mL/minute): No dosage adjustment necessary.^{1 49}

Severe renal impairment or end-stage renal disease: Not systematically evaluated.^{1 49}

Geriatric Patients

Adjunctive Therapy in Lennox-Gastaut Syndrome

Initially, 5 mg daily regardless of body weight.^{1 49} Subsequently titrate dosage slowly according to weight, but to half of the usual recommended dosage as tolerated.^{1 49} May initiate an additional titration to maximum dosage of 20 mg daily (in patients weighing ≤30 kg) or 40 mg daily (in patients weighing >30 kg) at 3 weeks if necessary and based on clinical response.^{1 49}

Pharmacogenomic Considerations in Dosing

Adjunctive Therapy in Lennox-Gastaut Syndrome

CYP2C19 poor metabolizers: Initially, 5 mg daily.^{1 49} Subsequently titrate dosage slowly according to weight, but to half of the usual recommended dosage as tolerated.^{1 49} May initiate an additional titration to maximum dosage of 20 mg daily (in patients weighing ≤30 kg) or 40 mg daily (in patients weighing >30 kg) at 3 weeks if necessary and based on clinical response.^{1 49}

Cautions for Clobazam

Contraindications

• Known hypersensitivity to clobazam or any ingredient in the formulation.^{1 49}

Warnings/Precautions

Warnings

Concomitant Use with Opioids

Concomitant use of benzodiazepines, including clobazam, and opioids may result in profound sedation, respiratory depression, coma, and death (see Boxed Warning).^{1 49 700 701 705 706 707} Substantial proportion of fatal opioid overdoses involve concurrent benzodiazepine use.^{700 701 705 706 707 711}

Reserve concomitant use of clobazam and opioids for patients in whom alternative treatment options are inadequate.^{1 49 700}

Advise patients and caregivers about the risk of respiratory depression and sedation when clobazam is used with opioids.^{1 49 900}

Abuse, Misuse, and Addiction

Risks of addiction, abuse, and misuse; can result in overdose or death (see Boxed Warning).^{1 49 900}

Risk is increased when benzodiazepines are combined with other medications, such as opioid pain relievers, alcohol, or illicit drugs, or administered in higher than recommended dosages.^{1 49 900}

Assess each patient’s risk prior to prescribing and throughout treatment.^{1 49 900} Standardized screening tools are available ([Web]).

Continued use of benzodiazepines may lead to clinically significant physical dependence; risk is increased with longer treatment duration and higher daily doses.^{1 49 900} To reduce risk of acute withdrawal reactions, gradually taper when reducing dosage or discontinuing therapy.^{1 49 900}

Other Warnings and Precautions

Concomitant Use of CNS Depressants

Risk of potentiated CNS depressant effects when used concomitantly with other CNS depressants or alcohol; caution patients.^{1 49}

Somnolence and Sedation

Somnolence and sedation commonly occur.^{1 2 3 6 19} Generally occur within first month of treatment and may diminish with continued therapy.^{1 6 19} Observed at all clinically effective dosages and appear to be dose related.^{1 2}

Monitor for somnolence and sedation, particularly during concomitant use of other CNS depressants (e.g., alcohol, opiate agonists, tricyclic antidepressants [TCAs], sedating antihistamines, other benzodiazepines).¹

Serious Dermatologic Reactions

Serious and sometimes life-threatening dermatologic reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), reported rarely in pediatric and adult patients during postmarketing experience worldwide.^{1 47 48} May occur at any time during therapy, but risk is greater during first 8 weeks of therapy or when clobazam is discontinued and then reinitiated.⁴⁷ Hospitalization was required in all cases; one case resulted in blindness and at least one death occurred.⁴⁷

Closely monitor patients for signs and symptoms of SJS and TEN, particularly during the initial 8 weeks of treatment or when reinitiating therapy.^{1 47} Discontinue therapy at the first sign of a rash unless clearly not drug related; if manifestations suggest SJS or TEN, do not reinitiate clobazam and consider alternative therapies.^{1 47} When switching from one anticonvulsant to another, consider that other anticonvulsants also may be associated with serious dermatologic reactions.⁴⁷

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity

Drug reaction with eosinophilia and systemic symptoms (DRESS, also known as multiorgan hypersensitivity), a potentially fatal or life-threatening reaction, reported in patients taking antiepileptic drugs.^{1 49 900}

Clinical presentation is variable, but typically includes eosinophilia, fever, rash, lymphadenopathy and/or facial swelling in association with other organ system involvement such as hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis, or others.^{1 49 900}

Early manifestations of hypersensitivity such as fever or lymphadenopathy may be present even though rash is not evident.^{1 49 900}

If signs and symptoms of DRESS occur, evaluate patients immediately. Discontinue clobazam if an alternative etiology cannot be established.^{1 49 900}

Suicidality Risk

Increased risk of suicidality (suicidal behavior or ideation) observed in an analysis of studies using various anticonvulsants in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%).¹ Increased suicidality risk was observed ≥1 week after initiation of anticonvulsant therapy and continued through 24 weeks.¹ Risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.¹

Closely monitor all patients currently receiving or beginning anticonvulsant therapy for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behavior or depression.¹

Balance risk of suicidality with risk of untreated illness.¹ Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality.¹ If suicidal thoughts or behavior emerges during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself.¹

Neonatal Sedation and Withdrawal Syndrome

Use of clobazam late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate.^{1 49}

Monitor neonates exposed to clobazam during pregnancy for sedation and signs of withdrawal and manage accordingly.^{1 49}

Specific Populations

Pregnancy

Pregnancy registry established. Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334 or [Web].¹

No adequate data in pregnant women.¹ Based on animal data, may cause fetal harm.¹

Possible dependence and subsequent withdrawal syndrome in neonates exposed to benzodiazepines during late pregnancy.¹ Observe neonates for symptoms of withdrawal and manage as clinically appropriate.¹

Lactation

Clobazam and its active metabolite are distributed into human milk.¹ Effects on milk production not known.¹ Consider benefits of breast-feeding and mother's clinical need for clobazam; also consider potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.¹

Monitor infants exposed to clobazam through breast milk for sedation, poor feeding, and poor weight gain.¹

Fertility

May impair fertility, based on studies in male and female rats.¹

Pediatric Use

Safety and efficacy not established in pediatric patients <2 years of age.¹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.¹

Because of the possibility of decreased clearance in geriatric patients, initiate therapy with a low dosage and titrate slowly.¹

Hepatic Impairment

Extensively metabolized by the liver; however, effects of hepatic impairment on pharmacokinetics of clobazam not fully characterized.^{1 13 45}

Initiate therapy at 5 mg daily (regardless of patient weight) and titrate slowly in patients with mild or moderate hepatic impairment (Child-Pugh class A or B).^{1 36} Insufficient information in patients with severe hepatic impairment.¹

Renal Impairment

Systemic exposure to clobazam or its active metabolite not substantially altered in patients with mild (Cl_cr >50–80 mL/minute) or moderate (Cl_cr 30–50 mL/minute) renal impairment.¹ No experience in patients with severe renal impairment or end-stage renal disease.¹

Not known whether clobazam or its active N-desmethylclobazam metabolite is dialyzable.¹

Pharmacogenomic Considerations

Genetic polymorphism of CYP2C19 can affect pharmacokinetic and pharmacodynamic response to clobazam.^{1 27 31 32 33} CYP2C19 is the principal enzyme involved in the metabolism of N-desmethylclobazam, the pharmacologically active metabolite of clobazam.¹ Plasma concentrations of N-desmethylclobazam are higher in poor CYP2C19 metabolizers compared with extensive CYP2C19 metabolizers.^{1 27 31 32 33}

Dosage adjustment is necessary in known poor CYP2C19 metabolizers.¹

Common Adverse Effects

Adverse effects generally similar to those observed with other benzodiazepines.^{6 9 13 19}

Somnolence or sedation,^{1 2} lethargy,^{1 2} drooling,^{1 2} vomiting,¹ constipation,^{1 2} dysphagia,¹ decreased or increased appetite,¹ cough,¹ upper respiratory tract infection,¹ pneumonia,¹ bronchitis,¹ urinary tract infection,¹ aggression,¹ insomnia,¹ irritability,¹ ataxia,¹ psychomotor hyperactivity,¹ dysarthria,¹ pyrexia,^{1 2} fatigue.¹

Drug Interactions

Metabolized principally by CYP3A4, and to a lesser extent by CYP2C19 and CYP2B6.^{1 27 42} Clobazam's active metabolite, N-desmethylclobazam, is metabolized principally by CYP2C19.^{1 27}

Clobazam and N-desmethylclobazam induce CYP3A4 in a concentration-dependent manner; N-desmethylclobazam also is a weak inhibitor of CYP2C9.¹ Clobazam also appears to inhibit CYP2D6.¹

Does not inhibit CYP1A2, 2C8, 2C9, 2C19, and 3A4 nor substantially induce CYP1A2 and CYP2C19 in vitro.¹

Clobazam does not inhibit uridine diphosphate-glucuronosyltransferase (UGT) 1A1, 1A4, 1A6, or 2B4 in vitro.¹ N-desmethylclobazam is a weak inhibitor of UGT 1A4, 1A6, and 2B4.¹

Drugs Metabolized by Hepatic Microsomal Enzymes

CYP2D6 substrates: Potential pharmacokinetic interaction (increased plasma concentrations of substrate); dosage adjustment of drugs metabolized by CYP2D6 may be necessary.^{1 36 42}

CYP3A4 substrates: Potential pharmacokinetic interaction (decreased plasma concentrations of substrate);^{1 42} however, manufacturer states dosage adjustment of drugs principally metabolized by CYP3A4 not necessary.¹

CYP1A2 substrates: Pharmacokinetic interaction not likely.^{1 42}

CYP2C9 substrates: Pharmacokinetic interaction not likely.^{1 42}

Drugs Affecting Hepatic Microsomal Enzymes

Potent or moderate CYP2C19 inhibitors: Potential pharmacokinetic interaction (increased exposure to N-desmethylclobazam and possible toxicity); clobazam dosage adjustment may be necessary.^{1 36 42}

Potent CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased exposure to clobazam).^{1 42}

Specific Drugs

Clobazam Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed following oral administration; peak plasma concentrations achieved within 0.5–4 hours after single- or multiple-dose administration of clobazam tablets under fasting conditions.^{1 6 13 19 25 36 39 42 45} Peak plasma concentrations achieved within 0.5–2 hours following single-dose administration of the oral suspension under fasting conditions.¹

Bioavailability of oral suspension similar to that of tablets under fasting conditions.¹ Oral films and tablets are bioequivalent following administration of single doses of 10 or 20 mg.^{49 50}

Median time to disintegration of oral film following placement on tongue is 82 seconds (range 18–245 seconds) for the 10-mg film and 105 seconds (range: 45–300 seconds) for the 20-mg film.⁵⁰

At therapeutic dosages, plasma concentrations of N-desmethylclobazam (an active metabolite) are approximately 3–5 times higher than those of clobazam.^{1 42}

Food

Food does not appear to substantially affect absorption from tablets; although not evaluated, food also unlikely to affect bioavailability of the oral suspension or oral film.^{1 6 13 19 49}

Special Populations

Limited data indicate no substantial pharmacokinetic differences between patients with hepatic impairment and healthy individuals.^{1 13 45}

No substantial pharmacokinetic differences between patients with mild (Cl_cr >50–80 mL/minute) or moderate (Cl_cr 30–50 mL/minute) renal impairment and those with normal renal function.¹ Not known if clobazam or N-desmethylclobazam is dialyzable;¹ limited evidence suggests clobazam concentrations are unaffected by hemodialysis.⁴⁰

Systemic exposure to N-desmethylclobazam is approximately 3–5 times higher in poor CYP2C19 metabolizers and approximately 2 times higher in intermediate CYP2C19 metabolizers than in extensive CYP2C19 metabolizers¹

Distribution

Extent

Highly lipophilic and distributes rapidly throughout the body.^{1 25}

Crosses the blood-brain barrier.²⁵

Distributes into human milk.¹

Plasma Protein Binding

Clobazam: Approximately 80–90%.^{1 25}

N-desmethylclobazam: Approximately 70%.^{1 25}

Elimination

Metabolism

Extensively metabolized in liver, primarily via N-demethylation (principally by CYP3A4 and, to a lesser extent, by CYP2C19 and CYP2B6) to pharmacologically active metabolite, N-desmethylclobazam.^{1 13 27} Potency of N-desmethylclobazam may be similar to or somewhat less than parent drug; therefore, active metabolite may contribute to efficacy and safety.^{1 6 13 19 25 31 32 42}

N-Desmethylclobazam is further metabolized by CYP2C19 to an inactive derivative.^{1 6 9 27 31 32 33}

Metabolism is subject to genetic polymorphism of CYP2C19.^{1 6 9 27 31 32 33 42}

Elimination Route

Eliminated mainly in urine (82%) as metabolites; only about 2% of dose is excreted as unchanged drug.¹

Half-life

Approximately 36–42 hours for clobazam and 71–82 hours for N-desmethylclobazam.^{1 13}

Special Populations

Some data suggest that clobazam may be more rapidly and extensively metabolized in children than in adults.^{6 19}

Decreased clearance observed in geriatric patients compared with younger age groups (ages 2–64).¹

Stability

Storage

Oral

Oral Film

20–25°C (may be exposed to 15–30°C).⁴⁹

Tablets

20–25°C.¹

Suspension

20–25°C.¹ Store bottle in upright position; use within 90 days of opening.¹

Actions

• 1,5-benzodiazepine with anticonvulsant and anxiolytic properties.^{1 2 3 6 9 14 19 34 36 44}

• Exact mechanism of anticonvulsant and anxiolytic actions unknown, but thought to involve allosteric binding of clobazam to the benzodiazepine site of the GABA type A (GABA_A) receptor, which in turn potentiates the inhibitory effects of GABA.^{1 6 9 19 34 36 46}

• Structurally similar to the 1,4-benzodiazepines (e.g., clonazepam, diazepam, lorazepam), but appears to have a broader spectrum of anticonvulsant activity and an improved adverse effect profile (e.g., less sedative effects).^{6 14 19 25 31 34 39}

• Metabolism of the drug is subject to genetic polymorphism of CYP2C19.^{1 6 9 27 31 32 33 42} Individuals with the CYP2C19*2/*2 genotype are described as poor metabolizers; those with the CYP2C19*1/*2 genotype are intermediate metabolizers, and those with CYP2C19*1/*1 are extensive metabolizers.^{1 33} Prevalence of poor CYP2C19 metabolizers in general population varies based on ethnic and racial background.^{1 9 27 31 33}

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).^{1 49}

• Risk of potentially fatal additive effects (e.g., profound sedation, respiratory depression, coma) if used concomitantly with opioids either therapeutically or illicitly.^{1 49 700} Avoid concomitant use of opioids unless use is supervised by clinician.^{1 49 700 700}

• Inform patients that the use of clobazam, even at recommended dosages, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose and death, especially when used in combination with other medications (e.g., opioid analgesics), alcohol, and/or illicit substances.^{1 49} Inform patients about the signs and symptoms of benzodiazepine abuse, misuse, and addiction; to seek medical help if they develop these signs and/or symptoms; and on the proper disposal of unused drug.^{1 49}

• Advise patients or caregivers that abrupt withdrawal of anticonvulsant drugs may increase their risk of seizure.^{1 49} Inform patients that continued use of clobazam may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction may precipitate acute withdrawal reactions, which can be life-threatening.^{1 49} Inform patients that in some cases, patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months.^{1 49} Instruct patients that discontinuation or dosage reduction of clobazam may require a slow taper.^{1 49}

• Risk of potentiated CNS depression with concurrent use of alcohol or other CNS depressants.^{1 49} Advise patients or caregivers to check with their clinician before using clobazam concomitantly with other CNS depressants (e.g., other benzodiazepines, TCAs, sedating antihistamines, alcohol).^{1 49}

• Risk of somnolence or sedation.¹ Caution patients against driving or operating hazardous machinery until they are reasonably certain that clobazam does not adversely affect their judgment, thinking, or motor skills.¹

• Inform patients or caregivers that clobazam is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients.^{1 49}

• Risk of rare but serious skin reactions, including SJS and TEN.^{1 47 48} Advise patient or caregivers to seek immediate medical attention at first appearance of a skin rash or other signs of hypersensitivity (e.g., blistering or peeling of skin, mouth sores, hives) while receiving clobazam.^{1 47}

• Risk of DRESS/multiorgan hypersensitivity.^{1 49} Instruct patients and caregivers that a fever or rash associated with signs of other organ system involvement (e.g., lymphadenopathy, hepatic dysfunction) may be drug-related and should be reported to their healthcare provider immediately.^{1 49} Clobazam should be discontinued immediately if a serious hypersensitivity reaction is suspected.^{1 49}

• Risk of suicidality (anticonvulsants, including clobazam, may increase risk of suicidal thoughts or actions in about 1 in 500 people).^{1 49} Advise patients, family members, and caregivers to be alert to day-to-day changes in mood, behavior, and actions and immediately inform their clinician of any new or worrisome behaviors (e.g., talking or thinking about wanting to hurt oneself or end one's life, withdrawing from friends and family, becoming depressed or experiencing worsening of existing depression, becoming preoccupied with death and dying, giving away prized possessions).^{1 49}

• Advise patients to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 49} Advise pregnant females that the use of clobazam late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns.^{1 49} Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant while taking clobazam.^{1 49}

• Advise women that clobazam may cause some hormonal contraceptives (e.g., oral contraceptives, patches, rings, implants, injections, intrauterine devices) to be less effective; importance of advising women to use additional nonhormonal forms of contraception during clobazam therapy and for 28 days after discontinuance of the drug.^{1 49}

• Instruct patients to notify their healthcare provider if they are breastfeeding or intend to breastfeed.¹ Instruct breastfeeding patients who have been administered clobazam to observe their infants for sedation, poor feeding, and poor weight gain, and to seek medical attention if they notice these signs.^{1 49}

• Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., kidney or liver disease, respiratory problems, depression or other mood disorders).^{1 49}

• Inform patients of other important precautionary information.^{1 49}

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.¹

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Related/similar drugs

Frequently asked questions

• What is the difference between Sympazan and Onfi?

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