Clobazam

Clobazam is a prescription medicine used to treat seizures associated with Lennox-Gastaut syndrome (LGS).

• Clobazam is available under the following different brand names: ONFI, Sympazan

Adult and pediatric dosage

Scored tablet (ONFI, generic): Schedule IV

• 10mg
• 20mg

Oral suspension (ONFI, generic): Schedule IV

• 2.5mg/mL

Oral soluble film (Sympazan): Schedule IV

• 5mg
• 10mg
• 20mg

Geriatric dosage

• Starting dose should be 5 mg/day for all elderly patients and titrated according to weight, but to half the typical adult dose
• Additional titration to the maximum daily dose (depending on weight either 20 mg/day or 40 mg/day) may be started on day 21
• Administer daily doses of more than 5 mg in divided doses every 12 hours

Seizures

• Adult dosage
  • Initiate at 5 mg orally every 12 hours; may titrate as tolerated up to 40 mg/day divided every 12 hours
• Pediatric dosage
  • Children weighing less than 30 kg
  • Starting dose: 5 mg orally once daily; titrate as tolerated up to 20 mg oral daily
  • After 7 days, may increase to 5 mg orally every 12 hours;  if needed, may increase to 10 mg orally every 12 hours after an additional 7 days
  • Children weighing more than 30 kg
  • Starting dose: 5 mg orally every 12 hours; titrate as tolerated up to 40 mg oral daily
  • After 7 days, may increase to 10 mg orally every 12 hours; if needed, may increase to 20 mg orally every 12 hours after an additional 7 days

CYP2C19 poor metabolizers

Adult and pediatric dosage

• Starting dose should be 5 mg/day and titrated according to weight, but to half the typical dose
• Additional titration to the maximum dose (20 mg/day or 40 mg/day), depending on the weight group) maybe started on day 21

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Clobazam include:

• sleepiness,
• drooling,
• constipation,
• cough,
• pain with urination,
• fever,
• acting aggressive, being angry, or violent,
• tiredness,
• difficulty sleeping,
• problems with breathing, and
• slurred speech

Serious side effects of Clobazam include:

• somnolence,
• sedation,
• ataxia,
• dysphagia, and
• skin and subcutaneous tissue disorders such as rash, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), urticaria.

Rare side effects of Clobazam include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Clobazam has severe interactions with the following drugs:
  • cobimetinib
  • doravirine
  • eliglustat
• Clobazam has serious interactions with at least 35 other drugs:
• Clobazam has moderate interactions with at least 199 other drugs.
• Clobazam has minor interactions with the following drugs:
  • pantoprazole
  • perampanel

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• History of hypersensitivity to drug or ingredients

Effects of drug abuse

• Addiction
• Overdose
• Death

Short-Term Effects

• See “What Are Side Effects Associated with Using Clobazam?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Clobazam?”

Cautions

• Somnolence or sedation; generally occurs within the first month of treatment and may diminish with continued treatment; caution patients about operating hazardous machinery, including automobiles until they are reasonably certain that therapy does not affect them adversely (eg, impair judgment, thinking, or motor skills)
• Serious skin reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported in both children and adults; monitor closely, especially during the first 8 weeks of treatment initiation or when reintroducing therapy; discontinue at the first sign of a drug-related rash and do not resume unless the rash is not drug-related; if signs or symptoms suggest SJS/TEN, do not resume therapy; alternative therapy should be considered
• Consider the history of substance abuse because of the predisposition of such patients to physical and/or psychological dependence; patients with a history of substance abuse should be under careful surveillance when receiving drug or other psychotropic agents because of the predisposition of such patients to habituation and dependence
• Use of drugs, particularly in patients at elevated risk of abuse, necessitates counseling about risks and proper use of the drug along with monitoring for signs and symptoms of abuse, misuse, and addiction; do not exceed recommended dosing frequency
• Avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (eg, opioid analgesics, stimulants); advise patients on proper disposal of the unused drug; if a substance use disorder is suspected, evaluate patient and institute (or refer them for) early treatment, as appropriate
• For patients using treated more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue therapy (a patient-specific plan should be used to taper the dose)
• Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages and those who have had longer durations of use
• In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months
• Patients treated with any antiepileptic drug for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior; should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated; behaviors of concern should be reported immediately to the healthcare provider
• Drug interaction overview
  • Concomitant use with other CNS depressants may increase the risk of sedation and somnolence; alcohol, as a CNS depressant, will interact to increase clobazam’s maximum plasma exposure by approximately 50%; caution patients or caregivers against simultaneous use with other CNS depressant drugs or alcohol, and caution that effects of other CNS depressants or alcohol may be potentiated
  • Weak CYP3A4 inducers may diminish the effectiveness of some hormonal contraceptives; additional non-hormonal forms of contraception are recommended when receiving therapy
  • Strong and moderate inhibitors of CYP2C19 may result in increased exposure to N-desmethylclobazam, the active metabolite of clobazam; this may increase the risk of dose-related adverse reactions; dosage adjustment may be necessary when co-administered with strong CYP2C19 inhibitors (eg, fluconazole, fluvoxamine, ticlopidine) or moderate CYP2C19 inhibitors (eg, omeprazole)
  • Coadministration of cannabidiol, a CYP3A4 and CYP2C19 substrate and a CYP2C19 inhibitor, with clobazam may increase the risk of clobazam-related adverse reactions; consider a reduction in dosage of cannabidiol or clobazam if adverse reactions known to occur with the drug are experienced
  • Drug therapy inhibits CYP2D6; dose adjustments of drugs metabolized by CYP2D6 may be necessary
• Withdrawal
  • As with all antiepileptic drugs, withdraw gradually to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus
  • Avoid abrupt discontinuation; taper by decreasing dose each week by 5-10 mg/day until discontinued
  • Withdrawal symptoms (eg, convulsions, psychosis, hallucinations, behavioral disorder, tremor, and anxiety) occur following abrupt discontinuation, risk is greater with higher doses

Pregnancy and Lactation

• Encourage pregnant patients (or their caregivers) to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry; toll-free number 1-888-233-2334; http://www.aedpregnancyregistry.org
• There are no adequate and well-controlled studies in pregnant women; available data suggest that the class of benzodiazepines is not associated with marked increases in risk for congenital anomalies; although some early epidemiological studies suggested a relationship between benzodiazepine drug use in pregnancy and congenital anomalies such as cleft lip and or palate, these studies had considerable limitations; more recently completed studies of benzodiazepine use in pregnancy have not consistently documented elevated risks for specific congenital anomalies; there is insufficient evidence to assess the effect of benzodiazepine pregnancy exposure on neurodevelopment
• There are clinical considerations regarding exposure to benzodiazepines during the second and third trimester of pregnancy or immediately before or during childbirth; these risks include decreased fetal movement and/or fetal heart rate variability, “floppy infant syndrome,” dependence, and withdrawal
• Administration of clobazam to pregnant rats and rabbits during the period of organogenesis or to rats throughout pregnancy and lactation resulted in developmental toxicity, including increased incidences of fetal malformations and mortality, at plasma exposures for clobazam and its major active metabolite, N-desmethylclobazam, below those expected at therapeutic doses in patients; data for other benzodiazepines suggest the possibility of long-term effects on neurobehavioral and immunological function in animals following prenatal exposure to benzodiazepines at clinically relevant doses; the drug should be used during pregnancy only if the potential benefit to mother justifies the potential risk to the fetus; advise a pregnant woman and women of childbearing age of potential risk to a fetus
• Infants born to mothers who have taken benzodiazepines during later stages of pregnancy can develop dependence, and subsequently withdrawal, during the postnatal period; clinical manifestations of withdrawal or neonatal abstinence syndrome may include hypertonia, hyperreflexia, hypoventilation, irritability, tremors, diarrhea, and vomiting; these complications can appear shortly after delivery to 3 weeks after birth and persist from hours to several months depending on the degree of dependence and pharmacokinetic profile of the benzodiazepine; symptoms may be mild and transient or severe; standard management for neonatal withdrawal syndrome has not yet been defined; observe newborns who are exposed to the drug in utero during later stages of pregnancy for symptoms of withdrawal and manage accordingly
• Labor and delivery
  • Administration of benzodiazepines immediately before or during childbirth can result in a floppy infant syndrome, which is characterized by lethargy, hypothermia, hypotonia, respiratory depression, and difficulty feeding; floppy infant syndrome occurs mainly within the first hours after birth and may last up to 14 days; observe exposed newborns for these symptoms and manage accordingly
• Lactation
  • The drug is excreted in human milk; postmarketing experience suggests that breastfed infants of mothers taking benzodiazepines, may have effects of lethargy, somnolence, and poor sucking; effect of the drug on milk production is unknown; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for drug and any potential adverse effects on the breastfed infant from the drug or underlying maternal condition; if exposing a breastfed infant to the drug, observe for any potential adverse effects