Clobazam - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Somnolence or Sedation: Monitor for central nervous system (CNS) depression.

Risk may be increased with concomitant use of other CNS depressants ( 5.4 , 5.5 ) Serious Dermatological Reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis): Discontinue clobazam at first sign of rash unless the rash is clearly not drug-related Suicidal Behavior and Ideation: Monitor for suicidal thoughts or behaviors 5.1 Risks from Concomitant Use with Opioids Concomitant use of benzodiazepines, including clobazam, and opioids may result in profound sedation, respiratory depression, coma, and death.

Because of these risks, reserve concomitant prescribing of benzodiazepines and opioids for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone.

If a decision is made to prescribe clobazam concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation.

Advise both patients and caregivers about the risks of respiratory depression and sedation when clobazam is used with opioids [see Drug Interactions ] .

5.2 Abuse, Misuse, and Addiction The use of benzodiazepines, including clobazam, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death.

Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death [see Drug Abuse and Dependence ] .

Before prescribing clobazam and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool).

Use of clobazam, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of clobazam along with monitoring for signs and symptoms of abuse, misuse, and addiction.

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug.

If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate.

5.3 Dependence and Withdrawal Reactions To reduce the risk of withdrawal reactions, use a gradual taper to discontinue clobazam or reduce the dosage [see Dosage and Administration ] .

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.

Acute Withdrawal Reactions The continued use of benzodiazepines, including clobazam, may lead to clinically significant physical dependence.

Abrupt discontinuation or rapid dosage reduction of clobazam after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) [see Drug Abuse and Dependence ] .

Protracted Withdrawal Syndrome In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months [see Drug Abuse and Dependence ] .

5.4 Potentiation of Sedation from Concomitant Use with Central Nervous System Depressants Since clobazam has a central nervous system (CNS) depressant effect, patients or their caregivers should be cautioned against simultaneous use with other CNS depressant drugs or alcohol, and cautioned that the effects of other CNS depressant drugs or alcohol may be potentiated [see Drug Interactions ] .

5.5 Somnolence or Sedation Clobazam causes somnolence and sedation.

In clinical trials, somnolence or sedation was reported at all effective doses and was dose-related.

In general, somnolence and sedation begin within the first month of treatment and may diminish with continued treatment.

Prescribers should monitor patients for somnolence and sedation, particularly with concomitant use of other central nervous system depressants.

Prescribers should caution patients against engaging in hazardous activities requiring mental alertness, such as operating dangerous machinery or motor vehicles, until the effect of clobazam is known.

5.6 Serious Dermatological Reactions Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with clobazam in both children and adults during the postmarketing period.

Patients should be closely monitored for signs or symptoms of SJS/TEN, especially during the first 8 weeks of treatment initiation or when re-introducing therapy.