General MedicationsORALBlack Box

CLORAZEPATE DIPOTASSIUM

Standard Dose

DOSAGE AND ADMINISTRATION FortheSymptomatic ReliefofAnxiety: Clorazepate dipotassium tablets are administeredorally in divided doses. The usual daily dose is 30mg.The dose should beadjustedgraduallywithintherange of 15 to 60 mg daily in accordancewith the response of the patient. In elderly or debilitatedpatientsit is advisable to initiate treatment at a daily dose of 7.5 to 15 mg. Clorazepate dipotassium tabletsmay also be administeredin a singledosedaily at bedtime; the recommendedinitialdose is 15 mg.After the initial dose, the response of the patient mayrequireadjustment of subsequent dosage.Lower doses may be indicated in the elderlypatient. Drowsinessmay occur at the initiation of treatment and withdosageincrement. For the Symptomatic Relief of Acute Alcohol Withdrawal: Thefollowing dosage scheduleisrecommended: 1st 24 hours (Day 1) 30 mginitially;followed by 30 to 60 mg in divideddoses 2nd 24 hours (Day 2) 45 to 90 mg in divideddoses 3rd 24 hours (Day 3) 22.5 to 45 mg in divided doses Day 4 15 to 30 mg in divideddoses Thereafter,graduallyreduce the daily dose to 7.5 to 15 mg.Discontinuedrugtherapy as soon as patient’s condition is stable. Themaximum recommendedtotaldailydose is 90 mg. Avoid excessive reductionsin the totalamount of drug administeredonsuccessive days. As an Adjunct to Antiepileptic Drugs: In order to minimizedrowsiness, the recommendedinitialdosages and dosageincrementsshould not be exceeded. Adults: Themaximum recommendedinitialdose in patients over 12 years old is 7.5 mg three times a day. Dosage should be increased by no more than 7.5mg every week and should not exceed 90 mg/day. Children (9-12 years): Themaximum recommendedinitial dose is 7.5 mgtwotimes a day. Dosage should be increased by no more than 7.5mg every week and should not exceed 60 mg/day. Discontinuation or DosageReduction of Clorazepate dipotassium tablets: To reduce the risk of withdrawalreactions,use a gradualtaper to discontinueClorazepate dipotassium tablets or reduce the dosage. If a patient develops withdrawalreactions,consider pausing the taper or increasingthe dosage to the previous tapereddosage level. Subsequentlydecreasethedosagemoreslowly (see WARNINGS and DRUG ABUSE AND DEPENDENCE ).

Max Dose

See official label

Primary Use

INDICATIONS AND USAGE Clorazepate dipotassium tablets are indicatedfor the management of anxiety disordersorfortheshort-term relief of the symptoms of anxiety.

Summary

Indications and usage INDICATIONS AND USAGE Clorazepate dipotassium tablets are indicatedfor the management of anxiety disordersorfortheshort-term relief of the symptoms of anxiety.

Anxiety or tensionassociatedwith the stress of everyday life usually does not require treatmentwith an anxiolytic.

Structured Monograph

Clinical summary

Indications and usage INDICATIONS AND USAGE Clorazepate dipotassium tablets are indicatedfor the management of anxiety disordersorfortheshort-term relief of the symptoms of anxiety. Anxiety or tensionassociatedwith the stress of everyday life usually does not require treatmentwith an anxiolytic. Clorazepate dipotassium tablets are indicated as adjunctivetherapy in themanagement of partialseizures. Theeffectiveness of Clorazepate dipotassium tablets in long-term management of anxiety, that is,more than 4 months, has not beenassessed by systematicclinicalstudies.Long-term studies in epilepticpatients,however, have showncontinuedtherapeuticactivity.Thephysician should reassessperiodically the usefulnessof the drug for the individualpatient. Clorazepate dipotassium tabletsare indicatedfor the symptomaticrelief of acute alcoholwithdrawal. Dosage and administration DOSAGE AND ADMINISTRATION FortheSymptomatic ReliefofAnxiety: Clorazepate dipotassium tablets are administeredorally in divided doses. The usual daily dose is 30mg.The dose should beadjustedgraduallywithintherange of 15 to 60 mg daily in accordancewith the response of the patient. In elderly or debilitatedpatientsit is advisable to initiate treatment at a daily dose of 7.5 to 15 mg. Clorazepate dipotassium tabletsmay also be administeredin a singledosedaily at bedtime; the recommendedinitialdose is 15 mg.After the initial dose, the response of the patient mayrequireadjustment of subsequent dosage.Lower doses may be indicated in the elderlypatient. Drowsinessmay occur at the initiation of treatment and withdosageincrement. For the Symptomatic Relief of Acute Alcohol Withdrawal: Thefollowing dosage scheduleisrecommended: 1st 24 hours (Day 1) 30 mginitially;followed by 30 to 60 mg in divideddoses 2nd 24 hours (Day 2) 45 to 90 mg in divideddoses 3rd 24 hours (Day 3) 22.5 to 45 mg in divided doses Day 4 15 to 30 mg in divideddoses Thereafter,graduallyreduce the daily dose to 7.5 to 15 mg.Discontinuedrugtherapy as soon as patient’s condition is stable. Themaximum recommendedtotaldailydose is 90 mg. Avoid excessive reductionsin the totalamount of drug administeredonsuccessive days. As an Adjunct to Antiepileptic Drugs: In order to minimizedrowsiness, the recommendedinitialdosages and dosageincrementsshould not be exceeded. Adults: Themaximum recommendedinitialdose in patients over 12 years old is 7.5 mg three times a day. Dosage should be increased by no more than 7.5mg every week and should not exceed 90 mg/day. Children (9-12 years): Themaximum recommendedinitial dose is 7.5 mgtwotimes a day. Dosage should be increased by no more than 7.5mg every week and should not exceed 60 mg/day. Discontinuation or DosageReduction of Clorazepate dipotassium tablets: To reduce the risk of withdrawalreactions,use a gradualtaper to discontinueClorazepate dipotassium tablets or reduce the dosage. If a patient develops withdrawalreactions,consider pausing the taper or increasingthe dosage to the previous tapereddosage level. Subsequentlydecreasethedosagemoreslowly (see WARNINGS and DRUG ABUSE AND DEPENDENCE ). Warnings and cautions WARNINGS Risks from Concomitant Use with Opioids: Concomitant use of benzodiazepines, including Clorazepate dipotassium tablets, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs 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 Clorazepate dipotassium tablets 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. In patients already receiving an opioid analgesic, prescribe a lower initial dose of Clorazepate dipotassium tablets than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking Clorazepate dipotassium tablets, prescribe a lower initial dose of the opioid and titrate based upon clinical response. Advise both patients and caregivers about the risks of respiratory depression and sedation when Clorazepate dipotassium tablets is used with opioids. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined (see PRECAUTIONS: Drug Interactions ). Abuse, Misuse, and Addiction: The use of benzodiazepines, including Clorazepate dipotassium tablets, 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,

Boxed Warning

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation (See WARNINGS and PRECAUTIONS ). The use of benzodiazepines, including Clorazepate dipotassium tablets, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing Clorazepate dipotassium tablets and throughout out treatment, assess each patient’s risk for abuse, misuse, and addiction (See WARNINGS ). The continued use of benzodiazepines, including Clorazepate dipotassium tablets, may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Abrupt discontinuation or rapid dosage reduction of Clorazepate dipotassium tablets after continued use may precipitate acute withdrawal reactions, which can be life- threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue Clorazepate dipotassium tablets or reduce the dosage (See DOSAGE AND ADMINISTRATION and WARNINGS ).

Monitoring

• WARNINGS Risks from Concomitant Use with Opioids: Concomitant use of benzodiazepines, including Clorazepate dipotassium tablets, and opioids may result in profound sedation, respiratory depression, coma, and death.
• Because of these risks, reserve concomitant prescribing of these drugs 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 Clorazepate dipotassium tablets 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.

Interaction Notes

• DRUG INTERACTIONS Theconcomitant use of benzodiazepines and opioidsincreases the riskof respiratorydepressionbecause of actionsatdifferentreceptor sites in the CNS that control respiration.Benzodiazepinesinteract at GABAA sites and opioidsinteractprimarilyatmu receptors.
• Whenbenzodiazepinesand opioids arecombined, the potentialforbenzodiazepinestosignificantlyworsenopioid-relatedrespiratorydepressionexists.Limitdosageandduration of concomitant use of benzodiazepines and opioids, and monitorpatients closelyforrespiratorydepressionandsedation.
• If Clorazepate dipotassium tablets is to be combined with other drugs acting on the central nervous system, careful consideration should be given to thepharmacology of the agentsto be employed.Animalexperienceindicates that clorazepatedipotassium prolongs thesleepingtimeafterhexobarbital or afterethylalcohol,increases the inhibitoryeffects of chlorpromazine, but does not exhibitmonoamineoxidaseinhibition.Clinicalstudies have shownincreasedsedationwithconcurrent hypnotic medications.Theactions of the benzodiazepines may be potentiated by barbiturates,narcotics,phenothiazines,monoamine oxidase inhibitors or other antidepressants.
• If Clorazepate dipotassium tablets are used to treatanxietyassociatedwithsomatic disease states,carefulattentionmust be paid to possible druginteractionwith concomitantmedication.