Brand Names

CLORAZEPATE DIPOTASSIUM
GEN-XENE
TRANXENE
TRANXENE SD

Boxed Warning

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).

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

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.

Contraindications

Clorazepate dipotassium tabletsare contraindicated in patientswith a knownhypersensitivityto the drug and in those withacutenarrow angle glaucoma.

Adverse Reactions

The side effectmostfrequentlyreported wasdrowsiness.Lesscommonlyreported (in descending order of occurrence)were:dizziness, various gastrointestinal complaints,nervousness, blurred vision, dry mouth,headache, and mentalconfusion.Other side effects included insomnia,transientskinrashes,fatigue,ataxia,genitourinarycomplaints,irritability,diplopia,depression,tremor, and slurredspeech. There have been reports of abnormalliver and kidneyfunction tests and of decrease in hematocrit. Decrease in systolicbloodpressurehas been observed. To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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. In bioavailabilitystudieswithnormalsubjects,theconcurrentadministration of antacidsattherapeuticlevelsdid not significantlyinfluencethebioavailability of Clorazepate dipotassium tablets.

Overdosage

Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal (see WARNINGS: Dependence and Withdrawal Reactions ). Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raise the concern that additional drugs and/or alcohol are involved in the overdosage. In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway management. Flumazenil, a specific benzodiazepine receptor antagonist indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic antidepressants) and in patients with long-term benzodiazepine use and physical dependency. The risk of withdrawal seizures with flumazenil use may be increased in patients with epilepsy. Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus). If the decision is made to use flumazenil, it should be used as an adjunct to, not as a substitute for, supportive management of benzodiazepine overdosage. See the flumazenil injection Prescribing Information. Consider contacting the Poison Help line (1-800-222-12

⚠ Caution

Medical Disclaimer: This information is for educational purposes only. Always consult a healthcare professional before taking any medication.