Clinical medicine profile
Clorazepate
Therapeutic agent (verify pharmacological class)
- Route
- See product SmPC
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
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, 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 and throughout out treatment, assess each patient's risk for abuse, misuse, and addiction (see WARNINGS ). The continued use of benzodiazepines, including clorazepate dipotassium, 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 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 or reduce the dosage (see DOSAGE AND ADMINISTRATION and WARNINGS ).
Contraindications
- CONTRAINDICATIONS Clorazepate dipotassium tablets are contraindicated in patients with a known hypersensitivity to the drug and in those with acute narrow angle glaucoma.
Precautions
- WARNINGS Risks from Concomitant Use with Opioids Concomitant use of benzodiazepines, including clorazepate dipotassium, 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 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 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, 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 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, 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: Abuse ).
- Before prescribing clorazepate dipotassium and throughout treatment, assess each patient's risk for abuse, misuse, and addiction (e.g., using a standardized screening tool).
- Use of clorazepate dipotassium, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of clorazepate dipotassium along with monitoring for signs and symptoms of abuse, misuse, and addiction.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
DOSAGE AND ADMINISTRATION For the Symptomatic Relief of Anxiety Clorazepate dipotassium tablets are administered orally in divided doses. The usual daily dose is 30 mg. The dose should be adjusted gradually within the range of 15 to 60 mg daily in accordance with the response of the patient. In elderly or debilitated patients it is advisable to initiate treatment at a daily dose of 7.5 to 15 mg. Clorazepate dipotassium tablets may also be administered in a single dose daily at bedtime; the recommended initial dose is 15 mg. After the initial dose, the response of the patient may require adjustment of subsequent dosage. Lower doses may be indicated in the elderly patient. Drowsiness may occur at the initiation of treatment and with dosage increment. For the Symptomatic Relief of Acute Alcohol Withdrawal The following dosage schedule is recommended: 1st 24 hours (Day 1) 30 mg initially; followed by 30 to 60 mg in divided doses 2nd 24 hours (Day 2) 45 to 90 mg in divided doses 3rd 24 hours (Day 3) 22.5 to 45 mg in divided doses Day 4 15 to 30 mg in divided doses Thereafter, gradually reduce the daily dose to 7.5 to 15 mg. Discontinue drug therapy as soon as patient's condition is stable. The maximum recommended total daily dose is 90 mg. Avoid excessive reductions in the total amount of drug administered on successive days. As an Adjunct to Antiepileptic Drugs In order to minimize drowsiness, the recommended initial dosages and dosage increments should not be exceeded. Adults The maximum recommended initial dose in patients over 12 years old is 7.5 mg three times a day. Dosage should be increased by no more than 7.5 mg every week and should not exceed 90 mg/day. Children (9 to 12 years) The maximum recommended initial dose is 7.5 mg two times a day. Dosage should be increased by no more than 7.5 mg every week and should not exceed 60 mg/day. Discontinuation or Dosage Reduction of Clorazepate Dipotassium To reduce the risk of withdrawal reactions, use a gradual taper to discontinue clorazepate dipotassium or reduce the dosage. If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level. Subsequently decrease the dosage more slowly (see WARNINGS and DRUG ABUSE AND DEPENDENCE ).
See label paediatric section if present; otherwise use paediatric formulary — do not extrapolate adult doses.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
- INDICATIONS AND USAGE Clorazepate dipotassium is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety.
- Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.
- Clorazepate dipotassium tablets are indicated as adjunctive therapy in the management of partial seizures.
- The effectiveness of clorazepate dipotassium tablets in long-term management of anxiety, that is, more than 4 months, has not been assessed by systematic clinical studies.
- Long-term studies in epileptic patients, however, have shown continued therapeutic activity.
- The physician should reassess periodically the usefulness of the drug for the individual patient.
- Clorazepate dipotassium tablets are indicated for the symptomatic relief of acute alcohol withdrawal.
Adverse effects
- ADVERSE REACTIONS The side effect most frequently reported was drowsiness.
- Less commonly reported (in descending order of occurrence) were: dizziness, various gastrointestinal complaints, nervousness, blurred vision, dry mouth, headache, and mental confusion.
- Other side effects included insomnia, transient skin rashes, fatigue, ataxia, genitourinary complaints, irritability, diplopia, depression, tremor, and slurred speech.
- There have been reports of abnormal liver and kidney function tests and of decrease in hematocrit.
- Decrease in systolic blood pressure has been observed.
- To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc. at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug interactions
Open multi-drug checker ↗- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Mechanism & disposition
Potentiation of effect of Gamma-Aminobutyrate [GABA].
Read complete mechanism
Potentiation of effect of Gamma-Aminobutyrate [GABA]. Mechanism is agent-specific. At receptor, enzyme, ion channel, transporter or microbial target level, the drug alters a physiological or pathological pathway to produce its therapeutic effect. Confirm precise molecular mechanism in current SmPC / pharmacology reference for this INN before high-stakes decisions.
Product-specific
Product-specific
See product SmPC
is about 2 days. The drug is metabolized in the liver and excreted primarily in the urine. Studies in healthy men have shown that clorazepate dipotassium has depressant effects on the central nervous system. Prolonged administration of single daily doses as high as 120 mg was wit...
Pregnancy, lactation & diet
Use only if potential benefit justifies potential risk; prefer agents with better reproductive data when alternatives exist.
Assess infant risk vs benefit of maternal therapy; prefer agents with lactation data.
Brands & loaded prices
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Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.