Pharmacologic class: Benzodiazepine
Therapeutic class: Anticonvulsant, anxiolytic
Controlled substance schedule IV
Pregnancy risk category D
Unclear. Thought to potentiate effects of gamma-aminobutyric acid and other neurotransmitters, promoting inhibitory neurotransmission at excitatory synapses.
Tablets: 3.75 mg, 7.5 mg, 15 mg
Indications and dosages
Adults: 7.5 to 15 mg P.O. two to four times daily
➣ Adjunctive therapy in partial seizure disorder
Adults and children older than age 12: Initially, 7.5 mg P.O. t.i.d.; increase by no more than 7.5 mg/week. Don't exceed 90 mg/day.
Children ages 9 to 12: Initially, 7.5 mg P.O. b.i.d.; increase by no more than 7.5 mg/week. Don't exceed 60 mg/day.
➣ Management of alcohol withdrawal
Adults: Initially, 30 mg P.O., followed by 15 mg P.O. two to four times daily on first day. On second day, give 45 to 90 mg P.O. in divided doses, then decrease gradually over subsequent days to 7.5 mg to 15 mg P.O. daily.
• Elderly or debilitated patients
• Benzodiazepine hypersensitivity
• Acute angle-closure glaucoma
• Concurrent ketoconazole or itraconazole therapy
• Children younger than age 9
Use cautiously in:
• depression or suicidal ideation
• psychotic reaction
• elderly patients
• females of childbearing age
• pregnant or breastfeeding patients.
• If GI upset occurs, give with food.
• When discontinuing therapy after long-term use, taper dosage gradually over 4 to 8 weeks to avoid withdrawal symptoms.
• Take suicide precautions if patient is depressed or anxious.
CNS: dizziness, drowsiness, lethargy, sedation, depression, fatigue, nervousness, confusion, irritability, headache, slurred speech, difficulty articulating words, stupor, rigidity, tremor, poor coordination
CV: hypertension, hypotension, palpitations
EENT: blurred or double vision
GI: dry mouth
Skin: rash, diaphoresis
Other: weight gain or loss, drug dependence or tolerance
Drug-drug. Antacids: altered clorazepate absorption rate
Antidepressants, antihistamines, opioids: additive CNS depression
Barbiturates, MAO inhibitors, other antidepressants, phenothiazines: potentiation of clorazepate effects
Cimetidine, disulfiram, fluoxetine, hormonal contraceptives, isoniazid, itraconazole, ketoconazole, metoprolol, propoxyphene, propranolol, valproic acid: decreased clorazepate metabolism, causing enhanced drug action or markedly increased CNS effects
Levodopa: decreased antiparkinsonian effect
Probenecid: rapid onset or prolonged action of clorazepate
Rifampin: increased metabolism and decreased efficacy of clorazepate
Theophylline: decreased sedative effect of clorazepate
Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase: increased levels
Drug-herbs. Chamomile, hops, kava, skullcap, valerian: increased CNS depression
Drug-behaviors. Alcohol use: increased CNS depression
Smoking: decreased drug absorption
• Assess for pregnancy before initiating therapy.
• Evaluate patient for depression, drug dependence, and drug tolerance.
• Monitor blood counts and liver function test results during long-term therapy; drug may cause neutropenia and jaundice.
• Instruct patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Tell patient to avoid smoking and use of alcohol or other CNS depressants.
☞ Caution patient not to stop therapy abruptly, because withdrawal symptoms may occur.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.