Tranxene

Action

Unclear. Thought to potentiate effects of gamma-aminobutyric acid and other neurotransmitters, promoting inhibitory neurotransmission at excitatory synapses.

Availability

Tablets: 3.75 mg, 7.5 mg, 15 mg

Indications and dosages

➣ Anxiety

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.

Dosage adjustment

• Elderly or debilitated patients

Contraindications

• Benzodiazepine hypersensitivity

• Acute angle-closure glaucoma

• Psychosis

• Concurrent ketoconazole or itraconazole therapy

• Children younger than age 9

Precautions

Use cautiously in:

• depression or suicidal ideation

• psychotic reaction

• elderly patients

• females of childbearing age

• pregnant or breastfeeding patients.

Administration

• 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.

Adverse reactions

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

Hematologic: neutropenia

Hepatic: jaundice

Skin: rash, diaphoresis

Other: weight gain or loss, drug dependence or tolerance

Interactions

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

Patient monitoring

• 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.

Patient teaching

• 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.

See 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.