CLORAZEPATE DIPOTASSIUM
| CLORAZEPATE DIPOTASSIUM (klor-az'e-pate) Novoclopate  , Tranxene, Tranxene-SDClassifications: anxiolytic; sedative-hypnotic; anticonvulsant; benzodiazepine; Therapeutic: antianxiety agent; sedative-hypnotic; anticonvulsant Prototype: Lorazepam Pregnancy Category: D Controlled Substance: Schedule IV |
Availability
3.75 mg, 7.5 mg, 15 mg capsules and tablets; 11.25 mg, 22.5 mg long acting tablets
Action
Anxiolytic benzodiazepine with moderately rapid onset of action and a long half-life. Benzodiazepines exert their effects through enhancement of GABA-benzodiazepine receptor complex. GABA is an inhibitory neurotransmitter. Clorazepate has depressant effects on the CNS, thus controlling anxiety associated with stress and also resulting in sedative effects.
Therapeutic Effect
Effective in controlling anxiety and withdrawal symptoms of alcohol.
Uses
Management of anxiety disorders, short-term relief of anxiety symptoms, as adjunct in management of partial seizures, and symptomatic relief of acute alcohol withdrawal.
Contraindications
Hypersensitivity to clorazepate and other benzodiazepines; acute narrow-angle glaucoma; depressive neuroses; pulmonary disease, COPD; psychotic reactions, drug abusers. Safe use during pregnancy (category D), lactation, and in children <9 y not established.
Cautious Use
Older adults; debilitated patients; hepatic disease; kidney disease; Parkinson's disease; neuromuscular disease; seizure disorders; bipolar disorder, mania, history of suicidal ideation.
Route & Dosage
| Anxiety Adult: PO 15 mg/d h.s., may increase to 15–60 mg/d in divided doses (max: 60 mg/d) Acute Alcohol Withdrawal Adult: PO 30 mg followed by 30–60 mg in divided doses (max: 90 mg/d), taper by 15 mg/d over 4 d to 7.5–15 mg/d until patient is stable Partial Seizures Adult: PO 7.5 mg t.i.d. Child (9–12 y): PO 3.75–7.5 mg b.i.d., may increase by no more than 3.75 mg/wk (max: 60 mg/d) |
Administration
Oral- Give with food to minimize gastric distress. Give antacid no less than 1 h before or 1 h after drug ingestion.
- Ensure that sustained-release form of drug is not chewed or crushed. It must be swallowed whole.
- Taper drug dose gradually over several days when drug is to be discontinued. Abrupt termination may lead to memory impairment, severe GI symptoms, muscle pain, restlessness, irritability, fatigue, insomnia.
- Store in light-resistant container at 15°–30° C (59°–86° F) unless otherwise specified.
Adverse Effects (≥1%)
Body as a Whole: Allergic reactions. CV: Hypotension. GI: GI disturbances, abnormal liver function tests, xerostomia. Hematologic: Decreased Hct, blood dyscrasias. CNS: Drowsiness, ataxia, dizziness, headache, paradoxical excitement, mental confusion, insomnia. Special Senses: Diplopia, blurred vision.Interactions
Drug: Alcohol and other cns depressants compound CNS depression; clorazepate increases effects of cimetidine, disulfiram, causing excessive sedation. Herbal: Ginkgo may decrease anticonvulsant effectiveness.Pharmacokinetics
Absorption: Decarboxylated in stomach; absorbed as active metabolite, desmethyldiazepam. Peak: 1 h. Duration: 24 h. Distribution: Crosses placenta; distributed into breast milk. Metabolism: In liver to oxazepam. Elimination: Primarily in urine. Half-Life: 30–200 h.Nursing Implications
Assessment & Drug Effects
- Drowsiness, a common side effect, is more likely to occur at initiation of therapy and with dose increments on successive days.
- Lab tests: Periodic blood counts and tests of liver and kidney function should be performed throughout therapy.
- Monitor patient with history of cardiovascular disease in early therapy for drug-induced responses. If systolic BP drops more than 20 mm Hg or if there is a sudden increase in pulse rate, withhold drug and notify physician.
Patient & Family Education
- Take drug as prescribed and do not change dose or abruptly stop taking the drug without physician's approval.
- Do not self-dose with OTC drugs (cold remedies, sleep medications, antacids) without consulting physician.
- Avoid driving and other potentially hazardous activities until reaction to drug is known.
- Do not use alcohol and other CNS depressants while on clorazepate therapy.
- If a woman becomes pregnant during therapy or intends to become pregnant, communicate with physician about the desirability of discontinuing the drug.
Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; 
Prototype drug