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Clorazepate

Clorazepate

Definition

Purpose

Description

Recommended dosage

Precautions

Side effects

Interactions

Resources

Definition

Clorazepate is a medication that belongs to a family of drugs called benzodiazepines—a group of pharmacologically active compounds used to produce a calming effect by relieving anxiety and tension. In the United States, clorazepate is sold under brand names Tranxene and Gen-XENE.

Purpose

Clorazepate is used for the treatment of anxiety and alcohol withdrawal. Moreover, clorazepate is an adjunct in the management of partial seizures.

Description

Clorazepate binds to different sites in the brain, causing them to shift into a state that is less excitable. It is very effective in treating anxiety and anxiety disorders. Moreover, anxiety associated with undergoing surgical procedures is controlled with clorazepate. Clorazepate alone is not efficacious in treating seizures; however, if used along with other standard seizure medications, such as phenobarbital, primidone, phenytoin, carbamazepine, and valproic acid, better seizure control may be achieved. Convulsions and anxiety associated with alcohol withdrawal are controlled with clorazepate.

Clorazepate is available in two different formulations. Clorazepate tablets come in 3.75 mg, 7.5 mg, and 15.0 mg doses, while slow-release tablets, administered once daily, are available in 11.25 mg and 22.5 mg strengths. Capsules are available in 3.75 mg, 7.5 mg, and 15.0 mg strengths.

Recommended dosage

If used for anxiety, the dose of clorazepate usually ranges anywhere from 15 mg to 60 mg daily in divided dose intervals. Usually, however, the average dose is 30 mg daily given in two to four doses. If slow-release formulation is used, the dose of either 11.25 mg or 22.5 mg is usually administered at bedtime. Slow-release products should not be used to initiate therapy.

Doses of clorazepate for the management of seizures differ in adult and pediatric populations. Patients who are nine to 12 years of age should be started on 3.75-7.5 mg twice daily. This dose should be increased by no more than 3.75 mg weekly. The maximum dose per day is 60 mg administered in two to three divided doses. Children older than 12 and adults should receive 7.5 mg two to three times daily. This can be increased to a higher dose by adding 7.5 mg at weekly intervals. The total daily dose should not exceed 90 mg daily administered in two to three doses. In patients undergoing alcohol withdrawal, the first dose is 30 mg. Treatment is continued with 15 mg two to four times daily for the maximum dose of 90 mg in one day. Once maximum dose is achieved, the dose is gradually decreased over subsequent days.

Precautions

Pregnant women should not take clorazepate. Patients who have narrow-angle glaucoma should not take clorazepate, as this may worsen their condition. Clorazepate should not be used in patients younger than nine years of age.

If depression coexists with anxiety, clorazepate should be used with caution as suicidal tendencies may be present. (One of the side effects with this medication is depression; if a patient has an underlying problem with depression, that problem can be exacerbated with clorazepate.) Patients should be cautioned against engaging in hazardous occupations requiring mental alertness, since clorazepate causes drowsiness and dizziness. Abrupt discontinuation of clorazepate has been associated with withdrawal symptoms and seizures. Hence, doses of clorazepate should be slowly decreased in patients who have been taking clorazepate continuously over several weeks. Other withdrawal symptoms may include nervousness, insomnia, irritability, diarrhea, and muscle aches. The doses for elderly

KEY TERMS

Benzodiazepines —A group of central nervous system depressants used to relieve anxiety or to induce sleep.

Glaucoma —A group of eye diseases characterized by increased pressure within the eye significant enough to damage eye tissue and structures. If untreated, glaucoma results in blindness.

patients, as well as patients with liver or kidney problems, may need to be decreased.

Side effects

The most common side effects include drowsiness, dizziness, and confusion. There are a few reports about behavioral changes associated with the use of clorazepate and they include rage, depression, irritability, and aggression.

Other side effects include vision disturbances—such as blurred and double vision—decreased libido, nausea, vomiting, either decreased or increased appetite, and diarrhea or constipation. In a few cases, clorazepate has been associated with liver toxicity where patients developed jaundice or fever. It is also known to cause a rash.

Interactions

Simultaneous use of clorazepate and dong quai, a Chinese herb, has been associated with excessive muscle relaxation and central nervous system depression. Other herbs that should not be used with clorazepate include ginkgo biloba and kava kava.

Omeprazole, a medication used to treat heartburn, should not be used together with clorazepate. Medicines to treat disorders associated with increased acid secretions—such as ranitidine, sucralfate, and pantoprazole—are not contraindicated with clorazepate. Valerian, an herb used as a sleep aid, binds to the same receptors in the brain as clorazepate; thus, the desired effects of clorazepate may not be seen in patients taking it and valerian at the same time.

Clorazepate may increase the effects of other drugs that cause drowsiness. These drugs include antihistamines (such as Benadryl), sedatives (usually used to treat insomnia), pain relievers, anxiety and seizure medicines, and muscle relaxants. Alcohol combined with clorazepate also causes excessive drowsiness.

See alsoAlcohol and related disorders; Antianxiety drugs and abuse-related disorders; Depression and depressive disorders.

Resources

BOOKS

Preston, John D., John H. O’Neal, and Mary C. Talaga. Handbook of Clinical Psychopharmacology for Therapists, 4th ed. Oakland, CA: New Harbinger Publications, 2004.

PERIODICALS

Lelong-Boulouard, Véronique, and others. “Interactions of Buprenorphine and Dipotassium Clorazepate on Anxiety and Memory Functions in the Mouse.” Drug and Alcohol Dependence 85.2 (Nov. 2006): 103–13.

Millan, Mark J., and others. “Anxiolytic Properties of Agomelatine, an Antidepressant with Melatoninergic and Serotonergic Properties: Role of 5-HT-Sub (2C) Receptor Blockade.” Psychopharmacology 177.4 (Feb. 2005): 1–12.

Quentin, Thomas, and others. “Clorazepate Affects Cell Surface Regulation of δ and k Opioid Receptors, Thereby Altering Buprenorphine-Induced Adaptation in the Rat Brain.” Brain Research 1063.1 (Nov. 2005): 84–95.

Rowlett, James K., and others. “Anti-Conflict Effects of Benzodiazepines in Rhesus Monkeys: Relationship with Therapeutic Doses in Humans and Role of GABA-Sub(A) Receptors.” Psychopharmacology 184.2 (Jan. 2006): 201–11.

Ajna Hamidovic, Pharm.D.
Ruth A. Wienclaw, PhD

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