Chlorzoxazone

(British Approved Name, US Adopted Name, rINN)

Drug Nomenclature

International Nonproprietary Names (INNs) in main languages (French, Latin, Russian, and Spanish):

Chlorzoxazone is a muscle relaxant medication that relieves muscle spasms and discomfort caused by strains, sprains, or other muscle injuries. It is typically prescribed as part of a comprehensive treatment plan, including rest, physical therapy, and other measures to alleviate musculoskeletal pain.

The exact mechanism of action of chlorzoxazone is not fully understood. Still, it is believed to act on the central nervous system by depressing the motor cortex and inhibiting multisynaptic reflex arcs.

Chlorzoxazone is commonly prescribed for conditions such as muscle strains, sprains, and other musculoskeletal injuries that result in painful muscle spasms.

Chlorzoxazone is usually taken orally, and the healthcare provider determines the dosage based on the individual’s condition.

Common side effects of chlorzoxazone may include drowsiness, dizziness, and gastrointestinal upset. It can cause sedation, and individuals taking this medication are often advised to avoid activities that require mental alertness, such as driving until they understand how the drug affects them.

Chlorzoxazone is typically prescribed for short-term use to relieve acute muscle spasms. Prolonged use is generally not recommended.

It may interact with other medications, including central nervous system depressants, and it’s essential to inform your healthcare provider about all the medications and supplements you are taking.

It’s crucial to use chlorzoxazone under the guidance of a healthcare professional, and the medication should be part of an overall treatment plan that addresses the underlying cause of muscle spasms or pain. If you have questions or concerns about chlorzoxazone, it’s best to discuss them with your healthcare provider.

Pharmacokinetics

Chlorzoxazone is reported to be completely absorbed after oral doses, and peak plasma concentrations are achieved after 1 to 2 hours. It is rapidly metabolized in the liver via the cytochrome P450 isoenzyme CYP2E1, mainly to 6-hydroxychlorzoxazone, and excreted in the urine primarily as the glucuronide metabolite. The elimination half-life of chlorzoxazone is about 1 hour.

Uses and Administration

Chlorzoxazone is a centrally-acting skeletal muscle relaxant with sedative properties. It is claimed to inhibit muscle spasms by exerting an effect primarily at the level of the spinal cord and sub-cortical areas of the brain. Its effects begin within an hour of an oral dose and last 3 to 4 hours.

It is used as an adjunct in the symptomatic treatment of painful muscle spasms associated with musculoskeletal conditions. The usual initial oral dose is 500 mg three or four times daily; the dose can often be reduced subsequently to 250 mg three or four times daily, although doses of up to 750 mg three or four times daily may be given if necessary. Chlorzoxazone is also given with analgesics in compound preparations.

Adverse Effects and Treatment

The most common adverse effects of chlorzoxazone are drowsiness and dizziness. There may occasionally also be gastrointestinal irritation, and gastrointestinal bleeding has been reported rarely. Other effects include headache, overstimulation, and rarely sensitivity reactions, including skin rashes, petechiae, ecchymoses, urticaria, and pruritus; angioedema or anaphylactoid reactions may occur very rarely. Some patients taking chlorzoxazone have developed jaundice and liver damage suspected to be caused by the drug. After overdosage, gastrointestinal disturbances may occur, including drowsiness, dizziness, headache, malaise, and sluggishness, followed by marked loss of muscle tone, hypotension, and respiratory depression. Emptying the stomach with lavage should be considered, followed by activated charcoal and supportive therapy.

Effects on the Liver

Hepatotoxicity, sometimes fatal, has been associated with chlorzoxazone treatment.

Porphyria

Chlorzoxazone is associated with acute porphyria attacks and is considered unsafe in patients with porphyric.

Torticollis

There has been a report of a patient with a spasmodic torticollis-like syndrome, consisting of tonic deviation of the head to the right, clenching of the teeth, and dysarthria, which developed repeatedly within 2 hours of ingesting chlorzoxazone for low back pain. Intravenous injection of benzatropine mesylate 1 mg gave rapid relief of symptoms.

Overdosage

Overdosage and coma occurred on two occasions in a patient taking chlorzoxazone; on the second occasion, the patient responded to intravenous flumazenil.

Precautions

Chlorzoxazone should not be given to patients with impaired liver function and should be stopped if signs of liver toxicity appear. Patients should be advised to report any signs or symptoms of possible liver toxicity to their doctor, such as fever, rash, jaundice, dark urine, anorexia, nausea, vomiting, or right upper quadrant pain. Chlorzoxazone may cause drowsiness; patients affected should not drive or operate machinery.

The urine of patients taking chlorzoxazone may be colored orange or reddish-purple by a phenolic metabolite.

Interactions

The CNS effects of chlorzoxazone may be enhanced by alcohol and other CNS depressants.

Disulfiram

A study of the efficacy of disulfiram as an inhibitor of the cytochrome P450 isoenzyme CYP2E1 (an enzyme involved in the metabolism of chlorzoxazone) found that a single 500-mg dose of disulfiram reduced plasma clearance of chlorzoxazone by 85%, resulting in a doubling of the latter’s peak plasma concentrations and prolongation of its elimination half-life from a mean of 0.92 to 5.1 hours.

Isoniazid

Isoniazid inhibited the clearance of chlorzoxazone by 56% when given to 10 slow acetylator subjects, increasing sedation, headache, and nausea. Two days after stopping isoniazid, there was a rebound increase in the clearance of chlorzoxazone by 56% over the pre-isoniazid clearance value. Similar but less pronounced effects have been reported in rapid acetylators with chlorzoxazone’s pharmacokinetic parameters returning to baseline values in 2 days.

Drug Nomenclature

International Nonproprietary Names (INNs) in main languages (French, Latin, Russian, and Spanish):

Synonyms: Chlorobenzoxazolinone; Chlorzoxazonum; Clorzoxazona; Klooritsoksatsoni; Klorzoxazon

BAN: Chlorzoxazone

INN: Chlorzoxazone [rINN (en)]

INN: Clorzoxazona [rINN (es)]

INN: Chlorzoxazone [rINN (fr)]

INN: Chlorzoxazonum [rINN (la)]

INN: Хлорзоксазон [rINN (ru)]

Chemical name: 5-Chlorobenzoxazol-2(3H)-one

Molecular formula: C7H4ClNO2 =169.6

CAS: 95-25-0

ATC code: M03BB03

Pharmacopoeias. In the US.

The United States Pharmacopeia 31, 2008, and Supplements 1 and 2 (Chlorzoxazone). A white or practically white, practically odorless, crystalline powder. Slightly soluble in water; sparingly soluble in alcohol, in isopropyl alcohol and methyl alcohol; soluble in alkali hydroxides and ammonia solutions. Store in airtight containers.