Carisoprodol

Pharmacogenomics:

Carisoprodol is metabolised in the liver mainly by CYP2C19 into its active metabolite, meprobamate. Genetic variation in CYP2C19 (e.g. poor metabolisers) may affect the pharmacokinetics of carisoprodol. The prevalence of poor metabolisers is approx 3-5% in Caucasians and African Americans and about 15-20% in Asians. Genetic testing for CYP2C19 may be considered prior to initiating carisoprodol treatment.

CYP2C19 poor metabolisers
Patients carrying 2 non-functional alleles (e.g. *2/*2, *2/*3, *3/*3) have an increase carisoprodol exposure and a 50% reduction in meprobamate exposure compared to CYP2C19 normal metabolisers, thus resulting in an increased risk of toxicity due the narrow therapeutic index of carisoprodol. The US Food and Drug Administration (US FDA) drug labelling suggests administering carisoprodol with caution in patients who are poor metabolisers. Closely monitor individuals with known reduced CYP2C19 activity for signs of excessive carisoprodol effects.

Carisoprodol May be taken with or without food.

Hypersensitivity to carbamates (e.g. meprobamate). History of acute intermittent porphyria.

Patient with history of drug abuse or acute alcoholism. CYP2C19 poor metabolisers. Avoid abrupt withdrawal. Renal and hepatic impairment. Pregnancy and lactation.

Significant: Psychological and physical dependence, abuse, tolerance (prolonged use), withdrawal symptoms (following abrupt discontinuation of prolonged use or high doses), CNS depression (e.g. sedation), seizures, allergic or idiosyncratic reactions.
Cardiac disorders: Tachycardia.
Gastrointestinal disorders: Nausea, vomiting, epigastric distress.
Nervous system disorders: Drowsiness, dizziness, headache.
Vascular disorders: Syncope.

PO: C

This drug may cause CNS depression, if affected, do not drive or operate machinery.

Monitor for signs of CNS effects (e.g. mental status, excessive drowsiness) at the beginning of treatment and periodically thereafter. Monitor relief of pain and/or muscle spasm, and signs of misuse, abuse and substance use disorder.

Symptoms: Headache, hypotension, seizures, delirium, hallucinations, dystonic reactions, nystagmus, blurred vision, mydriasis, euphoria, muscular incoordination, rigidity, CNS depression, respiratory depression, serotonin syndrome, coma. Management: Symptomatic and supportive treatment. Provide circulatory support through volume infusion and vasopressor agents, if necessary. Administer IV benzodiazepines for initial seizures; if seizures recur, phenobarbital may be given. In cases of severe CNS depression, may consider tracheal intubation to protect the airway and provide respiratory support. Activated charcoal may be administered for decontamination in cases of severe toxicity.

May cause additive effects with other CNS depressants (e.g. benzodiazepines, opioids, TCAs). Increased exposure of carisoprodol and decreased exposure of meprobamate (active metabolite) with CYP2C19 inhibitors (e.g. omeprazole, fluvoxamine). Decreased exposure of carisoprodol and increased exposure of meprobamate with CYP2C19 inducers (e.g. rifampicin) and low-dose aspirin.

May cause additive CNS effects with alcohol. Decreased exposure of carisoprodol and increased exposure of meprobamate with St. John's wort.

Description:
Mechanism of Action: Carisoprodol is a centrally acting skeletal muscle relaxant. Its exact mechanism is unknown, however, it appears to induce muscle relaxation by altering neuronal communication within the spinal cord and descending reticular formation of the brain.
Onset: Within 30 minutes.
Duration: 4-6 hours.
Pharmacokinetics:
Absorption: Absorbed from the gastrointestinal tract. Time to peak plasma concentration: 1.5-2 hours.
Distribution: Crosses the placenta and enters breast milk. Plasma protein binding: <70% (carisoprodol); <25% (meprobamate).
Metabolism: Metabolised in the liver by CYP2C19 into its active metabolite, meprobamate.
Excretion: Via urine (as metabolite). Elimination half-life: Approx 2 hours (carisoprodol); approx 10 hours (meprobamate).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2576, Carisoprodol. https://pubchem.ncbi.nlm.nih.gov/compound/Carisoprodol. Accessed Feb. 25, 2025.

Store between 20-25°C.

Muscle Relaxants

M03BA02 - carisoprodol ; Belongs to the class of carbamic esters. Used as centrally-acting muscle relaxants.

Dean L, Kane M. Carisoprodol Therapy and CYP2C19 Genotype. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US). 2017 Apr. Accessed 06/02/2025. PMID: 28520382

Annotation of FDA Label for Carisoprodol and CYP2C19. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 06/02/2025.

Anon. Carisoprodol. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 06/02/2025.

Brayfield A, Cadart C (eds). Carisoprodol. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/02/2025.

Carisoprodol Tablet (Oxford Pharmaceuticals, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/02/2025.

Carisoprodol. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 06/02/2025.

Carisoprodol. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 06/02/2025.

CYP2C19 - Carisoprodol. UpToDate Lexidrug, Pharmacogenomics Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 06/02/2025.

Soma Tablets for Oral Use, CIV (Meda Pharmaceuticals Inc.). U.S. FDA. https://www.fda.gov. Accessed 06/02/2025.