Pharmacology - Carisoprodol (Soma)

[Jatelka]

Carisoprodol is N-isopropyl-2-methyl-2-propyl-1,3-propanediol dicarbamate.

The molecular formula is C12H24N2O4 , and the molecular weight 260.33.

It is a white, crystalline powder, having a mild, characteristic odor and a bitter taste. It is slightly soluble in water; freely soluble in alcohol, in chloroform, and in acetone; and its solubility is practically independent of pH.

Mechanism of Action

The mechanism of action of Carisoprodol has not been clearly identified.
In animal models, muscle relaxation induced by Carisoprodol is associated with altered neuronal activity in the spinal cord and in the descending reticular formation of the brain.

Pharmacodynamics

Carisoprodol is a centrally acting skeletal muscle relaxant (ie: it has no direct effect on skeletal muscle). A metabolite of carisoprodol, Meprobamate, has anxiolytic and sedative properties (and is a Schedule IV substance). The degree to which these properties of Meprobamate contribute to the safety and efficacy of Carisoprodol is unknown.

Pharmacokinetics

Absorption: Absolute bioavailability of carisoprodol has not been determined. The time to maximal plasma concentrations is 1.5 to 2 hours, and this is dose proportional. Absorption is unaffected by food.

Metabolism: The major pathway of Carisoprodol metabolism is via CYP2C19 to form Meprobamate. This enzyme exhibits genetic polymorphism

Elimination: Carisoprodol is eliminated by both renal and non-renal routes with a terminal elimination half-life of approximately 2 hours. The half-life of Meprobamate is 10 hours.

Gender: Exposure to Carisoprodol is higher in female than in male subjects (approximately 30-50% on a weight adjusted basis). Overall exposure to Meprobamate is comparable between female and male subjects.

Patients with Reduced CYP2C19 Activity: Poor CYP2C19 metabolisers have a 4-fold increase in exposure to Carisoprodol, and 50% reduced exposure to Meprobamate compared to normall metabolizers. The prevalence of poor metabolizers in Caucasians and African Americans is 3-5% and in Asians is 15-20%.

Indications

Carisoprodol is indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults. It should only be used for up to two or three weeks.

Dosage

The therapeutic dose of Carisoprodol is 250 mg to 350 mg four times a day.

Adverse Effects

Common: Drowsiness, dizzyness and headache
Cardiovascular: Tachycardia, postural hypotension and facial flushing
Central Nervous System:Drowsiness, dizziness, vertigo, ataxia tremor, agitation, irritability, headache, depressive reactions, syncope, insomnia and seizures.
Gastrointestinal:Nausea, vomiting, and epigastric discomfort.
Heamatological: Low white and total blood counts

Interactions

As with all CNS depressants, Carisoprodol has an additive effect with other CNS depressants (including alcohol, benzodiazepines, opiates and tricyclic antidepressants)

CYP2C19 Inhibitors and Inducers

Co-administration of CYP2C19 inhibitors, such as Omeprazole or Fluvoxamine, with Carisoprodol results in increased plasma levels. Co-administration of CYP2C19 inducers, such as Rifampin or St. John's Wort, with Carisoprodol results in decreased plasma levels of Carisoprodol and increased levels of Meprobamate.

Drug Dependence, Withdrawal, and Abuse

Cases of dependence, withdrawal, and abuse have been reported with prolonged use. Withdrawal symptoms have been reported following abrupt cessation after prolonged use.

Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility
Long term studies have not been performed to evaluate the carcinogenic potential of Carisoprodol, nor has it been formally evaluated for effects on fertility.

Use In Specific Population

Pregnancy

There are no data on the use of Carisoprodol during human pregnancy. Animal studies have shown that Carisoprodol crosses the placenta and results in effects on fetal growth and postnatal survival.

Teratogenic effects:Animal studies have not adequately evaluated the teratogenic effects of Carisoprodol.

Non-teratogenic effects:In animal studies, Carisoprodol reduces fetal weights, postnatal weight gain, and postnatal survival at maternal doses equivalent to 1-1.5 times the human dose.

Nursing Mothers

Maternal use of Carisoprodol may lead to reduced or less effective infant feeding (due to sedation) and/or decreased milk production

Renal Impairment

The safety and pharmacokinetics of Carisoprodol with renal impairment has not been evaluated. Given that Carisoprodol is excreted via the kidneys, clearance is expected to be reduced in Renal Impairment.

Hepatic Impairment

The safety and pharmacokinetics of Carisoprodol in patients with hepatic impairment have not been evaluated. Since it is metabolized by the liver, caution should be taken in Hepatic Impairment.

Patients with Reduced CYP2C19 Activity

Patients with reduced CYP2C19 activity have higher exposure to Carisoprodol.

Overdose

Commonly produces CNS Depression.

Death, coma, respiratory depression, hypotension, seizures, delirium, hallucinations, dystonic reactions, nystagnus, anti-cholinergic effects such as blurred vision and mydriasis (pupil dilation), euphoria, muscular incoordination, rigidity, and/or headache have been reported with Carisoprodol overdosage.

Reputation Comments on this post:

Good info