There are no data on the use of Carisoprodol Tablets during human pregnancy. Animal studies indicate that carisoprodol crosses the placenta and results in adverse effects on fetal growth and postnatal survival. The primary metabolite of carisoprodol, meprobamate, is an approved anxiolytic. Retrospective, post-marketing studies do not show a consistent association between maternal use of meprobamate and an increased risk for particular congenital malformations.
Teratogenic effects: Animal studies have not adequately evaluated the teratogenic effects of carisoprodol. There was no increase in the incidence of congenital malformations noted in reproductive studies in rats, rabbits, and mice treated with meprobamate. Retrospective, post-marketing studies of meprobamate during human pregnancy were equivocal for demonstrating an increased risk of congenital malformations following first trimester exposure. Across studies that indicated an increased risk, the types of malformations were inconsistent.
Nonteratogenic effects: In animal studies, carisoprodol reduced fetal weights, postnatal weight gain, and postnatal survival at maternal doses equivalent to 1-1.5 times the human dose (based on a body surface area comparison). Rats exposed to meprobamate in-utero showed behavioral alterations that persisted into adulthood. For children exposed to meprobamate in-utero , one study found no adverse effects on mental or motor development or IQ scores. Carisoprodol Tablets should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
There is no information about the effects of Carisoprodol Tablets on the mother and the fetus during labor and delivery.
Very limited data in humans show that Carisoprodol Tablets are present in breast milk and may reach concentrations two to four times the maternal plasma concentrations. In one case report, a breast-fed infant received about 4-6% of the maternal daily dose through breast milk and experienced no adverse effects. However, milk production was inadequate and the baby was supplemented with formula. In lactation studies in mice, female pup survival and pup weight at weaning were decreased. This information suggests that maternal use of Carisoprodol Tablets may lead to reduced or less effective infant feeding (due to sedation) and/or decreased milk production. Caution should be exercised when Carisoprodol Tablets are administered to a nursing woman.
The efficacy, safety, and pharmacokinetics of Carisoprodol Tablets in pediatric patients less than 16 years of age have not been established.
The efficacy, safety, and pharmacokinetics of Carisoprodol Tablets in patients over 65 years old have not been established.
The safety and pharmacokinetics of Carisoprodol Tablets in patients with renal impairment have not been evaluated. Since
Carisoprodol Tablets are excreted by the kidney, caution should be exercised if Carisoprodol Tablets are administered to patients with impaired renal function. Carisoprodol Tablets are dialyzable by hemodialysis and peritoneal dialysis.
The safety and pharmacokinetics of carisoprodol in patients with hepatic impairment have not been evaluated. Since Carisoprodol Tablets are metabolized in the liver, caution should be exercised if Carisoprodol Tablets are administered to patients with impaired hepatic function.
Patients with reduced CYP2C19 activity have higher exposure to Carisoprodol Tablets. Therefore, caution should be exercised in administration of Carisoprodol Tablets to these patients. [see Clinical Pharmacology (12.3)].
Carisoprodol Tablets are not a controlled substance [see Warnings and Precautions (5.2)]. Discontinuation of carisoprodol in animals or in humans after chronic administration can produce withdrawal signs, and there are published case reports of human carisoprodol dependence.
In vitro studies demonstrate that carisprodol elicits barbiturate-like effects. Animal behavior studies indicate that carisoprodol produces rewarding effects. Monkeys self administer carisoprodol. Drug discrimination studies using rats indicate that carisoprodol has positive reinforcing and discriminative effects similar to barbital, meprobamate, and chlordiazepoxide.
Overdosage of Carisoprodol Tablets commonly produces CNS depression. Death, coma, respiratory depression, hypotension, seizures, delirium, hallucinations, dystonic reactions, nystagmus, blurred vision, mydriasis, euphoria, muscular incoordination, rigidity, and/or headache have been reported with Carisoprodol Tablets overdosage. Many of the Carisoprodol Tablets overdoses have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol). The effects of an overdose of Carisoprodol Tablets and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) can be additive even when one of the drugs has been taken in the recommended dosage. Fatal accidental and non-accidental overdoses of carisoprodol have been reported alone or in combination with CNS depressants.
Treatment of Overdosage: Basic life support measures should be instituted as dictated by the clinical presentation of the Carisoprodol Tablets overdose. Induced emesis is not recommended due to the risk of CNS and respiratory depression, which may increase the risk of aspiration pneumonia. Gastric lavage should be considered soon after ingestion (within one hour). Circulatory support should be administered with volume infusion and vasopressor agents if needed. Seizures should be treated with intravenous benzodiazepines and the reoccurrence of seizures may be treated with phenobarbital. In cases of severe CNS depression, airway protective reflexes may be compromised and tracheal intubation should be considered for airway protection and respiratory support.
The following types of treatment have been used successfully with an overdose of meprobamate, a metabolite of carisoprodol: activated charcoal (oral or via nasogastric tube), forced diuresis, peritoneal dialysis, and hemodialysis (carisoprodol is also dialyzable). Careful monitoring of urinary output is necessary and overhydration should be avoided. Observe for possible relapse due to incomplete gastric emptying and delayed absorption. For more information on the management of an overdose of carisoprodol, contact a Poison Control Center.
The mechanism of action of carisoprodol in relieving discomfort associated with acute painful musculoskeletal conditions has not been clearly identified.
In animal studies, muscle relaxation induced by carisoprodol is associated with altered interneuronal activity in the spinal cord and in the descending reticular formation of the brain.
Carisoprodol is a centrally acting skeletal muscle relaxant that does not directly relax skeletal muscles.
A metabolite of carisoprodol, meprobamate, has anxiolytic and sedative properties. The degree to which these properties of meprobamate contribute to the safety and efficacy of Carisoprodol Tablets is unknown.
The pharmacokinetics of carisoprodol and its metabolite meprobamate were studied in a crossover study of 24 healthy subjects (12 male and 12 female) who received single doses of 350 mg Carisoprodol (see Table 2). The C max of meprobamate was 2.5 ± 0.5 μg/mL (mean ± SD) after administration of a single 350 mg dose of carisoprodol, which is approximately 30% of the C max of meprobamate (approximately 8 μg/mL) after administration of a single 400 mg dose of meprobamate.
Table 2. Pharmacokinetic Parameters of Carisoprodol and Meprobamate (Mean ± SD, n=24)
|350 mg Carisoprodol|
|C max (µg/mL)||1.8 ± 1.0|
|AUC inf (µg*hr/mL)||7.0 ± 5.0|
|T max (hr)||1.7 ± 0.8|
|T 1/2 (hr)||2.0 ± 0.5|
|C max (µg/mL)||2.5 ± 0.5|
|AUC inf (µg*hr/mL)||46 ± 9.0|
|T max (hr)||4.5 ± 1.9|
|T 1/2 (hr)||9.6 ± 1.5|
Absorption: Absolute bioavailability of carisoprodol has not been determined. The mean time to peak plasma concentrations (T max ) of carisoprodol was approximately 1.5 to 2 hours. Co-administration of a high-fat meal with Carisoprodol (350 mg tablet) had no effect on the pharmacokinetics of carisoprodol. Therefore, Carisoprodol Tablets may be administered with or without food.
Metabolism: The major pathway of carisoprodol metabolism is via the liver by cytochrome enzyme CYP2C19 to form meprobamate. This enzyme exhibits genetic polymorphism (see Patients with Reduced CYP2C19 Activity below).
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 approximately 10 hours.
Gender: Exposure of carisoprodol is higher in female than in male subjects (approximately 30-50% on a weight adjusted basis). Overall exposure of meprobamate is comparable between female and male subjects.
Patients with Reduced CYP2C19 Activity: Carisoprodol Tablets should be used with caution in patients with reduced CYP2C19 activity. Published studies indicate that patients who are poor CYP2C19 metabolizers have a 4-fold increase in exposure to carisoprodol, and concomitant 50% reduced exposure to meprobamate compared to normal CYP2C19 metabolizers. The prevalence of poor metabolizers in Caucasians and African Americans is approximately 3-5% and in Asians is approximately 15-20%.
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