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 should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

8.2 Labor and Delivery
There is no information about the effects of Carisoprodol on the mother and the fetus during labor and delivery.

8.3 Nursing Mothers
Very limited data in humans show that Carisoprodol is 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 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.

Since Carisoprodol may cause drowsiness and/or dizziness, patients should be advised to assess their individual response to Carisoprodol before engaging in potentially hazardous activities such as driving a motor vehicle or operating machinery

Patients should be advised to avoid alcoholic beverages while taking Carisoprodol and to check with their doctor before taking other CNS depressants such as benzodiazepines, opioids, tricyclic antidepressants, sedating antihistamines, or other sedatives

In Study 1, patients were randomized to one of three treatment groups (i.e., Carisoprodol Tablets 350 mg, or placebo). In the study patients received study medication three times a day and at bedtime for seven days.

The primary endpoints were the relief from starting backache and the global impression of change, as reported by patients, on Study Day 3. Both endpoints were scored on a 5-point rating scale from 0 (worst outcome) to 4 (best outcome) in both studies. The primary statistical comparison was between the Carisoprodol 250 mg and placebo groups in both studies.

The proportion of patients who used concomitant acetaminophen, NSAIDs, tramadol, opioid agonists, other muscle relaxants, and benzodiazepines was similar in the treatment groups.

The results for the primary efficacy evaluations in the acute, low back pain studies are presented in Table 3.

Table 3. Results of the Primary Efficacy Endpoints* in Study 1

Study Parameter Placebo Carisoprodol Tablets 350 mg

1 Number of Patients n=269 n=273
Relief for Starting Backache, Mean (SE)† 1.4(0.1) 1.8 (0.1)
Difference between Carisoprodol and Placebo, Mean (SE)† (95% CI) 0.4
(0.2,0.6)
Global Impression of Change, Mean (SE)† 1.9(0.1) 2.2 (0.1)
Difference between Carisoprodol and Placebo, Mean (SE)† (95% CI) 0.3
(0.1,0.4)

*The primary efficacy endpoints (Relief from Starting Backache and Global Impression of Change) were assessed by the patients on Study Day #3. These endpoints were scored on a 5-point rating scale from 0 (worst outcome) to 4 (best outcome).

†Mean is the least squared mean and SE is the standard error of the mean.

Patients treated with Carisoprodol experienced improvement in function as measured by the Roland-Morris Disability Questionnaire (RMDQ) score on Days 3 and 7.

Treatment of Overdosage: Basic life support measures should be instituted as dictated by the clinical presentation of the Carisoprodol 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.

Most cases of dependence, withdrawal, and abuse occurred in patients who have had a history of addiction or who used Carisoprodol tablets in combination with other drugs with abuse potential. Withdrawal symptoms have been reported following abrupt cessation after prolonged use.

To reduce the chance of Carisoprodol dependence, withdrawal, or abuse, Carisoprodol tablets should be used with caution in addictionprone patients and in patients taking other CNS depressants including alcohol, and Carisoprodol should not be used more than two to three weeks for the relief of acute musculoskeletal discomfort.

One of the metabolites of Carisoprodol, meprobamate (a controlled substance), may cause dependence.

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.