the full pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety of carisoprodol is unknown.

soprodol poses a risk of overdosage which may lead to death, cns and respiratory depression, hypotension, seizures and other disorders [see overdosage (10)]. post-marketing experience cases of carisoprodol abuse and dependence have been reported in patients with prolonged use and a history of drug abuse. although most of these patients took other drugs of abuse, some patients solely abused carisoprodol. withdrawal symptoms have been reported following abrupt cessation of carisoprodol after prolonged use. reported withdrawal symptoms included insomnia, vomiting, abdominal cramps, headache, tremors, muscle twitching, ataxia, hallucinations, and psychosis. one of carisoprodol’s metabolites, meprobamate (a controlled substance), may also cause dependence [see clinical pharmacology (12.3)]. to reduce the risk of carisoprodol abuse assess the risk of abuse prior to prescribing. after prescribing, limit the length of treatment to three weeks for the relief of acute musculoskeletal discomfort, keep careful prescription records, monitor for signs of abuse and overdose, and educate patients and their families about abuse and on proper storage and disposal. 5.3 seizures there have been post-marketing reports of seizures in patients who received carisoprodol. most of these cases have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol) [see overdosage (10)].

isoprodol, respectively, discontinued due to adverse events; and 0.5%, 0.5%, and 1.8% of patients treated with placebo, 250 mg of carisoprodol, and 350 mg of carisoprodol, respectively, discontinued due to central nervous system adverse reactions. table 1 displays adverse reactions reported with frequencies greater than 2% and more frequently than placebo in patients treated with carisoprodol in the two trials described above. table 1. patients with adverse reactions in controlled studies adverse reaction placebo (n=560) n (%) carisoprodol 250 mg (n=548) n (%) carisoprodol 350 mg (n=279) n (%) drowsiness 31 (6) 73 (13) 47 (17) dizziness 11 (2) 43 (8) 19 (7) headache 11 (2) 26 (5) 9 (3) 6.2 postmarketing experience the following events have been reported during postapproval use of carisoprodol. because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. cardiovascular: tachycardia, postural hypotension, and facial flushing [see overdosage (10)]. central nervous system: drowsiness, dizziness, vertigo, ataxia, tremor, agitation, irritability, headache, depressive reactions, syncope, insomnia, and seizures [see overdosage (10)]. gastrointestinal: nausea, vomiting, and epigastric discomfort. hematologic: leukopenia, pancytopenia

the full pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety of carisoprodol is unknown.

timated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data human data retrospective case-control and cohort studies of meprobamate use during the first trimester of pregnancy have not consistently identified an increased risk or pattern of major birth defects. for children exposed to meprobamate in-utero, one study found no adverse effect on mental or motor development or iq scores. animal data embryofetal development studies in animals have not been completed. in a published pre- and post-natal development animal study, pregnant mice administered carisoprodol orally at 300, 750, or 1200 mg/kg/day (approximately 1-, 2.6-, and 4.1-times the mrhd based on bsa comparison) from 7-days prior to gestation through birth and from lactation through weaning resulted in reduced fetal weights, postnatal weight gain, and postnatal survival at 2.6- and 4.1-times the mrhd. 8.2 lactation risk summary data from published literature report that carisoprodol and its metabolite, meprobamate, are present in breastmilk. there are no data on the effect of carisoprodol on milk production. there is one report of sedation in an infant who was breastfed by a mother taking carisoprodol (see clinical considerations). because there have been no consistent reports of adverse events in breastfed infants over decades of use, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for carisoprodol and any potential adverse effects on the breastfed infant from carisoprodol or from the underlying maternal condition. clinical considerations infants exposed to carisoprodol through breast milk should be monitored for sedation. 8.4 pediatric use the efficacy, safety, and pharmacokinetics of carisoprodol in pediatric patients less than 16 years of age have not been established. 8.5 geriatric use the efficacy, safety, and pharmacokinetics of carisoprodol in patients over 65 years old have not been established. 8.6 renal impairment the safety and pharmacokinetics of carisoprodol in patients with renal impairment have not been evaluated. since carisoprodol is excreted by the kidney, caution should be exercised if carisoprodol is administered to patients with impaired renal function. carisoprodol is dialyzable by hemodialysis and peritoneal dialysis. 8.7 hepatic impairment the safety and pharmacokinetics of carisoprodol in patients with hepatic impairment have not been evaluated. since carisoprodol is metabolized in the liver, caution should be exercised if carisoprodol is administered to patients with impaired hepatic function. 8.8 patients with reduced cyp2c19 activity patients with reduced cyp2c19 activity have higher exposure to carisoprodol. therefore, caution should be exercised in administration of carisoprodol to these patients. [see clinical pharmacology (12.3)].