carisoprodol 350 MG Oral Tablet [Vanadom]

INDICATIONS AND USAGE Carisoprodol Tablets, USP are indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults. Limitation of Use Carisoprodol Tablets, USP should only be used for short periods (up to two or three weeks) because adequate evidence of effectiveness for more prolonged use has not been established and because acute, painful musculoskeletal conditions are generally of short duration [ see Dosage and Administration (2) ]. Carisoprodol Tablet is a muscle relaxant indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults. (1) Limitation of Use : Should only be used for acute treatment periods up to two or three weeks (1)

DOSAGE AND ADMINISTRATION The recommended dose of Carisoprodol tablets, USP is 250 mg to 350 mg three times a day and at bedtime. The recommended maximum duration of carisoprodol tablets, USP use is up to two or three weeks. • Recommended dose is 250 mg to 350 mg three times a day and at bedtime. (2)

WARNINGS AND PRECAUTIONS Due to sedative properties, may impair ability to perform hazardous tasks such as driving or operating machinery (5.1) Additive sedative effects when used with other CNS depressants including alcohol (5.1) Cases of abuse, dependence and withdrawal (5.2, 9.2, 9.3) Seizures (5.3) 5.1 Sedation Carisoprodol tablets have sedative properties (in the low back pain trials, 13% to 17% of patients who received carisoprodol tablets experienced sedation compared to 6% of patients who received placebo) [ see ADVERSE REACTIONS (6.1) ] and may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a motor vehicle or operating machinery. There have been post-marketing reports of motor vehicle accidents associated with the use of carisoprodol tablets. Since the sedative effects of carisoprodol tablets and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive, appropriate caution should be exercised with patients who take more than one of these CNS depressants simultaneously. 5.2 Abuse, Dependence and Withdrawal Carisoprodol, the active ingredient in carisoprodol tablets, has been subject to abuse, dependence, and withdrawal, misuse and criminal diversion. [ see Drug Abuse and Dependence (9.1, 9.2, 9.3) ] . Abuse of carisoprodol tablets 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 tablets 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 tablets 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 tablets. Most of these cases have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol) [ see Overdosage (10) ].

CONTRAINDICATIONS Carisoprodol tablets, USP is contraindicated in patients with a history of acute intermittent porphyria or a hypersensitivity reaction to a carbamate such as meprobamate. • Acute intermittent porphyria (4) • Hypersensitivity reactions to a carbamate such as meprobamate (4)

CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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. 12.2 Pharmacodynamics 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 is unknown. 12.3 Pharmacokinetics 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 250 mg and 350 mg carisoprodol (see Table 2). The exposure of carisoprodol and meprobamate was dose proportional between the 250 mg and 350 mg doses. 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) 250 mg Carisoprodol 350 mg Carisoprodol Carisoprodol C max (µg/mL) 1.2 ± 0.5 1.8 ± 1.0 AUC inf (µg*hr/mL) 4.5 ± 3.1 7.0 ± 5.0 T max (hr) 1.5 ± 0.8 1.7 ± 0.8 T 1/2 (hr) 1.7 ± 0.5 2.0 ± 0.5 Meprobamate C max (µg/mL) 1.8 ± 0.3 2.5 ± 0.5 AUC inf (µg * hr/mL) 32 ± 6.2 46 ± 9.0 T max (hr) 3.6 ± 1.7 4.5 ± 1.9 T 1/2 (hr) 9.7 ± 1.7 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 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 to 50% on a weight adjusted basis). Overall exposure of meprobamate is comparable between female and male subjects. Patients with Reduced CYP2C19 Activity: Carisoprodol 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 to 5% and in Asians is approximately 15 to 20%.