CARISOPRODOL TABLETS, USP, 350 MG

Carisoprodol Tablets, USP are available as 350 mg, round, white tablets for oral administration. Carisoprodol 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. Carisoprodol is present as a racemic mixture. Chemically, carisoprodol is (±)-2-Methyl-2-propyl-1,3-propanediol carbamate isopropylcarbamate and the molecular formula is C 12 H 24 N 2 O 4 , with a molecular weight of 260.33. The structural formula is: Other ingredients in Carisoprodol Tablets, USP include lactose monohydrate NF, sodium starch glycolate NF, povidone NF, sodium lauryl sulfate NF, microcrystalline cellulose (PH 101) NF, and magnesium stearate NF. Carisoprodol Structural Formula

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)

The recommended dose of Carisoprodol Tablets is 250 mg to 350 mg three times a day and at bedtime. The recommended maximum duration of Carisoprodol Tablets use is up to two or three weeks. Recommended dose is 250 mg to 350 mg three times a day and at bedtime. (2)

Carisoprodol Tablets are 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)

Most common adverse reactions (incidence > 2%) are drowsiness, dizziness, and headache (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Granulation Technology, Inc. at 1-973-276-0740 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect rates observed in practice. The data described below are based on 1387 patients pooled from two double blind, randomized, multicenter, placebo controlled, one-week trials in adult patients with acute, mechanical, lower back pain [see Clinical Studies (14)]. In these studies, patients were treated with 250 mg of Carisoprodol, 350 mg of Carisoprodol, or placebo three times a day and at bedtime for seven days. The mean age was about 41 years old with 54% females and 46% males and 74 % Caucasian, 16 % Black, 9% Asian, and 2% other. There were no deaths and there were no serious adverse reactions in these two trials. In these two studies, 2.7%, 2%, and 5.4%, of patients treated with placebo, 250 mg of Carisoprodol, and 350 mg of Carisoprodol, 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 Post-marketing 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

CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) - additive sedative effects ( 5.1, 7.1 ) 7.1 CNS Depressants The sedative effects of Carisoprodoland other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive. Therefore, caution should be exercised with patients who take more than one of these CNS depressants simultaneously. Concomitant use of Carisoprodol and Meprobamate, a metabolite of Carisoprodol, is not recommended [ see Warnings and Precautions (5.1) ]. 7.2 CYP2C19 Inhibitors and Inducers Carisoprodol is metabolized in the liver by CYP2C19 to form meprobamate [ see Clinical Pharmacology (12.3) ]. Co-administration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine, with Carisoprodol could result in increased exposure of carisoprodol and decreased exposure of meprobamate. Co-administration of CYP2C19 inducers, such as rifampin or St. John’s Wort, with Carisoprodol could result in decreased exposure of carisoprodol and increased exposure of meprobamate. Low dose aspirin also showed an induction effect on CYP2C19. The full pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety of Carisoprodol is unknown.

Storage: Store at controlled room temperature 20° - 25°C (68° - 77°F) [see USP Controlled Room Temperature].