Carisoprodol

CARISOPRODOL- carisoprodol tablet
Blenheim Pharmacal, Inc.

1 INDICATIONS AND USAGE

Carisoprodol Tablets are indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults.
Carisoprodol Tablets 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) ] .

2 DOSAGE AND ADMINISTRATION

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

3 DOSAGE FORMS AND STRENGTHS

Carisoprodol Tablets, USP 350 mg are white, round, unscored tablets; imprinted “WW 176”.

4 CONTRAINDICATIONS

Carisoprodol Tablets are contraindicated in patients with a history of acute intermittent porphyria or a hypersensitivity reactions to a carbamate such as meprobamate

5 WARNINGS AND PRECAUTIONS

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 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 Drug Dependence, Withdrawal, and Abuse

In the postmarketing experience with Carisoprodol Tablets, cases of dependence, withdrawal, and abuse have been reported with prolonged use. 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. However, there have been post-marketing adverse event reports of Carisoprodol Tablets-associated abuse when used without 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.

Carisoprodol Tablets, and one of its metabolites, meprobamate (a controlled substance), may cause dependence [see Clinical Pharmacology (12.3) ].

5.3 Seizures

There have been postmarketing 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)].

6 ADVERSE REACTIONS

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 the study, patients were treated with 350 mg of Carisoprodol Tablets, 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 the study, 2.7% and 5.4%, of patients treated with placebo and 350 mg of Carisoprodol Tablets, respectively, discontinued due to adverse events; and 0.5% and 1.8% of patients treated with placebo and 350 mg of Carisoprodol Tablets, 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 Tablets in the trial described above.

Table 1 – Patients with Adverse Reactions in Controlled Studies

Adverse Reaction		Placebo (n=560) n(%)	Carisoprodol 350 mg (n=279) n(%)
Drowsiness		31(6)	47(17)
Dizziness		11(2)	19(7)
Headache		11(2)	9(3)

6.2 Postmarketing Experience

The following events have been reported during postapproval use of Carisoprodol Tablets. 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.

Hematologics: Leukopenia, pancytopenia

7 DRUG INTERACTIONS

7.1 CNS Depressants

The sedative effects of Carisoprodol Tablets and 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 Tablets are metabolized in the liver by CYP2C19 to form meprobamate [see Clinical Pharmacology(12.1)]. Co-administration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine, with Carisoprodol Tablets 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 Tablets could result in decreased exposure of carisoprodol and increased exposure of meprobamate. Low dose aspirin also showed induction effect on CYP2C19. The full pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety of Carisoprodol Tablets is unknown.