FDA Label for Carisoprodol
View Indications, Usage & Precautions
- 1. INDICATIONS AND USAGE
- 2. DOSAGE AND ADMINISTRATION
- 3. DOSAGE FORMS AND STRENGTHS
- 4. CONTRAINDICATIONS
- 5.1 SEDATION
- 5.2 ABUSE, DEPENDENCE, AND WITHDRAWAL
- 5.3 SEIZURES
- 6.1 CLINICAL STUDIES EXPERIENCE
- 6.2 POST-MARKETING EXPERIENCE
- 7.1 CNS DEPRESSANTS
- 7.2 CYP2C19 INHIBITORS AND INDUCERS
- 8.1 PREGNANCY: PREGNANCY CATEGORY C.
- TERATOGENIC EFFECTS
- NONTERATOGENIC EFFECTS
- 8.2 LABOR AND DELIVERY
- 8.3 NURSING MOTHERS
- 8.4 PEDIATRIC USE
- 8.5 GERIATRIC USE
- 8.6 RENAL IMPAIRMENT
- 8.7 HEPATIC IMPAIRMENT
- 8.8 PATIENTS WITH REDUCED CYP2C19 ACTIVITY
- 9.1 CONTROLLED SUBSTANCE
- 9.2 ABUSE
- 9.3 DEPENDENCE
- 10 OVERDOSAGE
- OTHER
- 11 DESCRIPTION
- 12.1 MECHANISM OF ACTION
- 12.2 PHARMACODYNAMICS
- 12.3 PHARMACOKINETICS
- 13.1 CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
- 14 CLINICAL STUDIES
- 16 HOW SUPPLIED/STORAGE AND HANDLING
- STORAGE AND HANDLING
- 17 PATIENT COUNSELING INFORMATION
- 17.1 SEDATION
- 17.2 AVOIDANCE OF ALCOHOL AND OTHER CNS DEPRESSANTS
- 17.3 CARISOPRODOL SHOULD ONLY BE USED FOR SHORT-TERM TREATMENT
- PRINCIPAL DISPLAY PANEL - 60 TABLETS BOTTLE LABEL
Carisoprodol Product Label
The following document was submitted to the FDA by the labeler of this product Proficient Rx Lp. The document includes published materials associated whith this product with the essential scientific information about this product as well as other prescribing information. Product labels may durg indications and usage, generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, warnings, inactive ingredients, etc.
1. Indications And Usage
2. Dosage And Administration
3. Dosage Forms And Strengths
4. Contraindications
5.1 Sedation
5.2 Abuse, Dependence, And Withdrawal
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) ].
6.1 Clinical Studies Experience
Adverse Reaction | Placebo (n=560) n (%) | Carisoprodol 250 mg (n=548) n (%) | Carisoprodol 350 mg (n=279) n (%) |
---|---|---|---|
6.2 Post-Marketing Experience
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 seizure [ see Overdosage (10) ].
Gastrointestinal: Nausea, vomiting, and epigastric discomfort.
Hematologic: Leukopenia, pancytopenia.
7.1 Cns Depressants
7.2 Cyp2c19 Inhibitors And Inducers
8.1 Pregnancy: Pregnancy Category C.
There are no data on the use of carisoprodol during human pregnancy. Animal studies indicate that carisoprodol crosses the placenta and results in adverse effects on fetal growth and postnatal survival. The primary metabolite of carisoprodol, meprobamate, is an approved anxiolytic. Retrospective, post-marketing studies do not show a consistent association between maternal use of meprobamate and an increased risk for particular congenital malformations.
Teratogenic Effects
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
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 is administered to a nursing woman.
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
9.1 Controlled Substance
9.2 Abuse
9.3 Dependence
10 Overdosage
Overdosage of carisoprodol commonly produces CNS depression. Death, coma, respiratory depression, hypotension, seizures, delirium, hallucinations, dystonic reactions, nystagmus, blurred vision, mydriasis, euphoria, muscular incoordination, rigidity, and/or headache have been reported with carisoprodol overdosage. Serotonin syndrome has been reported with carisoprodol intoxication. Many of the carisoprodol overdoses have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol). The effects of an overdose of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) can be additive even when one of the drugs has been taken in the recommended dosage. Fatal accidental and non-accidental overdoses of carisoprodol have been reported alone or in combination with CNS depressants.
Other
Treatment of Overdosage: Basic life support measures should be instituted as dictated by the clinical presentation of the carisoprodol overdose. Vomiting should not be induced because of the risk of CNS and respiratory depression, and subsequent aspiration. 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.
For decontamination in cases of severe toxicity, activated charcoal should be considered in a hospital setting in patients with large overdoses who present early and are not demonstrating CNS depression and can protect their airway.
For more information on the management of an overdose of carisoprodol, contact a Poison Control Center.
Absorption: Absolute bioavailability of carisoprodol has not been determined. The mean time to peak plasma concentrations (Tmax) 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 30-50% 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 3-5% and in Asians is approximately 15-20%.
11 Description
Carisoprodol tablets USP are available as 350 mg, white tablets. 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 N-isopropyl-2-methyl-2-propyl-1,3-propanediol dicarbamate and the molecular formula is C12 H24 N2 O4 , with a molecular weight of 260.33. The structural formula is:
Other ingredients in the Carisoprodol tablets USP drug product include lactose monohydrate, microcrystalline cellulose, maize starch, croscarmellose sodium, povidone, talc, and magnesium stearate.
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
250 mg Carisoprodol | 350 mg Carisoprodol | |
---|---|---|
Carisoprodol | ||
Cmax (μg/mL) | ||
AUCinf (μg*hr/mL) | ||
Tmax (hr) | ||
T1/2 (hr) | ||
Meprobamate | ||
Cmax (μg/mL) | ||
AUCinf (μg*hr/mL) | ||
Tmax (hr) | ||
T1/2 (hr) |
13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long term studies in animals have not been performed to evaluate the carcinogenic potential of carisoprodol.
Carisoprodol was not formally evaluated for genotoxicity. In published studies, carisoprodol was mutagenic in the in vitro mouse lymphoma cell assay in the absence of metabolizing enzymes, but was not mutagenic in the presence of metabolizing enzymes. Carisoprodol was clastogenic in the in vitro chromosomal aberration assay using Chinese hamster ovary cells with or without the presence of metabolizing enzymes. Other types of genotoxic tests resulted in negative findings. Carisoprodol was not mutagenic in the Ames reverse mutation assay using S. typhimurium strains with or without metabolizing enzymes, and was not clastogenic in an in vivo mouse micronucleus assay of circulating blood cells.
Carisoprodol was not formally evaluated for effects on fertility. Published reproductive studies of carisoprodol in mice found no alteration in fertility although an alteration in reproductive cycles characterized by a greater time spent in estrus was observed at a carisoprodol dose of 1200 mg/kg/day. In a 13-week toxicology study that did not determine fertility, mouse testes weight and sperm motility were reduced at a dose of 1200 mg/kg/day. In both studies, the no effect level was 750 mg/kg/day, corresponding to approximately 2.6 times the human equivalent dosage of 350 mg four times a day, based on a body surface area comparison. The significance of these findings for human fertility is not known.
14 Clinical Studies
Table 3. Results of the Primary Efficacy Endpointsain Studies 1 and 2 | ||||
Study | Parameter | Placebo | ||
Number of Patients | ||||
Relief from Starting Backache, Mean (SE)b | ||||
Global Impression of Change, Mean (SE)b | ||||
Number of Patients | ||||
Relief from Starting Backache, Mean (SE)b | ||||
Global Impression of Change, Mean (SE)b | ||||
16 How Supplied/Storage And Handling
Carisoprodol tablets USP, 350 mg : White to off-white circular biconvex tablets, debossed with logo-mark "OP" and product number "35" on one side and no mark on the other side; available in bottles of 20, 30, 60, 90, 120.
Storage And Handling
Storage:
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
17 Patient Counseling Information
Patients should be advised to contact their physician if they experience any adverse reactions to carisoprodol.
17.1 Sedation
17.2 Avoidance Of Alcohol And Other Cns Depressants
17.3 Carisoprodol Should Only Be Used For Short-Term Treatment
Patients should be advised that treatment with carisoprodol should be limited to acute use (up to two or three weeks) for the relief of acute, musculoskeletal discomfort. In the post-marketing experience with carisoprodol, cases of dependence, withdrawal, and abuse have been reported with prolonged use. If the musculoskeletal symptoms still persist, patients should contact their healthcare provider for further evaluation.
Principal Display Panel - 60 Tablets Bottle Label
CIV
350 mg
orient PHARMA CO.,Ltd.
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