SOMA (carisoprodol) Tablets are available as 250 mg and 350 mg round, 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 C₁₂H₂₄N₂O₄ , with a molecular weight of 260.33. The structural formula is:

Other ingredients in the SOMA drug product include alginic acid, magnesium stearate, potassium sorbate, starch, and tribasic calcium phosphate.

SOMA is indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults. SOMA 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].

The recommended dose of SOMA is 250 mg to 350 mg three times a day and at bedtime. The recommended maximum duration of SOMA use is up to two or three weeks.

Dosage Forms And Strengths

250 mg Tablets: round, convex, white tablets, inscribed with SOMA 250

350 mg Tablets: round, convex, white tablets, inscribed with SOMA 350

Storage And Handling

250mg Tablets: round, convex, white tablets, inscribed with SOMA 250; available in bottles of 100 (NDC 0037-2250-10).

350mg Tablets: round, convex, white tablets, inscribed with SOMA 350; available in bottles of 100 (NDC 0037-2001-01).

Storage

Store at 25° C (77° F); excursions permitted between 15° and 30° C (59° and 86° F) (see USP Controlled Room Temperature).

MedPointe Pharmaceuticals, MedPointe Healthcare Inc. Somerset, NJ 08873. FDA Rev date: 9/13/2007

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]. In these studies, patients were treated with 250 mg of SOMA, 350 mg of SOMA, 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 SOMA, and 350 mg of SOMA, respectively, discontinued due to adverse events; and 0.5%, 0.5%, and 1.8% of patients treated with placebo, 250 mg of SOMA, and 350 mg of SOMA, 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 SOMA in the two trials described above.

Table 1: Patients with Adverse Reactions in Controlled Studies

Postmarketing Experience

The following events have been reported during postapproval use of SOMA. 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].

Central Nervous System: Drowsiness, dizziness, vertigo, ataxia, tremor, agitation, irritability, headache, depressive reactions, syncope, insomnia, and seizures [see OVERDOSAGE].

Gastrointestinal: Nausea, vomiting, and epigastric discomfort. Hematologic: Leukopenia, pancytopenia

CNS Depressants

The sedative effects of SOMA 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 SOMA and meprobamate, a metabolite of SOMA, is not recommended [see Warnings and PRECAUTIONS].

CYP2C19 Inhibitors and Inducers

Carisoprodol is metabolized in the liver by CYP2C19 to form meprobamate [see CLINICAL PHARMACOLOGY]. Co-administration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine, with SOMA 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 SOMA 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 SOMA is unknown.

Included as part of the PRECAUTIONS section.

Sedation

SOMA may have sedative properties (in the low back pain trials, 13% to 17% of patients who received SOMA experienced sedation compared to 6% of patients who received placebo) [see ADVERSE REACTIONS] 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.

Since the sedative effects of SOMA 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.

Drug Dependence, Withdrawal, and Abuse

In the postmarketing experience with SOMA, 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 SOMA in combination with other drugs with abuse potential. Withdrawal symptoms have been reported following abrupt cessation after prolonged use. To reduce the chance of SOMA dependence, withdrawal, or abuse, SOMA should be used with caution in addiction-prone patients and in patients taking other CNS depressants including alcohol, and SOMA should be not be used more than two to three weeks for the relief of acute musculoskeletal discomfort.

One of the metabolites of SOMA, meprobamate (a controlled substance), may cause dependence [see CLINICAL PHARMACOLOGY].

Seizures

There have been postmarketing reports of seizures in patients who received SOMA. Most of these cases have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol) [see OVERDOSAGE].

NonClinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals have not been performed to evaluate the carcinogenic potential of carisoprodol.

SOMA 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.

SOMA 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.

Use In Specific Population

Pregnancy: Pregnancy Category C.

There are no data on the use of SOMA 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: 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: 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. SOMA should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

Labor and Delivery

There is no information about the effects of SOMA on the mother and the fetus during labor and delivery.

Nursing Mothers

Very limited data in humans show that SOMA 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 SOMA may lead to reduced or less effective infant feeding (due to sedation) and/or decreased milk production. Caution should be exercised when SOMA is administered to a nursing woman.

Pediatric Use

The efficacy, safety, and pharmacokinetics of SOMA in pediatric patients less than 16 years of age have not been established.

Geriatric Use

The efficacy, safety, and pharmacokinetics of SOMA in patients over 65 years old have not been established.

Renal Impairment

The safety and pharmacokinetics of SOMA in patients with renal impairment have not been evaluated. Since SOMA is excreted by the kidney, caution should be exercised if SOMA is administered to patients with impaired renal function. Carisoprodol is dialyzable by hemodialysis and peritoneal dialysis.

Hepatic Impairment

The safety and pharmacokinetics of SOMA in patients with hepatic impairment have not been evaluated. Since SOMA is metabolized in the liver, caution should be exercised if SOMA is administered to patients with impaired hepatic function.

Patients with Reduced CYP2C19 Activity

Patients with reduced CYP2C19 activity have higher exposure to carisoprodol. Therefore, caution should be exercised in administration of SOMA to these patients [see CLINICAL PHARMACOLOGY].

Drug Abuse And Dependence

[see Warnings and PRECAUTIONS]

Overdosage of SOMA 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 SOMA overdosage. Many of the SOMA overdoses have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol). The effects of an overdose of SOMA 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 SOMA have been reported alone or in combination with CNS depressants.

Treatment of Overdosage: Basic life support measures should be instituted as dictated by the clinical presentation of the SOMA overdose. Induced emesis is not recommended due to the risk of CNS and respiratory depression, which may increase the risk of aspiration pneumonia. Gastric lavage should be considered soon after ingestion (within one hour). 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.

The following types of treatment have been used successfully with an overdose of meprobamate, a metabolite of SOMA: activated charcoal (oral or via nasogastric tube), forced diuresis, peritoneal dialysis, and hemodialysis (carisoprodol is also dialyzable). Careful monitoring of urinary output is necessary and overhydration should be avoided. Observe for possible relapse due to incomplete gastric emptying and delayed absorption. For more information on the management of an overdose of SOMA, contact a Poison Control Center.

SOMA is contraindicated in patients with a history of acute intermittent porphyria or a hypersensitivity reaction to a carbamate such as meprobamate.

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.

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 SOMA is unknown.

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 SOMA (see Table 2). The exposure of carisoprodol and meprobamate was dose proportional between the 250 mg and 350 mg doses. The Cmax of meprobamate was 2.5 ± 0.5 ug/mL (mean ± SD) after administration of a single 350 mg dose of SOMA, which is approximately 30% of the Cmax of meprobamate (approximately 8 ug/mL) after administration of a single 400 mg dose of meprobamate.

Table 2. Pharmacokinetic Parameters of Carisoprodol and Meprobamate (Mean ± SD, n=24)

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 SOMA (350 mg tablet) had no effect on the pharmacokinetics of carisoprodol. Therefore, SOMA 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: SOMA 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%.

Clinical Studies

The safety and efficacy of SOMA for the relief of acute, idiopathic mechanical low back pain was evaluated in two, 7-day, double blind, randomized, multicenter, placebo controlled, U.S. trials (Studies 1 and 2). Patients had to be 18 to 65 years old and had to have acute back pain (≤ 3 days of duration) to be included in the trials. Patients with chronic back pain; at increased risk for vertebral fracture (e.g., history of osteoporosis); with a history of spinal pathology (e.g., herniated nucleus pulposis, spondylolisthesis or spinal stenosis); with inflammatory back pain, or with evidence of a neurologic deficit were excluded from participation. Concomitant use of analgesics (e.g., acetaminophen, NSAIDs, tramadol, opioid agonists), other muscle relaxants, botulinum toxin, sedatives (e.g., barbiturates, benzodiazepines, promethazine hydrochloride), and anti-epileptic drugs was prohibited.

In Study 1, patients were randomized to one of three treatment groups (i.e., SOMA 250 mg, SOMA 350 mg, or placebo) and in Study 2 patients were randomized to two treatment groups (i.e., SOMA 250 mg or placebo). In both studies, patients received study medication three times a day and at bedtime for seven days.

The primary endpoints were the relief from starting backache and the global impression of change, as reported by patients, on Study Day #3. Both endpoints were scored on a 5-point rating scale from 0 (worst outcome) to 4 (best outcome) in both studies. The primary statistical comparison was between the SOMA 250 mg and placebo groups in both studies.

The proportion of patients who used concomitant acetaminophen, NSAIDs, tramadol, opioid agonists, other muscle relaxants, and benzodiazepines was similar in the treatment groups.

The results for the primary efficacy evaluations in the acute, low back pain studies are presented in Table 3.

Table 3: Results of the Primary Efficacy Endpoints^a in Studies 1 and 2

Patients treated with SOMA experienced improvement in function as measured by the Roland-Morris Disability Questionnaire (RMDQ) score on Days 3 and 7.

Patients should be advised to contact their physician if they experience any adverse reactions to SOMA.

Sedation

Since SOMA may cause drowsiness and/or dizziness, patients should be advised to assess their individual response to SOMA before engaging in potentially hazardous activities such as driving a motor vehicle or operating machinery [see Warnings and PRECAUTIONS].

Avoidance of Alcohol and Other CNS Depressants

Patients should be advised to avoid alcoholic beverages while taking SOMA and to check with their doctor before taking other CNS depressants such as benzodiazepines, opioids, tricyclic antidepressants, sedating antihistamines, or other sedatives [see Warnings and PRECAUTIONS].

SOMA Should Only Be Used for Short-Term Treatment

Patients should be advised that treatment with SOMA should be limited to acute use (up to two or three weeks) for the relief of acute, musculoskeletal discomfort. If symptoms still persist, patients should contact their healthcare provider for further evaluation.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

CARISOPRODOL - ORAL

(kar-iss-oh-PRO-dole)

COMMON BRAND NAME(S): Soma

USES: This medication is used to treat pain and discomfort from muscle injuries such as strains, sprains, and spasms. It is usually used along with rest, physical therapy, and other treatments (e.g., anti-inflammatory medication).

Carisoprodol is called a centrally acting muscle relaxant. It works on the nerves to relieve muscle pain. It may also relieve pain by calming your nervous system.

HOW TO USE: Take this medication by mouth with or without food, usually 4 times a day or as directed by your doctor.

Dosage is based on your medical condition and response to treatment. Your doctor will usually direct you to take this medication for your current injury only. Do not save this drug for future use. Follow your doctor's directions on when to reduce your dose, take it less often, or stop taking it.

This medication may cause dependence, especially if it has been used regularly for an extended time or if it has been used in high doses. In such cases, withdrawal reactions (e.g., stomach cramps, trouble sleeping, headache, nausea) may occur if you suddenly stop this drug. To prevent withdrawal when stopping extended/regular treatment with this drug, gradually reduce the dosage as directed. Consult your doctor or pharmacist for more details, and report any withdrawal reactions immediately.

Though it is very unlikely to occur, this medication can also result in abnormal drug-seeking behavior (addiction/habit-forming). Do not increase your dose, take it more frequently or use it for a longer time than prescribed. Properly stop the medication when so directed. This will lessen the chances of becoming addicted.

Tell your doctor if your symptoms persist or worsen after 2 to 3 weeks.

SIDE EFFECTS: Dizziness, drowsiness, headache, unusually fast heartbeat, low blood pressure, or face flushing may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Sometimes carisoprodol may cause a very rare but serious reaction (idiosyncratic) that occurs within minutes or hours of the first dose of this medication. Seek immediate medical attention and do not take more of the medication if you experience: extreme weakness, inability to move your legs/arms, shaky/unsteady movement, pain in your joints, vision changes (double vision, inability to see), widened pupils, mental/mood changes (e.g., agitation, restlessness, unexplained mood swings, confusion).

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking carisoprodol, tell your doctor or pharmacist if you are allergic to it; or to meprobamate, tybamate, or mebutamate; or if you have any other allergies. Also tell your doctor if you have ever had an unusual reaction to carisoprodol or any of the medications listed above.

This medication should not be used if you have a certain medical condition. Before using this medication, tell your doctor if you have: acute intermittent porphyria.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney problems, liver problems, history of regular alcohol/drug abuse, asthma, seizure disorder.

To reduce dizziness and lightheadedness, get up slowly when rising from a seated or lying position.

This drug may make you dizzy or drowsy; use caution engaging in activities requiring alertness such as driving, swimming or using machinery. Avoid alcoholic beverages.

This medication is not recommended for use during pregnancy. It may rarely harm an unborn baby. Consult your doctor for more details and to discuss reliable forms of birth control. If you become pregnant while taking this medication, tell your doctor immediately.

This medication passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: melatonin, other muscle relaxants (e.g., cyclobenzaprine, methocarbamol).

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-anxiety drugs (e.g., diazepam), anti-seizure drugs (e.g., carbamazepine), medicine for sleep (e.g., zolpidem, temazepam), narcotic pain relievers (e.g., codeine), psychiatric medications (e.g., phenothiazines such as chlorpromazine or tricyclics such as amitriptyline), tranquilizers. Alcoholic beverages will also increase the drowsiness effect.

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain drowsiness-causing ingredients. Ask your pharmacist about the safe use of those products.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store in a tightly closed container at room temperature between 59-86 degrees F (15-30 degrees C) away from moisture and sunlight. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.