Soma Compound

Soma Compound (carisoprodol and aspirin tablets, USP) is a fixed-dose combination product containing the following two products:

• 200 mg of carisoprodol, a centrally-acting muscle relaxant
• 325 mg of aspirin, an analgesic with antipyretic and anti-inflammatory properties.

It is available as a two-layered, white and orange, round tablet for oral administration.

Carisoprodol: Chemically, carisoprodol is N-isopropyl-2-methyl-2-propyl-1,3-propanediol dicarbamate and its molecular formula is C12H24N2O4, with a molecular weight of 260.33. The structural formula of carisoprodol is:

Aspirin: Chemically, aspirin (acetylsalicyclic acid) is 2-(acetyloxy)-, benzoic acid and its molecular formula is C9H8O4, with a molecular weight of 180.16. The structural formula of aspirin is:

Other ingredients in the Soma Compound (carisoprodol and aspirin) drug product are croscarmellose sodium, FD&C Red #40, FD&C Yellow #6, hypromellose, magnesium stearate, microcrystalline cellulose, povidone, starch, and stearic acid.

Mechanism of Action

Carisoprodol: 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.

Aspirin: The mechanism of action of aspirin in relieving pain is by inhibition of the body's production of prostaglandins, which are thought to cause pain sensations by stimulating muscle contractions and dilating blood vessels.

Pharmacodynamics

Carisoprodol: Carisoprodol is a centrally-acting 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.

Aspirin: Aspirin is a non-narcotic analgesic with anti-inflammatory and anti-pyretic activity. Inhibition of prostaglandin biosynthesis appears to account for most of its anti-inflammatory and for at least part of its analgesic and antipyretic properties. In the CNS, aspirin works on the hypothalamus heat-regulating center to reduce fever. Aspirin can cause serious gastrointestinal injury including bleeding, obstruction, and perforations from ulcers possibly by inhibition of the production of prostaglandins, compromising the defenses of the gastric mucosa and the activity of substances involved in tissue repair and ulcer healing (see WARNINGS). Aspirin inhibits platelet aggregation by irreversibly inhibiting prostaglandin cyclo-oxygenase. This effect lasts for the life of the platelet and prevents the formation of the platelet aggregating factor thromboxane A2.

Pharmacokinetics

Carisoprodol

The pharmacokinetics of carisoprodol and its metabolite meprobamate were studied in a study of 24 healthy subjects (12 male and 12 female) who received single doses of 350 mg of carisoprodol (see Table 1). The Cmax 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 Cmax of meprobamate (approximately 8 μg/mL) after administration of a single 400 mg dose of meprobamate.

Table 1: Pharmacokinetic Parameters of Carisoprodol and Meprobamate (Mean ± SD, n=24)

Absolute bioavailability of carisoprodol has not been determined. After administration of a single dose of 350 mg of carisoprodol, 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 350 mg of carisoprodol had no effect on the pharmacokinetics of carisoprodol.

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).

Carisoprodol is eliminated by both renal and non-renal routes with a terminal elimination half-life of approximately 2 hours after administration of a single dose of 350 mg of carisoprodol. The half-life of meprobamate is approximately 10 hours after administration of a single dose of 350 mg of carisoprodol.

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.

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 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%.

Aspirin

The rate of aspirin absorption from the gastrointestinal (GI) tract is dependent upon the presence or absence of food, gastric pH (the presence or absence of GI antacids), and other physiologic factors. Following absorption, aspirin is hydrolyzed to salicylic acid in the gut wall and during first-pass metabolism with peak plasma levels of salicylic acid occurring within 1 to 2 hours of dosing.

Salicylic acid is widely distributed to all tissues and fluids in the body including the central nervous system (CNS), breast milk, and fetal tissues. The highest concentrations are found in the plasma, liver, kidneys, heart, and lungs. The protein binding of salicylate is concentration dependent, i.e., nonlinear. At plasma concentrations of salicylic acid < 100 μg/mL and > 400 μg/mL, approximately 90 and 76 percent of plasma salicylate is bound to albumin, respectively.

Aspirin, which has a half-life of about 15 minutes, is hydrolyzed in the plasma to salicylic acid such that plasma levels of aspirin may not be detectable 1 to 2 hours after dosing. Salicylic acid, which has a plasma half life of approximately 6 hours, is conjugated in the liver to form salicyluric acid, salicyl phenolic glucuronide, salicyl acyl glucuronide, gentisic acid, and gentisuric acid. At higher serum concentrations of salicylic acid, the total clearance of salicylic acid decreases due to the limited ability of the liver to form both salicyluric acid and phenolic glucuronide. Following toxic doses of aspirin (e.g., > 10 grams), the plasma half-life of salicylic acid may be increased to over 20 hours.

The elimination of salicylic acid is constant in relation to the plasma salicylic acid concentration. Following therapeutic doses of aspirin, approximately 75, 10, 10, and 5 percent is found excreted in the urine as salicyluric acid, salicylic acid, a phenolic glucuronide of salicylic acid, and an acyl glucuronide of salicylic acid, respectively. As the urinary pH rises above 6.5, the renal clearance of free salicylate increases from less than 5 percent to greater than 80 percent. Alkalinization of the urine is a key concept in the management of salicylate overdose (see OVERDOSAGE, Treatment of Overdosage). Clearance of salicylic acid is also reduced in patients with renal impairment.

Do not take aspirin and carisoprodol without first talking to your doctor if you have acute intermittent porphyria.

Before taking this medication, tell your doctor if you have

• kidney disease,
• liver disease,
• a stomach or intestinal ulcer,
• a bleeding or blood-clotting disorder.

You may not be able to take aspirin and carisoprodol, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

It is not known whether aspirin and carisoprodol will be harmful to an unborn baby. Do not take aspirin and carisoprodol without first talking to your doctor if you are pregnant or could become pregnant during treatment.

It is not known whether aspirin and carisoprodol passes into breast milk. Do not take aspirin and carisoprodol without first talking to your doctor if you are breast-feeding a baby.

Aspirin and carisoprodol is not approved for use in children younger than 12 years of age. Also, do not use any medication that contains aspirin to treat a child or teenager who has a fever, flu symptoms, or chicken pox without first talking to a doctor. In children younger than 20 years of age, aspirin may increase the risk of Reye's syndrome, a rare but often fatal condition.

Use caution when driving, operating machinery, or performing other hazardous activities. Aspirin and carisoprodol may cause dizziness or drowsiness. If you experience dizziness or drowsiness, avoid these activities.

Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while taking aspirin and carisoprodol. Also, in combination with aspirin, alcohol can be damaging to the stomach.

To report SUSPECTED ADVERSE REACTIONS, contact Meda Pharmaceuticals Inc. at 1-800-526-3840 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

The following adverse reactions which have occurred with the administration of the individual products alone may also occur with the use of Soma Compound (carisoprodol and aspirin) . The following events have been reported during post-approval individual use of carisoprodol and aspirin. 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.

Carisoprodol: The following events have been reported during post-approval 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.

Tachycardia, postural hypotension, and facial flushing (see OVERDOSAGE).

Drowsiness, dizziness, vertigo, ataxia, tremor, agitation, irritability, headache, depressive reactions, syncope, insomnia, and seizures (see OVERDOSAGE).

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

Aspirin: The most common adverse reactions associated with the use of aspirin have been gastrointestinal, including abdominal pain, anorexia, nausea, vomiting, gastritis, and occult bleeding (see WARNINGS, Serious Gastrointestinal Adverse Reactions and PRECAUTIONS, Gastrointestinal Adverse Reactions). Other adverse reactions associated with the use of aspirin include elevated liver enzymes, rash, pruritus, purpura, intracranial hemorrhage, interstitial nephritis, acute renal failure, and tinnitus. Tinnitus may be a symptom of high serum salicylate levels (see OVERDOSAGE).

Drug Abuse And Dependence

Carisoprodol is not a controlled substance (see WARNINGS).

Discontinuation of carisoprodol in animals or in humans after chronic administration can produce withdrawal signs, and there are published case reports of human carisoprodol dependence.

In vitro studies demonstrate that carisoprodol elicits barbiturate-like effects. Animal behavioral studies indicate that carisoprodol produces rewarding effects. Monkeys self administer carisoprodol. Drug discrimination studies using rats indicate that carisoprodol has positive reinforcing and discriminating effects similar to barbital, meprobamate, and chlordiazepoxide.

Read the entire FDA prescribing information for Soma Compound (Carisoprodol and Aspirin)

Aspirin a pain reliever and fever reducer, in a group of drugs called salicylates. Aspirin works by reducing substances in the body that cause pain and inflammation.

Carisoprodol is a muscle relaxant. It works by blocking nerve impulses (or pain sensations) that are sent to the brain.

Aspirin and carisoprodol is a combination medicine used short-term to treat painful muscular conditions.

Aspirin and carisoprodol may also be used for purposes not listed in this medication guide.

Carisoprodol may be habit-forming. Misuse of habit-forming medicine can cause addiction, overdose, or death. Selling or giving away this medicine is against the law.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of aspirin and carisoprodol can be fatal.

Overdose symptoms may include ringing in your ears, severe dizziness or drowsiness, muscle stiffness, loss of coordination, confusion, hallucinations, hearing or vision problems, thirst, sweating, fever, vomiting, diarrhea, weak or shallow breathing, seizures, or loss of consciousness.

Taking this medicine with other drugs that make you sleepy or slow your breathing can cause dangerous side effects or death. Ask your doctor before taking a sleeping pill, narcotic pain medicine, prescription cough medicine, a muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• clopidogrel;

• meprobamate;

• methotrexate;

• rifampin;

• St. John's wort;

• blood pressure medication;

• insulin or oral diabetes medicine;

• antifungal medicine--fluconazole, voriconazole;

• a blood thinner--warfarin, Coumadin, Jantoven;

• NSAIDs (nonsteroidal anti-inflammatory drugs)--aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others; or

• a stomach acid reducer--esomeprazole, omeprazole, Prilosec, Nexium, or others.

This list is not complete. Other drugs may interact with aspirin and carisoprodol, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.