|
WARNINGS - On very rare occasions, the first dose of carisoprodol has been followed by idiosyncratic reactions with symptoms appearing within minutes or hours. These may include extreme weakness, transient quadriplegia, dizziness, ataxia, temporary loss of vision, diplopia, mydriasis, dysarthria, agitation, euphoria, confusion, and disorientation. Although symptoms usually subside over the course of the next several hours, discontinue ‘Soma’ Compound with Codeine and initiate appropriate supportive and symptomatic therapy, which may include epinephrine and/or antihistamines. In severe cases, corticosteroids may be necessary. Severe reactions have been manifested by asthmatic episodes, fever, weakness, dizziness, angioneurotic edema, smarting eyes, hypotension, and anaphylactoid shock.
The effects of carisoprodol with agents such as alcohol, other CNS depressants or psychotropic drugs may be additive. Appropriate caution should be exercised with patients who take one or more of these agents simultaneously with ‘Soma’ Compound with Codeine.
Contains sodium metabisulfate, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
PRECAUTIONS-General: To avoid excessive accumulation of carisoprodol, aspirin, or their metabolites, use ‘Soma’ Compound with Codeine with caution in patients with compromised liver or kidney function, or in elderly or debilitated patients (see CLINICAL PHARMACOLOGY). Use with caution in patients with history of gastritis or peptic ulcer, in patients on anticoagulant therapy, and in addiction-prone individuals.
Ultra-rapid Metabolizers of Codeine
Some individuals may be ultra-rapid metabolizers due to a specific CYP2D6*2x2 genotype. These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labeled dosage regiments, individuals who are ultra-rapid metabolizers may experience overdose symptoms such as extreme sleepiness, confusion or shallow breathing.
The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1-10% in Caucasians, 3% in African Americans, and 16-28% in North Africans, Ethiopians and Arabs. Data is not available for other ethnic groups.
When physicians prescribe codeine-containing drugs, they should choose the lowest effective dose for the shortest period of time and should inform their patients about these risks and the signs of morphine overdose. ( See PRECAUTIONS-Nursing Mothers)
Information for Patients: Caution patients that this drug 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.
Caution patients with a predisposition for gastrointestinal bleeding that concomitant use of aspirin and alcohol may have an additive effect in this regard.
Caution patients that dosage of medications used for gout, arthritis, or diabetes may have to be adjusted when aspirin is administered or discontinued ( see Drug Interactions).
Caution patients that some people have a variation in a liver enzyme and change codeine into morphine more rapidly and completely than other people. These people are ultra-rapid metabolizers and are more likely to have a higher-than-normal levels of morphine in their blood after taking codeine which can result in overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. In most cases, it is unknown if someone is an ultra-rapid codeine metabolizer.
Nursing mothers taking codeine can also have higher morphine levels in their breast milk if they are ultra-rapid metabolizers. These higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies. Instruct nursing mothers to watch for signs of morphine toxicity in their infants including increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Instruct nursing mothers to talk to the baby’s doctor immediately if they notice these signs and, if they cannot reach the doctor right away, to take the baby to an emergency room or call 911 (or local emergency services).
Drug Interactions: Clinically important interactions may occur when certain drugs are administered concomitantly with aspirin or aspirin–containing drugs.
1.Oral Anticoagulants-By interfering with platelet function or decreasing plasma prothrombin concentration, aspirin enhances the potential for bleeding in patients on anticoagulants.
2. Methotrexate-aspirin enhances the toxic effects of this drug.
3. Probenicid and Sulfinpyrazone-large doses of aspirin reduce the uricosuric effect of both drugs. Renal excretion of salicylate may also be reduced.
4. Oral Antidiabetic Drugs-enhancement of hypoglycemia may occur.
5. Antacids-to the extent that they raise urinary pH, antacids may substantially decrease plasma salicylate concentrations; conversely, their withdrawal can result in a substantial increase.
6. Ammonium Chloride-this and other drugs that acidify a relatively alkaline urine can elevate plasma salicylate concentrations.
7. Ethyl Alcohol-enhanced aspirin –induced fecal blood loss has been reported.
8.Corticosteroids- salicylate plasma levels may be decreased when adrenal corticosteroids are given, and may be increased substantially when they are discontinued.
Carcinogenesis, Mutagenesis, Impairment of Fertility: No long-term studies have been done with ‘Soma’ Compound with Codeine.
Pregnancy-Teratogenic Effects: Pregnancy Category C. Adequate animal reproduction studies have not been conducted with ‘Soma’ Compound with Codeine. It is also not known whether ‘Soma’ Compound with Codeine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. ‘Soma’ Compound with Codeine should be given to a pregnant woman only if clearly needed.
Studies in rodents have shown salicylates to be teratogenic when given in early gestation, and embryocidal when given in later gestation in doses considerably greater than usual therapeutic doses in humans. Studies in women who took aspirin during pregnancy have not demonstrated an increased incidence of congenital abnormalities in the offspring.
Labor and Delivery: Ingestion of aspirin near term or prior to delivery may prolong delivery or lead to bleeding in mother, fetus, or neonate.
Nursing Mothers: Carisoprodol is excreted in human milk in concentrations two-to-four times that in maternal plasma. Aspirin is excreted in human milk in moderate amounts and can produce a bleeding tendency in nursing infants. Because of the potential for serious adverse reaction in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.
Codeine is secreted into human milk. In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and low dose-dependent. Despite the common use of codeine products to manage postpartum pain, reports of adverse events in infants are rare. However, some women are ultra-rapid metabolizers of codeine. These women achieve higher-than-expected serum levels of codeine’s active metabolite, morphine, leading to higher-than-expected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants. Therefore, maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants.
The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1-10% in Caucasians, 3% in African Americans, and 16-28% in North Africans, Ethiopians and Arabs. Data is not available for other ethnic groups.
The risk of infant exposure to codeine and morphine through breat milk should be weighed against the benefits of breastfeeding for both the mother and baby. Caution should be exercised when codeine is administered to a nursing woman. If a codeine containing product is selected, the lowest dose should be prescribed for the shortest period of time to achieve the desired clinical effect. Mothers using codeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of neonatal toxicity, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone, in their baby. Nursing mothers who are ultra-rapid metabolizers may also experience overdose symptoms such as extreme sleepiness, confusion or shallow breathing. Prescribers should closely monitor mother-infant pairs and notify treating pediatricians about the use of codeine during breastfeeding. ( See PRECAUTIONS-General- Ultra-rapid Metabolizers of Codeine)
Pediatric Use: Safety and effectiveness in pediatric patients below the age of twelve have not been established.
|
