warnings
WARNINGS Carisoprodol: Sedation Carisoprodol has sedative properties 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. Since the sedative effects of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricylic 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 Carisoprodol, the active ingredient in SOMA, has been subject to abuse, dependence, withdrawal, misuse and criminal diversion (see DRUG ABUSE AND DEPENDENCE ). Abuse of SOMA poses a risk of overdose which may lead to death, CNS and respiratory depression, hypotension, seizures and other disorders (see OVERDOSAGE ). Post-marketing cases of carisoprodol, abuse and dependence have been reported in patients with prolonged use and a history of drug abuse. Although most of these patients took other drugs of abuse, some patients solely abused carisoprodol. Withdrawal symptoms have been reported following abrupt cessation after prolonged use. Reported withdrawal symptoms include insomnia, vomiting, abdominal cramps, headache, tremors, muscle twitching, ataxia, hallucinations, and psychosis. One of carisoprodol’s metabolites, meprobamate, (a controlled substance), may also cause dependence (see CLINICAL PHARMACOLOGY ). To reduce the risk of SOMA abuse, assess the risk of abuse prior to prescribing. After prescribing, limit the length of treatment to three weeks for the relief of acute muscolosketal discomfort, keep careful prescription records, monitor for signs of abuse and overdose, and educate patients and their families about abuse and on proper storage and disposal. Aspirin: Serious Gastrointestinal Adverse Reactions Aspirin can cause serious gastrointestinal (GI) adverse reactions including bleeding, perforation, and obstruction of the stomach, small intestine, or large intestine, which can be fatal. Aspirin-associated serious GI adverse reactions can occur anywhere along the GI tract, at any time, with or without warning symptoms. Patients at higher risk of aspirin-associated serious upper GI adverse reactions include patients with a history of aspirin associated GI bleeding from ulcers (complicated ulcers), a history of aspirin-associated ulcers (uncomplicated ulcers), geriatric patients, patients with poor baseline health status, patients taking higher doses of aspirin, and patients taking concomitant anticoagulants, NSAIDs, and/or large amounts of alcohol. To minimize the risk for aspirin-associated GI serious adverse reactions, the lowest effective aspirin dose should be used for the shortest possible duration. Anaphylaxis and Anaphylactoid Reactions Aspirin may cause an increased risk of serious anaphylaxis and anaphylactoid reactions, which can occur in patients without known prior exposure to aspirin (see CONTRAINDICATIONS ). Patients with a serious anaphylaxis and anaphylactoid reaction should receive emergency care. Codeine Phosphate: Death Related to Ultra-Rapid Metabolism of Codeine to Morphine Respiratory depression and death have occurred in children who receive codeine in the post-operative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6 [CYP2D6] or high morphine concentrations). Deaths have also occurred in nursing infants who were exposed to high levels of morphine in breast milk because their mothers were ultra-rapid metabolizers of codeine (see PRECAUTIONS – Nursing Mothers ). Some individuals may be ultra-rapid metabolizers because of a specific CYP2D6 genotype (gene duplications denoted as *1/*1xN or *1/*2xN). 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 to 10% in Caucasians, 3% in African Americans, and 16 to 28% in North Africans, Ethiopians, and Arabs. Data are not available for other ethnic groups. 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 regimens, individuals who are ultra-rapid metabolizers may have life-threatening or fatal respiratory depression or experience signs of overdose (such as extreme sleepiness, confusion, or shallow breathing) (see OVERDOSAGE ). Children with obstructive sleep apnea who are treated with codeine for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to the respiratory depressant effects of codeine that has been rapidly metabolized to morphine. Codeine is contraindicated for post-operative pain management in all pediatric patients undergoing tonsillectomy and/or adenoidectomy (see CONTRAINDICATIONS ). When prescribing codeine-containing drug, healthcare providers should choose the lowest effective dose for the shortest period of time and inform patients and caregivers about these risks and the signs of morphine overdose (see OVERDOSAGE ). Respiratory Depression Respiratory depression is a serious adverse reaction of opioid agonists, including codeine phosphate. Opioid-associated respiratory depression is more likely to occur in geriatric patients, debilitated patients, in non-tolerant patients who are given large initial doses of opioids, and in patients who are receiving concomitant respiratory depressants (e.g. other opioids, benzodiazepines, tricyclic antidepressants, phenothiazines, skeletal muscle relaxants, alcohol). In addition, patients with chronic obstructive pulmonary disease (COPD), restrictive lung disease, decreased respiratory drive, and/or respiratory depression are at a greater risk of opioid-associated respiratory depression. Opioid-associated respiratory depression may be increased in patients with increased intracranial pressure (e.g., patients with head trauma, intracranial lesions). Abuse and Diversion Codeine phosphate is a Schedule III controlled substance. Administration of opioids including codeine phosphate has been associated with abuse. Healthcare professionals should contact their State Professional Licensing Board or State Substances Authority for information on how to prevent or detect abuse or diversion of codeine phosphate. Dependence and Tolerance Use of opioids, including codeine phosphate, can result in psychological and/or physical dependence. Withdrawal symptoms associated with abrupt opioid discontinuation include restlessness, irritability, anxiety, lacrimation, rhinorrhea, sweating, chills, mydriasis, insomnia, diarrhea, tachypnea, tachycardia, and/or hypertension. The use of opioids, including codeine phosphate, use can result in tolerance – the need for increasing doses to maintain a desired effect in the absence of other factors (e.g., disease progression). Gastrointestinal Obstruction Opiods, including codeine phosphate, may cause gastrointestinal obstruction. Sedation Opioids, including codeine phosphate, may impair the mental and physical abilities required for the performance of potentially hazardous tasks such as driving a motor vehicle or operating machinery. Since the sedative effects of codeine phosphate and other CNS depressants (e.g., other opioids, benzodiazepines, tricyclic antidepressants, skeletal muscle relaxants, alcohol) may be additive, appropriate caution should be exercised with patients who take more than one of these CNS depressants simultaneously. Hypotension The use of opioids, including codeine phosphate, may cause hypotension. Opioid-associated hypotension is more likely in patients with dehydration or with the concomitant use of drugs associated with hypotension.