Drug Interactions between aspirin / carisoprodol / codeine and methylene blue

GENERALLY AVOID: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may result in profound sedation, respiratory depression, coma, and death. The risk of hypotension may also be increased with some CNS depressants (e.g., alcohol, benzodiazepines, phenothiazines).

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect, with cautious titration and dosage adjustments when needed. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Cough medications containing opioids (e.g., codeine, hydrocodone) should not be prescribed to patients using benzodiazepines or other CNS depressants including alcohol. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

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GENERALLY AVOID: Coadministration of narcotic analgesics with monoamine oxidase inhibitors (MAOIs) has been associated with rare reports of anxiety, confusion, hypotension, respiratory depression, cyanosis, and coma. The mechanism of interaction is unknown, but may involve potentiation of central nervous system (CNS) and respiratory depressant effects by MAOIs. There have also been reports of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea. Some opioids such as fentanyl, meperidine, methadone, tapentadol, and tramadol can inhibit serotonin reuptake. However, serotonin syndrome has also occurred with other opioids. Concomitant use of pentazocine with MAOIs may also cause CNS excitation and hypertension through their respective effects on catecholamines.

MANAGEMENT: Narcotic analgesics should generally not be used with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with opioids.

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