Drug Interactions between aspirin / carisoprodol / codeine and st. john's wort

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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MONITOR: Coadministration of codeine or dihydrocodeine with CYP450 3A4 inducers such as St. John's Wort may result in lower codeine or dihydrocodeine plasma concentrations, higher levels of the inactive metabolite norcodeine or dihydronorcodeine, and less metabolism via CYP450 2D6, resulting in lower morphine or dihydromorphine levels, respectively. This interaction may lead to reduced codeine or dihydrocodeine efficacy and potentially initiate the onset of withdrawal symptoms in patients who are physically dependent. In addition, patients may be at an increased risk of CNS and/or respiratory-depressant effects from increased levels of codeine or dihydrocodeine once concomitant therapy with the CYP450 3A4 inducer is ceased. Also, opioids may potentiate the serotonergic effects and CNS depressant effects of St. John's Wort and increase the risk of serotonin syndrome. The potential for serotonin syndrome has primarily been reported with the phenylpiperidine opioids (e.g., meperidine, fentanyl) and tramadol, which are known to possess some serotonergic activity, although a few cases have involved other opioids such as codeine.

MANAGEMENT: Caution and clinical monitoring are advised if codeine or dihydrocodeine are to be used in combination with St. John's Wort, particularly when it is added to or withdrawn from therapy. Dosage adjustments may be required. Some manufacturers of products containing codeine recommend against using codeine concomitantly with CYP450 3A4 inducers. Patients should be advised to monitor for symptoms of serotonin excess or serotonin syndrome. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately, and supportive care rendered as necessary. Patients should also be advised to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these medications affect them.

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MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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