Drug Interactions between aspirin / carisoprodol / codeine and ifosfamide / mesna

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: Centrally-acting agents such as antiemetics, sedatives, narcotics, or antihistamines may add to the neurotoxic effects of ifosfamide. Administration of ifosfamide can cause CNS toxicity, which necessitates careful monitoring of the patient. Neurologic manifestations include somnolence, confusion, hallucinations, blurred vision, psychotic behavior, extrapyramidal symptoms, urinary incontinence, seizures, and in some instances, coma. There have also been reports of peripheral neuropathy. Ifosfamide neurotoxicity may occur within a few hours to a few days after initial administration and typically resolves within 48 to 72 hours of ifosfamide discontinuation. However, symptoms may persist for longer periods of time, and recovery has occasionally been incomplete. Fatal outcomes have been reported. There have also been reports of recurrence of CNS toxicity after several uneventful treatment courses.

MANAGEMENT: Due to the potential for additive effects, centrally-acting agents should be used with caution in combination with ifosfamide. Patients should be advised to avoid driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them. If ifosfamide-induced encephalopathy occurs, both ifosfamide and non-essential concomitant CNS agents should be discontinued. Supportive therapy should be initiated and maintained until complete resolution of neurotoxicity.

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MONITOR: Centrally-acting agents such as antiemetics, sedatives, narcotics, or antihistamines may add to the neurotoxic effects of ifosfamide. Administration of ifosfamide can cause CNS toxicity, which necessitates careful monitoring of the patient. Neurologic manifestations include somnolence, confusion, hallucinations, blurred vision, psychotic behavior, extrapyramidal symptoms, urinary incontinence, seizures, and in some instances, coma. There have also been reports of peripheral neuropathy. Ifosfamide neurotoxicity may occur within a few hours to a few days after initial administration and typically resolves within 48 to 72 hours of ifosfamide discontinuation. However, symptoms may persist for longer periods of time, and recovery has occasionally been incomplete. Fatal outcomes have been reported. There have also been reports of recurrence of CNS toxicity after several uneventful treatment courses.

MANAGEMENT: Due to the potential for additive effects, centrally-acting agents should be used with caution in combination with ifosfamide. Patients should be advised to avoid driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them. If ifosfamide-induced encephalopathy occurs, both ifosfamide and non-essential concomitant CNS agents should be discontinued. Supportive therapy should be initiated and maintained until complete resolution of neurotoxicity.

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