Drug Interactions between amifampridine and aspirin / caffeine / dihydrocodeine

MONITOR: The use of amifampridine is associated with a dose-related risk of seizures, and the risk may be further increased when coadministered with other drugs that can reduce the seizure threshold. Seizures have occurred in patients without a history of seizures taking amifampridine at recommended dosages and at various times after initiation of treatment. Reported incidence is approximately 2%. Many of the patients were taking medications or had comorbid medical conditions that may have lowered the seizure threshold.

MANAGEMENT: Caution is advised if amifampridine is coadministered with any substance that can reduce the seizure threshold, particularly in the elderly and in patients with other risk factors for seizures (e.g., head trauma; brain tumor; severe hepatic cirrhosis; metabolic disorders; CNS infections; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; diabetes treated with oral hypoglycemic agents or insulin). Consider discontinuation or dose reduction of amifampridine in patients who experience a seizure during treatment. Use of amifampridine is contraindicated in patients with a history of seizures.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.