Drug Interactions between amifampridine and fluoxetine / olanzapine

MONITOR: It is uncertain whether olanzapine causes clinically significant prolongation of the QT interval. In pooled studies of adults as well as pooled studies of adolescents, there were no significant differences between olanzapine and placebo in the proportion of patients experiencing potentially important changes in ECG parameters, including QT, QTcF (Fridericia-corrected), and PR intervals. In clinical trials, clinically meaningful QTc prolongations (QTcF >=500 msec at any time post-baseline in patients with baseline QTcF <500 msec) occurred in 0.1% to 1% of patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. Published studies have generally reported no significant effect of olanzapine on QTc interval, although both QTc prolongation and QTc shortening have also been reported. There have been a few isolated case reports of QT prolongation in patients receiving olanzapine. However, causality is difficult to establish due to confounding factors such as concomitant use of drugs that cause QT prolongation and underlying conditions that may predispose to QT prolongation (e.g., hypokalemia, congenital long QT syndrome, preexisting conduction abnormalities).

MANAGEMENT: Some authorities recommend caution when olanzapine is used with drugs that are known to cause QT prolongation. ECG monitoring may be advisable in some cases, such as in patients with a history of cardiac arrhythmias or congenital or family history of long QT syndrome. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

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 such as antidepressants, antimalarials, neuroleptics, phenothiazines, and quinolones. 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.

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.