Cardiac Events and Fatalities with 5-HT1 Agonists

Serious adverse cardiac events, including acute myocardial infarction, have been reported within a few hours following administration of AXERT® (almotriptan malate). Life-threatening disturbances of cardiac rhythm and death have been reported within a few hours following the administration of other triptans. Considering the extent of use of triptans in patients with migraine, the incidence of these events is extremely low.

AXERT® can cause coronary vasospasm; at least one of these events occurred in a patient with no cardiac history and with documented absence of coronary artery disease. Because of the close proximity of the events to use of AXERT®, a causal relationship cannot be excluded. Patients who experience signs or symptoms suggestive of angina following dosing should be evaluated for the presence of coronary artery disease (CAD) or a predisposition to Prinzmetal's variant angina before receiving additional doses of medication, and should be monitored electrocardiographically if dosing is resumed and similar symptoms recur.

Premarketing Experience with AXERT® in Adults

Among the 3865 subjects/patients who received AXERT® in premarketing clinical trials, one patient was hospitalized for observation after a scheduled electrocardiogram (ECG) was found to be abnormal (negative T-waves on the left leads) 48 hours after taking a single 6.25 mg dose of almotriptan. The patient, a 48-year-old female, had previously taken 3 other doses for earlier migraine attacks. Myocardial enzymes at the time of the abnormal ECG were normal. The patient was diagnosed as having had myocardial ischemia and that she had a family history of coronary disease. An ECG performed 2 days later was normal, as was a follow-up coronary angiography. The patient recovered without incident.

Postmarketing Experience with AXERT® in Adults

Serious cardiovascular events have been reported in association with the use of AXERT®. The uncontrolled nature of postmarketing surveillance, however, makes it impossible to definitively determine the proportion of the reported cases that were actually caused by almotriptan or to reliably assess causation in individual cases [see Adverse Reactions (6.3)].

Patients with Documented Coronary Artery Disease

Because of the potential of this class of compound (5-HT1 agonists) to cause coronary vasospasm, AXERT® should not be given to patients with documented ischemic or vasospastic coronary artery disease [see Contraindications (4.1)].

Patients with Risk Factors for CAD

It is strongly recommended that AXERT® not be given to patients in whom unrecognized CAD is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient's medical history, electrocardiographic or other investigations reveal findings indicative of, or consistent with, coronary artery vasospasm or myocardial ischemia, AXERT® should not be administered [see Contraindications (4.1)].

For patients with risk factors predictive of CAD, who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of AXERT® take place in the setting of a physician's office or similar medically staffed and equipped facility unless the patient has previously received AXERT®. Because cardiac ischemia can occur in the absence of clinical symptoms, consideration should be given to obtaining on the first occasion of use an ECG during the interval immediately following AXERT®, in these patients with risk factors. It is recommended that patients who are intermittent long-term users of AXERT® and who have or acquire risk factors predictive of CAD, as described above, undergo periodic interval cardiovascular evaluation as they continue to use AXERT®.

The systematic approach described above is intended to reduce the likelihood that patients with unrecognized cardiovascular disease will be inadvertently exposed to AXERT®. The ability of cardiac diagnostic procedures to detect all cardiovascular diseases or predisposition to coronary artery vasospasm is modest at best. Cardiovascular events associated with triptan treatment have occurred in patients with no cardiac history and with documented absence of coronary artery disease.