Serious cardiac events, including myocardial infarction and coronary artery vasospasm, have occurred following the use of AXERT® (almotriptan malate) Tablets.These events are extremely rare and most have been reported in patients with risk factors predictive of CAD. Events reported in association with drugs in this class have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation (see CONTRAINDICATIONS, WARNINGS and PRECAUTIONS).

Incidence in Controlled Clinical Trials

Adverse events were assessed in controlled clinical trials that included 1840 patients who received one or two doses of AXERT® and 386 patients who received placebo.

The most common adverse events during treatment with AXERT® were nausea, somnolence, headache, paresthesia, and dry mouth. In long-term open-label studies where patients were allowed to treat multiple attacks for up to one year, 5% (63 out of 1347 patients) withdrew due to adverse experiences.

Table 2 lists the adverse events that occurred in at least 1% of the patients treated with AXERT®, and at an incidence greater than in patients treated with placebo, regardless of drug relationship. These events reflect experience gained under closely monitored conditions of clinical trials in a highly selected patient population. In actual clinical practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ.

Table 2. Incidence of Adverse Events in Controlled Clinical Trials (Reported in at Least 1% of Patients Treated with AXERT®, and at an Incidence Greater than Placebo)

AXERT® is generally well tolerated. Most adverse events were mild in intensity and were transient, and did not lead to long-lasting effects.The incidence of adverse events in controlled clinical trials was not affected by gender, weight, age, presence of aura, or use of prophylactic medications or oral contraceptives. There were insufficient data to assess the effect of race on the incidence of adverse events.

Other Events

In this section, the frequencies of less commonly reported adverse events are presented. However, the role of AXERT® in their causation cannot be reliably determined. Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, etc., limit the value of the quantitative frequency estimates provided. Event frequencies are calculated as the number of patients who used AXERT® in controlled clinical trials and reported an event, divided by the total number of patients exposed to AXERT® in these studies.All reported events are included, except the ones already listed in the previous table, those unlikely to be drug-related, and those poorly characterized. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are those occurring in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; and rare adverse events are those occurring in fewer than 1/1000 patients.

Body: Frequent: headache. Infrequent: abdominal cramp or pain, asthenia, chills, back pain, chest pain, neck pain, fatigue, and rigid neck. Rare: fever and photosensitivity reaction.

Cardiovascular: Infrequent: vasodilation, palpitations, and tachycardia. Rare: hypertension and syncope.

Digestive: Infrequent: diarrhea, vomiting, and dyspepsia. Rare: colitis, gastritis, gastroenteritis, esophageal reflux, increased thirst, and increased salivation.

Metabolic: Infrequent: hyperglycemia and increased serum creatine phosphokinase. Rare: increased gamma glutamyl transpeptidase and hypercholesteremia.

Musculo-Skeletal: Infrequent: myalgia and muscular weakness. Rare: arthralgia, arthritis, and myopathy.

Nervous: Frequent: dizziness and somnolence. Infrequent: tremor, vertigo, anxiety, hypesthesia, restlessness, CNS stimulation, insomnia, and shakiness. Rare: change in dreams, impaired concentration, abnormal coordination, depressive symptoms, euphoria, hyperreflexia, hypertonia, nervousness, neuropathy, nightmares, and nystagmus.

Respiratory: Infrequent: pharyngitis, rhinitis, dyspnea, laryngismus, sinusitis, bronchitis, and epistaxis. Rare: hyperventilation, laryngitis, and sneezing.

Skin: Infrequent: diaphoresis, dermatitis, erythema, pruritus, and rash.

Special Senses: Infrequent: ear pain, conjunctivitis, eye irritation, hyperacusis, and taste alteration. Rare: diplopia, dry eyes, eye pain, otitis media, parosmia, scotoma, and tinnitus.

Urogenital: Infrequent: dysmenorrhea.

Post marketing Experience

The following section enumerates potentially important adverse events that have occurred in clinical practice and that have been reported spontaneously to various surveillance systems.The events enumerated represent reports arising from both domestic and non-domestic use of almotriptan and exclude those events already listed elsewhere as adverse reactions, or those events too general to be informative. Because the reports cite events reported spontaneously from worldwide post marketing experience, frequency of events and the role of almotriptan in their causation cannot be reliably determined.

Cardiovascular: Coronary artery vasospasm, intermediate coronary syndrome, and myocardial infarction.

Neurological: Seizures have been reported with 5-HT₁ agonists, including almotriptan.

Drug Abuse And Dependence

Although the abuse potential of AXERT® (almotriptan malate) Tablets has not been specifically assessed, no abuse of, tolerance to, withdrawal from, or drug-seeking behavior was observed in patients who received AXERT® in clinical trials or their extensions.The 5-HT_1B/1D agonists, as a class, have not been associated with drug abuse.

(see also CLINICAL PHARMACOLOGY, Drug Interactions)

Ergot-Containing Drugs

These drugs have been reported to cause prolonged vasospastic reactions.Because there is a theoretical basis that these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and AXERT® within 24 hours of each other should be avoided (see CONTRAINDICATIONS).

Monoamine Oxidase Inhibitors

Co administration of moclobemide resulted in a 27% decrease in almotriptan clearance and an increase in Cmax of approximately 6%.No dose adjustment is necessary.

Other 5-HT_1B/1D Agonists

Concomitant use of other 5-HT1B/1D agonists within 24 hours of treatment with AXERT® is contraindicated (see CONTRAINDICATIONS).

Propranolol

The pharmacokinetics of almotriptan were not affected by co administration of propranolol.

Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome Cases of life-threatening serotonin syndrome have been reported during combined use of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) and triptans (See WARNINGS - Serotonin Syndrome).

Verapamil

Co administration of almotriptan and verapamil resulted in a 24% increase in plasma concentrations of almotriptan.No dose adjustment is necessary.

Ketoconazole and Other Potent CYP3A4 Inhibitors

Co administration of almotriptan and the potent CYP3A4 inhibitor ketoconazole (400 mg q.d. for 3 days) resulted in an approximately 60% increase in the area under the plasma concentration-time curve and maximal plasma concentrations of almotriptan. Although the interaction between almotriptan and other potent CYP3A4 inhibitors (e.g., itraconazole, ritonavir, and erythromycin) has not been studied, increased exposures to almotriptan may be expected when almotriptan is used concomitantly with these medications.

Drug/Laboratory Test Interactions

AXERT® is not known to interfere with commonly employed clinical laboratory tests.

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