Axert (Almotriptan malate) should only be used where a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with Axert (Almotriptan malate) , the diagnosis of migraine should be reconsidered before Axert (Almotriptan malate) is administered to treat any subsequent attacks.

In adolescents age 12 to 17 years, efficacy of Axert (Almotriptan malate) on migraine-associated symptoms (nausea, photophobia, and phonophobia) was not established. Axert (Almotriptan malate) is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine .

Safety and effectiveness of Axert (Almotriptan malate) have not been established for cluster headache which is present in an older, predominantly male population.

The recommended dose of Axert (Almotriptan malate) in adults and adolescents age 12 to 17 years is 6.25 mg to 12.5 mg, with the 12.5 mg dose tending to be a more effective dose in adults. As individuals may vary in their response to different doses of Axert (Almotriptan malate) , the choice of dose should be made on an individual basis.

If the headache is relieved after the initial Axert (Almotriptan malate) dose but returns, the dose may be repeated after 2 hours. The effectiveness of a second dose has not been established in placebo-controlled trials. The maximum daily dose should not exceed 25 mg. The safety of treating an average of more than four migraines in a 30-day period has not been established.

Axert (Almotriptan malate) Tablets are available as white, coated, circular, biconvex tablets in the following dosage strengths:

6.25 mg tablet with red code imprint "2080"

12.5 mg tablet with blue stylized imprint "A."

As with other triptans, significant elevations in systemic blood pressure have been reported on rare occasions with Axert (Almotriptan malate) use in patients with and without a history of hypertension; very rarely these increases in blood pressure have been associated with significant clinical events. Axert (Almotriptan malate) is contraindicated in patients with uncontrolled hypertension . In normotensive healthy subjects and patients with hypertension controlled by medication, small, but clinically insignificant, increases in mean systolic (0.21 and 4.87 mm Hg, respectively) and diastolic (1.35 and 0.26 mm Hg, respectively) blood pressure relative to placebo were seen over the first 4 hours after oral administration of 12.5 mg of almotriptan.

An 18% increase in mean pulmonary artery pressure was seen following dosing with another triptan in a study evaluating subjects undergoing cardiac catheterization.

Serious cardiac reactions, including myocardial infarction, have occurred following the use of Axert (Almotriptan malate) Tablets. These reactions are extremely rare and most have been reported in patients with risk factors predictive of CAD. Reactions reported in association with triptans have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation .

The following adverse reactions are discussed in more detail in other sections of the labeling:

Risk of Myocardial Ischemia and Infarction and Other Adverse Cardiac Events

Sensations of Pain, Tightness, Pressure in the Chest and/or Throat, Neck, and Jaw

Cerebrovascular Events and Fatalities

Other Vasospasm-Related Events, Including Peripheral Vascular Ischemia and Colonic Ischemia

Serotonin Syndrome

Increases in Blood Pressure

Adverse events were assessed in controlled clinical trials that included 1840 adult patients who received one or two doses of Axert (Almotriptan malate) and 386 adult patients who received placebo. The most common adverse reactions during treatment with Axert (Almotriptan malate) 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 1 year, 5% (63 out of 1347 patients) withdrew due to adverse experiences.

Adverse events were assessed in controlled clinical trials that included 362 adolescent patients who received Axert (Almotriptan malate) and 172 adolescent patients who received placebo. The most common adverse reactions during treatment with Axert (Almotriptan malate) were dizziness, somnolence, headache, paresthesia, nausea, and vomiting. In a long-term, open-label study where patients were allowed to treat multiple attacks for up to 1 year, 2% (10 out of 420 adolescent patients) withdrew due to adverse events.

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

For additional detailed information on drug interactions, see .

Co-administration of almotriptan and oral ketoconazole, a potent CYP3A4 inhibitor, resulted in an approximately 60% increase in exposure of almotriptan. Increased exposures to almotriptan may be expected when almotriptan is used concomitantly with other potent CYP3A4 inhibitors.

In patients concomitantly using potent CYP3A4 inhibitors, the recommended starting dose of Axert (Almotriptan malate) is 6.25 mg. The maximum daily dose should not exceed 12.5 mg within a 24-hour period. Concomitant use of Axert (Almotriptan malate) and potent CYP3A4 inhibitors should be avoided in patients with renal or hepatic impairment.

Safety and efficacy of Axert (Almotriptan malate) in pediatric patients under the age of 12 years have not been established. The pharmacokinetics, efficacy, and safety of Axert (Almotriptan malate) have been evaluated in adolescent patients, age 12 to 17 years .

In a clinical study, Axert (Almotriptan malate) 6.25 mg and 12.5 mg were found to be effective for the relief of migraine headache pain in adolescent patients age 12 to 17 years. Efficacy on migraine-associated symptoms (nausea, photophobia, and phonophobia) was not established. The most common adverse reactions (incidence of ≥1%) associated with Axert (Almotriptan malate) treatment were dizziness, somnolence, headache, paresthesia, nausea, and vomiting . The safety and tolerability profile of Axert (Almotriptan malate) treatment in adolescents is similar to the profile observed in adults.

Postmarketing experience with other triptans include a limited number of reports that describe pediatric patients who have experienced clinically serious adverse events that are similar in nature to those reported rarely in adults.

Patients and volunteers receiving single oral doses of 100 to 150 mg of almotriptan did not experience significant adverse events. Six additional normal volunteers received single oral doses of 200 mg without serious adverse events. During clinical trials with Axert (Almotriptan malate) (almotriptan malate), one patient ingested 62.5 mg in a 5-hour period and another patient ingested 100 mg in a 38-hour period. Neither patient experienced adverse reactions.

Based on the pharmacology of triptans, hypertension or other more serious cardiovascular symptoms could occur after overdosage.

Gastrointestinal decontamination (i.e., gastric lavage followed by activated charcoal) should be considered in patients suspected of an overdose with Axert (Almotriptan malate) . Clinical and electrocardiographic monitoring should be continued for at least 20 hours even if clinical symptoms are not observed.

It is unknown what effect hemodialysis or peritoneal dialysis has on plasma concentrations of almotriptan.

Axert (Almotriptan malate) Tablets contain almotriptan malate, a selective 5-hydroxytryptamine (5-HT) receptor agonist. Almotriptan malate is chemically designated as 1-[[[3-[2-(Dimethylamino)ethyl]-1H-indol-5-yl]methyl]sulfonyl]pyrrolidine (±)-hydroxybutanedioate (1:1) and its structural formula is:

Its empirical formula is CHNOS-CHO, representing a molecular weight of 469.56. Almotriptan is a white to slightly yellow crystalline powder that is soluble in water. Axert (Almotriptan malate) for oral administration contains almotriptan malate equivalent to 6.25 or 12.5 mg of almotriptan. Each compressed tablet contains the following inactive ingredients: mannitol, cellulose, povidone, sodium starch glycolate, sodium stearyl fumarate, titanium dioxide, hypromellose, polyethylene glycol, propylene glycol, iron oxide (6.25 mg only), FD&C Blue No. 2 (12.5 mg only), and carnauba wax.

The efficacy of Axert (Almotriptan malate) was established in three multi-center, randomized, double-blind, placebo-controlled European trials. Patients enrolled in these studies were primarily female (86%) and Caucasian (more than 98%), with a mean age of 41 years (range of 18 to 72). Patients were instructed to treat a moderate to severe migraine headache. Two hours after taking one dose of study medication, patients evaluated their headache pain. If the pain had not decreased in severity to mild or no pain, the patient was allowed to take an escape medication. If the pain had decreased to mild or no pain at 2 hours but subsequently increased in severity between 2 and 24 hours, it was considered a relapse and the patient was instructed to take a second dose of study medication. Associated symptoms of nausea, vomiting, photophobia, and phonophobia were also evaluated.

In these studies, the percentage of patients achieving a response (mild or no pain) 2 hours after treatment was significantly greater in patients who received either Axert (Almotriptan malate) 6.25 mg or 12.5 mg, compared with those who received placebo. A higher percentage of patients reported pain relief after treatment with the 12.5 mg dose than with the 6.25 mg dose. Doses greater than 12.5 mg did not lead to a significantly better response. These results are summarized in Table 3.

The estimated probability of achieving pain relief within 2 hours following initial treatment with Axert (Almotriptan malate) in adults is shown in Figure 1.

This Kaplan-Meier plot is based on data obtained in the three placebo-controlled clinical trials that provided evidence of efficacy (Studies 1, 2, and 3). Patients not achieving pain relief by 2 hours were censored at 2 hours.

For patients with migraine-associated photophobia, phonophobia, nausea, and vomiting at baseline, there was a decreased incidence of these symptoms following administration of Axert (Almotriptan malate) compared with placebo.

Two to 24 hours following the initial dose of study medication, patients were allowed to take an escape medication or a second dose of study medication for pain response. The estimated probability of patients taking escape medication or a second dose of study medication over the 24 hours following the initial dose of study medication is shown in Figure 2.

This Kaplan-Meier plot is based on data obtained in the three placebo-controlled trials that provided evidence of efficacy (Studies 1, 2, and 3). Patients not using additional treatment were censored at 24 hours. Remedication was not allowed within 2 hours after the initial dose of Axert (Almotriptan malate) .

The efficacy of Axert (Almotriptan malate) was unaffected by the presence of aura; by gender, weight, or age of the patient; or by concomitant use of common migraine prophylactic drugs (e.g., beta-blockers, calcium channel blockers, and tricyclic antidepressants); or oral contraceptives. There were insufficient data to assess the effect of race on efficacy.

The efficacy of Axert (Almotriptan malate) in adolescent patients age 12 to 17 years was evaluated in a double-blind, randomized, placebo-controlled study. Patients enrolled in that study had at least a 1-year history of migraine attacks with or without aura usually lasting 4 hours or more (when untreated). Patients enrolled in the study were primarily females (60%) and Caucasian (75%), while 15% of patients were black, and 10% were of other races. Patients were instructed to treat a moderate to severe migraine headache. Two hours after taking one dose of study medication, patients evaluated their headache pain. Associated symptoms of nausea, photophobia, and phonophobia were also evaluated.

In this study, the percentage of patients achieving a pain relief response (mild or no pain) 2 hours after treatment was statistically significantly greater in patients who received Axert (Almotriptan malate) 6.25 mg or 12.5 mg compared with those who received placebo. There was no additional benefit on pain relief provided by the 12.5 mg dose. The 2-hour pain relief results are summarized in Table 4.

The estimated probability of achieving pain relief within 2 hours following initial treatment with Axert (Almotriptan malate) in adolescents age 12 to 17 years is shown in Figure 3.

The prevalence of the migraine-associated symptoms (nausea, photophobia, and phonophobia) at 2 hours after taking the dose was not significantly different between patients who received Axert (Almotriptan malate) 6.25 mg or 12.5 mg and those who received placebo.

Axert (Almotriptan malate) Tablets are available as follows:

See