Almotriptan Malate

Dosage Forms And Strengths

AXERTR® (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.”

Storage And Handling

AXERT® (almotriptan malate) Tablets are available as follows:

6.25 mg: White, coated, circular, biconvex tablets with red code imprint “2080.”

Unit Dose (aluminum blister pack)

6 tablets - NDC 50458-211-01

12.5 mg: White, coated, circular, biconvex tablets with blue stylized imprint “A.”

Unit Dose (aluminum blister pack)

12 tablets - NDC 50458-210-01

Store at °C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].

Manufactured by: Janssen-Ortho, LLC Gurabo, Puerto Rico 00778. Revised : May 2017.

Contraindications

• Known or suspected ischemic heart disease (e.g., angina pectoris, history of MI, documented silent ischemia).1

• Coronary artery vasospasm (e.g., Prinzmetal variant angina).1

• Uncontrolled hypertension.1

• Other serious underlying cardiovascular disease.1

• Cerebrovascular syndromes (e.g., stroke of any type, TIA).1

• Peripheral vascular disease or ischemic bowel disease.1

• Hemiplegic or basilar migraine.1

• Treatment within previous 24 hours with another 5-HT1 receptor agonist or an ergot alkaloid.1 (See Specific Drugs under Interactions.)

• Known hypersensitivity to almotriptan or any ingredient in the formulation.1

Warnings/Precautions

Careful Diagnosis of Migraine

Use only in patients in whom a clear diagnosis of migraine has been established.1

If first migraine attack treated with almotriptan fails to respond to the drug, reconsider diagnosis before administering almotriptan to treat subsequent attacks.1

Exclude other potentially serious neurologic disorders before administering almotriptan to patients not previously diagnosed with migraine or to those with atypical symptoms.1

Cardiac Effects

Possible myocardial ischemia and/or infarction and coronary vasospasm, even in patients without a history of CAD.1 5 22 Contraindicated in patients with ischemic or vasospastic heart disease.1

Possible fatal or life-threatening cardiac rhythm disturbances (e.g., ventricular tachycardia or fibrillation).1 22 Discontinue if such disturbances occur.22

Tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw occur frequently but usually are noncardiac in origin.1 22 Manufacturer states that patients with symptoms suggestive of angina after receiving almotriptan should be evaluated for the presence of CAD or predisposition to Prinzmetal variant angina before receiving additional doses; if administration is resumed and such signs or symptoms recur, ECG evaluation recommended.1

Patients at Risk for CAD

Perform cardiovascular evaluation prior to initiating therapy in patients with multiple cardiovascular risk factors (e.g., postmenopausal women; men >40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, family history of CAD) who have not previously received 5-HT1 receptor agonist therapy.1 22

If evaluation provides evidence of CAD or coronary vasospasm, do not administer the drug.1

If results of evaluation are satisfactory, consider administering the initial dose in a medically supervised setting followed immediately by an ECG.1 22

Periodic cardiovascular evaluation recommended in patients with risk factors for CAD if receiving intermittent long-term therapy.1

Cerebrovascular Events

Possible cerebral or subarachnoid hemorrhage and stroke, sometimes fatal.1 22 (See Careful Diagnosis of Migraine under Cautions.) Discontinue therapy if a cerebrovascular event occurs.1 22

Risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA) may be increased in patients with migraine.1

Other Vasospastic Effects

Possible noncoronary vasospastic reactions (e.g., peripheral vascular ischemia, GI ischemia and infarction with abdominal pain and bloody diarrhea, splenic infarction, Raynaud’s syndrome);1 22 transient or permanent blindness and partial vision loss reported very rarely in patients receiving 5-HT1 receptor agonists.1

If signs or symptoms suggestive of vasospasm occur following administration, evaluate patient to rule out vasospastic reaction before administering additional doses.1

Hypertensive Effects

Substantial increases in BP, including hypertensive crisis with acute impairment of organ systems, reported rarely with 5-HT1 receptor agonists in patients with or without history of hypertension.1 5 22

Increases in mean pulmonary arterial pressure observed following administration of a 5-HT1 receptor agonist to patients undergoing cardiac catheterization.1

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported in patients receiving 5-HT1 receptor agonists, particularly in those receiving SSRIs or SNRIs concomitantly.1 11 (See Specific Drugs under Interactions.) Also may occur in patients receiving MAO inhibitors or tricyclic antidepressants concomitantly.22

Symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).1 11

If manifestations of serotonin syndrome occur, discontinue almotriptan and any concurrently administered serotonergic agents and initiate supportive and symptomatic treatment.33

Medication Overuse Headache

Overuse of drugs indicated for management of acute migraine attacks (e.g., use of 5-HT1 receptor agonists, ergotamine, opiates, or certain analgesic combinations on a regular basis for ≥10 days per month) may result in migraine-like daily headaches or a marked increase in frequency of migraine attacks.22 31 32

Detoxification, including withdrawal of overused drugs; treatment of withdrawal symptoms (e.g., transient worsening of headaches); and consideration of prophylactic migraine therapy may be necessary.22 31 32

Sensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis) reported.1

Potential for cross-sensitivity between almotriptan, which contains a sulfonyl group, and sulfonamides not systematically evaluated.1 Use almotriptan with caution in patients with known hypersensitivity to sulfonamides.1

Ocular Effects

Possible accumulation of almotriptan in melanin-rich tissues (e.g., eye) over time, resulting in potential toxicity in these tissues with extended use.1

Specific Populations

Category C.1

Distributed into milk in rats; not known whether distributed into milk in humans.1 Caution advised if almotriptan is used.1

Safety and efficacy not established in children <12 years of age.1

Safety and tolerability in adolescents 12–17 years of age similar to that in adults.1 Serious adverse events reported in limited number of pediatric patients receiving 5-HT1 receptor agonists.1

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.1 (See Geriatric Patients under Dosage and Administration.)

Use with caution; dosage adjustment recommended.1 (See Hepatic Impairment under Dosage and Administration and see Drugs Affecting Hepatic Microsomal Enzymes under Interactions.)

Use with caution; dosage adjustment recommended.1 (See Renal Impairment under Dosage and Administration and see Drugs Affecting Hepatic Microsomal Enzymes under Interactions.)

Common Adverse Effects

Adults: Nausea,1 paresthesia,1 dry mouth.1

Adolescents: Dizziness,1 17 somnolence,1 17 headache,1 paresthesia,1 17 nausea,1 17 vomiting.1

Absorption

Bioavailability

Well absorbed from GI tract.19 Absolute bioavailability is approximately 70%.1 19 20

Peak plasma concentrations attained within 1–3 hours after oral administration.1 19 20

Rate and extent of absorption in adolescents 12–17 years of age is similar to that in adults.1

Food

Food does not affect pharmacokinetics.1 10

Distribution

Extent

Appears to be widely distributed throughout the body.20

Distributed into milk in rats; not known whether distributed into milk in humans.1

Plasma Protein Binding

Approximately 35%.1

Elimination

Metabolism

Metabolized to inactive metabolites principally via MAO-mediated oxidative deamination, CYP3A4, and CYP2D6, with minor contribution of flavin monooxygenase.1 19

Elimination Route

Excreted in urine (75%) and feces (13%), with 40% of dose recovered in urine as unchanged drug.1

Half-life

3–4 hours.1 19 20

Special Populations

Pharmacokinetics not evaluated in patients with hepatic impairment.1 Based on mechanism of almotriptan clearance, maximum decrease in clearance of 60% would be expected.1

In patients with moderate or severe renal impairment, clearance is reduced by approximately 40 or 65%, respectively; peak plasma concentrations increased by approximately 80% in these patients.1

In healthy geriatric patients, clearance is decreased, resulting in increases in half-life and AUC compared with younger adults; not considered clinically important.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Since almotriptan is used as needed, it does not have a daily dosing schedule. Call your doctor promptly if your symptoms do not improve after using almotriptan.

After taking a almotriptan tablet, you must wait two (2) hours before taking a second tablet. Do not take more than two (2) almotriptan tablets in 24 hours.

Do not take almotriptan within 24 hours before or after using another migraine headache medicine, including:

• eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, Treximet), zolmitriptan (Zomig); or
• ergot medicine such as ergotamine (Ergomar, Cafergot, Migergot), dihydroergotamine (D.H.E. 45, Migranal), or methylergonovine (Methergine).

Almotriptan may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Your pharmacist can provide more information about almotriptan.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Serious cardiac reactions, including myocardial infarction, have occurred following the use of AXERTR® (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 myocardialischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

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 [see WARNINGS AND PRECAUTIONS]
• Sensations of Pain, Tightness, Pressure in the Chest and/or Throat, Neck, and Jaw [see WARNINGS AND PRECAUTIONS]
• Cerebrovascular Events and Fatalities [see WARNINGS AND PRECAUTIONS]
• Other Vasospasm-Related Events, Including Peripheral Vascular Ischemia and Colonic Ischemia [see WARNINGS AND PRECAUTIONS]
• Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]
• Increases in Blood Pressure [see WARNINGS AND PRECAUTIONS]

Adverse events were assessed in controlled clinical trials that included 1840 adult patients who received one or two doses of AXERTR® and 386 adult patients who received placebo. The most common adverse reactions during treatment with AXERTR® 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 AXERTR® and 172 adolescent patients who received placebo. The most common adverse reactions during treatment with AXERTR® 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.

Commonly-Observed Adverse Reactions In Double-Blind, Placebo- Controlled AXERTR® Clinical Trials

Table 1 lists the adverse events that occurred in at least 1% of the adult patients treated with AXERTR®, and at an incidence greater than in patients treated with placebo, regardless of drug relationship.

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

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.

Table 2 lists the adverse reactions reported by 1% or more of AXERTR®-treated adolescents age 12 to 17 years in 1 placebo-controlled, double-blind clinical trial.

Table 2. Adverse Reactions Reported by ≥1% of Adolescent Patients Treated with AXERTR® in 1 Placebo-Controlled, Double-Blind Clinical Trial

Other Adverse Reactions Observed In AXERTR® Clinical Trials

In the paragraphs that follow, the frequencies of less commonly reported adverse clinical reactions are presented. The reports include adverse reactions in 5 adult controlled studies and 1 adolescent controlled study. Variability associated with adverse reaction reporting, the terminology used to describe adverse reactions, etc., limit the value of the quantitative frequency estimates provided. Reaction frequencies are calculated as the number of patients who used AXERTR® and reported a reaction divided by the total number of patients exposed to AXERTR® (n=3047, all doses). All reported reactions are included except those already listed in the previous table, those too general to be informative, and those not reasonably associated with the use of the drug. Reactions are further classified within system organ class and enumerated in order of decreasing frequency using the following definitions: frequent adverse reactions are those occurring in 1/100 or more patients, infrequent adverse reactions are those occurring in fewer than 1/100 to 1/1000 patients, and rare adverse reactions 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, Dyspepsia, Gastroenteritis, and Increased thirst. Rare: Colitis, Gastritis, Esophageal reflux, and Increased salivation.

Metabolic: Infrequent: Hyperglycemia and Increased serum creatine phosphokinase. Rare: Increased gamma glutamyl transpeptidase and Hypercholesteremia.

Musculo-Skeletal: Infrequent: Myalgia. Rare: Arthralgia, Arthritis, Myopathy, and Muscle weakness.

Nervous: Frequent: Dizziness and Somnolence. Infrequent: Tremor, Vertigo, Anxiety, Hypoesthesia, Restlessness, CNS stimulation, and Shakiness. Rare: Change in dreams, Impaired concentration, Abnormal coordination, Depressive symptoms, Euphoria, Hyperreflexia, Hypertonia, Nervousness, Neuropathy, Nightmares, Nystagmus, and Insomnia.

Respiratory: Infrequent: Pharyngitis, Rhinitis, Dyspnea, Laryngismus, Sinusitis, and Bronchitis. Rare: Hyperventilation, Laryngitis, Sneezing, and Epistaxis.

Skin: Infrequent: Diaphoresis, Pruritus, and Rash. Rare: Dermatitis and Erythema.

Special Senses: Infrequent: Ear pain and Tinnitus. Rare: Diplopia, Dry eyes, Eye pain, Otitis media, Parosmia, Scotoma, Conjunctivitis, Eye irritation, Hyperacusis, and Taste alteration.

Urogenital: Infrequent: Dysmenorrhea.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of AXERTR® . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Hypersensitivity reactions (including angioedema, anaphylactic reactions and anaphylactic shock)

Psychiatric Disorders: Confusional state, Restlessness

Nervous System Disorders: Hemiplegia, Hypoesthesia, Seizures

Eye Disorders: Blepharospasm, Visual impairment, Vision blurred

Ear and Labyrinth Disorders: Vertigo

Cardiac Disorders: Acute myocardial infarction, Coronary artery vasospasm, Angina pectoris, Tachycardia

Gastrointestinal Disorders: Abdominal discomfort, Abdominal pain, Abdominal pain upper, Colitis, Hypoesthesia oral, Swollen tongue

Skin and Subcutaneous Tissue Disorders: Cold sweat, Erythema, Hyperhidrosis

Musculoskeletal, Connective Tissue, and Bone Disorders: Arthralgia, Myalgia, Pain in extremity

Reproductive System and Breast Disorders: Breast pain

General Disorders: Malaise, Peripheral coldness.

Read the entire FDA prescribing information for Axert (Almotriptan Malate)