IMITREX tablets contain sumatriptan succinate, a selective 5‑HT 1B/1D receptor agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure: The empirical formula is C 14 H 21 N 3 O 2 S•C 4 H 6 O 4 , representing a molecular weight of 413.5. Sumatriptan succinate is a white to off‑white powder that is readily soluble in water and in saline. Each IMITREX tablet for oral administration contains 35, 70, or 140 mg of sumatriptan succinate equivalent to 25, 50, or 100 mg of sumatriptan, respectively. Each tablet also contains the inactive ingredients croscarmellose sodium, dibasic calcium phosphate, magnesium stearate, microcrystalline cellulose, and sodium bicarbonate. Each 100-mg tablet also contains hypromellose, iron oxide, titanium dioxide, and triacetin. Imitrex Tablets chemical structure

IMITREX tablets are indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use: • Use only if a clear diagnosis of migraine headache has been established. If a patient has no response to the first migraine attack treated with IMITREX, reconsider the diagnosis of migraine before IMITREX is administered to treat any subsequent attacks. • IMITREX is not indicated for the prevention of migraine attacks. • Safety and effectiveness of IMITREX tablets have not been established for cluster headache. IMITREX is a serotonin (5-HT 1B/1D ) receptor agonist (triptan) indicated for acute treatment of migraine with or without aura in adults. Limitations of Use: • Use only if a clear diagnosis of migraine headache has been established. • Not indicated for the prophylactic therapy of migraine attacks. • Not indicated for the treatment of cluster headache.

25-mg Tablets: White, triangular-shaped, film-coated, and debossed with “I” on one side and “25” on the other. Each tablet contains 35 mg of sumatriptan succinate equivalent to 25 mg of sumatriptan. 50-mg Tablets: White, triangular-shaped, film-coated, and debossed with “IMITREX 50” on one side and a chevron shape (^) on the other. Each tablet contains 70 mg of sumatriptan succinate equivalent to 50 mg of sumatriptan. 100-mg Tablets: Pink, triangular-shaped, film-coated, and debossed with “IMITREX 100” on one side and a chevron shape (^) on the other. Each tablet contains 140 mg of sumatriptan succinate equivalent to 100 mg of sumatriptan. Tablets: 25 mg, 50 mg, and 100 mg

• Single dose of 25-mg, 50-mg, or 100-mg tablet. • A second dose should only be considered if some response to the first dose was observed. Separate doses by at least 2 hours. • Maximum dose in a 24-hour period: 200 mg. • Maximum single dose should not exceed 50 mg in patients with mild to moderate hepatic impairment

Dosing Information The recommended dose of IMITREX tablets is 25 mg, 50 mg, or 100 mg. Doses of 50 mg and 100 mg may provide a greater effect than the 25-mg dose, but doses of 100 mg may not provide a greater effect than the 50-mg dose. Higher doses may have a greater risk of adverse reactions . If the migraine has not resolved by 2 hours after taking IMITREX tablets, or returns after a transient improvement, a second dose may be administered at least 2 hours after the first dose. The maximum daily dose is 200 mg in a 24-hour period. Use after IMITREX Injection If the migraine returns following an initial treatment with IMITREX (sumatriptan) injection, additional single IMITREX tablets (up to 100 mg/day) may be given with an interval of at least 2 hours between tablet doses. The safety of treating an average of more than 4 headaches in a 30-day period has not been established

Dosing in Patients with Hepatic Impairment If treatment is deemed advisable in the presence of mild to moderate hepatic impairment, the maximum single dose should not exceed 50 mg .

• Myocardial ischemia/infarction and Prinzmetal’s angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors. • Arrhythmias: Discontinue IMITREX if occurs. • Chest/throat/neck/jaw pain, tightness, pressure, or heaviness: Generally not associated with myocardial ischemia; evaluate for coronary artery disease in patients at high risk. • Cerebral hemorrhage, subarachnoid hemorrhage, and stroke: Discontinue IMITREX if occurs. • Gastrointestinal ischemic reactions and peripheral vasospastic reactions: Discontinue IMITREX if occurs. • Medication overuse headache: Detoxification may be necessary. • Serotonin syndrome: Discontinue IMITREX if occurs. • Seizures: Use with caution in patients with epilepsy or a lowered seizure threshold. 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina The use of IMITREX tablets is contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of IMITREX tablets. Some of these reactions occurred in patients without known CAD. IMITREX tablets may cause coronary artery vasospasm (Prinzmetal’s angina), even in patients without a history of CAD. Perform a cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving IMITREX tablets. If there is evidence of CAD or coronary artery vasospasm, IMITREX tablets are contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of IMITREX tablets in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of IMITREX tablets. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of IMITREX tablets

Arrhythmias Life-threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following the administration of 5-HT 1 agonists. Discontinue IMITREX tablets if these disturbances occur. IMITREX tablets are contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders

Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure Sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw commonly occur after treatment with IMITREX tablets and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of IMITREX tablets is contraindicated in patients with CAD and those with Prinzmetal’s variant angina

Cerebrovascular Events Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT 1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT 1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue IMITREX tablets if a cerebrovascular event occurs. Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, exclude other potentially serious neurological conditions. IMITREX tablets are contraindicated in patients with a history of stroke or TIA

Other Vasospasm Reactions IMITREX tablets may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud’s syndrome. In patients who experience symptoms or signs suggestive of non-coronary vasospasm reaction following the use of any 5-HT 1 agonist, rule out a vasospastic reaction before receiving additional IMITREX tablets. Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5‑HT 1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT 1 agonists has not been clearly established

Medication Overuse Headache Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary

Serotonin Syndrome Serotonin syndrome may occur with IMITREX tablets, particularly during coadministration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors . Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue IMITREX tablets if serotonin syndrome is suspected

Increase in Blood Pressure Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients treated with 5-HT1 agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with IMITREX. IMITREX tablets are contraindicated in patients with uncontrolled hypertension

Anaphylactic/Anaphylactoid Reactions Anaphylactic/anaphylactoid reactions have occurred in patients receiving IMITREX. Such reactions can be life-threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens. IMITREX tablets are contraindicated in patients with a history of hypersensitivity reaction to IMITREX

Seizures Seizures have been reported following administration of IMITREX. Some have occurred in patients with either a history of seizures or concurrent conditions predisposing to seizures. There are also reports in patients where no such predisposing factors are apparent. IMITREX tablets should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.

7.1 Ergot-Containing Drugs Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and IMITREX tablets within 24 hours of each other is contraindicated

Monoamine Oxidase-A Inhibitors MAO‑A inhibitors increase systemic exposure by 7-fold. Therefore, the use of IMITREX tablets in patients receiving MAO‑A inhibitors is contraindicated

Other 5-HT 1 Agonists Because their vasospastic effects may be additive, coadministration of IMITREX tablets and other 5‑HT 1 agonists (e.g., triptans) within 24 hours of each other is contraindicated

Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome Cases of serotonin syndrome have been reported during coadministration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors .