Rizatriptan: uses, appearance and warnings

MAXALT ® and MAXALT-MLT ® are indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 6 to 17 years old. Limitations of Use MAXALT 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 MAXALT, the diagnosis of migraine should be reconsidered before MAXALT is administered to treat any subsequent attacks. MAXALT is not indicated for use in the management of hemiplegic or basilar migraine [see Contraindications (4) ] . MAXALT is not indicated for the prevention of migraine attacks. Safety and effectiveness of MAXALT have not been established for cluster headache. MAXALT is a serotonin (5-HT) 1B/1D receptor agonist (triptan) indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 6 to 17 years of age ( 1 ) Limitations of Use : Use only after clear diagnosis of migraine has been established ( 1 ) Not indicated for the prophylactic therapy of migraine ( 1 ) Not indicated for the treatment of cluster headache ( 1 )

MAXALT Tablets: 10 mg ( 3 ) MAXALT-MLT Orally Disintegrating Tablets: 10 mg ( 3 ) MAXALT Tablets 10 mg tablets are pale pink, capsule-shaped, compressed tablets coded MAXALT on one side and MRK 267 on the other. MAXALT-MLT Orally Disintegrating Tablets 10 mg orally disintegrating tablets are white to off-white, round lyophilized tablets debossed with a modified square on one side.

MAXALT Tablets, 10 mg, are pale pink, capsule-shaped, compressed tablets coded MAXALT on one side and MRK 267 on the other: NDC 78206-142-01, carton of 18 tablets. MAXALT-MLT Orally Disintegrating Tablets, 10 mg, are white to off-white, round lyophilized orally disintegrating tablets debossed with a modified square on one side, and measuring 12.0-13.8 mm (side-to-side) with a peppermint flavor. Each orally disintegrating tablet is individually packaged in a blister inside an aluminum pouch (sachet). They are supplied as follows: NDC 78206-143-01, 6 × unit of use carrying case of 3 orally disintegrating tablets (18 tablets total). Storage Store MAXALT Tablets at room temperature, 15°C-30°C (59°F-86°F). Store MAXALT-MLT Orally Disintegrating Tablets at room temperature, 15°C-30°C (59°F-86°F).

MAXALT is contraindicated in patients with: Ischemic coronary artery disease (angina pectoris, history of myocardial infarction, or documented silent ischemia), or other significant underlying cardiovascular disease [see Warnings and Precautions (5.1) ] . Coronary artery vasospasm including Prinzmetal's angina [see Warnings and Precautions (5.1) ] . History of stroke or transient ischemic attack (TIA) [see Warnings and Precautions (5.4) ] . Peripheral vascular disease (PVD) [see Warnings and Precautions (5.5) ] . Ischemic bowel disease [see Warnings and Precautions (5.5) ] . Uncontrolled hypertension [see Warnings and Precautions (5.8) ] . Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, ergotamine-containing medication, or ergot-type medication (such as dihydroergotamine or methysergide) [see Drug Interactions (7.2 and 7.3) ] . Hemiplegic or basilar migraine [see Indications and Usage (1) ] . Concurrent administration or recent discontinuation (i.e., within 2 weeks) of a MAO-A inhibitor [see Drug Interactions (7.5) and Clinical Pharmacology (12.3) ] . Hypersensitivity to rizatriptan or any of the excipients (angioedema and anaphylaxis seen) [see Adverse Reactions (6.2) ] . History of ischemic heart disease or coronary artery vasospasm ( 4 ) History of stroke or transient ischemic attack ( 4 ) Peripheral vascular disease ( 4 ) Ischemic bowel disease ( 4 ) Uncontrolled hypertension ( 4 ) Recent (within 24 hours) use of another 5-HT 1 agonist (e.g., another triptan), or of an ergotamine-containing medication ( 4 ) Hemiplegic or basilar migraine ( 4 ) MAO-A inhibitor used in the past 2 weeks ( 4 ) Hypersensitivity to rizatriptan or any of the excipients ( 4 )

Myocardial ischemia, myocardial infarction, and Prinzmetal's angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors ( 5.1 ) Arrhythmias: Discontinue dosing if occurs ( 5.2 ) Chest/throat/neck/jaw pain, tightness, pressure, or heaviness; Generally not associated with myocardial ischemia; Evaluate patients at high risk ( 5.3 ) Cerebral hemorrhage, subarachnoid hemorrhage, and stroke: Discontinue dosing if occurs ( 5.4 ) Gastrointestinal ischemic events, peripheral vasospastic reactions: Discontinue dosing if occurs ( 5.5 ) Medication overuse headache: Detoxification may be necessary ( 5.6 ) Serotonin syndrome: Discontinue dosing if occurs ( 5.7 ) 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina MAXALT should not be given to patients with ischemic or vasospastic coronary artery disease. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of MAXALT. Some of these reactions occurred in patients without known coronary artery disease (CAD). 5-HT 1 agonists, including MAXALT may cause coronary artery vasospasm (Prinzmetal's Angina), even in patients without a history of CAD. Triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) should have a cardiovascular evaluation prior to receiving MAXALT. If there is evidence of CAD or coronary artery vasospasm, MAXALT should not be administered [see Contraindications (4) ]. For patients who have a negative cardiovascular evaluation, consideration should be given to administration of the first MAXALT dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following MAXALT administration. Periodic cardiovascular evaluation should be considered in intermittent long-term users of MAXALT who have cardiovascular risk factors. 5.2 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 MAXALT if these disturbances occur. 5.3 Chest, Throat, Neck and/or Jaw Pain/Tightness/Pressure As with other 5-HT 1 agonists, sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck and jaw commonly occur after treatment with MAXALT and are usually non-cardiac in origin. However, if a cardiac origin is suspected, patients should be evaluated. Patients shown to have CAD and those with Prinzmetal's variant angina should not receive 5-HT 1 agonists. 5.4 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, transient ischemic attack). Discontinue MAXALT if a cerebrovascular event occurs. As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, care should be taken to exclude other potentially serious neurological conditions. MAXALT should not be administered to patients with a history of stroke or transient ischemic attack [see Contraindications (4) ] . 5.5 Other Vasospasm Reactions 5-HT 1 agonists, including MAXALT, 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, the suspected vasospasm reaction should be ruled out before receiving additional MAXALT doses. 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 have not been clearly established. 5.6 Medication Overuse Headache Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or a combination of 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. 5.7 Serotonin Syndrome Serotonin syndrome may occur with triptans, including MAXALT particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions (7.5) ] . 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 can occur within minutes to hours of receiving a new or a greater dose of a serotonergic medication. MAXALT treatment should be discontinued if serotonin syndrome is suspected [see Drug Interactions (7.4) and Patient Counseling Information (17) ] . …

The following adverse reactions are discussed in more detail in other sections of the labeling: Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina [see Warnings and Precautions (5.1) ] . Arrhythmias [see Warnings and Precautions (5.2) ]. Chest, Throat, Neck and/or Jaw Pain/Tightness/Pressure [see Warnings and Precautions (5.3) ] . Cerebrovascular Events [see Warnings and Precautions (5.4) ] . Other Vasospasm Reactions [see Warnings and Precautions (5.5) ] . Medication Overuse Headache [see Warnings and Precautions (5.6) ] . Serotonin Syndrome [see Warnings and Precautions (5.7) ] . Increase in Blood Pressure [see Warnings and Precautions (5.8) ] . …

7.1 Propranolol The dose of MAXALT should be adjusted in propranolol-treated patients, as propranolol has been shown to increase the plasma AUC of rizatriptan by 70% [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ] . 7.2 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 MAXALT within 24 hours is contraindicated [see Contraindications (4) ] . 7.3 Other 5-HT 1 Agonists Because their vasospastic effects may be additive, co-administration of MAXALT and other 5-HT 1 agonists within 24 hours of each other is contraindicated [see Contraindications (4) ] . …