Rizatriptan Orally Disintegrating Tablets

• If you have an allergy to rizatriptan or any other part of this medicine (rizatriptan orally disintegrating tablets).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: High blood pressure or some types of migraine headaches like hemiplegic or basilar migraine.
• If you have ever had any of these health problems: Chest pain or pressure; diseased arteries going to the legs or arms; heart attack; heart disease; poor blood flow in the heart, brain, bowel, or kidney; stroke; or a heartbeat that is not normal like Wolff-Parkinson-White syndrome.
• If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking this medicine within 14 days of those drugs can cause very bad high blood pressure.
• If you have taken almotriptan, eletriptan, frovatriptan, naratriptan, sumatriptan, or zolmitriptan in the last 24 hours.
• If you have taken ergotamine, methysergide, dihydroergotamine, or any drug like them in the last 24 hours.

This is not a list of all drugs or health problems that interact with this medicine (rizatriptan orally disintegrating tablets).

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Feeling sleepy.
• Feeling of heaviness or pressure.
• A burning, numbness, or tingling feeling that is not normal.
• Upset stomach or throwing up.
• Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Rizatriptan Benzoate Orally Disintegrating Tablets, USP 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

• Rizatriptan benzoate orally disintegrating tablets, USP 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 rizatriptan benzoate orally disintegrating tablets, USP, the diagnosis of migraine should be reconsidered before rizatriptan benzoate orally disintegrating tablets, USP are administered to treat any subsequent attacks.
• Rizatriptan benzoate orally disintegrating tablets, USP are not indicated for use in the management of hemiplegic or basilar migraine [see Contraindications (4)].
• Rizatriptan benzoate orally disintegrating tablets, USP are not indicated for the prevention of migraine attacks.
• Safety and effectiveness of rizatriptan benzoate orally disintegrating tablets, USP have not been established for cluster headache.

Rizatriptan Benzoate Orally Disintegrating Tablets, USP

• 5 mg orally disintegrating tablets, USP are white to off white, round tablets debossed with ‘5’ on one side.
• 10 mg orally disintegrating tablets, USP are white to off white, round tablets debossed with ‘10’ on one side.

Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina

Rizatriptan Benzoate Orally Disintegrating Tablets, USP 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 rizatriptan benzoate. Some of these reactions occurred in patients without known coronary artery disease (CAD). 5-HT1 agonists including rizatriptan benzoate 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 rizatriptan benzoate. If there is evidence of CAD or coronary artery vasospasm, rizatriptan benzoate should not be administered [see Contraindications (4)]. For patients who have a negative cardiovascular evaluation, consideration should be given to administration of the first rizatriptan benzoate dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following rizatriptan benzoate administration. Periodic cardiovascular evaluation should be considered in intermittent long-term users of rizatriptan benzoate who have cardiovascular risk factors.

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-HT1 agonists. Discontinue rizatriptan benzoate if these disturbances occur.

Chest, Throat, Neck and/or Jaw Pain/Tightness/Pressure

As with other 5-HT1 agonists, sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck and jaw commonly occur after treatment with rizatriptan benzoate 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-HT1 agonists.

Cerebrovascular Events

Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 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 rizatriptan benzoate 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. Rizatriptan benzoate should not be administered to patients with a history of stroke or transient ischemic attack [see Contraindications (4)].

Other Vasospasm Reactions

5-HT1 agonists, including rizatriptan benzoate, 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-HT1 agonist, the suspected vasospasm reaction should be ruled out before receiving additional rizatriptan benzoate doses.
Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 agonists have not been clearly established.

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.

Serotonin Syndrome

Serotonin syndrome may occur with triptans, including rizatriptan benzoate 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. Rizatriptan benzoate treatment should be discontinued if serotonin syndrome is suspected [see Drug Interactions (7.4)and Patient Counseling Information (17)].

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 with and without a history of hypertension receiving 5-HT1 agonists, including rizatriptan benzoate. In healthy young adult male and female patients who received maximal doses of rizatriptan benzoate (10 mg every 2 hours for three doses), slight increases in blood pressure (approximately 2-3 mmHg) were observed. Rizatriptan benzoate is contraindicated in patients with uncontrolled hypertension [see Contraindications (4)].

Propranolol

The dose of rizatriptan benzoate 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)].

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 rizatriptan benzoate within 24 hours is contraindicated [see Contraindications (4)].

Other 5-HT1 Agonists

Because their vasospastic effects may be additive, coadministration of rizatriptan benzoate and other 5-HT1 agonists within 24 hours of each other is contraindicated [see Contraindications (4)].

SSRIs/SNRIs and Serotonin Syndrome

Cases of serotonin syndrome have been reported during coadministration of triptans and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) [see Warnings and Precautions (5.7)].

Monoamine Oxidase Inhibitors

Rizatriptan benzoate is contraindicated in patients taking MAO-A inhibitors and non-selective MAO inhibitors. A specific MAO-A inhibitor increased the systemic exposure of rizatriptan and its metabolite [see Contraindications (4)and Clinical Pharmacology (12.3)].

Rizatriptan Benzoate Orally Disintegrating Tablets, USP, 5 mg, are white to off-white, uncoated, circular tablet plain on one side and ‘5’ debossed on other side, and measuring ‘5.90 – 6.10 mm’ (side-to-side) with a menthol flavor. 3 orally disintegrating tablets are packaged in a blister. They are supplied as follows:

NDC 43817-133-03, 1 blister containing 3 unit-dose (1 x 3) orally disintegrating tablets.

NDC 43817-133-04, 1 carton containing 18 unit-dose (6 blisters of 3 unit-dose (1 x 3)) orally disintegrating tablets along with leaflet.

Rizatriptan Benzoate Orally Disintegrating Tablets, USP , 10 mg, are white to off-white, uncoated, circular tablet plain on one side and ‘10’ debossed on other side, and measuring ‘7.90 – 8.10 mm’ (side-to-side) with a menthol flavor. 3 orally disintegrating tablets are packaged in a blister. They are supplied as follows:

NDC 43817-135-03, 1 blister containing 3 unit-dose (1 x 3) orally disintegrating tablets.

NDC 43817-135-04, 1 carton containing 18 unit-dose (6 blisters of 3 unit-dose (1 x 3)) orally disintegrating tablets along with leaflet.

Storage

Store Rizatriptan benzoate orally disintegrating tablets, USP at room temperature between 59°F to 86°F (15°C to 30°C)

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

PHARMACIST: Dispense a Patient Information Leaflet with each prescription.