Rizatriptan Benzoate

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].
• Arrhythmias [see WARNINGS AND PRECAUTIONS].
• Chest, Throat, Neck and/or Jaw Pain/Tightness/Pressure [see WARNINGS AND PRECAUTIONS].
• Cerebrovascular Events [see WARNINGS AND PRECAUTIONS].
• Other Vasospasm Reactions [see WARNINGS AND PRECAUTIONS].
• Medication Overuse Headache [see WARNINGS AND PRECAUTIONS].
• Serotonin Syndrome [see WARNINGS AND PRECAUTIONS].
• Increase in Blood Pressure [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

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.

Adults

Adverse reactions to MAXALT were assessed in controlled clinical trials that included over 3700 adult patients who received single or multiple doses of MAXALT Tablets. The most common adverse reactions during treatment with MAXALT (≥5% in either treatment group and greater than placebo) were asthenia/fatigue, somnolence, pain/pressure sensation and dizziness. These adverse reactions appeared to be dose related.

Table 1 lists the adverse reactions (incidence ≥2% and greater than placebo) after a single dose of MAXALT in adults.

Table 1: Incidence (≥2% and Greater than Placebo) of Adverse Reactions After a Single Dose of MAXALT Tablets or Placebo in Adults

The frequencies of adverse reactions in clinical trials did not increase when up to three doses were taken within 24 hours. Adverse reaction frequencies were also unchanged by concomitant use of drugs commonly taken for migraine prophylaxis (including propranolol), oral contraceptives, or analgesics. The incidences of adverse reactions were not affected by age or gender. There were insufficient data to assess the impact of race on the incidence of adverse reactions.

In the following section, the frequencies of less commonly reported adverse events are presented that were not reported in other sections of the labeling. Because the reports include events observed in open studies, the role of MAXALT in their causation cannot be reliably determined. Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, limit the value of the quantitative frequency estimates provided. Event frequencies are calculated as the number of patients who used MAXALT and reported an event divided by the total number of patients exposed to MAXALT (N=3716). All reported events occurred at an incidence ≥1%, or are believed to be reasonably associated with the use of the drug. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are those defined as those occurring in at least ( > )1/100 patients; infrequent adverse experiences are those occurring in 1/100 to 1/1000 patients; and rare adverse experiences are those occurring in fewer than 1/1000 patients.

General: Infrequent was facial edema. Rare were syncope and edema/swelling.

Atypical Sensations: Frequent were warm sensations.

Cardiovascular: Frequent was palpitation. Infrequent were tachycardia, cold extremities, and bradycardia.

Digestive: Frequent were diarrhea and vomiting. Infrequent were dyspepsia, tongue edema and abdominal distention.

Musculoskeletal: Infrequent were muscle weakness, stiffness, myalgia and muscle cramp/spasm.

Neurological/Psychiatric: Frequent were hypoesthesia, euphoria and tremor. Infrequent were vertigo, insomnia, confusion/disorientation, gait abnormality, memory impairment, and agitation.

Respiratory: Frequent was dyspnea. Infrequent was pharyngeal edema.

Special Senses: Infrequent were blurred vision and tinnitus. Rare was eye swelling.

Skin and Skin Appendage: Frequent was flushing. Infrequent were sweating, pruritus, rash, and urticaria. Rare was erythema, hot flashes.

The adverse reaction profile seen with MAXALT-MLT Orally Disintegrating Tablets was similar to that seen with MAXALT Tablets.

Pediatric Patients 6 To 17 Years Of Age

Adverse reactions to MAXALT-MLT were assessed in a controlled clinical trial in the acute treatment of migraines (Study 7) that included a total of 1382 pediatric patients 6-17 years of age, of which 977 (72%) administered at least one dose of study treatment (MAXALT-MLT and/or placebo) [see Clinical Studies]. The incidence of adverse reactions reported for pediatric patients in the acute clinical trial was similar in patients who received MAXALT to those who received placebo. The adverse reaction pattern in pediatric patients is expected to be similar to that in adults.

In the following section, the frequencies of less commonly reported adverse events are presented. Because the reports include events observed in open studies, the role of MAXALT-MLT in their causation cannot be reliably determined. Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, limit the value of the quantitative frequency estimates provided.

Event frequencies are calculated as the number of pediatric patients 6 to 17 years of age who used MAXALT-MLT and reported an event divided by the total number of patients exposed to MAXALTMLT (N=1068). All reported events occurred at an incidence ≥1%, or are believed to be reasonably associated with the use of the drug. Events are further classified within system organ class and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are those occurring in ( > )1/100 pediatric patients; infrequent adverse experiences are those occurring in 1/100 to 1/1000 pediatric patients; and rare adverse experiences are those occurring in fewer than 1/1000 patients.

General: Frequent was fatigue.

Ear and labyrinth disorders: Infrequent was hypoacusis.

Gastrointestinal disorders: Frequent was abdominal discomfort.

Nervous system disorders: Infrequent were coordination abnormal, disturbance in attention, and presyncope.

Psychiatric disorders: Infrequent was hallucination.

Postmarketing Experience

The following section enumerates potentially important adverse events that have occurred in clinical practice and which have been reported spontaneously to various surveillance systems. The events enumerated include all except those already listed in other sections of the labeling or those too general to be informative. Because the reports cite events reported spontaneously from worldwide postmarketing experience, frequency of events and the role of MAXALT in their causation cannot be reliably determined.

Neurological/Psychiatric: Seizure.

General: Allergic conditions including anaphylaxis/anaphylactoid reaction, angioedema, wheezing, and toxic epidermal necrolysis [see CONTRAINDICATIONS].

Special Senses: Dysgeusia.

Included as part of the PRECAUTIONS section.

No overdoses of MAXALT were reported during clinical trials in adults.

Some adult patients who received 40 mg of MAXALT either a single dose or as two doses with a 2- hour interdose interval had dizziness and somnolence.

In a clinical pharmacology study in which 12 adult subjects received MAXALT, at total cumulative doses of 80 mg (given within four hours), two of the subjects experienced syncope, dizziness, bradycardia including third degree AV block, vomiting, and/or incontinence.

In the long-term, open label study, involving 606 treated pediatric migraineurs 12 to 17 years of age (of which 432 were treated for at least 12 months), 151 patients (25%) took two 10-mg doses of MAXALTMLT within a 24-hour period. Adverse reactions for 3 of these patients included abdominal discomfort, fatigue, and dyspnea.

In addition, based on the pharmacology of MAXALT, hypertension or myocardial ischemia could occur after overdosage. Gastrointestinal decontamination, (i.e., gastric lavage followed by activated charcoal) should be considered in patients suspected of an overdose with MAXALT. Clinical and electrocardiographic monitoring should be continued for at least 12 hours, even if clinical symptoms are not observed.

The effects of hemo- or peritoneal dialysis on serum concentrations of rizatriptan are unknown.

MAXALT®
(max-awlt)

and

MAXALT-MLT® rizatriptan benzoate

Tablets and Orally Disintegrating Tablets

Read this Patient Information before you start taking MAXALT® and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

Unless otherwise stated, the information in this Patient Information leaflet applies to both MAXALT Tablets and to MAXALT-MLT® Orally Disintegrating Tablets.

What is MAXALT?

MAXALT is a prescription medicine that belongs to a class of medicines called Triptans. MAXALT is available as a traditional tablet (MAXALT) and as an orally disintegrating tablet (MAXALT-MLT).

MAXALT and MAXALT-MLT are used to treat migraine attacks with or without aura in adults and in children 6 to 17 years of age.

MAXALT is not to be used to prevent migraine attacks.

MAXALT is not for the treatment of hemiplegic or basilar migraines.

It is not known if MAXALT is safe and effective for the treatment of cluster headaches.

It is not known if taking more than 1 dose of MAXALT in 24 hours is safe and effective in children 6 to 17 years of age.

It is not known if MAXALT is safe and effective in children under 6 years of age.

Who should not take MAXALT?

Do not take MAXALT if you:

• have or have had heart problems
• have or have had a stroke or a transient ischemic attack (TIA)
• have or have had blood vessel problems including ischemic bowel disease
• have uncontrolled high blood pressure
• have taken other Triptan medicines in the last 24 hours
• have taken ergot-containing medicines in the last 24 hours
• have hemiplegic or basilar migraines
• take monoamine oxidase (MAO) inhibitor or have taken a MAO inhibitor within the last 2 weeks
• are allergic to rizatriptan benzoate or any of the ingredients in MAXALT. See the end of this leaflet for a complete list of ingredients in MAXALT.

Talk to your doctor before taking this medicine if you have any of the conditions listed above or if you are not sure if you take any of these medicines.

What should I tell my doctor before taking MAXALT?

Before you take MAXALT, tell your doctor if you:

• have or have had heart problems, high blood pressure, chest pain, or shortness of breath
• have any risk factors for heart problems or blood vessel problems such as:
  • high blood pressure
  • high cholesterol
  • smoking
  • obesity
  • diabetes
  • family history of heart problems
  • you are post menopausal
  • you are a male over 40
• have phenylketonuria (PKU). MAXALT-MLT orally disintegrating tablets contain phenylalanine.
• have kidney or liver problems
• have any other medical condition
• are pregnant or plan to become pregnant. It is not known if MAXALT will harm your unborn baby. If you become pregnant while taking MAXALT, talk to your healthcare provider about registering with the pregnancy registry at the Merck National Service Center. You can enroll in this registry by calling 1-800-986-8999. The purpose of this registry is to collect information about the safety of MAXALT in pregnancy.
• are breastfeeding or plan to breastfeed. It is not known if MAXALT passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take MAXALT.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

MAXALT and other medicines may affect each other causing side effects. MAXALT may affect the way other medicines work, and other medicines may affect how MAXALT works.

Especially tell your doctor if you take:

• propranolol containing medicines such as Inderal®, Inderal® LA, or Innopran® XL
• medicines used to treat mood disorders, including selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs).

Ask your doctor or pharmacist for a list of these medicines, if you are not sure.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I take MAXALT?

• Take MAXALT exactly as your doctor tells you to take it.
• Your doctor will tell you how much MAXALT to take and when to take it.
• To take MAXALT-MLT:
  • Leave MAXALT-MLT orally disintegrating tablets in the package it comes in until you are ready to take it. When you are ready to take it:
    • Remove the blister from the foil pouch. Do not push the MAXALT-MLT orally disintegrating tablet through the blister.
    • Peel open the blister pack with dry hands and place the MAXALT-MLT orally disintegrating tablet on your tongue. The tablet will dissolve and be swallowed with your saliva. No liquid is needed to take the orally disintegrating tablet.
• If your headache comes back after your first MAXALT dose:
  • For adults: a second dose may be taken 2 hours after the first dose. Do not take more than 30 mg of MAXALT in a 24-hour period (for example, do not take more than 3 10-mg tablets in a 24-hour period).
  • For children 6 to 17 years of age: It is not known if taking more than 1 dose of MAXALT in 24 hours is safe and effective. Talk to your doctor about what to do if your headache does not go away or comes back.
• If you take too much MAXALT, call your doctor or go to the nearest hospital emergency room right away.

What should I avoid while taking MAXALT?

MAXALT may cause dizziness, weakness, or fainting. If you have these symptoms, do not drive a car, use machinery, or do anything that needs you to be alert.

What are the possible side effects of MAXALT?

MAXALT may cause serious side effects. Call your doctor or go to the nearest hospital emergency room right away if you think you are having any of the serious side effects of MAXALT including:

• heart attack. Symptoms of a heart attack may include:
  • chest discomfort in the center of your chest that lasts for more than a few minutes or that goes away and comes back
  • chest discomfort that feels like uncomfortable pressure, squeezing, fullness or pain
  • pain or discomfort in your arms, back, neck, jaw or stomach
  • shortness of breath with or without chest discomfort
  • breaking out in a cold sweat
  • nausea or vomiting
  • feeling lightheaded
• stroke. Symptoms of a stroke may include the following sudden symptoms:
  • numbness or weakness in your face, arm or leg, especially on one side of your body
  • confusion, problems speaking or understanding
  • problems seeing in 1 or both of your eyes
  • problems walking, dizziness, loss of balance or coordination
  • severe headache with no known cause
• blood vessel problems. Symptoms of blood vessel problems may include:
  • stomach pain
  • bloody diarrhea
  • vision problems
  • coldness and numbness of hands and feet
• serotonin syndrome. A condition called serotonin syndrome can happen when Triptan medicines such as MAXALT are taken with certain other medicines. Symptoms of serotonin syndrome may include:
  • agitation
  • hallucinations
  • coma
  • fast heartbeat
  • fast changes in your blood pressure
  • increased body temperature
  • muscle spasm
  • loss of coordination
  • nausea, vomiting or diarrhea
• increased blood pressure.

The most common side effects of MAXALT in adults include:

• feeling sleepy or tired
• pain or pressure in your chest or throat
• dizziness

Tell your doctor if you have any side effect that bothers you or that does not go away.

If you take MAXALT too often, this may result in you getting chronic headaches. In such cases, you should contact your doctor, as you may have to stop taking MAXALT.

These are not all the possible side effects of MAXALT. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store MAXALT?

• Store MAXALT at room temperature between 59°F to 86°F (15°C to 30°C).
• Safely throw away medicine that is out of date or no longer needed.

Keep MAXALT and all medicines out of the reach of children.

General Information about the safe and effective use of MAXALT.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use MAXALT for a condition for which it was not prescribed. Do not give MAXALT to other people, even if they have the same symptoms that you have. It may harm them.

This Patient Information leaflet summarizes the most important information about MAXALT. If you would like more information, talk to your doctor. You can ask your pharmacist or doctor for information about MAXALT that is written for health professionals.

For more information, go to www.maxalt.com or call 1-800-986-8999.

What are the ingredients in MAXALT?

Active ingredient in MAXALT and MAXALT-MLT orally disintegrating tablets :

rizatriptan benzoate.

Inactive ingredients in MAXALT: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, ferric oxide (red), and magnesium stearate.

Inactive ingredients in MAXALT-MLT orally disintegrating tablets : gelatin, mannitol, glycine, aspartame, and peppermint flavor.

MAXALT-MLT orally disintegrating tablets contain aspartame, a source of phenylalanine.

Phenylketonurics :

MAXALT-MLT orally disintegrating tablets 5-mg contain 1.1 mg of phenylalanine. MAXALT-MLT orally disintegrating tablets 10-mg contain 2.1 mg of phenylalanine.

This Patient Information has been approved by the U.S. Food and Drug Administration.

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

After taking a rizatriptan tablet, you must wait two (2) hours before taking a second tablet. Do not take more than 30 mg of rizatriptan in 24 hours.

• Prescription Migraine Medications

Vascular Headaches

Acute treatment of migraine attacks with or without aura in adults1 12 13 and pediatric patients 6–17 years of age.1 24 Efficacy in reducing migraine-associated symptoms (nausea, photophobia, phonophobia) in pediatric patients not established.1 24

Not recommended for management of hemiplegic or basilar migraine or for prophylaxis of migraine.1

Safety and efficacy not established for management of cluster headaches.1

Metabolized by MAO-A.1

Does not inhibit CYP3A4/5, 1A2, 2C9, 2C19, or 2E1; inhibits CYP2D6 only at high concentrations.1

Specific Drugs