Maxalt Description

MAXALT contains rizatriptan benzoate, a selective 5-hydroxytryptamine1B/1D (5-HT1B/1D ) receptor agonist.

Rizatriptan benzoate is described chemically as: N,N -dimethyl-5-(1 H -1,2,4-triazol-1-ylmethyl)-1 H -indole-3-ethanamine monobenzoate and its structural formula is:

Its empirical formula is C15 H19 N5 ?C7 H6 O2 , representing a molecular weight of the free base of 269.4. Rizatriptan benzoate is a white to off-white, crystalline solid that is soluble in water at about 42 mg per mL (expressed as free base) at 25°C.

MAXALT Tablets and MAXALT-MLT Orally Disintegrating Tablets are available for oral administration in strengths of 5 and 10 mg (corresponding to 7.265 mg or 14.53 mg of the benzoate salt, respectively). Each compressed tablet contains the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, ferric oxide (red), and magnesium stearate.

Each lyophilized orally disintegrating tablet contains the following inactive ingredients: gelatin, mannitol, glycine, aspartame, and peppermint flavor.

Maxalt Indications And Usage

MAXALT is indicated for the acute treatment of migraine attacks with or without aura in adults.

MAXALT is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine (see CONTRAINDICATIONS). Safety and effectiveness of MAXALT have not been established for cluster headache, which is present in an older, predominantly male population.

Maxalt Contraindications

MAXALT should not be given to patients with ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm, including Prinzmetal?s variant angina, or other significant underlying cardiovascular disease (see WARNINGS ).

Because MAXALT may increase blood pressure, it should not be given to patients with uncontrolled hypertension (see WARNINGS ).

MAXALT should not be used within 24 hours of treatment with another 5-HT1 agonist, or an ergotamine-containing or ergot-type medication like dihydroergotamine or methysergide.

MAXALT should not be administered to patients with hemiplegic or basilar migraine.

Concurrent administration of MAO inhibitors or use of rizatriptan within 2 weeks of discontinuation of MAO inhibitor therapy is contraindicated (see CLINICAL PHARMACOLOGY, Drug Interactions and PRECAUTIONS, Drug Interactions ).

MAXALT is contraindicated in patients who are hypersensitive to rizatriptan or any of its inactive ingredients.

Maxalt Side Effects

MAXALT should only be used where a clear diagnosis of migraine has been established.

Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events: Because of the potential of this class of compounds (5-HT1B/1D agonists) to cause coronary vasospasm, MAXALT should not be given to patients with documented ischemic or vasospastic coronary artery disease (see CONTRAINDICATIONS ). It is strongly recommended that rizatriptan not be given to patients in whom unrecognized coronary artery disease (CAD) is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient?s medical history, electrocardiographic or other investigations reveal findings indicative of, or consistent with, coronary artery vasospasm or myocardial ischemia, rizatriptan should not be administered (see CONTRAINDICATIONS ).

For patients with risk factors predictive of CAD, who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of rizatriptan take place in the setting of a physician?s office or similar medically staffed and equipped facility unless the patient has previously received rizatriptan. Because cardiac ischemia can occur in the absence of clinical symptoms, consideration should be given to obtaining on the first occasion of use an electrocardiogram (ECG) during the interval immediately following MAXALT, in these patients with risk factors.

It is recommended that patients who are intermittent long-term users of MAXALT and who have or acquire risk factors predictive of CAD, as described above, undergo periodic interval cardiovascular evaluation as they continue to use MAXALT.

The systematic approach described above is intended to reduce the likelihood that patients with unrecognized cardiovascular disease will be inadvertently exposed to rizatriptan.

Cardiac Events and Fatalities Associated with 5-HT1 Agonists: Serious adverse cardiac events, including acute myocardial infarction, have been reported within a few hours following the administration of rizatriptan. Life-threatening disturbances of cardiac rhythm and death have been reported within a few hours following the administration of other 5-HT1 agonists. Considering the extent of use of 5-HT1 agonists in patients with migraine, the incidence of these events is extremely low. MAXALT can cause coronary vasospasm. Because of the close proximity of the events to MAXALT use, a causal relationship cannot be excluded. In the cases where there has been known underlying coronary artery disease, the relationship is uncertain.

Premarketing experience with rizatriptan: Among the 3700 patients with migraine who participated in premarketing clinical trials of MAXALT, one patient was reported to have chest pain with possible ischemic ECG changes following a single dose of 10 mg.

Postmarketing experience with rizatriptan: Serious cardiovascular events have been reported in association with the use of MAXALT. The uncontrolled nature of postmarketing surveillance, however, makes it impossible to determine definitively the proportion of the reported cases that were actually caused by rizatriptan or to reliably assess causation in individual cases.

Cerebrovascular Events and Fatalities Associated with 5-HT1 Agonists: Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported 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 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. It should be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack).

Other Vasospasm-Related Events: 5-HT1 agonists may cause vasospastic reactions other than coronary artery vasospasm. Both peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea have been reported with 5-HT1 agonists.

Increase in Blood Pressure: Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions in patients receiving 5-HT1 agonists with and without a history of hypertension. In healthy young male and female subjects who received maximal doses of MAXALT (10 mg every 2 hours for 3 doses), slight increases in blood pressure (approximately 2-3 mmHg) were observed. Rizatriptan is contraindicated in patients with uncontrolled hypertension (see CONTRAINDICATIONS).

An 18% increase in mean pulmonary artery pressure was seen following dosing with another 5-HT1 agonist in a study evaluating subjects undergoing cardiac catheterization.

Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome may occur with triptans, including MAXALT treatment, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). If concomitant treatment with rizatriptan and an SSRI (e.g., fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram) or SNRI (e.g., venlafaxine, duloxetine) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. 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) (see PRECAUTIONS, Drug Interactions).

Maxalt Precautions

General

As with other 5-HT1B/1D agonists, sensations of tightness, pain, pressure, and heaviness have been reported after treatment with MAXALT in the precordium, throat, neck and jaw. These events have not been associated with arrhythmias or definite ischemic ECG changes in clinical trials (one patient experienced chest pain with possible ischemic ECG changes). Because drugs in this class may cause coronary artery vasospasm, patients who experience signs or symptoms suggestive of angina following dosing should be evaluated for the presence of CAD or a predisposition to Prinzmetal?s variant angina before receiving additional doses of medication, and should be monitored electrocardiographically if dosing is resumed and similar symptoms recur. Similarly, patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud?s syndrome following the use of any 5-HT1 agonist are candidates for further evaluation (see WARNINGS).

Rizatriptan should also be administered with caution to patients with diseases that may alter the absorption, metabolism, or excretion of drugs (see CLINICAL PHARMACOLOGY, Special Populations).

Renally Impaired Patients: Rizatriptan should be used with caution in dialysis patients due to a decrease in the clearance of rizatriptan (see CLINICAL PHARMACOLOGY, Special Populations).

Hepatically Impaired Patients: Rizatriptan should be used with caution in patients with moderate hepatic insufficiency due to an increase in plasma concentrations of approximately 30% (see CLINICAL PHARMACOLOGY, Special Populations).

For a given attack, if a patient has no response to the first dose of rizatriptan, the diagnosis of migraine should be reconsidered before administration of a second dose.

Binding To Melanin-containing Tissues

The propensity for rizatriptan to bind melanin has not been investigated. Based on its chemical properties, rizatriptan may bind to melanin and accumulate in melanin rich tissue (e.g., eye) over time. This raises the possibility that rizatriptan could cause toxicity in these tissues after extended use. There were, however, no adverse ophthalmologic changes related to treatment with rizatriptan in the one year dog toxicity study. Although no systematic monitoring of ophthalmologic function was undertaken in clinical trials, and no specific recommendations for ophthalmologic monitoring are offered, prescribers should be aware of the possibility of long-term ophthalmologic effects.

Phenylketonurics

Phenylketonuric patients should be informed that MAXALT-MLT Orally Disintegrating Tablets contain phenylalanine (a component of aspartame). Each 5-mg orally disintegrating tablet contains 1.05 mg phenylalanine, and each 10-mg orally disintegrating tablet contains 2.10 mg phenylalanine.

Information For Patients

Migraine or treatment with MAXALT may cause somnolence in some patients. Dizziness has also been reported in some patients receiving MAXALT. Patients should, therefore, evaluate their ability to perform complex tasks during migraine attacks and after administration of MAXALT.

Physicians should instruct their patients to read the patient package insert before taking MAXALT. See the accompanying PATIENT INFORMATION leaflet.

Patients should be cautioned about the risk of serotonin syndrome with the use of rizatriptan or other triptans, especially during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) (see WARNINGS).

Maxalt-mlt Orally Disintegrating Tablets

Patients should be instructed not to remove the blister from the outer pouch until just prior to dosing. The blister pack should then be peeled open with dry hands and the orally disintegrating tablet placed on the tongue, where it will dissolve and be swallowed with the saliva.

Laboratory Tests

No specific laboratory tests are recommended for monitoring patients prior to and/or after treatment with MAXALT.

Drug Interactions

(See alsoCLINICAL PHARMACOLOGY, Drug Interactions.)

Propranolol: Rizatriptan 5 mg should be used in patients taking propranolol, as propranolol has been shown to increase the plasma concentrations of rizatriptan by 70% (see CLINICAL PHARMACOLOGY, Drug Interactions; DOSAGE AND ADMINISTRATION).

Ergot-containing drugs: Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because there is a theoretical basis that these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and rizatriptan within 24 hours is contraindicated (see CONTRAINDICATIONS).

Other 5-HT1 agonists: The administration of rizatriptan with other 5-HT1 agonists has not been evaluated in migraine patients. Because their vasospastic effects may be additive, coadministration of rizatriptan and other 5-HT1 agonists within 24 hours of each other is not recommended (see CONTRAINDICATIONS).

Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome: Cases of life-threatening serotonin syndrome have been reported during combined use of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) and triptans (see WARNINGS).

Monoamine oxidase inhibitors: Rizatriptan should not be administered to patients taking MAO-A inhibitors and non-selective MAO inhibitors; it has been shown that moclobemide (a specific MAO-A inhibitor) increased the systemic exposure of rizatriptan and its metabolite (see CLINICAL PHARMACOLOGY, Drug Interactions; CONTRAINDICATIONS).

Drug/Laboratory Test Interactions

MAXALT is not known to interfere with commonly employed clinical laboratory tests.

Carcinogenesis, Mutagenesis, Impairment of fertility

Carcinogenesis: The lifetime carcinogenic potential of rizatriptan was evaluated in a 100-week study in mice and a 106-week study in rats at oral gavage doses of up to 125 mg/kg/day. Exposure data were not obtained in those studies, but plasma AUC?s of parent drug measured in other studies after 5 and 21 weeks of oral dosing in mice and rats, respectively, indicate that the exposures to parent drug at the highest dose level in the carcinogenicity studies would have been approximately 150 times (mice) and 240 times (rats) average AUC?s measured in humans after three 10 mg doses, the maximum recommended total daily dose. There was no evidence of an increase in tumor incidence related to rizatriptan in either species.

Mutagenesis: Rizatriptan, with and without metabolic activation, was neither mutagenic, nor clastogenic in a battery of in vitro and in vivo genetic toxicity studies, including: the microbial mutagenesis (Ames) assay, the in vitro mammalian cell mutagenesis assay in V-79 Chinese hamster lung cells, the in vitro alkaline elution assay in rat hepatocytes, the in vitro chromosomal aberration assay in Chinese hamster ovary cells and the in vivo chromosomal aberration assay in mouse bone marrow.

Impairment of Fertility: In a fertility study in rats, altered estrus cyclicity and delays in time to mating were observed in females treated orally with 100 mg/kg/day rizatriptan. Plasma drug exposure (AUC) at this dose was approximately 225 times the exposure in humans receiving the maximum recommended daily dose (MRDD) of 30 mg. The no-effect dose was 10 mg/kg/day (approximately 15 times the human exposure at the MRDD). There were no other fertility-related effects in the female rats. There was no impairment of fertility or reproductive performance in male rats treated with up to 250 mg/kg/day (approximately 550 times the human exposure at the MRDD).

Pregnancy

Pregnancy Category C

In a general reproductive study in rats, birth weights and pre- and post-weaning weight gain were reduced in the offspring of females treated prior to and during mating and throughout gestation and lactation with doses of 10 and 100 mg/kg/day. Maternal drug exposures (AUC) at these doses were approximately 15 and 225 times, respectively, the exposure in humans receiving the maximum recommended daily dose (MRDD) of 30 mg. In a pre- and post-natal developmental toxicity study in rats, an increase in mortality of the offspring at birth and for the first three days after birth, a decrease in pre- and post-weaning weight gain, and decreased performance in a passive avoidance test (which indicates a decrease in learning capacity of the offspring) were observed at doses of 100 and 250 mg/kg/day. The no-effect dose for all of these effects was 5 mg/kg/day, approximately 7.5 times the exposure in humans receiving the MRDD. With doses of 100 and 250 mg/kg/day, the decreases in average weight of both the male and female offspring persisted into adulthood. All of these effects on the offspring in both reproductive toxicity studies occurred in the absence of any apparent maternal toxicity.

In embryofetal development studies, no teratogenic effects were observed when pregnant rats and rabbits were administered doses of 100 and 50 mg/kg/day, respectively, during organogenesis. Fetal weights were decreased in conjunction with decreased maternal weight gain at the highest doses (maternal exposures approximately 225 and 115 times the human exposure at the MRDD in rats and rabbits, respectively). The developmental no-effect dose in these studies was 10 mg/kg/day in both rats and rabbits (maternal exposures approximately 15 times human exposure at the MRDD). Toxicokinetic studies demonstrated placental transfer of drug in both species.

There are no adequate and well-controlled studies in pregnant women; therefore, rizatriptan should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Merck & Co., Inc. maintains a registry to monitor the pregnancy outcomes of women exposed to MAXALT while pregnant. Healthcare providers are encouraged to report any prenatal exposure to MAXALT by calling the Pregnancy Registry at (800) 986-8999.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when MAXALT is administered to women who are breast-feeding. Rizatriptan is extensively excreted in rat milk, at a level of 5-fold or greater than maternal plasma levels.

Pediatric Use

Safety and effectiveness of rizatriptan in pediatric patients have not been established; therefore, MAXALT is not recommended for use in patients under 18 years of age.

The efficacy of MAXALT Tablets (5 mg) in patients aged 12 to 17 years was not established in a randomized placebo-controlled trial of 291 adolescent migraineurs (see Clinical Studies). Adverse events observed were similar in nature to those reported in clinical trials in adults. Postmarketing experience with other triptans includes a limited number of reports that describe pediatric patients who have experienced clinically serious adverse events that are similar in nature to those reported rarely in adults. The long-term safety of rizatriptan in pediatric patients has not been studied.

Geriatric Use

The pharmacokinetics of rizatriptan were similar in elderly (aged ? 65 years) and in younger adults. Because migraine occurs infrequently in the elderly, clinical experience with MAXALT is limited in such patients. In clinical trials, there were no apparent differences in efficacy or in overall adverse experience rates between patients under 65 years of age and those 65 and above (n=17).

Maxalt Overdosage

No overdoses of MAXALT were reported during clinical trials.

Rizatriptan 40 mg (administered as either a single dose or as two doses with a 2-hour interdose interval) was generally well tolerated in over 300 patients; dizziness and somnolence were the most common drug-related adverse effects.

In a clinical pharmacology study in which 12 subjects received rizatriptan, at total cumulative doses of 80 mg (given within four hours), two subjects experienced syncope and/or bradycardia. One subject, a female aged 29 years, developed vomiting, bradycardia, and dizziness beginning three hours after receiving a total of 80 mg rizatriptan (administered over two hours); a third degree AV block, responsive to atropine, was observed an hour after the onset of the other symptoms. The second subject, a 25 year old male, experienced transient dizziness, syncope, incontinence, and a 5-second systolic pause (on ECG monitor) immediately after a painful venipuncture. The venipuncture occurred two hours after the subject had received a total of 80 mg rizatriptan (administered over four hours).

In addition, based on the pharmacology of rizatriptan, hypertension or other more serious cardiovascular symptoms 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 Supplemental Patient Material

Patient Information About

MAXALT® (max-awlt) and MAXALT-MLT®

for Migraine

Generic name: rizatriptan benzoate

Please read this information before you start taking MAXALT . Also, read the leaflet each time you renew your prescription, just in case anything has changed. Remember, this leaflet does not take the place of careful discussions with your doctor. You and your doctor should discuss MAXALT when you start taking your medication and at regular checkups.

MAXALT is a medication used for the treatment of migraine attacks in adults. MAXALT is a member of a class of drugs called selective 5-HT1B/1D receptor agonists.

It is available as a traditional tablet (MAXALT) and as an orally disintegrating tablet (MAXALT-MLT . Unless otherwise stated, the information contained in this leaflet applies both to MAXALT Tablets and to MAXALT-MLT Orally Disintegrating Tablets.

Tell your doctor about your symptoms. Your doctor will decide if you have migraine. Use MAXALT only for a migraine attack. MAXALT should not be used to treat headaches that might be caused by other, more serious conditions.

You will find more information about migraine at the end of this leaflet.

Your doctor has prescribed either a 5-mg or 10-mg dosage of MAXALT or MAXALT-MLT for your migraine attack. When you have a migraine headache, take your medication as directed by your doctor.

Maxalt Tablets

If you are using MAXALT Tablets, swallow the tablet whole with liquid.

Maxalt-mlt Orally Disintegrating Tablets

If you are using MAXALT-MLT, leave the orally disintegrating tablet in its package until you are ready to take it. Remove the blister from the foil pouch. Do not push the tablet through the blister; rather, peel open the blister pack with dry hands and place the tablet on your tongue. The tablet will dissolve rapidly and be swallowed with your saliva. No liquid is needed to take the orally disintegrating tablet.

If your headache comes back after your initial dose, a second dose may be taken anytime after 2 hours of administering the first dose. For any attack where you have no response to the first dose, do not take a second dose without first consulting with your doctor. Do not take more than 30 mg of MAXALT in a 24-hour period (for example, do not take more than three 10-mg tablets in a 24-hour period).

If you are receiving propranolol, you should use the 5-mg dose of MAXALT or MAXALT-MLT, up to a maximum of 3 doses (15 mg total) in a 24-hour period.

If your condition worsens, seek medical attention.

Do not take MAXALT if you:

• have had a serious allergic reaction to MAXALT or any of its ingredients
• have uncontrolled high blood pressure
• have heart disease or history of heart disease
• are currently taking monoamine oxidase (MAO) inhibitors such as phenelzine sulfate (NARDIL® ) or tranylcypromine sulfate (PARNATE® ) for mental depression, or have taken MAO inhibitors within the last two weeks.

MAXALT should not be used within 24 hours of treatment with another 5-HT1 agonist such as sumatriptan (IMITREX® ), naratriptan (AMERGE? ) or zolmitriptan (ZOMIG? ); or ergotamine-type medications such as ergotamine (BELLERGAL-S® , CAFERGOT® , ERGOMAR® , WIGRAINE® ), dihydro-ergotamine (D.H.E. 45® ), or methysergide (SANSERT® ).      

Tell your doctor:

• about any past or present medical problems
  
• about any history of high blood pressure, chest pain, shortness of breath, heart disease, or stroke
  
• about any risk factors for heart disease or blood vessel disease
  • high blood pressure or diabetes
  • high cholesterol
  • obesity
  • smoking
  • family history of heart disease or blood vessel disease
  • post menopausal
  • male over 40
• about any allergies you have or have had
  
• if you are pregnant or plan to become pregnant
  
• if you are breast-feeding or plan to breast-feed
  
• about all drugs you are taking or plan to take, including those obtained without a prescription, and those you normally take for a migraine.
  
• if you take selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs), two types of drugs for depression or other disorders. Common SSRIs are CELEXA® (citalopram HBr), LEXAPRO® (escitalopram oxalate), PAXIL® (paroxetine), PROZAC® /SARAFEM® (fluoxetine), SYMBYAX® (olanzapine/fluoxetine), ZOLOFT® (sertraline), and fluvoxamine. Common SNRIs are CYMBALTA® (duloxetine) and EFFEXOR® (venlafaxine).

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

Phenylketonurics: MAXALT-MLT 5-mg and 10-mg orally disintegrating tablets contain 1.05 and 2.10 mg phenylalanine, respectively.

Do not use MAXALT if you are pregnant, think you might be pregnant, are trying to become pregnant, or are not using adequate contraception, unless you have discussed this with your doctor.

Do not take MAXALT with any other drug in the same class within 24 hours, such as sumatriptan (IMITREX® ), naratriptan (AMERGE? ) or zolmitriptan (ZOMIG? ).

Do not take MAXALT within 24 hours of taking ergotamine-type medications such as ergotamine (BELLERGAL-S® , CAFERGOT® , ERGOMAR® , WIGRAINE® ), dihydro-ergotamine (D.H.E. 45® ) or methysergide (SANSERT® ) to treat your migraine.

Do not take MAXALT when you are taking monoamine oxidase (MAO) inhibitors, such as phenelzine sulfate (NARDIL® ) or tranylcypromine sulfate (PARNATE® ) for mental depression, or if it has been less than two weeks since you stopped taking an MAO inhibitor.

Ask your doctor for instructions about taking MAXALT if you are now taking propranolol (INDERAL® ). (See How should I take MAXALT? section.)

Ask your doctor for instructions about taking MAXALT if you are now taking selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs), two types of drugs for depression or other disorders. (See What should I tell my doctor before and during treatment with MAXALT? section.)

Like all prescription drugs, MAXALT can cause side effects. In studies, MAXALT was generally well-tolerated. The side effects were usually mild and temporary. The following is not a complete list of side effects reported with MAXALT. Do not rely on this leaflet alone for information about side effects. Ask your doctor to discuss with you the more complete list of side effects.

In studies, the most common side effects reported were:

• dizziness
• sleepiness, tiredness, fatigue
• pain or pressure sensation (e.g., in the chest or throat)

If you experience dizziness, sleepiness, tiredness or fatigue, you should evaluate your ability to perform complex tasks such as driving or operating heavy machinery.

Other, less common side effects reported in studies or general use were related to the:

Heart and blood vessels - Alterations in heartbeat, increased blood pressure and cold extremities.

Muscles - Muscle weakness, stiffness, and spasm; and muscle and bone pain.

Nervous system - Nervousness, decreased mental sharpness, tremor, headache, abnormal sensation, vertigo, sleep disturbance, mood and personality changes, alterations in speech and movement, memory impairment, confusion, dream abnormality and seizure.

Digestive system - Stomach upset, diarrhea, dry mouth, constipation, gas, thirst, acid reflux, difficulty swallowing, changes in appetite, burping and inability of the tongue to move.

Skin - Flushing (redness of the face lasting a short time), hot flashes, sweating, itching, rash, acne and skin reaction to sunlight.

Respiratory - Difficult or rapid breathing, dryness or discomfort of the throat or nose, nosebleed, yawning and sinus disorder, cold-like symptoms, cough, and hiccups.

Special Senses - Visual disturbances, ringing in the ears, ear pain, eye discomfort, swelling or tearing, alterations in hearing and smelling, visual intolerance to light, and bad taste.

Miscellaneous - Allergic reactions including swelling of face, lips, tongue and/or throat which may cause difficulty in breathing and/or swallowing, wheezing, hives, rash, and severe sloughing of the skin. Also chills, heat sensitivity, swelling, bloating, hangover effect, fever, fainting, dizziness on standing up, warm/cold sensations, dehydration and changes in urination and menstruation.

As with other drugs in this class, there have been very rare reports of heart attack and stroke generally occurring in patients with risk factors for heart and blood vessel disease (see What should I tell my doctor before and during treatment with MAXALT?).

Tell your doctor about these or any other symptoms. If the symptoms persist or worsen, seek medical attention promptly. In addition, tell your doctor if you experience any symptoms that suggest an allergic reaction (see Miscellaneous above) after taking MAXALT.

If you take more medication than you have been told to take, you should contact your doctor, hospital emergency department, or nearest poison control center immediately.

Migraine is an intense, throbbing, typically one-sided headache that often includes nausea, vomiting, sensitivity to light, and sensitivity to sound. According to many migraine sufferers, the pain and symptoms from a migraine headache are more intense than the pain and symptoms of a common headache.

Some people may have visual symptoms before the headache, such as flashing lights or wavy lines, called an aura.

Migraine attacks typically last for hours or, rarely, for more than a day, and they can return frequently. The severity and frequency of migraine attacks may vary.

Based on your symptoms, your doctor will decide whether you have migraine.

Migraine headaches tend to occur in members of the same family. Both men and women get migraine, but it is more common in women.

Certain things are thought to trigger migraine attacks in some people. Some of these triggers are:

• certain foods or beverages (e.g., cheese, chocolate, citrus fruit, caffeine, alcohol)
• stress
• change in a behavior (e.g., under/oversleeping; missing a meal; change in diet)
• hormonal changes in women (e.g., menstruation)

You may be able to prevent migraine attacks or diminish their frequency if you understand what specifically triggers your attacks. Keeping a headache diary may help you identify and monitor the possible migraine triggers you encounter. Once the triggers are identified, you and your doctor can modify your treatment and lifestyle appropriately.

Treatment with MAXALT:

• Reduces swelling of blood vessels surrounding the brain. This swelling results in the headache pain of a migraine attack.
  
• Blocks the release of substances from nerve endings that cause more pain and other symptoms of migraine.
  
• Interrupts the sending of specific pain signals to your brain.

It is thought that each of these actions contributes to relief of your symptoms by MAXALT.

Keep your medicine in a safe place where children cannot reach it. It may be harmful to children. Store your medication away from heat, light, moisture, and at a controlled room temperature 59°-86°F (15°-30°C). If your medication has expired, throw it away as instructed. If your doctor decides to stop your treatment, do not keep any leftover medicine unless your doctor tells you to do so. Throw away your medicine as instructed. Be sure that the discarded tablets are out of the reach of children.

If you are storing MAXALT-MLT, do not remove the blister from the outer aluminum pouch until you are ready to take the medication inside.

This leaflet provides a summary of information about MAXALT. If you have any questions or concerns about either MAXALT or migraine, talk to your doctor. In addition, talk to your pharmacist or other health care provider.

MAXALT Tablets are manufactured for:

MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

By:

MSD, Ltd. Cramlington

Northumberland, NE23 3JU, UK

MAXALT-MLT Orally Disintegrating Tablets are manufactured for:

MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

By:

Catalent UK Swindon, Zydis Ltd.

Swindon, Wiltshire, SN5 8RU, UK

US Patent No.: 5,298,520

Issued August 2007

9652505

Maxalt Information For Patients

Migraine or treatment with MAXALT may cause somnolence in some patients. Dizziness has also been reported in some patients receiving MAXALT. Patients should, therefore, evaluate their ability to perform complex tasks during migraine attacks and after administration of MAXALT.

Physicians should instruct their patients to read the patient package insert before taking MAXALT. See the accompanying PATIENT INFORMATION leaflet.

Patients should be cautioned about the risk of serotonin syndrome with the use of rizatriptan or other triptans, especially during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) (see WARNINGS).

Maxalt Patient Information About

MAXALT® (max-awlt) and MAXALT-MLT®

for Migraine

Generic name: rizatriptan benzoate

Please read this information before you start taking MAXALT . Also, read the leaflet each time you renew your prescription, just in case anything has changed. Remember, this leaflet does not take the place of careful discussions with your doctor. You and your doctor should discuss MAXALT when you start taking your medication and at regular checkups.

MAXALT is a medication used for the treatment of migraine attacks in adults. MAXALT is a member of a class of drugs called selective 5-HT1B/1D receptor agonists.

It is available as a traditional tablet (MAXALT) and as an orally disintegrating tablet (MAXALT-MLT . Unless otherwise stated, the information contained in this leaflet applies both to MAXALT Tablets and to MAXALT-MLT Orally Disintegrating Tablets.

Tell your doctor about your symptoms. Your doctor will decide if you have migraine. Use MAXALT only for a migraine attack. MAXALT should not be used to treat headaches that might be caused by other, more serious conditions.

You will find more information about migraine at the end of this leaflet.

Your doctor has prescribed either a 5-mg or 10-mg dosage of MAXALT or MAXALT-MLT for your migraine attack. When you have a migraine headache, take your medication as directed by your doctor.

Maxalt Tablets

If you are using MAXALT Tablets, swallow the tablet whole with liquid.

Maxalt-mlt Orally Disintegrating Tablets

If you are using MAXALT-MLT, leave the orally disintegrating tablet in its package until you are ready to take it. Remove the blister from the foil pouch. Do not push the tablet through the blister; rather, peel open the blister pack with dry hands and place the tablet on your tongue. The tablet will dissolve rapidly and be swallowed with your saliva. No liquid is needed to take the orally disintegrating tablet.

If your headache comes back after your initial dose, a second dose may be taken anytime after 2 hours of administering the first dose. For any attack where you have no response to the first dose, do not take a second dose without first consulting with your doctor. Do not take more than 30 mg of MAXALT in a 24-hour period (for example, do not take more than three 10-mg tablets in a 24-hour period).

If you are receiving propranolol, you should use the 5-mg dose of MAXALT or MAXALT-MLT, up to a maximum of 3 doses (15 mg total) in a 24-hour period.

If your condition worsens, seek medical attention.

Do not take MAXALT if you:

• have had a serious allergic reaction to MAXALT or any of its ingredients
• have uncontrolled high blood pressure
• have heart disease or history of heart disease
• are currently taking monoamine oxidase (MAO) inhibitors such as phenelzine sulfate (NARDIL® ) or tranylcypromine sulfate (PARNATE® ) for mental depression, or have taken MAO inhibitors within the last two weeks.

MAXALT should not be used within 24 hours of treatment with another 5-HT1 agonist such as sumatriptan (IMITREX® ), naratriptan (AMERGE? ) or zolmitriptan (ZOMIG? ); or ergotamine-type medications such as ergotamine (BELLERGAL-S® , CAFERGOT® , ERGOMAR® , WIGRAINE® ), dihydro-ergotamine (D.H.E. 45® ), or methysergide (SANSERT® ).      

Tell your doctor:

• about any past or present medical problems
  
• about any history of high blood pressure, chest pain, shortness of breath, heart disease, or stroke
  
• about any risk factors for heart disease or blood vessel disease
  • high blood pressure or diabetes
  • high cholesterol
  • obesity
  • smoking
  • family history of heart disease or blood vessel disease
  • post menopausal
  • male over 40
• about any allergies you have or have had
  
• if you are pregnant or plan to become pregnant
  
• if you are breast-feeding or plan to breast-feed
  
• about all drugs you are taking or plan to take, including those obtained without a prescription, and those you normally take for a migraine.
  
• if you take selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs), two types of drugs for depression or other disorders. Common SSRIs are CELEXA® (citalopram HBr), LEXAPRO® (escitalopram oxalate), PAXIL® (paroxetine), PROZAC® /SARAFEM® (fluoxetine), SYMBYAX® (olanzapine/fluoxetine), ZOLOFT® (sertraline), and fluvoxamine. Common SNRIs are CYMBALTA® (duloxetine) and EFFEXOR® (venlafaxine).

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

Phenylketonurics: MAXALT-MLT 5-mg and 10-mg orally disintegrating tablets contain 1.05 and 2.10 mg phenylalanine, respectively.

Do not use MAXALT if you are pregnant, think you might be pregnant, are trying to become pregnant, or are not using adequate contraception, unless you have discussed this with your doctor.

Do not take MAXALT with any other drug in the same class within 24 hours, such as sumatriptan (IMITREX® ), naratriptan (AMERGE? ) or zolmitriptan (ZOMIG? ).

Do not take MAXALT within 24 hours of taking ergotamine-type medications such as ergotamine (BELLERGAL-S® , CAFERGOT® , ERGOMAR® , WIGRAINE® ), dihydro-ergotamine (D.H.E. 45® ) or methysergide (SANSERT® ) to treat your migraine.

Do not take MAXALT when you are taking monoamine oxidase (MAO) inhibitors, such as phenelzine sulfate (NARDIL® ) or tranylcypromine sulfate (PARNATE® ) for mental depression, or if it has been less than two weeks since you stopped taking an MAO inhibitor.

Ask your doctor for instructions about taking MAXALT if you are now taking propranolol (INDERAL® ). (See How should I take MAXALT? section.)

Ask your doctor for instructions about taking MAXALT if you are now taking selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs), two types of drugs for depression or other disorders. (See What should I tell my doctor before and during treatment with MAXALT? section.)

Like all prescription drugs, MAXALT can cause side effects. In studies, MAXALT was generally well-tolerated. The side effects were usually mild and temporary. The following is not a complete list of side effects reported with MAXALT. Do not rely on this leaflet alone for information about side effects. Ask your doctor to discuss with you the more complete list of side effects.

In studies, the most common side effects reported were:

• dizziness
• sleepiness, tiredness, fatigue
• pain or pressure sensation (e.g., in the chest or throat)

If you experience dizziness, sleepiness, tiredness or fatigue, you should evaluate your ability to perform complex tasks such as driving or operating heavy machinery.

Other, less common side effects reported in studies or general use were related to the:

Heart and blood vessels - Alterations in heartbeat, increased blood pressure and cold extremities.

Muscles - Muscle weakness, stiffness, and spasm; and muscle and bone pain.

Nervous system - Nervousness, decreased mental sharpness, tremor, headache, abnormal sensation, vertigo, sleep disturbance, mood and personality changes, alterations in speech and movement, memory impairment, confusion, dream abnormality and seizure.

Digestive system - Stomach upset, diarrhea, dry mouth, constipation, gas, thirst, acid reflux, difficulty swallowing, changes in appetite, burping and inability of the tongue to move.

Skin - Flushing (redness of the face lasting a short time), hot flashes, sweating, itching, rash, acne and skin reaction to sunlight.

Respiratory - Difficult or rapid breathing, dryness or discomfort of the throat or nose, nosebleed, yawning and sinus disorder, cold-like symptoms, cough, and hiccups.

Special Senses - Visual disturbances, ringing in the ears, ear pain, eye discomfort, swelling or tearing, alterations in hearing and smelling, visual intolerance to light, and bad taste.

Miscellaneous - Allergic reactions including swelling of face, lips, tongue and/or throat which may cause difficulty in breathing and/or swallowing, wheezing, hives, rash, and severe sloughing of the skin. Also chills, heat sensitivity, swelling, bloating, hangover effect, fever, fainting, dizziness on standing up, warm/cold sensations, dehydration and changes in urination and menstruation.

As with other drugs in this class, there have been very rare reports of heart attack and stroke generally occurring in patients with risk factors for heart and blood vessel disease (see What should I tell my doctor before and during treatment with MAXALT?).

Tell your doctor about these or any other symptoms. If the symptoms persist or worsen, seek medical attention promptly. In addition, tell your doctor if you experience any symptoms that suggest an allergic reaction (see Miscellaneous above) after taking MAXALT.

If you take more medication than you have been told to take, you should contact your doctor, hospital emergency department, or nearest poison control center immediately.

Migraine is an intense, throbbing, typically one-sided headache that often includes nausea, vomiting, sensitivity to light, and sensitivity to sound. According to many migraine sufferers, the pain and symptoms from a migraine headache are more intense than the pain and symptoms of a common headache.

Some people may have visual symptoms before the headache, such as flashing lights or wavy lines, called an aura.

Migraine attacks typically last for hours or, rarely, for more than a day, and they can return frequently. The severity and frequency of migraine attacks may vary.

Based on your symptoms, your doctor will decide whether you have migraine.

Migraine headaches tend to occur in members of the same family. Both men and women get migraine, but it is more common in women.

Certain things are thought to trigger migraine attacks in some people. Some of these triggers are:

• certain foods or beverages (e.g., cheese, chocolate, citrus fruit, caffeine, alcohol)
• stress
• change in a behavior (e.g., under/oversleeping; missing a meal; change in diet)
• hormonal changes in women (e.g., menstruation)

You may be able to prevent migraine attacks or diminish their frequency if you understand what specifically triggers your attacks. Keeping a headache diary may help you identify and monitor the possible migraine triggers you encounter. Once the triggers are identified, you and your doctor can modify your treatment and lifestyle appropriately.

Treatment with MAXALT:

• Reduces swelling of blood vessels surrounding the brain. This swelling results in the headache pain of a migraine attack.
  
• Blocks the release of substances from nerve endings that cause more pain and other symptoms of migraine.
  
• Interrupts the sending of specific pain signals to your brain.

It is thought that each of these actions contributes to relief of your symptoms by MAXALT.

Keep your medicine in a safe place where children cannot reach it. It may be harmful to children. Store your medication away from heat, light, moisture, and at a controlled room temperature 59°-86°F (15°-30°C). If your medication has expired, throw it away as instructed. If your doctor decides to stop your treatment, do not keep any leftover medicine unless your doctor tells you to do so. Throw away your medicine as instructed. Be sure that the discarded tablets are out of the reach of children.

If you are storing MAXALT-MLT, do not remove the blister from the outer aluminum pouch until you are ready to take the medication inside.

This leaflet provides a summary of information about MAXALT. If you have any questions or concerns about either MAXALT or migraine, talk to your doctor. In addition, talk to your pharmacist or other health care provider.

MAXALT Tablets are manufactured for:

MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

By:

MSD, Ltd. Cramlington

Northumberland, NE23 3JU, UK

MAXALT-MLT Orally Disintegrating Tablets are manufactured for:

MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

By:

Catalent UK Swindon, Zydis Ltd.

Swindon, Wiltshire, SN5 8RU, UK

US Patent No.: 5,298,520

Issued August 2007

9652505