Home – Rizatriptan Benzoate

Rizatriptan Benzoate

Breckenridge Pharmaceutical, Inc.
Natco Pharma Limited

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use rizatriptan benzoate tablets safely and effectively. See full prescribing information for rizatriptan benzoate tablets.Rizatriptan benzoate tablets, for oral use Initial U.S. Approval:1998 RECENT MAJOR CHANGESINDICATIONS AND USAGERizatriptan benzoate tablets are 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) DOSAGE AND ADMINISTRATION Adults: 5 mg or 10 mg single dose; separate repeat doses by at least two hours; maximum dose in a 24-hour period: 30 mg (2.1) Adjust dose if co-administered with propranolol (2.4) DOSAGE FORMS AND STRENGTHS Rizatriptan benzoate tablets: 5 and 10 mg (3) CONTRAINDICATIONS 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-HT1 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 rizatriptanbenzoatetablets (4) WARNINGS AND PRECAUTIONS· 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)Side Effects6.1To report SUSPECTED ADVERSE REACTIONS, contact Breckenridge Pharmaceutical, Inc., at www.bpirx.comFDA at 1-800-FDA-1088 or www.fda.gov/medwatch. USE IN SPECIFIC POPULATIONS8.1 See 17 for PATIENT COUNSELING INFORMATION and FDA approved patient labeling. Information describing the use and dosing of rizatriptan benzoate in pediatric patients (6 to 17 years old) is approved for Merck & Co., Inc.'s Rizatriptan Benzoate Tablets. However, due to Merck & Co., Inc.'s marketing exclusivity rights, this drug product is not labeled for pediatric use

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS & USAGE
2 DOSAGE & ADMINISTRATION
3 DOSAGE FORMS & STRENGTHS
4 RIZATRIPTAN BENZOATE CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
6 RIZATRIPTAN BENZOATE ADVERSE REACTIONS
- 6.1 Clinical Trials Experience
- 6.2 Postmarketing Experience
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
10 OVERDOSAGE
11 RIZATRIPTAN BENZOATE DESCRIPTION
12 CLINICAL PHARMACOLOGY
- 12.1 Mechanism of Action
- 12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
- 13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility
14 CLINICAL STUDIES
- 14.1 Adults
- 14.2 Pediatric Patients 6 to 17 Years of Age
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
Rizatriptan Benzoate Tablets, 5mg-Carton of 18 Tablets
Rizatriptan Benzoate Tablets, 10mg-Carton of 18 Tablets

FULL PRESCRIBING INFORMATION

1 INDICATIONS & USAGE

Information related to usage of rizatriptan benzoate in pediatric patients (6 to 17 years old) is approved for Merck & Co., Inc.’s Rizatriptan Benzoate Tablets. However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric patient (6 to 17 years old) usage information.

Limitations of Use

Rizatriptanbenzoatetablets are not indicated for the prevention of migraine attacks.

Safety and effectiveness of rizatriptanbenzoatetablets have not been established for cluster headache.

2 DOSAGE & ADMINISTRATION

2.1 Dosing Information in Adults

[see Clinical Studies (14.1)]
Redosing in Adults

2.2 Dosing Information in Pediatric Patients (Age 6 to 17 Years)

2.4 Dosage Adjustment for Patients on Propranolol

Adult Patients
In adult patients taking propranolol, only the 5 mg dose of rizatriptanbenzoatetablets is recommended, up to a maximum of 3 doses in any 24-hour period (15 mg) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Pediatric Patients
Dosage adjustment information of rizatriptan benzoate for pediatric patients (6 to 17 years old) taking propranolol is approved for Merck & Co., Inc.'s Rizatriptan Benzoate Tablets. However, due to Merck & Co., Inc.'s marketing exclusivity rights, this drug product is not labeled with that dosage adjustment information.

3 DOSAGE FORMS & STRENGTHS

Rizatriptanbenzoatetablet

5 mg, are light pink to pink-colored, capsule-shaped, biconvex, uncoated tablets with "NAT" on one side and "123" on the other side.
10 mg, are light pink to pink-colored, capsule-shaped, biconvex, uncoated tablets with "NAT" on one side and "121" on the other side.

4 CONTRAINDICATIONS

Rizatriptanbenzoatetablets are 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-HT₁ 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.

· 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 rizatriptanbenzoatetablets (angioedema and anaphylaxis seen) [see Adverse Reactions (6.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina

₁
[see Contraindications (4)].

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-HT₁ agonists. Discontinue rizatriptanbenzoatetablets if these disturbances occur.

5.3 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 rizatriptanbenzoatetablets 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.

5.4 Cerebrovascular Events

₁₁
[see Contraindications (4)]

5.5 Other Vasospasm Reactions

₁₁
₁₁

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 rizatriptanbenzoatetablets particularly during coadministration 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. Rizatriptanbenzoatetablets treatment should be discontinued if serotonin syndrome is suspected [see Drug Interactions (7.4) and Patient Counseling Information (17)].

5.8 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 rizatriptanbenzoatetablets. In healthy young adult male and female patients who received maximal doses of rizatriptanbenzoatetablets (10 mg every 2 hours for 3 doses), slight increases in blood pressure (approximately 2-3 mmHg) were observed. Rizatriptanbenzoatetablets are contraindicated in patients with uncontrolled hypertension [see Contraindications (4)].

6 ADVERSE REACTIONS

Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina [see Warnings and Precautions (5.1)].
Arrhythmias [see Warnings and Precautions (5.2)].
Chest and or 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)].

6.1 Clinical Trials Experience

Incidence in Controlled Clinical Trials

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

Neurological
Adverse Reactions	% of Patients
Adverse Reactions	Rizatriptan benzoate tablets 5 mg (N=977)	Rizatriptan benzoate tablets 10 mg (N=1167)	Placebo (N=627)
Atypical Sensations	4	5	4
Paresthesia	3	4	<2
Pain and other Pressure Sensations	6	9	3
Chest Pain: tightness/pressure and/or heaviness	<2	3	1
Neck/throat/jaw: pain/tightness/pressure	<2	2	1
Regional Pain: tightness/pressure and/or heaviness	<1	2	0
Pain, location unspecified	3	3	<2
Digestive	9	13	8
Dry Mouth	3	3	1
Nausea	4	6	4
Dizziness	4	9	5
Headache	<2	2	<1
Somnolence	4	8	4
Other Asthenia/fatigue	4	7	2

Other Events Observed in Association with the Administration of Rizatriptan Benzoate Tablets in Adults

General:
Atypical Sensations:
Cardiovascular:
Digestive:
Musculoskeletal:
Neurological/Psychiatric:
Respiratory:
Special Senses:
Skin and Skin Appendage:

6.2 Postmarketing Experience

Neurological/Psychiatric:
General: [see Contraindications (4)].

Special Senses: Dysgeusia.

7 DRUG INTERACTIONS

7.1 Propranolol

The dose of rizatriptanbenzoatetablets 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 rizatriptanbenzoatetablets within 24 hours is contraindicated [see Contraindications (4)].

7.3 Other 5-HT1 Agonists

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

7.4 SSRIs/SNRIs and Serotonin Syndrome

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

7.5 Monoamine Oxidase Inhibitors

Rizatriptan benzoate tablets are 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)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

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

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. 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, associated with a maternal plasma exposure (AUC) approximately 7.5 times that 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 effects on the offspring in both 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 tested. 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.

8.3 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 rizatriptanbenzoatetablets are administered to a nursing woman. Rizatriptan is extensively excreted in rat milk, with levels in milk at least 5-fold higher than levels in maternal plasma.

8.4 Pediatric Use

Information related to the efficacy and safety of rizatriptan benzoate in the acute treatment of migraine in patients aged 6 to 17 years is approved for Merck & Co., Inc.’s Rizatriptan Benzoate Tablets. However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that information [see Clinical Studies (14.2)].

8.5 Geriatric Use

Clinical studies of rizatriptanbenzoatetablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Although the pharmacokinetics of rizatriptan were similar in elderly (aged ≥65 years) and in younger adults (n=17), in general, dose selection for an elderly patient should be cautious, starting at the low end of the dosing range. This reflects the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease) should have a cardiovascular evaluation prior to receiving rizatriptanbenzoatetablets[see Warnings and Precautions (5.1)].

10 OVERDOSAGE

11 DESCRIPTION

_1B/1D_1B/1D

₁₅₁₉₅₇₆₂

Rizatriptan benzoate 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: ferric oxide (red), lactose monohydrate, magnesium stearate, microcrystalline cellulose and pregelatinized starch.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

_1B/1D_1B/1D

12.3 Pharmacokinetics

Absorption

Rizatriptan is completely absorbed following oral administration. The mean oral absolute bioavailability of the rizatriptan benzoate tablet is about 45%, and mean peak plasma concentrations (C_max) are reached in approximately 1-1.5 hours (T_max). The presence of a migraine headache did not appear to affect the absorption or pharmacokinetics of rizatriptan. Food has no significant effect on the bioavailability of rizatriptan but delays the time to reach peak concentration by an hour. In clinical trials, rizatriptan benzoate tablets were administered without regard to food.

The bioavailability and C_max of rizatriptan were similar following administration of rizatriptan benzoate tablets and rizatriptan benzoate orally disintegrating tablets, but the rate of absorption is somewhat slower with rizatriptan benzoate orally disintegrating tablets, with T_max delayed by up to 0.7 hour. AUC of rizatriptan is approximately 30% higher in females than in males. No accumulation occurred on multiple dosing.

Distribution

The mean volume of distribution is approximately 140 liters in male subjects and 110 liters in female subjects. Rizatriptan is minimally bound (14%) to plasma proteins.

Metabolism

The primary route of rizatriptan metabolism is via oxidative deamination by monoamine oxidase-A (MAO-A) to the indole acetic acid metabolite, which is not active at the 5-HT_1B/1Dreceptor. N-monodesmethyl-rizatriptan, a metabolite with activity similar to that of parent compound at the 5-HT_1B/1Dreceptor, is formed to a minor degree. Plasma concentrations of N-monodesmethyl-rizatriptan are approximately 14% of those of parent compound, and it is eliminated at a similar rate. Other minor metabolites, the N-oxide, the 6-hydroxy compound, and the sulfate conjugate of the 6-hydroxy metabolite are not active at the 5-HT_1B/1Dreceptor.

Elimination

¹⁴¹⁴

Cytochrome P450 Isoforms
_i
Special Populations
Geriatric:

Information related to the pharmacokinetics of rizatriptan in pediatric migraineurs 6 to 17 years of age is approved for Merck & Co., Inc.‘s Rizatriptan Benzoate Tablets. However, due to Merck & Co., Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.
Gender: _0-_∞_max_max
Hepatic impairment:
Renal impairment: ²_0-_∞²
Race:
Drug Interactions
[See also Drug Interactions (7).]
Monoamine oxidase inhibitors: _max[see Contraindications (4) and Drug Interactions (7.5)]
Propranolol: [see Dosage and Administration (2.4) and Drug Interactions (7.1)]
Nadolol/Metoprolol:
Paroxetine: [see Warnings and Precautions (5.7), Drug Interactions (7.4), and Patient Counseling Information (17)]
Oral contraceptives:

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility

Carcinogenesis:

Mutagenesis: Rizatriptan was neither mutagenic nor clastogenic in a battery of in vitro and in vivo genetic toxicity studies, including: the microbial mutagenesis (Ames) assay, in vitro mammalian cell mutagenesis and chromosomal aberration assays, and the in vivo chromosomal aberration assay in mouse.

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. 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).

14 CLINICAL STUDIES

14.1 Adults

The efficacy of rizatriptan benzoate tablets were established in four multicenter, randomized, placebo-controlled trials. Patients enrolled in these studies were primarily female (84%) and Caucasian (88%), with a mean age of 40 years (range of 18 to 71). Patients were instructed to treat a moderate to severe headache. Headache response, defined as a reduction of moderate or severe headache pain to no or mild headache pain, was assessed for up to 2 hours (Study 1) or up to 4 hours after dosing (Studies 2, 3 and 4). Associated symptoms of nausea, photophobia, and phonophobia and maintenance of response up to 24 hours post-dose were evaluated. A second dose of rizatriptan benzoate tablets were allowed 2 to 24 hours after dosing for treatment of recurrent headache in Studies 1 and 2. Additional analgesics and/or antiemetics were allowed 2 hours after initial treatment for rescue in all four studies.

Table 2: Response Rates 2 Hours Following Treatment of Initial Headache

in Studies 1, 2, 3, and 4

^* ^{p value < 0.05 in comparison with placebo. ^†p value < 0.05 in comparison with 5 mg ^‡Results for initial headache only.}
Study	Placebo	Rizatriptan benzoate tablets 5 mg	Rizatriptan benzoate tablets 10 mg
1	35% (n=304)	62% ^* (n=458)	71% ^*,† (n=456)
2 ^‡	37% (n=82)	—	77% ^* (n=320)
3	23% (n=80)	63% ^* (n=352)	—
4	40% (n=159)	60% ^* (n=164)	67% ^* (n=385)

Figure 1: Estimated Probability of Achieving an Initial Headache

Response by 2 Hours in Pooled Studies 1, 2, 3, and 4^††
Rizatriptan Benzoate

Figure 2: Estimated Probability of Patients Taking a Second Dose of rizatriptan benzoate tablets or Other Medication for Migraines Over the 24 Hours Following the Initial Dose of Study Treatment in Pooled Studies 1, 2, 3, and 4^†††

14.2 Pediatric Patients 6 to 17 Years of Age

Information contained in a clinical study relating to the efficacy of rizatriptan benzoate orally disintegrating tablets in pediatric patients (6 to 17 years old) is approved for Merck & Co., Inc.'s Rizatriptan Benzoate Tablets. However, due to Merck & Co., Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.

16 HOW SUPPLIED/STORAGE AND HANDLING

Rizatriptan benzoate tablets, 5 mg, are light pink to pink-colored, capsule-shaped, biconvex, uncoated tablets with "NAT" on one side and "123" on the other side. They are supplied as follows:

NDC 51991-354-99, Blister of 6 tablets

NDC 51991-354-78, Carton of 18 tablets (3 x 6 blisters) unit dose tablets.

NDC 51991-355-99, Blister of 6 tablets

NDC
Storage

17 PATIENT COUNSELING INFORMATION

See FDA-Approved Patient Labeling (Patient Information).
Risk of Myocardial Ischemia and/or Infarction, Prinzmetal's Angina, Other Vasospasm-related Events, and Cerebrovascular Events
[see Warnings and Precautions (5.1, 5.2, 5.4, 5.5)]
Serotonin Syndrome
) [see Warnings and Precautions (5.7), Drug Interactions (7.4),and Clinical Pharmacology (12.3)]

Pregnancy

[see Use in Specific Populations (8.1)]

Pregnancy

Inform patients that rizatriptan benzoate tablets should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus [see Use in Specific Populations (8.1)].

Nursing Mothers

Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.3)].

Ability To Perform Complex Tasks

Medication Overuse Headache
[see Warnings and Precautions (5.6)]

NATCO PHARMA LIMITED
Kothur- 509228,
A.P, India.

Distributed by:

Breckenridge Pharmaceutical, Inc.,

Patient Information

Rizatriptan Benzoate Tablets

What are rizatriptan benzoate tablets?

Rizatriptan benzoate tablets are a prescription medicine that belongs to a class of medicines called Triptans. Rizatriptan benzoate tablets are available as a traditional tablet and as an orally disintegrating tablet.

Rizatriptan benzoate tablets are used to treat migraine attacks with or without aura in adults.

Rizatriptan benzoate tablets are not to be used to prevent migraine attacks.

Rizatriptan benzoate tablets are not for the treatment of hemiplegic or basilar migraines.

It is not known if rizatriptan benzoate tablets are safe and effective for the treatment of cluster headaches.

Who should not take rizatriptan benzoate tablets ?

Do not take rizatriptan benzoate tablets 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 rizatriptan benzoate tablets. See the end of this leaflet for a complete list of ingredients in rizatriptan benzoate tablets.

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 r izatriptan benzoate tablets ?

Before you take rizatriptan benzoate tablets, 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:

o high blood pressure

o high cholesterol

o smoking

o obesity

o diabetes

o family history of heart problems

o you are post menopausal

o you are a male over 40

· have kidney or liver problems

· have any other medical condition

· are pregnant or plan to become pregnant. It is not known if rizatriptan benzoate tablets will harm your unborn baby. If you become pregnant while taking rizatriptan benzoate tablets, talk to your healthcare provider

· are breastfeeding or plan to breastfeed. It is not known if rizatriptan benzoate passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take rizatriptan benzoate tablets.

Tell your doctor about all the medicines you take, including prescription and nonprescription

medicines, vitamins, and herbal supplements.

Rizatriptan benzoate tablets and other medicines may affect each other causing side effects. Rizatriptan benzoate tablets may affect the way other medicines work, and other medicines may affect how rizatriptan benzoate tablets 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 rizatriptan benzoate tablets ?

· Take rizatriptan benzoate tablets exactly as your doctor tells you to take it.

· Your doctor will tell you how much rizatriptan benzoate tablets to take and when to take it.

· If your headache comes back after your first rizatriptan benzoate tablets dose:

o For adults: a second dose may be taken 2 hours after the first dose. Do not take more than 30 mg of rizatriptan benzoate tablets in a 24-hour period (for example, do not take more than 3 10 mg tablets in a 24-hour period).

· If you take too much rizatriptan benzoate tablets, call your doctor or go to the nearest hospital emergency room right away.

What should I avoid while taking rizatriptan benzoate tablets ?

Rizatriptan benzoate tablets 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 rizatriptan benzoate tablets ?

Rizatriptan benzoate tablets 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 rizatriptan benzoate tablets including:

· heart attack. Symptoms of a heart attack may include:

o chest discomfort in the center of your chest that lasts for more than a few minutes or that goes away and comes back

o chest discomfort that feels like uncomfortable pressure, squeezing, fullness or pain

o pain or discomfort in your arms, back, neck, jaw or stomach

o shortness of breath with or without chest discomfort

o breaking out in a cold sweat

o nausea or vomiting

o feeling lightheaded

· stroke. Symptoms of a stroke may include the following sudden symptoms:

o numbness or weakness in your face, arm or leg, especially on one side of your body

o confusion, problems speaking or understanding

o problems seeing in 1 or both of your eyes

o problems walking, dizziness, loss of balance or coordination

o severe headache with no known cause

· blood vessel problems. Symptoms of blood vessel problems may include:

o stomach pain

o bloody diarrhea

o vision problems

o coldness and numbness of hands and feet

· serotonin syndrome. A condition called serotonin syndrome can happen when Triptan medicines such as rizatriptan benzoate tablets are taken with certain other medicines. Symptoms of serotonin syndrome may include:

o agitation

o hallucinations

o coma

o fast heartbeat

o fast changes in your blood pressure

o increased body temperature

o muscle spasm

o loss of coordination

o nausea, vomiting or diarrhea

· increased blood pressure

The most common side effects of rizatriptan benzoate tablets 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 rizatriptan benzoate tablets 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 rizatriptan benzoate tablets.

These are not all the possible side effects of rizatriptan benzoate tablets. 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 rizatriptan benzoate tablets ?

· Store rizatriptan benzoate tablets at 68°F to 77°F (20°C to 25°C).

· Safely throw away medicine that is out of date or no longer needed.

Keep rizatriptan benzoate tablets and all medicines out of the reach of children.

General Information about the safe and effective use of rizatriptan benzoate tablets .

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

Information related to the usage of rizatriptan benzoate tablets and rizatriptan benzoate orally disintegrating tablets for pediatric patients aged 6 to 17 years is approved for Merck & Co., Inc.’s Rizatriptan Benzoate Tablets. However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.

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

For more information, go to www.fda.gov/med watch.or call FDA at 1-800-FDA-1088.

What are the ingredients in rizatriptan benzoate tablets ?

Active ingredient in rizatriptan benzoate tablets :

Rizatriptan benzoate.

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

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

Rizatriptan benzoate tablets are manufactured by:

NATCO PHARMA LIMITED

Kothur- 509228,

A.P, India.

Distributed by:

Breckenridge Pharmaceutical, Inc.,

Boca Raton, FL 33487

Rev.: 00/Oct/2012

Ta.