RIZATRIPTAN BENZOATE

RIZATRIPTAN BENZOATE — rizatriptan benzoate tablet, orally disintegrating
RIZATRIPTAN BENZOATE- rizatriptan benzoate tablet, orally disintegrating
Bionpharma Inc.,

1 INDICATIONS AND USAGE

Rizatriptan Benzoate Orally Disintegrating Tablets are indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 6 to 17 years old.

Limitations of Use

• Rizatriptan benzoate orally disintegrating tablets should only be used where a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with rizatriptan benzoate orally disintegrating tablets, USP, the diagnosis of migraine should be reconsidered before rizatriptan benzoate orally disintegrating tablets, USP are administered to treat any subsequent attacks.
• Rizatriptan benzoate orally disintegrating tablets are not indicated for use in the management of hemiplegic or basilar migraine [see Contraindications (4)] .
• Rizatriptan benzoate orally disintegrating tablets are not indicated for the prevention of migraine attacks.
• Safety and effectiveness of Rizatriptan benzoate orally disintegrating tablets have not been established for cluster headache.

2 DOSAGE AND ADMINISTRATION

2.1 Dosing Information in Adults

The recommended starting dose of rizatriptan benzoate orally disintegrating tablets is either 5 mg or 10 mg for the acute treatment of migraines in adults. The 10-mg dose may provide a greater effect than the 5-mg dose, but may have a greater risk of adverse reactions [see Clinical Studies (14.1)].

Redosing in Adults

Although the effectiveness of a second dose or subsequent doses has not been established in placebo-controlled trials, if the migraine headache returns, a second dose may be administered 2 hours after the first dose. The maximum daily dose should not exceed 30 mg in any 24-hour period. The safety of treating, on average, more than four headaches in a 30-day period has not been established.

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

Dosing in pediatric patients is based on the patient’s body weight. The recommended dose of rizatriptan benzoate is 5 mg in patients weighing less than 40 kg (88 lb), and 10 mg in patients weighing 40 kg (88 lb) or more.

The efficacy and safety of treatment with more than one dose of rizatriptan benzoate orally disintegrating tablets, USP within 24 hours in pediatric patients 6 to 17 years of age have not been established.

2.3 Administration of Rizatriptan Benzoate Orally Disintegrating Tablets USP

For rizatriptan benzoate orally disintegrating tablets, USP, administration with liquid is not necessary. Orally disintegrating tablets are packaged in a blister within an outer carton and patients should not remove the blister from the outer carton 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.

2.4 Dosage Adjustment for Patients on Propranolol

Adult Patients

In adult patients taking propranolol, only the 5 mg dose of Rizatriptan benzoate orally disintegrating tablets, USP are 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

For pediatric patients weighing ≥40 kg (88 lb), taking propranolol, only a single 5 mg dose of rizatriptan benzoate tablets, USP is recommended (maximum dose of 5 mg in a 24-hour period). Rizatriptan benzoate orally disintegrating tablets, should not be prescribed to propranolol-treated pediatric patients who weigh less than 40 kg (88 lb) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

Rizatriptan Benzoate Orally Disintegrating Tablets

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

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

4 CONTRAINDICATIONS

Rizatriptan Benzoate is contraindicated in patients with:

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

5 WARNINGS AND PRECAUTIONS

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

Rizatriptan Benzoate Orally Disintegrating Tablets should not be given to patients with ischemic or vasospastic coronary artery disease. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of Rizatriptan Benzoate. Some of these reactions occurred in patients without known coronary artery disease (CAD). 5-HT ₁ agonists including Rizatriptan Benzoate may cause coronary artery vasospasm (Prinzmetal’s Angina), even in patients without a history of CAD.

Triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) should have a cardiovascular evaluation prior to receiving Rizatriptan Benzoate. If there is evidence of CAD or coronary artery vasospasm, Rizatriptan Benzoate should not be administered [see Contraindications (4)] . For patients who have a negative cardiovascular evaluation, consideration should be given to administration of the first Rizatriptan benzoate dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following Rizatriptan benzoate administration. Periodic cardiovascular evaluation should be considered in intermittent long-term users of Rizatriptan benzoate who have cardiovascular risk factors.

5.2 Arrhythmias

Life threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following the administration of 5-HT ₁ agonists. Discontinue Rizatriptan benzoate if these disturbances occur.