Rizatriptan Benzoate

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

There are several physiological and molecular processes implicated in the pathophysiology of migraine. Vasodilation of intracranial extracerebral blood vessels, particularly those supplying the dura mater, has been associated with migraine pain. Activation of the trigeminovascular system leads to the release of vasoactive neuropeptides from the trigeminal nerve innervating the intracranial vessels and dura mater. Vasoactive neuropeptides cause perivascular inflammation and vasodilation in the periphery. Migraine-associated nausea and vomiting are thought to arise from the activation of central and nociceptive sensory neurons that project to autonomic brain-stem nuclei and higher subcortical and cortical pain processing centres. An imbalance in serotonin (5-HT) levels has also been documented: 5-HT binds to 5-HT1B and 5-HT1D receptors to promote trigeminal neuronal firing and vasoconstriction.

Rizatriptan is a selective agonist at the 5-HT1B and 5-HT1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system. It binds to these receptors with high affinity.9 The exact mechanism of action of rizatriptan has not been fully elucidated; however, several documented pharmacological actions of rizatriptan may contribute to its antimigraine effects. Rizatriptan causes vasoconstriction of intracranial extracerebral blood vessels, which is thought to occur primarily via 5-HT1B receptors. Rizatriptan also inhibits nociceptive neurotransmission in trigeminal pain pathways. It attenuates the release of vasoactive neuropeptides by the trigeminal nerve, which is thought to occur via neurogenic and central 5-HT1D receptors. Rizatriptan inhibited neurogenic dural vasodilation and plasma protein extravasation in animal studies.

Single doses of 5 or 10 mg of Rizatriptan Tablets is indicated for the acute treatment of migraines in adults. Doses should be separated by at least 2 hours; no more than 30 mg should be taken in any 24-hour period.

Dosage adjustment for special case: The choice of dose should therefore be made on an individual basis,
weighing the possible benefit of the 10-mg dose with the potential risk for increased adverse events. The safety of treating, on average, more than four headaches in a 30-day period has not been established. Patients receiving propranolol: In patients receiving propranolol, the 5-mg dose of Rizatriptan should be used, up to a maximum of 3 doses in any 24-hour period.

Administration of Rizatriptan Benzoate Tablets, administration with liquid is not necessary. Orally disintegrating tablets are packaged in a blister within an outer aluminum pouch and patients should not 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.

Rizatriptan 5 mg should be used in patients taking propranolol. Ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and rizatriptan within 24 hours is contraindicated. Coadministration of rizatriptan and other 5-HT1 agonists within 24 hours of each other is not recommended. Rizatriptan should not be administered to patients taking MAO-A inhibitors and non-selective MAO inhibitors.

Rizatriptan Benzoate 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.

As Rizatriptan Benzoate may increase blood pressure, it should not be given to patients with uncontrolled hypertension. Rizatriptan Benzoate is contraindicated in patients who are hypersensitive to rizatriptan or any of its inactive ingredients.

Cardiac events are rare and most have been reported in patients with risk factors predictive of CAD. Cardiac events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation. In general, chills, heat sensitivity, facial edema, hangover effect, and abdominal distention were reported infrequently. Rarely fever, orthostatic effects, syncope and edema/swelling were reported.

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. 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 rizatriptan is administered to women who are nursing mother.

Rizatriptan Benzoate should only be used where a clear diagnosis of migraine has been established. Rizatriptan Benzoate should not be given to patients with documented ischemic or vasospastic coronary artery disease.

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. Rizatriptan should be used with caution in patients with moderate hepatic insufficiency.

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.

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

Use in the Elderly: 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 rizatriptan 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.

No overdoses of Rizatriptan 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; dizziness and somnolence were the most common drug-related adverse effects. 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 Rizatriptan.

5-HT Agonists

Store in a cool and dry place below 30°C. Protect from light. Keep out of reach of children.