Brands, Medical Use, Clinical Data
- Anti-migraine Agents
- Vasoconstrictor Agents
- Anti-inflammatory Agents
- Selective Serotonin Agonists
Brands / Synonyms
Maxalt; Maxalt-MLT; MK 462 Free Base; Risatriptan; Rizatriptan benzoat; Rizatriptan benzoate
For treatment of acute migraine attacks.
Rizatriptan is a selective 5-hydroxytryptamine receptor subtype agonist indicated for the acute treatment of migraine attacks with or without aura in adults. Rizatriptan is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Rizatriptan is an agonist for a vascular 5-hydroxytryptamine receptor subtype (probably a member of the 5-HT1D family) having only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Rizatriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Rizatriptan in humans.
Mechanism of Action
Rizatriptan binds with high affinity to human 5-HT1B and 5-HT1D receptors leading to cranial blood vessel constriction.
Rapid following oral administration. Bioavailability is 45%. Food has no effect on the bioavailability of rizatriptan. However, administering rizatriptan with food will delay by 1 hour the time to reach peak plasma concentration. The rate of absorption is not affected by the presence of a migraine attack.
Symptoms of overdose include dizziness, fainting, heart and blood vessel problems, high blood pressure, loss of bowel and bladder control, slow heartbeat, and vomiting.
Biotrnasformation / Drug Metabolism
Rizatriptan is metabolized by monoamine oxidase A isoenzyme (MAO-A) to an inactive indole acetic acid metabolite. In addition, several other inactive metabolites are formed. An active metabolite, N-monodesmethyl-rizatriptan, with pharmacological activity similar to that of the parent compound has been identified in small concentrations (14%) in the plasma.
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.
Because MAXALT may increase blood pressure, it should not be given to patients with uncontrolled hypertension
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. MAXALT is contraindicated in patients who are hypersensitive to rizatriptan or
any of its inactive ingredients.
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%.
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.
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.
Selective serotonin reuptake inhibitors (SSRIs): SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) have been reported, rarely, to cause weakness, hyperreflexia, and incoordination when coadministered with 5-HT1 agonists. If concomitant treatment with rizatriptan and an SSRI is clinically warranted, appropriate observation of the patient is advised. No clinical or pharmacokinetic interactions were observed when Rizatriptan 10 mg was administered with paroxetine.
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.
Drug/Laboratory Test Interactions: Rizatriptan is not known to interfere with commonly employed clinical laboratory tests.