indication

For treatment of acute migraine attacks with or without aura.

pharmacology

Rizatriptan is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptors. It is structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonists and has only a weak affinity for 5-HT_1A, 5-HT_5A, 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

Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT1B receptor agonism.

toxicity

Symptoms of overdose include dizziness, fainting, heart and blood vessel problems, high blood pressure, loss of bowel and bladder control, slow heartbeat, and vomiting.

biotransformation

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.

absorption

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.

half life

2-3 hours

route of elimination

Approximately 14% of an oral dose is excreted in urine as unchanged rizatriptan while 51% is excreted as indole acetic acid metabolite, indicating substantial first pass metabolism.

drug interactions

Citalopram: Increased risk of CNS adverse effects

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Dihydroergotamine: Possible severe and prolonged vasoconstriction

Ergotamine: Possible severe and prolonged vasoconstriction

Escitalopram: Increased risk of CNS adverse effects

Fluoxetine: Increased risk of CNS adverse effects

Fluvoxamine: Increased risk of CNS adverse effects

Isocarboxazid: The MAO inhibitor, isocarboxazid, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.

Methysergide: Possible severe and prolonged vasoconstriction

Moclobemide: The MAO inhibitor, moclobemide, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.

Nefazodone: Increased risk of CNS adverse effects

Paroxetine: Increased risk of CNS adverse effects

Phenelzine: The MAO inhibitor, phenelzine, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.

Propranolol: Propranolol increases the effect and toxicity of rizatriptan

Tramadol: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Tranylcypromine: The MAO inhibitor, Tranylcypromine, may reduce the metabolism and clearance of the serotonin 5-HT1D receptor agonist, Rizatriptan. Risk of serotonin syndrome and Rizatriptan toxicity. Concomitant therapy should be avoided.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Zolmitriptan: Concomitant use of two serotonin 5-HT1D receptor agonists, such as zolmitriptan and rizatriptan, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.