Brands, Medical Use, Clinical Data
- Anti-migraine Agents
- Vasoconstrictor Agents
- Anti-inflammatory Agents
- Selective Serotonin Agonists
Brands / Synonyms
Zomig; Zomig Nasal; Zomig-ZMT
For the acute treatment of adult migraine (with or without auras)
Zolmitriptan is a selective 5-hydroxytryptamine receptor subtype agonist indicated for the acute treatment of migraine attacks with or without aura in adults. Zolmitriptan is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Zolmitriptan 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 Zolmitriptan 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 Zolmitriptan in humans.
Mechanism of Action
Zolmitriptan binds with high affinity to human 5-HT1B and 5-HT1D receptors leading to cranial blood vessel constriction. Current theories proposed to explain the etiology of migraine headache suggest that symptoms are due to local cranial vasodilatation and/or to the release of sensory neuropeptides (vasoactive intestinal peptide, substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system. The therapeutic activity of zolmitriptan for the treatment of migraine headache can most likely be attributed to the agonist effects at the 5HT1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.
Biotrnasformation / Drug Metabolism
Zolmitriptan should not be given to patients with ischemic heart disease (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 Zolmitriptan may increase blood pressure, it should not be given to patients with uncontrolled hypertension. Zolmitriptan should not be used within 24 hours of treatment with another 5HT1 agonist, or an ergotamine-containing or ergot-type medication like dihydroergotamine or methysergide. Zolmitriptan should not be administered to patients with hemiplegic or basilar migraine. Concurrent administration of MAO A inhibitors or use of zolmitriptan within 2 weeks of discontinuation of MAO A inhibitor therapy is contraindicated. Zolmitriptan is contraindicated in patients who are hypersensitive to zolmitriptan or any of its inactive ingredients.
All drug interaction studies were performed in healthy volunteers using a single 10 mg dose of zolmitriptan and a
single dose of the other drug except where otherwise noted.
Fluoxetine: The pharmacokinetics of zolmitriptan as well as its effect on blood pressure were
unaffected by 4 weeks of pretreatment with oral fluoxetine (20 mg/day).
MAO Inhibitors: Following one week of administration of 150 mg bid moclobemide, a specific MAO-A
inhibitor, there was an increase of about 25% in both Cmax and AUC for zolmitriptan and a 3-fold increase
in the Cmax and AUC of the active N-desmethyl metabolite of zolmitriptan.
Selegiline, a selective MAO-B inhibitor, at a dose of 10 mg/day for 1 week, had no effect on the pharmacokinetics
of zolmitriptan and its metabolite.
Propranolol: Cmax and AUC of zolmitriptan increased 1.5-fold after one week of dosing
with propranolol (160 mg/day). Cmax and AUC of the N-desmethyl metabolite were reduced by 30% and 15%,
respectively. There were no interactive effects on blood pressure or pulse rate following administration of
propranolol with zolmitriptan.
Acetaminophen: A single 1 g dose of acetaminophen does not alter the pharmacokinetics of
zolmitriptan and its N-desmethyl metabolite. However, zolmitriptan delayed the Tmax of acetaminophen by
Metoclopramide: A single 10 mg dose of metoclopramide had no effect on the pharmacokinetics of
zolmitriptan or its metabolites.
Oral Contraceptives: Retrospective analysis of pharmacokinetic data across studies indicated that
mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives compared to
those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and
50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect
of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied.
Cimetidine: Following the administration of cimetidine, the half life and AUC of a 5 mg dose of
zolmitriptan and its active metabolite were approximately doubled.
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 zolmitriptan within 24 hours of each other should be avoided.
MAO-A inhibitors increase the systemic exposure of zolmitriptan. Therefore, the use of zolmitriptan in patients
receiving MAO-A inhibitors is contraindicated.
Concomitant use of other 5-HT1B/1D agonists within 24 hours of ZOMIG treatment is not recommended..
Following administration of cimetidine, the half life and AUC of zolmitriptan and its active metabolites were
Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) have been
reported, rarely, to cause weakness, hyperreflexia, and incoordination when coadministered with 5HT1
agonists. If concomitant treatment with zolmitriptan and an SSRI is clinically warranted, appropriate observation of
the patient is advised.
Drug/Laboratory Test Interactions
Zolmitriptan is not known to interfere with commonly employed clinical laboratory tests.