Zolmitriptan

Pronunciation: ZOLE-mih-TRIP-tan
Class: Serotonin 5-HT 1 receptor antagonist

Trade Names

Zomig
- Tablets 2.5 mg
- Tablets 5 mg

Zomig
- Spray, nasal 5 mg

Zomig ZMT
- Tablets, orally disintegrating 2.5 mg

Zomig Rapimelt (Canada)

Pharmacology

Selective agonist for the vascular serotonin (5-HT) receptor subtype, causing vasoconstriction of cranial arteries and inhibition of pro-inflammatory neuropeptide release.

Slideshow: Living with Your Migraines: Tips for Treatment and Prevention

Pharmacokinetics

Absorption

Vd is about 7 L/kg. It is well absorbed after oral administration of both conventional tablets and the orally disintegrating tablets. T max for oral disintegrating tablets is 3 h and for conventional tablets is 1.5 h. Bioavailability is about 40%.

Distribution

Plasma protein binding is about 25%.

Metabolism

Converted to an active N-desmethyl metabolite such that the metabolite concentrations are about 2/ 3 that of zolmitriptan.

Elimination

The t ½ is 3 h. About 8% of the dose is recovered in urine as unchanged drug. Mean total plasma Cl is about 31.5 mL/min/kg and 25.9 mL/min/kg for nasal spray. Cl is renal tubular secretion.

Special Populations

Renal Function Impairment

Cl was reduced 25% in patients with severe renal function impairment. No change in Cl was found in moderately renally impaired patients.

Hepatic Function Impairment

In severely hepatically impaired patients, the C max , T max , and AUC were increased 1.5-, 2-, and 3-fold, respectively. When dosed orally, the effect of hepatic disease on zolmitriptan nasal spray has not been evaluated. Administer with caution in subjects with liver disease, generally using doses less than 2.5 mg.

Gender

Mean plasma concentrations were up to 1.5-fold higher in women than men.

Indications and Usage

Short-term treatment of migraine attacks with/without aura.

Contraindications

Ischemic heart disease or in patients with Prinzmetal angina; symptoms consistent with possible ischemic heart disease; uncontrolled hypertension; symptomatic Wolff-Parkinson-White syndrome; use within 24 h of treatment with another 5-HT agonist or an ergotamine-containing or ergot-like medication; coadministration of, or within 2 wk of discontinuation of, an MAO inhibitor, management of hemiplegic or basilar migraines.

Dosage and Administration

Adults

PO Initial recommended dose is up to 2.5 mg (eg, ½ tablet) with fluids; max recommended single dose is 5 mg. If headache returns, the dose may be repeated after 2 h, not to exceed 10 mg within a 24-h period. The effectiveness of a second dose, if the initial dose is ineffective, has not been determined.

Adults

Intranasal One dose of 5 mg for acute migraine. If headache returns, dose may be repeated after 2 h (max, 10 mg per 24 h). Response is individual. Doses lower than 5 mg can only be achieved through the use of an oral formulation. Make the choice of dose and route of administration on an individual basis.

Storage/Stability

Store tablets, orally-disintegrating tablets, and nasal spray at controlled room temperature (68° to 77°F). Protect from light and moisture.

Drug Interactions

5-HT 1 agonists (eg, sumatriptan)

Avoid use within 24 h of each other.

Cimetidine

Zolmitriptan levels and t ½ may be increased.

Ergot-containing or ergot-type drugs (eg, methysergide)

May cause additive prolonged vasospastic reactions. Avoid use within 24 h of each other.

MAO inhibitors (eg, phenelzine)

Do not use zolmitriptan concurrently or within 2 wk of discontinuation of a MAO inhibitor.

Selective serotonin reuptake inhibitors (eg, fluoxetine)

Combined use may cause weakness, hyperreflexia, and incoordination.

Sibutramine

Serotonin syndrome, including CNS irritability, motor weakness, shivering, myoclonus, and altered consciousness, may occur.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Palpitations; coronary artery vasospasm, transient myocardial ischemia, angina pectoris, MI (postmarketing).

CNS

Paresthesia, dizziness, somnolence, vertigo, hyperesthesia (at least 2%); headache (postmarketing).

EENT

Nasal cavity discomfort (at least 2%).

GI

Unusual taste (21% intranasal); dry mouth, dyspepsia, dysphagia, nausea (at least 2%); ischemic colitis, GI infarction or necrosis (postmarketing).

Hypersensitivity

Anaphylaxis or anaphylactoid reactions, angioedema (postmarketing).

Musculoskeletal

Myalgia.

Miscellaneous

Asthenia, pain, chest/throat/neck pain, tightness, or heaviness, warm or cold sensations, sweating (at least 2%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Safety and efficacy in patients older than 65 yr of age not established.

Hepatic Function

Use with caution; use doses less than 2.5 mg.

Cardiac events/Vasoconstriction

Serious coronary events, though extremely rare, can occur after administration of 5-HT 1 agonists. Administer first dose in health care provider's office to patients at possible risk of unrecognized coronary disease. If symptoms consistent with angina occur, conduct ECG evaluation for ischemic changes. May cause coronary vasospasm in patients with history of coronary artery disease (CAD).

Cerebrovascular events

Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported with 5-HT 1 agonists.

Hypertensive crisis

Elevation in BP, including hypertensive crisis, have been reported.

Phenylalanine

Orally-disintegrating tablets contain phenylalanine. Do not administer orally disintegrating tablet to patient with phenylketonuria without first discussing with health care provider.

Overdosage

Symptoms

Sedation.

Patient Information

  • Advise patient to read the patient information leaflet before starting therapy and again with each refill.
  • Explain that drug is to be used only during migraine and does not prevent or reduce the number of attacks. Emphasize that the drug is used only to treat actual migraine attack and should not be used to prevent headaches or treat headaches caused by other conditions.
  • Advise patient that drug is to be taken as soon as symptoms of migraine appear. A second dose may be taken if symptoms return, but no sooner than 2 h following the first dose. For a given attack, if there is no response to the first tablet, do not take a second dose without first consulting with health care provider.
  • Advise patient not to take more than 10 mg per day.
  • Advise patient that safety of treating more than 4 headaches in a 30-day period with nasal spray (or 3 headaches in a 30-day period with tablets) has not been established and to inform health care provider if headaches are occurring more frequently.
  • Advise patient to immediately notify health care provider if any of the following occur after taking a dose of sumatriptan: severe chest pain or chest pain that does not go away; sudden and/or severe stomach pain; shortness of breath; wheezing; swelling of eyelids, face, or lips.
  • Advise patient that if tightness, pain, pressure, or heaviness in chest, throat, neck, or jaw occurs when using sumatriptan, to discuss these symptoms with health care provider before using again.
  • Advise patient to notify health care provider if feelings of tingling, heat, flushing, tiredness, dizziness, heaviness, or pressure occur after treatment.
  • Advise patient that drug may cause fatigue or dizziness and to use caution while driving or performing other activities requiring mental alertness.
  • Advise patient to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreen and wear protective clothing to avoid photosensitivity reactions.
  • Instruct patient to continue taking prescribed migraine prophylactic medications daily as directed.
  • Advise patient not currently taking a migraine prophylactic drug to discuss the use of such drugs with health care provider.

Copyright © 2009 Wolters Kluwer Health.

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