Generic Name: zolmitriptan nasal

Brand Names: Zomig

Uses

Vascular Headaches

Acute treatment of migraine attacks with or without aura.

Not recommended for management of hemiplegic or basilar migraine or for prophylaxis of migraine.

Safety and efficacy not established for management of cluster headaches.

Dosage and Administration

Administration

Administer orally or intranasally.

Oral Administration

Administer orally as conventional or orally disintegrating tablets without regard to meals.

To achieve a dose <2.5 mg, manually break the scored 2.5-mg conventional tablet in half. Do not break orally disintegrating tablets.

Just prior to administration of orally disintegrating tablet, remove tablet from blister package; peel open blister package, place tablet on tongue to dissolve, and swallow with saliva.

Administration of orally disintegrating tablet with liquid is not necessary.

Intranasal Administration

Administer intranasally as a single spray into 1 nostril.

Do not spray contents into eyes.

To administer, blow nose gently and remove protective cap just before use. Hold nasal spray device gently and do not press plunger until tip is placed into nostril. Block one nostril by pressing firmly on side of nose and put tip into other nostril as far as feels comfortable. Tilt head slightly back and breathe gently through nose while pressing plunger firmly with thumb; a click may be heard. Keep head tilted slightly back and remove tip of device from nose; breathe gently through mouth for 5–10 seconds. Liquid may be felt in nose or back of throat. Consult manufacturer’s patient information for complete directions.

Single-use spray pump; discard after use.

Dosage

Due to similarity in systemic exposure, dosage adjustments with oral and intranasal formulations should be similar; doses <5 mg can be achieved only through use of oral formulations.

Adults

Vascular Headaches

Migraine

Oral

Initially, ≤2.5 mg. In clinical studies, single oral doses of 1 (not commercially available in US), 2.5, or 5 mg were effective, but the 2.5- and 5-mg doses were effective in a greater proportion of patients. The 5-mg dose appears to offer little additional benefit and is associated with increased risk of adverse effects.

If headache recurs, dose may be repeated after ≥2 hours.

Following failure to respond to first dose, reconsider diagnosis of migraine prior to administration of a second dose.

Intranasal

5 mg (1 spray) as a single dose; individualize selection of dosage and administration route.

If headache recurs, dose may be repeated after 2 hours.

Following failure to respond to first dose, reconsider diagnosis of migraine prior to administration of a second dose.

Prescribing Limits

Adults

Vascular Headaches

Migraine

Oral

Maximum 10 mg in any 24-hour period.

Safety of treating an average of >3 headaches per 30-day period has not been established.

Intranasal

Maximum 10 mg in any 24-hour period.

Safety of treating an average of >4 headaches per 30-day period has not been established.

Special Populations

Hepatic Impairment

Generally use <2.5 mg as a single oral dose in patients with moderate to severe hepatic impairment; concurrent BP monitoring recommended.

Recommended doses can be achieved only with oral formulations; use of intranasal formulation not recommended.

Cautions

Contraindications

• Known or suspected ischemic heart disease (e.g., angina pectoris, history of MI, documented silent ischemia).
• Coronary artery vasospasm (e.g., Prinzmetal variant angina).
• Other serious underlying cardiovascular disease (e.g., uncontrolled hypertension).
• Cerebrovascular syndromes (e.g., stroke syndromes, TIAs).
• Hemiplegic or basilar migraine.
• Treatment within previous 24 hours with another 5-HT₁ receptor agonist or an ergot alkaloid. (See Specific Drugs under Interactions.)
• Concurrent or recent (within 2 weeks) treatment with an MAO-A inhibitor. (See Specific Drugs under Interactions.)
• Known sensitivity to zolmitriptan or any ingredient in the formulation.

Warnings/Precautions

Warnings

Use only in patients in whom a clear diagnosis of migraine has been established.

Cardiac Effects

Risk of coronary vasospasm, myocardial ischemia and/or infarction, life-threatening cardiac rhythm disturbances, and death with use of 5-HT₁ receptor agonists.

Use not recommended in patients with symptomatic Wolff-Parkinson-White syndrome or cardiac arrhythmias associated with other accessory pathway conduction disorders.

Use not recommended in patients with known or suspected ischemic or vasospastic heart disease or in patients in whom unrecognized CAD is likely (e.g., postmenopausal women; men >40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, or family history of CAD) unless there is satisfactory evidence from prior cardiovascular evaluation that patient does not have CAD, ischemic heart disease, or other underlying cardiovascular disease.

Administer initial dose to patients with risk factors for CAD who have completed satisfactory cardiovascular evaluation under medical supervision (e.g., in clinician's office, possibly followed by ECG) unless patient previously received the drug.

Periodic cardiovascular evaluation recommended in patients with risk factors for CAD if receiving intermittent long-term therapy.

Patients with symptoms suggestive of angina after receiving zolmitriptan should be evaluated for the presence of CAD or predisposition to Prinzmetal variant angina before receiving additional doses.

Cerebrovascular Events

Possible cerebral or subarachnoid hemorrhage, stroke, and other cerebrovascular events, sometimes fatal, with use of 5-HT₁ receptor agonists.

Risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA) may be increased in patients with migraine.

Other Cardiovascular or Vasospastic Effects

Peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea reported with use of 5-HT₁ receptor agonists. Further evaluation recommended if signs or symptoms of decreased arterial flow (e.g., ischemic bowel syndrome, Raynaud's syndrome) occur following administration.

Substantial increases in BP, including hypertensive crises, reported rarely with 5-HT₁ receptor agonists in patients with or without history of hypertension.

Increases in mean pulmonary artery pressure observed following administration of a 5-HT₁ receptor agonist to patients with suspected CAD who were undergoing cardiac catheterization.

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported during concurrent therapy with 5-HT₁ receptor agonists (“triptans”) and SSRIs or selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs). Symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).

Local Effects

Possible local irritation or soreness after intranasal administration. Adverse effects perceived in nasopharynx, occasionally severe, usually resolve within 1 hour.

No clinically important nasopharyngeal changes observed by examination following repeated use for up to 1 year’s duration.

General Precautions

Ocular Effects

Possible accumulation of zolmitriptan and/or its metabolites in melanin-rich tissues (e.g., eye) over time, resulting in potential toxicity in these tissues with extended use.

Phenylketonuria

Each 2.5- or 5-mg Zomig-ZMT^® orally disintegrating tablet contains aspartame, which is metabolized in GI tract to provide 2.81 or 5.62 mg of phenylalanine, respectively. Conventional tablets do not contain aspartame.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Caution advised if zolmitriptan is used.

Pediatric Use

Safety and efficacy not established in children <18 years of age; use not recommended.

Geriatric Use

Pharmacokinetic profile similar to that in younger adults. However, patients >65 years of age were excluded from clinical studies; safety and efficacy not established.

Hepatic Impairment

Substantial elevation of BP observed in some patients with moderate-to-severe hepatic impairment following 10-mg oral dose. Use with caution in patients with hepatic impairment; BP monitoring and dosage adjustment recommended.

Common Adverse Effects

Dizziness, paresthesia, hyperesthesia, neck/throat/jaw/chest symptoms (e.g., pain, tightness, pressure, heaviness), nausea, somnolence, warm or cold sensation, asthenia, dry mouth, dyspepsia; with intranasal therapy, also nasal cavity disorder/discomfort, unusual taste.

Interactions

Appears to be metabolized by CYP1A2; active N-desmethyl metabolite appears to be further metabolized by MAO-A.

Specific Drugs

Pharmacokinetics

Absorption

Bioavailability

Well absorbed after oral administration, with peak plasma concentrations attained within 1.5 hours (conventional tablets) or 3 hours (orally disintegrating tablets). Rapidly absorbed via the nasopharynx after intranasal administration, with peak plasma concentrations attained within 3 hours.

Mean absolute bioavailability after oral administration is approximately 40%; mean bioavailability of nasal solution is 102% compared with oral tablet.

Mean plasma concentrations after oral administration are increased by up to 1.5-fold in females compared with males.

Food

Food does not substantially affect bioavailability.

Distribution

Plasma Protein Binding

25%.

Elimination

Metabolism

Undergoes hepatic metabolism to form 3 principal metabolites, including N-desmethyl zolmitriptan (5-HT_1B/1D potency is 2–6 times that of zolmitriptan). Formation of N-desmethyl zolmitriptan may depend on CYP1A2; MAO-A appears to mediate metabolism of N-desmethyl zolmitriptan.

Elimination Route

Excreted in urine (65%) and feces (30%) as unchanged drug and metabolites; dose recovered in urine as unchanged drug (8%) and indole acetic acid (31%), N-oxide (7%), and N-desmethyl (4%) metabolites.

Half-life

Approximately 3 hours for zolmitriptan and active N-desmethyl metabolite after oral or intranasal administration.

Special Populations

In patients with severe hepatic impairment, peak plasma concentrations, time to achieve peak plasma concentrations, and AUC are 1.5-, 2-, and 3-fold higher, respectively, than in healthy individuals after oral administration. Pharmacokinetics of nasal spray not evaluated in patients with hepatic impairment.

In patients with severe renal impairment (Cl_cr 5–25 mL/minute), clearance is reduced by 25% after oral administration; no substantial change in clearance in patients with moderate renal impairment (Cl_cr 26–50 mL/minute). Pharmacokinetics of nasal spray not evaluated in patients with renal impairment.

Stability

Storage

Oral

Conventional and Orally Disintegrating Tablets

20–25°C; protect from light and moisture.

Intranasal

Solution

20–25°C.

Actions

• Binds with high affinity to 5-HT_1B and 5-HT_1D receptors.
• Structurally and pharmacologically related to other selective 5-HT_1B/1D receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan).
• Precise mechanism of action not established; may ameliorate migraine through selective constriction of certain intracranial blood vessels, inhibition of neuropeptide release, and reduced transmission in trigeminal pain pathway.

Advice to Patients

• Importance of immediately informing clinician of occurrence of tightness, pain, pressure, or heaviness in chest, throat, jaw, or neck; sudden or severe abdominal pain; shortness of breath or wheezing; heart throbbing; facial swelling (e.g., eyelids, face, lips); tongue, mouth or throat swelling; rash or hives and of not taking zolmitriptan again until evaluated by a clinician. Importance of informing clinician of any other symptoms not understood by patient.
• Importance of adhering to prescribed directions for use. Importance of patient reading manufacturer's patient information before initial use and each time prescription is refilled.
• For patients taking zolmitriptan orally disintegrating tablets, importance of not removing tablet from blister package until just before administering dose; importance of peeling blister open and placing tablet on tongue to dissolve and be swallowed with saliva.
• Importance of informing patients with phenylketonuria that orally disintegrating tablets contain aspartame.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary supplements, and herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).
• Importance of informing patients of risk of serotonin syndrome with concurrent use of zolmitriptan and an SSRI or SNRI. Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions August 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.