Zomig - Drug Monograph

Introduction

Zomig (zolmitriptan) is a selective serotonin receptor agonist (triptan) specifically developed for the acute treatment of migraine with or without aura in adults. It belongs to a class of medications that represent a significant advancement in migraine-specific therapy, offering targeted relief for this debilitating neurological condition.

Mechanism of Action

Zomig exerts its therapeutic effects through selective agonism of serotonin (5-HT) receptors, primarily the 5-HT1B and 5-HT1D receptors. This dual mechanism results in:

• Cranial vasoconstriction of dilated blood vessels
• Inhibition of pro-inflammatory neuropeptide release
• Reduction of trigeminal nerve transmission

The drug does not act as a general vasoconstrictor but specifically targets the pathophysiological processes involved in migraine attacks.

Indications

FDA-approved indications:

• Acute treatment of migraine with aura in adults
• Acute treatment of migraine without aura in adults

Zomig is not indicated for migraine prophylaxis, cluster headache, hemiplegic migraine, or basilar migraine.

Dosage and Administration

• Initial dose: 2.5 mg or 5 mg at migraine onset
• Maximum single dose: 5 mg
• Maximum daily dose: 10 mg (within 24 hours)
• Minimum dosing interval: 2 hours

• Conventional tablets: 2.5 mg and 5 mg
• Orally disintegrating tablets (Zomig-ZMT): 2.5 mg and 5 mg
• Nasal spray: 5 mg

• Hepatic impairment: Maximum dose 2.5 mg
• Renal impairment (CrCl <25 mL/min): Maximum dose 2.5 mg
• Elderly: Use with caution due to increased sensitivity
• Pediatrics: Safety and efficacy not established

Pharmacokinetics

• Oral bioavailability: ~40%
• Tmax: 2-3 hours (tablets); 15 minutes (nasal spray)
• Food delays absorption but does not affect overall bioavailability

• Protein binding: ~25%
• Volume of distribution: ~7 L/kg
• Crosses blood-brain barrier

• Primarily hepatic via CYP450 1A2 and MAO-A
• Active metabolite: N-desmethyl zolmitriptan (2-6 times more potent)

• Half-life: 3 hours (zolmitriptan); 3.5 hours (active metabolite)
• Renal excretion: ~65% (primarily as metabolites)
• Fecal excretion: ~30%

Contraindications

• History of coronary artery disease or coronary vasospasm
• Uncontrolled hypertension
• History of stroke or transient ischemic attack
• Peripheral vascular disease
• Ischemic bowel disease
• Hemiplegic or basilar migraine
• Severe hepatic impairment
• Within 24 hours of another 5-HT1 agonist or ergotamine-containing medication
• Hypersensitivity to zolmitriptan or any component

Warnings and Precautions

• May cause coronary artery vasospasm, myocardial ischemia, or infarction
• Perform cardiovascular evaluation in patients with multiple risk factors
• Monitor for chest pain, shortness of breath, or irregular heartbeat

• Risk of cerebrovascular events including stroke and hemorrhage

• Use more than 10 days per month may lead to medication overuse headache

• Risk particularly with concomitant SSRI/SNRI use

• Use cautiously in patients with hepatic impairment
• Potential for increased blood pressure
• Not recommended during pregnancy unless clearly needed
• Excreted in breast milk - use with caution during breastfeeding

Drug Interactions

• MAO inhibitors: Contraindicated within 2 weeks of MAOI use (increases AUC by 75%)
• CYP1A2 inhibitors (cimetidine, fluvoxamine): Increase zolmitriptan exposure
• Other 5-HT1 agonists: Additive vasoconstrictive effects
• Ergot derivatives: Contraindicated within 24 hours
• SSRIs/SNRIs: Increased risk of serotonin syndrome
• Propranolol: Increases zolmitriptan AUC by 50%

Adverse Effects

• Dizziness (9-12%)
• Somnolence (5-8%)
• Asthenia (3-7%)
• Nausea (4-6%)
• Paresthesia (5-7%)
• Chest tightness/pressure (4-6%)
• Throat/neck discomfort (3-5%)

• Coronary artery vasospasm
• Myocardial infarction
• Cerebrovascular events
• Serotonin syndrome
• Severe hypersensitivity reactions
• Medication overuse headache

Monitoring Parameters

• Cardiovascular risk evaluation
• Blood pressure
• Liver function tests (if indicated)
• Renal function assessment

• Frequency of use (to prevent medication overuse)
• Blood pressure monitoring in hypertensive patients
• Signs of cardiovascular events
• Symptoms of serotonin syndrome
• Headache response and recurrence

• Liver function (with chronic use)
• Development of medication overuse headache
• Changes in headache pattern

Patient Education

• Use at first sign of migraine for best results
• Do not exceed recommended dosage
• Wait at least 2 hours between doses
• Do not use more than 3 doses in 24 hours
• Do not use with other migraine medications without consulting healthcare provider
• Report chest pain, shortness of breath, or unusual sensations immediately
• Inform all healthcare providers of Zomig use
• Avoid driving or operating machinery if drowsy or dizzy
• Store at room temperature away from moisture
• Orally disintegrating tablets: Place on tongue, allow to dissolve, swallow with saliva

• Chest pain, pressure, or tightness
• Severe or sudden headache different from usual migraine
• Speech difficulties
• Vision changes
• Weakness or numbness on one side
• Allergic reactions (swelling, difficulty breathing)

References

1. Dahlöf CG, Mathew N. Cardiovascular safety of 5HT1B/1D agonists--is there a cause for concern? Cephalalgia. 1998;18(8):539-545. 2. Rapoport AM, Ramadan NM, Adelman JU, et al. Optimizing the dose of zolmitriptan (Zomig) for the acute treatment of migraine. Neurology. 1997;49(4):1210-1218. 3. Zomig [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2021. 4. Tfelt-Hansen P, De Vries P, Saxena PR. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000;60(6):1259-1287. 5. Dodick D, Lipton RB, Martin V, et al. Consensus statement: cardiovascular safety profile of triptans (5-HT agonists) in the acute treatment of migraine. Headache. 2004;44(5):414-425. 6. Tepper SJ, Millson D. Safety profile of the triptans. Expert Opin Drug Saf. 2003;2(2):123-132. 7. FDA-approved drug label: Zomig (zolmitriptan). Accessdata.fda.gov. Accessed January 2024.