Cluster headache, treatment (off-label): Nasal inhalation (available as a 2.5 or 5 mg dose per nasal sprayer) or oral: Usual dose: 5 to 10 mg at the onset of cluster headache (maximum single dose: 10 mg) (Bahra 2000; Cittadini 2006; Rapoport 2007).
Menstrual migraine, prophylaxis (off-label use): Oral: 2.5 mg 2 to 3 times daily starting 2 days prior to the expected onset of menses and continued through to 5 days after the onset of menses (7 days total) (Tuchman 2008).
Migraine, moderate to severe, acute treatment:
Note: Do not use within 24 hours of an ergotamine preparation or a different triptan. Limit use to <10 days per month to avoid medication-overuse headache. Administration early in the course of a migraine attack, at the first sign of pain, may improve response to treatment. When attack is complicated by severe nausea or vomiting, a nonoral preparation may be more effective (AHS [Ailani 2021]).
Oral: 2.5 mg as a single dose; if symptoms persist or return, may repeat dose after ≥2 hours. Maximum: 5 mg/dose; 10 mg per 24 hours (Bird 2014; manufacturer’s labeling).
Nasal inhalation: 2.5 to 5 mg as a single dose; if symptoms persist or return, may repeat dose after ≥2 hours. Maximum: 5 mg/dose; 10 mg per 24 hours (Dodick 2005; manufacturer’s labeling). Note: Some experts recommend a large initial dose, as it may be more effective than multiple smaller doses (Schwedt 2021).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment provided in manufacturer’s labeling; however, zolmitriptan clearance is reduced in patients with severe renal impairment (CrCl 5 to 25 mL/minute).
Oral:
Tablet:
Mild impairment: There is no dosage adjustment provided in the manufacturer’s labeling.
Moderate to severe impairment: Initial: 1.25 mg (maximum: 5 mg per 24 hours in severe impairment).
Orally disintegrating tablet:
Mild impairment: There is no dosage adjustment provided in the manufacturer’s labeling.
Moderate to severe impairment: Use is not recommended.
Nasal inhalation:
Mild impairment: No dosage adjustment necessary.
Moderate to severe impairment: Use is not recommended.
(For additional information see "Zolmitriptan: Pediatric drug information")
Migraine: Children ≥12 years and Adolescents: Intranasal: Nasal inhalation:
Initial dose: 2.5 mg; may titrate as individual response may vary; maximum single dose: 5 mg/dose; Note: Administer at the onset of migraine headache.
Second dose: May repeat in 2 hours if the migraine headache has not resolved or returns after transient improvement; maximum daily dose: 10 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in manufacturer's labeling; however, zolmitriptan clearance is reduced in patients with severe renal impairment (CrCl 5 to 25 mL/minute).
Nasal inhalation: Children ≥12 years and Adolescents: Not recommended in patients with moderate or severe hepatic impairment.
Refer to adult dosing. Initiate therapy at the low end of the dosing range.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Nasal:
Zomig: 2.5 mg (6 ea); 5 mg (6 ea)
Generic: 2.5 mg (6 ea); 5 mg (1 ea, 6 ea)
Tablet, Oral:
Zomig: 2.5 mg [scored]
Zomig: 5 mg
Generic: 2.5 mg, 5 mg
Tablet Disintegrating, Oral:
Zomig ZMT: 2.5 mg [DSC], 5 mg [DSC] [contains aspartame; orange flavor]
Generic: 2.5 mg, 5 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Nasal:
Zomig: 2.5 mg (2 ea); 5 mg (6 ea)
Tablet, Oral:
Zomig: 2.5 mg
Generic: 2.5 mg
Tablet Disintegrating, Oral:
Zomig Rapimelt: 2.5 mg [contains aspartame]
Generic: 2.5 mg
Administer as soon as migraine headache starts.
Tablet: May be broken in half to achieve a smaller initial dose.
Orally-disintegrating tablet: Must be taken whole; do not break, crush, or chew. Place on tongue and allow to dissolve. Administration with liquid is not required.
Nasal spray: Blow nose gently prior to use. After removing protective cap, instill device into nostril. Block opposite nostril; breathe in gently through nose while pressing plunger of spray device. Breathe gently through mouth for 5-10 seconds.
Administer as soon as migraine headache starts.
Nasal spray: Blow nose gently prior to use. After removing protective cap, instill device into nostril, tilt head back slightly. Block opposite nostril; breathe in gently through nose while pressing plunger of spray device. Breathe gently through mouth for 5 to 10 seconds.
Migraine, moderate to severe, acute treatment:
Nasal inhalation: Acute treatment of migraine with or without aura in adults and pediatric patients ≥12 years.
Oral: Acute treatment of migraine with or without aura in adults.
Cluster headache, treatment; Menstrual migraines (short-term prevention)
ZOLMitriptan may be confused with SUMAtriptan
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Gastrointestinal: Unpleasant taste (nasal: adults: 17% to 21%; children & adolescents: 6% to 10%)
1% to 10%:
Cardiovascular: Chest pain (oral: 2% to 4%), chest pressure (nasal: 1% to <2%), facial edema (nasal: 1% to <2%), palpitations (nasal: 1% to <2%), cardiac arrhythmia (≤1%), hypertension (≤1%), syncope (≤1%), tachycardia (≤1%)
Central nervous system: Dizziness (adults: 6% to 10%; children & adolescents: 2%), paresthesia (5% to 10%), drowsiness (4% to 8%), local alterations in temperature sensations (oral: 5% to 7%), sensation of pressure (oral: 2% to 5%), hyperesthesia (nasal: 1% to 5%), (1% to 5%), flushing sensation (nasal: 4%), pain (nasal: 2% to 4%), vertigo (oral: 2%), chills (nasal: 1% to <2%), depersonalization (nasal: 1% to <2%), headache (1% to <2%), agitation (≤1%), amnesia (≤1%), anxiety (≤1%), depression (≤1%), emotional lability (oral: ≤1%), insomnia (≤1%), nervousness (nasal: ≤1%)
Dermatologic: Diaphoresis (oral: 2% to 3%), pruritus (≤1%), skin rash (≤1%), urticaria (≤1%)
Gastrointestinal: Nausea (adults: 4% to 9%; children & adolescents: 2%), xerostomia (2% to 5%), dyspepsia (oral: 2% to 3%), dysphagia (1% to 2%), abdominal pain (nasal: 1% to <2%), vomiting (1% to <2%)
Genitourinary: Urinary frequency (oral: ≤1%), urinary urgency (≤1%)
Hypersensitivity: Hypersensitivity reaction (≤1%)
Local: Local pain (4% to 10%; neck/throat/jaw), application site irritation (nasal: 3%)
Neuromuscular & skeletal: Weakness (oral: 5% to 9%; nasal: 3%), arthralgia (nasal: 1% to <2%), myalgia (nasal: 1% to <2%)
Otic: Tinnitus (≤1%)
Renal: Polyuria (≤1%)
Respiratory: Nasal discomfort (nasal: 3%), constriction of the pharynx (nasal: 2%), pressure on pharynx (nasal: 1% to <2%), bronchitis (nasal: ≤1%), cough (nasal: ≤1%), dyspnea (nasal: ≤1%), epistaxis (nasal: ≤1%), laryngeal edema (nasal: ≤1%), pharyngitis (nasal: ≤1%), rhinitis (nasal: ≤1%), sinusitis (nasal: ≤1%)
<1%, postmarketing, and/or case reports: Abnormal dreams, abnormality in thinking, altered sense of smell, amblyopia, anaphylactoid reaction, anaphylaxis, angina pectoris, angioedema, apathy, ataxia, atrial fibrillation, back pain, bradycardia, breast carcinoma, breast neoplasm, bruise, cellulitis, cerebral ischemia, colitis, confusion, conjunctivitis, constipation, convulsions, coronary artery vasospasm, cyanosis, cyst, cystitis, diarrhea, dry eye syndrome, dysmenorrhea, eczema, eructation, erythema, erythema multiforme, euphoria, eye pain, fever, fibrocystic breast disease, flu-like symptoms, gastritis, gastrointestinal carcinoma, gastrointestinal infarction, gastrointestinal necrosis, genitourinary neoplasm, gingivitis, hallucination, hepatic neoplasm, hiccups, hypertensive crisis, hyperthyroidism, hypertonia, hyperventilation, increased appetite, increased bronchial secretions, increased thirst, infection, intestinal obstruction, irritability, ischemic colitis, ischemic heart disease, lacrimation, laryngitis, leukopenia, mania, menorrhagia, myocardial infarction, neoplasm, neuropathy, otalgia, photophobia, pneumonia, psychosis, pyelonephritis, renal pain, salivation, seizure, serotonin syndrome, sialadenitis, skin neoplasm, splenic infarction, stomatitis, tardive dyskinesia, tenosynovitis, thrombophlebitis, thyroid edema, tongue edema, tremor, twitching, urinary tract infection, uterine fibroid enlargement, uterine hemorrhage, vaginitis, vasodilation, ventricular fibrillation, ventricular tachycardia, visual field defect, voice disorder, yawning
Hypersensitivity to zolmitriptan or any component of the formulation; ischemic coronary artery disease (angina pectoris, history of myocardial infarction [MI], or documented silent ischemia); coronary artery vasospasm, including Prinzmetal variant angina, or other significant underlying cardiovascular disease; Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders; peripheral vascular disease; ischemic bowel disease; uncontrolled hypertension; recent use (within 24 hours) of treatment with another 5-HT1 agonist, or an ergotamine-containing or ergot-type medication like dihydroergotamine or methysergide; history of stroke, transient ischemic attack, or history of hemiplegic migraine or migraine with brainstem aura; coadministration of monoamine oxidase A (MAO A) inhibitors or use of zolmitriptan within 2 weeks of discontinuation of MAO A inhibitor therapy.
Documentation of allergenic cross-reactivity for triptans is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Canadian labeling: Additional contraindications (not in US labeling): Valvular heart disease; ophthalmoplegic migraine.
Concerns related to adverse effects:
• Cardiac events: Coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia/fibrillation, cardiac arrest, and death have been reported within a few hours of 5-HT1 agonist administration; use is contraindicated in patients with ischemic or vasospastic coronary artery disease. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal's angina before receiving additional doses; if dosing is resumed and similar symptoms recur, monitor with ECG. Patients with Prinzmetal's variant angina, Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders should not receive zolmitriptan.
• Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke have been reported with 5-HT1 agonist administration and some have resulted in fatalities. Do not administer to patients with a history of stroke or TIA; discontinue use if a cerebrovascular event occurs.
• Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension. Use is contraindicated in patients with uncontrolled hypertension.
• Vasospasm-related events: Peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud syndrome have been reported with 5-HT1 agonists. In patients who experience signs or symptoms suggestive of a vasospastic reaction following use of a 5-HT1 agonist, rule out a vasospastic reaction before receiving additional doses.
• Visual effects: Rarely, partial vision loss and blindness (transient and permanent) have been reported with 5-HT1 agonists.
Disease-related concerns:
• Coronary artery disease: Should not be given to patients who have risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) without adequate cardiac evaluation. Patients with suspected CAD should have cardiovascular evaluation to rule out CAD before considering use; if cardiovascular evaluation is “satisfactory,” first dose should be given in the healthcare provider's office (consider ECG monitoring). Periodic evaluation of cardiovascular status should be done in all patients.
• Hepatic impairment: Use with caution in patients with hepatic impairment. Drug clearance may be reduced leading to increased plasma concentrations. With moderate to severe hepatic impairment, dosage reduction of the oral product is recommended; use of orally disintegrating tablet and nasal inhalation are not recommended in moderate to severe hepatic impairment.
Concurrent drug therapy issues:
• Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, labile blood pressure, hyper-reflexia, incoordination, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (eg, SSRIs, SNRIs, TCAs, MAO inhibitors) or agents which reduce zolmitriptan's metabolism.
Special populations:
• Older adult: Older adult patients are more likely to have underlying cardiovascular disease and hepatic or renal impairment; use with caution. Cardiovascular evaluation is recommended for older adult patients with other cardiovascular risk factors prior to initiation of therapy.
Dosage form specific issues:
• Phenylalanine: Zomig-ZMT tablets contain phenylalanine.
Other warnings/precautions:
• Appropriate use: Only indicated for acute treatment of migraine headache; not indicated for migraine prophylaxis (used off-label for menstrual migraine prophylaxis) or for the treatment of cluster headache. Acute migraine agents (eg, triptans, opioids, ergotamine, or a combination of the agents) used for 10 or more days per month may lead to worsening of headaches (medication overuse headache); withdrawal treatment may be necessary in the setting of overuse. The safety of treating >3 headaches (oral) or >4 headaches (nasal inhalation) during a 30 day period has not been established. If a patient does not respond to the first dose, the diagnosis of migraine should be reconsidered; rule out underlying neurologic disease in patients with atypical headache and in patients with no prior history of migraine.
Serious adverse events have been reported with triptans in pediatric patients, including zolmitriptan; like adults, those reported have been rare and similar in nature.
Substrate of CYP1A2 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Bromocriptine: May enhance the adverse/toxic effect of Serotonin 5-HT1D Receptor Agonists (Triptans). Management: Consider alternatives to this combination when possible. If combined, monitor for increased bromocriptine and triptan toxicities. Risk D: Consider therapy modification
Cimetidine: May increase the serum concentration of ZOLMitriptan. Management: Limit the maximum single dose of zolmitriptan to 2.5 mg, not to exceed 5 mg in 24 hours, when coadministered with cimetidine. Risk D: Consider therapy modification
Droxidopa: Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the hypertensive effect of Droxidopa. Risk C: Monitor therapy
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Monoamine Oxidase Inhibitors: Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase the serum concentration of Serotonin 5-HT1D Receptor Agonists (Triptans). Risk X: Avoid combination
Serotonergic Agents (High Risk): Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
SUMAtriptan: Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the adverse/toxic effect of SUMAtriptan. Risk X: Avoid combination
Information related to zolmitriptan use in pregnancy is limited in comparison to other medications in this class (Källén 2011; Nezvalová-Henriksen 2010; Nezvalová-Henriksen 2012; Nezvalová-Henriksen 2013; Spielmann 2018).
Until additional information is available, other agents are preferred for the initial treatment of migraine in pregnancy (MacGregor 2014; Worthington 2013).
It is not known if zolmitriptan is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Until additional information is available, other agents are preferred for the treatment of migraine in breastfeeding women (Worthington 2013).
Some products may contain phenylalanine.
Headache severity, signs/symptoms suggestive of angina; blood pressure; ECG with first dose in patients with likelihood of unrecognized coronary disease, such as patients with significant hypertension, hypercholesterolemia, obese patients, patients with diabetes, smokers with other risk factors or strong family history of coronary artery disease
Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries and sensory nerves of the trigeminal system; causes vasoconstriction and reduces inflammation associated with antidromic neuronal transmission correlating with relief of migraine
Absorption: Well absorbed
Distribution: Vd: Oral: 7 L/kg; Nasal spray: 8.4 L/kg
Protein binding: 25%
Metabolism: Converted to an active N-desmethyl metabolite (2-6 times more potent than zolmitriptan at 5-HT1B and 5-HT1D receptors)
Bioavailability: 40% (not impacted by food); mean bioavailability of nasal spray compared with oral tablet: 102%
Half-life elimination: 3 hours
Time to peak, serum: Tablet: 1.5 hours; Orally-disintegrating tablet and nasal spray: 3 hours
Excretion: Urine (~60% to 65% total dose; 8% of total dose as unchanged drug; 4% of total dose as N-desmethyl metabolite); feces (30%)
Altered kidney function: Clearance of oral zolmitriptan was reduced 25% in patients with severe renal impairment (CrCl 5 to 25 mL/minute).
Hepatic function impairment: In severely hepatically impaired patients, the Cmax, Tmax, and AUC were increased 1.5-, 2-, and 3-fold, respectively, when dosed orally.
Sex: Mean plasma concentrations of oral zolmitriptan were up to 1.5-fold higher in women than men.
Solution (ZOLMitriptan Nasal)
2.5 mg (per each): $111.45
5 mg (per each): $105.58 - $111.45
Solution (Zomig Nasal)
2.5 mg (per each): $117.31
5 mg (per each): $117.31
Tablet, orally-disintegrating (ZOLMitriptan Oral)
2.5 mg (per each): $50.13 - $55.45
5 mg (per each): $55.42 - $61.30
Tablets (ZOLMitriptan Oral)
2.5 mg (per each): $1.40 - $55.45
5 mg (per each): $1.40 - $61.67
Tablets (Zomig Oral)
2.5 mg (per each): $155.24
5 mg (per each): $155.23
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