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ZOLMitriptan

Pronunciation

(zohl mi TRIP tan)

Index Terms

  • 311C90

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Nasal:

Zomig: 2.5 mg (6 ea); 5 mg (6 ea)

Tablet, Oral:

Zomig: 2.5 mg [scored]

Zomig: 5 mg

Generic: 2.5 mg, 5 mg

Tablet Dispersible, Oral:

Zomig ZMT: 2.5 mg, 5 mg [contains aspartame; orange flavor]

Generic: 2.5 mg, 5 mg

Brand Names: U.S.

  • Zomig
  • Zomig ZMT

Pharmacologic Category

  • Antimigraine Agent
  • Serotonin 5-HT1B, 1D Receptor Agonist

Pharmacology

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

Metabolism

Converted to an active N-desmethyl metabolite (2-6 times more potent than zolmitriptan at 5-HT1B and 5-HT1D receptors)

Excretion

Urine (~60% to 65% total dose; 8% of total dose as unchanged drug; 4% of total dose as N-desmethyl metabolite); feces (30%)

Time to Peak

Serum: Tablet: 1.5 hours; Orally-disintegrating tablet and nasal spray: 3 hours

Half-Life Elimination

3 hours

Protein Binding

25%

Special Populations: Renal Function Impairment

Clearance of oral zolmitriptan was reduced 25% in patients with severe renal impairment (CrCl 5-25 mL/minute).

Special Populations: 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.

Special Populations: Gender

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

Use: Labeled Indications

Migraines:

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.

Use: Unlabeled

Short-term prevention of menstrual migraines

Contraindications

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 or basilar migraine; coadministration of monoamine oxidase A (MAO A) inhibitors or use of zolmitriptan within 2 weeks of discontinuation of MAO A inhibitor therapy; hypersensitivity to zolmitriptan or any component of the formulation.

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.

Dosing: Adult

Migraine:

Initial dose: Note: Administer at the onset of migraine headache.

Nasal inhalation: 2.5 mg (maximum single dose: 5 mg)

Oral:

Tablet: 1.25 to 2.5 mg (maximum single dose: 5 mg)

Orally disintegrating tablet: 2.5 mg (maximum single dose: 5 mg)

Second dose (either nasal inhalation or oral): May repeat in 2 hours if the migraine headache has not resolved or returns after transient improvement (maximum daily dose: 10 mg)

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)

Dosage adjustment for concomitant therapy with cimetidine: Maximum single dose: 2.5 mg (maximum daily dose: 5 mg)

Dosing: Geriatric

Refer to adult dosing. Initiate therapy at the low end of the dosing range.

Dosing: Pediatric

Migraine: Children ≥12 years and Adolescents: Nasal inhalation: Refer to adult dosing.

Dosing: Renal Impairment

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).

Dosing: Hepatic Impairment

Oral:

Tablet:

Mild impairment: There is no dosage adjustment provided in the manufacturer’s labeling.

Moderate to severe impairment: Initial: 1.25 mg (maximum daily dose: 5 mg 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: Use is not recommended.

Administration

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.

Dietary Considerations

Some products may contain phenylalanine.

Storage

Store at 20°C to 25°C (68°F to 77°F). Protect tablets from light and moisture.

Drug Interactions

Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Cimetidine: May increase the serum concentration of ZOLMitriptan. Monitor therapy

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

Droxidopa: Serotonin 5-HT1D Receptor Agonists may enhance the hypertensive effect of Droxidopa. Monitor therapy

Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Avoid combination

MAO Inhibitors: May decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination

Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy

Propranolol: May increase the serum concentration of ZOLMitriptan. Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Tedizolid. Monitor therapy

SUMAtriptan: Serotonin 5-HT1D Receptor Agonists may enhance the adverse/toxic effect of SUMAtriptan. Avoid combination

TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Adverse Reactions

>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% (Limited to important or life-threatening): Amblyopia, anaphylactoid reaction, anaphylaxis, angina pectoris, ataxia, atrial fibrillation, bradycardia, breast carcinoma, breast neoplasm, cerebral ischemia, confusion, convulsions, coronary artery vasospasm, cyanosis, erythema multiforme, fibrocystic breast disease, gastrointestinal carcinoma, gastrointestinal infarction, gastrointestinal necrosis, genitourinary neoplasm, hallucination, hepatic neoplasm, hypertensive crisis, hyperthyroidism, infection, intestinal obstruction, ischemic colitis, ischemic heart disease, mania, myocardial infarction, neoplasm, pneumonia, psychosis, pyelonephritis, seizure, serotonin syndrome, sialadenitis, skin neoplasm, splenic infarction, tardive dyskinesia, urinary tract infection, uterine fibroid enlargement, vaginitis, vasodilatation, ventricular fibrillation, ventricular tachycardia, visual field defect

Warnings/Precautions

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’s 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:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• 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:

• Elderly: Elderly patients are more likely to have underlying cardiovascular disease and hepatic or renal impairment; use with caution. Cardiovascular evaluation is recommended for elderly 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.

Monitoring Parameters

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

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Information related to zolmitriptan use in pregnancy is limited (Källén, 2011; Nezvalová-Henriksen, 2010; Nezvalová-Henriksen, 2012). Until additional information is available, other agents are preferred for the initial treatment of migraine in pregnancy (Da Silva, 2012; MacGregor, 2012; Williams, 2012).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience loss of strength and energy, fatigue, sensation of warmth, dry mouth, nasal irritation, or change in taste. Have patient report immediately to prescriber signs of a heart attack (angina; pain in arms, back, neck, jaw, or stomach; shortness of breath; cold sweats; severe dizziness; passing out; or severe nausea or vomiting), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), severe headache, vision changes, blindness, constipation, diarrhea, severe nausea, severe vomiting, severe abdominal pain, bloody stools, weight loss, leg cramps, feeling of heaviness in legs, sensation of cold, burning or aching in feet or toes, shortness of breath, mood changes, burning or numbness feeling, or signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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