Zomig

Zolmitriptan · Tablet, Film Coated · Oral

Prescription (Rx) Serotonin-1b and Serotonin-1d Receptor Agonist

Uses

1 INDICATIONS AND USAGE ZOMIG is indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use Only use ZOMIG if a clear diagnosis of migraine has been established. If a patient has no response to ZOMIG treatment for the first migraine attack, reconsider the diagnosis of migraine before ZOMIG is administered to treat any subsequent attacks. ZOMIG is not indicated for the prevention of migraine attacks. Safety and effectiveness of ZOMIG have not been established for cluster headache. ZOMIG is a serotonin (5-HT) 1B/1D receptor agonist (triptan) indicated for the acute treatment of migraine with or without aura in adults (1) Limitations of Use : Use only after a clear diagnosis of migraine has been established (1) Not indicated for the prophylactic therapy of migraine (1) Not indicated for the treatment of cluster headache (1)

Dosage and administration

Recommended starting dose: 1.25 mg or 2.5 mg (2.1) Maximum single dose: 5 mg (2.1) May repeat dose after 2 hours if needed; not to exceed 10 mg in any 24-hour period (2.1) Moderate or Severe Hepatic Impairment: 1.25 mg recommended (2.3, 8.6) 2.1 Dosing Information The recommended starting dose of ZOMIG is 1.25 mg or 2.5 mg. The 1.25 mg dose can be achieved by manually breaking the functionally-scored 2.5 mg tablet in half. The maximum recommended single dose of ZOMIG is 5 mg. In controlled clinical trials, a greater proportion of patients had headache response following a 2.5 mg or 5 mg dose than following a 1 mg dose. There was little added benefit from the 5 mg dose compared to the 2.5 mg dose, but adverse reactions were more frequent with the 5 mg dose. If the migraine has not resolved by 2 hours after taking ZOMIG, or returns after a transient improvement, a second dose may be administered at least 2 hours after the first dose. The maximum daily dose is 10 mg in any 24-hour period. The safety of ZOMIG in the treatment of an average of more than three migraines in a 30-day period has not been established. 2.3 Dosing in Patients with Hepatic Impairment The recommended dose of ZOMIG in patients with moderate to severe hepatic impairment is 1.25 mg (one-half of one 2.5 mg ZOMIG tablet) because of increased zolmitriptan blood levels in these patients and elevation of blood pressure in some of these patients. Limit the total daily dose in patients with severe hepatic impairment to no more than 5 mg per day. 2.4 Dosing in Patients taking Cimetidine If ZOMIG is co-administered with cimetidine, limit the maximum single dose of ZOMIG to 2.5 mg, not to exceed 5 mg in any 24-hour period [see Drug Interactions (7.5), Clinical Pharmacology (12.3)] .

Dosage forms and strengths

2.5 mg Tablets: Yellow colored, round, biconvex film-coated tablets debossed with 101 on one side and deep breakline on other side. 5 mg Tablets: Pink colored, round, biconvex film-coated tablets debossed with 102 on one side and plain on the other side. Tablets: 2.5 mg functionally-scored (3) Tablets: 5 mg (not scored) (3)

Contraindications

4 CONTRAINDICATIONS ZOMIG is contraindicated in patients with: Ischemic coronary artery disease (angina pectoris, history of myocardial infarction, or documented silent ischemia), other significant underlying cardiovascular disease, or coronary artery vasospasm including Prinzmetal’s angina [see Warnings and Precautions (5.1)]. Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2)]. History of stroke, transient ischemic attack (TIA), or history of hemiplegic or basilar migraine because these patients are at a higher risk of stroke [see Warnings and Precautions (5.4)] . Peripheral vascular disease (PVD) [see Warnings and Precautions (5.5)] . Ischemic bowel disease [see Warnings and Precautions (5.5)] . Uncontrolled hypertension [see Warnings and Precautions (5.8)]. Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, ergotamine-containing medication, or ergot-type medication (such as dihydroergotamine or methysergide) [see Drug Interactions (7.1, 7.3)] . Concurrent administration of a monoamine oxidase (MAO)-A inhibitor or recent use of a MAO-A inhibitor (that is within 2 weeks) [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)] . Known hypersensitivity to ZOMIG (angioedema and anaphylaxis seen) [see Adverse Reactions (6.2)] . History of coronary artery disease (CAD) or coronary vasospasm (4) Symptomatic Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders (4) History of stroke, transient ischemic attack, or hemiplegic or basilar migraine (4) Peripheral vascular disease (4) Ischemic bowel disease (4) Uncontrolled hypertension (4) Recent (within 24 hours) use of another 5-HT 1 agonist (e.g., another triptan), or an ergotamine-containing medication (4) Monoamine oxidase (MAO)-A inhibitor used in past 2 weeks (4) Known hypersensitivity to ZOMIG or zolmitriptan orally disintegrating tablets (4)

Warnings and precautions

Myocardial Ischemia/Infarction, and Prinzmetal’s Angina : Perform cardiac evaluation in patients with multiple cardiovascular risk factors (5.1) Arrhythmias : Discontinue ZOMIG if occurs (5.2) Chest/Throat/Neck/Jaw Pain, Tightness, and Pressure : Generally not associated with myocardial ischemia; evaluate for CAD in patients at high risk (5.3) Cerebral Hemorrhage, Subarachnoid Hemorrhage, and Stroke : Discontinue ZOMIG if occurs (5.4) Gastrointestinal Ischemic Reactions and Peripheral Vasospastic Reactions : Discontinue ZOMIG if occurs (5.5) Medication Overuse Headache : Detoxification may be necessary (5.6) Serotonin Syndrome : Discontinue ZOMIG if occurs (5.7, 7.4) 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina ZOMIG is contraindicated in patients with ischemic or vasospastic coronary artery disease (CAD) . There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of ZOMIG. Some of these reactions occurred in patients without known CAD. 5-HT 1 agonists including ZOMIG may cause coronary artery vasospasm (Prinzmetal’s Angina), even in patients without a history of CAD. Perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving ZOMIG. Do not administer ZOMIG if there is evidence of CAD or coronary artery vasospasm [see Contraindications (4)] . For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first ZOMIG dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following ZOMIG administration. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of ZOMIG. 5.2 Arrhythmias Life‑threatening disturbances of cardiac rhythm including ventricular tachycardia and ventricular fibrillation leading to death have been reported within a few hours following the administration of 5-HT 1 agonists. Discontinue ZOMIG if these disturbances occur. ZOMIG is contraindicated in patients with Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Contraindications (4)] . 5.3 Chest, Throat, Neck and Jaw Pain/Tightness/Pressure As with other 5-HT 1 agonists, sensations of tightness, pain, and pressure in the chest, throat, neck, and jaw commonly occur after treatment with ZOMIG and is usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. 5-HT 1 agonists including ZOMIG is contraindicated in patients with CAD or Prinzmetal’s variant angina [see Contraindications (4)]. 5.4 Cerebrovascular Events Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT 1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT 1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with symptoms atypical for migraine, exclude other potentially serious neurological conditions. ZOMIG is contraindicated in patients with a history of stroke or transient ischemic attack [see Contraindications (4) ] . 5.5 Other Vasospasm Reactions 5-HT 1 agonists, including ZOMIG, may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud’s syndrome. In patients who experience symptoms or signs suggestive of a vasospastic reaction following the use of any 5-HT 1 agonist, rule out a vasospastic reaction before receiving additional ZOMIG doses [see Contraindications (4)] . Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT 1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT 1 agonists have not been clearly established. 5.7 Serotonin Syndrome Serotonin syndrome may occur with triptans, including ZOMIG, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions (7.5)] . Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually rapidly occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue ZOMIG if serotonin syndrome is suspected [see Drug Interactions (7.4)] . 5.8 Increase in Blood Pressure Significant elevations in systemic blood pressure have been reported in patients treated with 5-HT 1 agonists including patients without a history of hypertension; very rarely, these increases in blood pressure have been associated with serious adverse reactions. In healthy subjects treated with 5 mg of ZOMIG, an increase of 1 and 5 mm Hg in the systolic and diastolic blood pressure, respectively, was seen. In a study of patients with moderate to severe liver impairment, 7 of 27 patients experienced 20 to 80 mm Hg elevations in systolic and/or diastolic blood pressure after a dose of 10 mg of ZOMIG.

Side effects

The following adverse reactions are described elsewhere in other sections of the prescribing information: Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina [see Warnings and Precautions (5.1)] . Arrhythmias [see Warnings and Precautions (5.2)] . Chest and or Throat, Neck and Jaw Pain/Tightness/Pressure [see Warnings and Precautions (5.3)] . Cerebrovascular Events [see Warnings and Precautions (5.4)] . Other Vasospasm Reactions [see Warnings and Precautions (5.5)] . Medication Overuse Headache [see Warnings and Precautions (5.6)] . Serotonin Syndrome [see Warnings and Precautions (5.7)] . Increase in Blood Pressure [see Warnings and Precautions (5.8)] . Most common adverse reactions (≥5% and > placebo) were neck/throat/jaw pain/tightness/pressure, dizziness, paresthesia, asthenia, somnolence, warm/cold sensation, nausea, heaviness sensation, and dry mouth (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Avema Pharma Solutions at 1-877-753-3935 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. In a long-term, open-label study where patients were allowed to treat multiple migraine attacks for up to 1 year, 8% (167 out of 2,058) withdrew from the trial because of adverse reaction. The most common adverse reactions (≥5% and > placebo) in these trials were neck/throat/jaw pain, dizziness, paresthesia, asthenia, somnolence, warm/cold sensation, nausea, heaviness sensation, and dry mouth. Table 1 lists the adverse reactions that occurred in ≥ 2% of the 2,074 patients in any one of the ZOMIG 1 mg, 2.5 mg, or 5 mg dose groups in the controlled clinical trials of ZOMIG in patients with migraines (Studies 1, 2, 3, 4, and 5) [see Clinical Studies (14) ] . Only adverse reactions that were at least 2% more frequent in a ZOMIG group compared to the placebo group are included. Several of the adverse reactions appear dose related, notably paresthesia, sensation of heaviness or tightness in chest, neck, jaw, and throat, dizziness, somnolence and possibly asthenia and nausea. Table 1: Adverse Reaction Incidence in Five Pooled Placebo-Controlled Migraine Clinical Trials * Placebo (n=401) ZOMIG 1 mg (n=163) ZOMIG 2.5 mg (n=498) ZOMIG 5 mg (n=1012) ATYPICAL SENSATIONS 6% 12% 12% 18% Paresthesia (all types) 2% 5% 7% 9% Warm/cold sensation 4% 6% 5% 7% PAIN AND PRESSURE SENSATIONS 7% 13% 14% 22% Chest - pain/tightness/pressure and/or heaviness 1% 2% 3% 4% Neck/throat/jaw - pain/tightness/pressure 3% 4% 7% 10% Heaviness other than chest or neck 1% 1% 2% 5% Other- Pressure/tightness/heaviness 0% 2% 2% 2% DIGESTIVE 8% 11% 16% 14% Dry mouth 2% 5% 3% 3% Dyspepsia 1% 3% 2% 1% Dysphagia 0% 0% 0% 2% Nausea 4% 4% 9% 6% NEUROLOGICAL 10% 11% 17% 21% Dizziness 4% 6% 8% 10% Somnolence 3% 5% 6% 8% Vertigo 0% 0% 0% 2% OTHER Asthenia 3% 5% 3% 9% Sweating 1% 0% 2% 3% * Only adverse reactions that were at least 2% more frequent in a ZOMIG group compared to the placebo group are included. There were no differences in the incidence of adverse reactions in controlled clinical trials in the following subgroups: gender, weight, age, use of prophylactic medications, or presence of aura. There were insufficient data to assess the impact of race on the incidence of adverse reactions. Less Common Adverse Reactions with ZOMIG Tablets: In the paragraphs that follow, the frequencies of less commonly reported adverse clinical reactions are presented. Because the reports include reactions observed in open and uncontrolled studies, the role of ZOMIG in their causation cannot be reliably determined. Furthermore, variability associated with adverse reaction reporting, the terminology used to describe adverse reactions, etc., limit the value of the quantitative frequency estimates provided. Adverse reaction frequencies were calculated as the number of patients who used ZOMIG tablets and reported a reaction divided by the total number of patients exposed to ZOMIG tablets (n=4,027). Reactions were further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: infrequent adverse reactions (those occurring in 1/100 to 1/1,000 patients) and rare adverse reactions (those occurring in less than 1/1,000 patients). General: Infrequent were allergic reactions. Cardiovascular: Infrequent were arrhythmias, hypertension, and syncope. Rare was tachycardia. Neurological: Infrequent were agitation, anxiety, depression, emotional lability and insomnia; Rare were amnesia, hallucinations, and cerebral ischemia. Skin: Infrequent were pruritus, rash and urticaria. Urogenital : Infrequent were polyuria, urinary frequency and urinary urgency. 6.2 Postmarketing Experience The following adverse reactions were identified during post approval use of ZOMIG. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The reactions enumerated include all except those already listed in the Clinical Trials Experience section above or the Warnings and Precautions section. Hypersensitivity Reactions: As with other 5‑HT 1B/1D agonists, there have been reports of anaphylaxis, anaphylactoid, and hypersensitivity reactions including angioedema in patients receiving ZOMIG. ZOMIG is contraindicated in patients with a history of hypersensitivity reaction to ZOMIG.

Drug interactions

7.1 Ergot-containing Drugs Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and ZOMIG within 24 hours of each other is contraindicated [see Contraindications (4)] . 7.2 MAO-A Inhibitors MAO-A inhibitors increase the systemic exposure of zolmitriptan and its active N-desmethyl metabolite. Therefore, the use of ZOMIG in patients receiving MAO-A inhibitors is contraindicated [see Contraindications (4), Clinical Pharmacology (12.3)] . 7.3 5-HT1B/1D agonists Concomitant use of other 5-HT 1B/1D agonists (including triptans) within 24 hours of ZOMIG treatment is contraindicated because the risk of vasospastic reactions may be additive [see Contraindications (4)] . 7.4 Selective Serotonin Reuptake Inhibitors and Serotonin Norepinephrine Reuptake Inhibitors Cases of life-threatening serotonin syndrome have been reported during co-administration of triptans and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) [see Warnings and Precautions (5.7)] . 7.5 Cimetidine Following administration of cimetidine, the half-life and blood levels of zolmitriptan and its active N-desmethyl metabolite were approximately doubled [see Clinical Pharmacology (12.3)] . If cimetidine and ZOMIG are used concomitantly, limit the maximum single dose of ZOMIG to 2.5 mg, not to exceed 5 mg in any 24-hour period [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)] .

Use in specific populations

Pregnancy: Based on animal data, may cause fetal harm (8.1) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of ZOMIG in pregnant women. In reproductive toxicity studies in rats and rabbits, oral administration of zolmitriptan to pregnant animals resulted in embryolethality and fetal abnormalities (malformations and variations) at clinically relevant exposures (see Data). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The estimated rates of major birth defects (2.2%-2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data have suggested that women with migraine may be at increased risk of preeclampsia during pregnancy. Data Animal Data When zolmitriptan was administered to pregnant rats during the period of organogenesis at oral doses of 100, 400, and 1200 mg/kg/day (plasma exposures (AUCs) ≈280, 1100, and 5000 times the human AUC at the maximum recommended human dose (MRHD) of 10 mg/day), there was a dose-related increase in embryolethality. A no-effect dose for embryolethality was not established. When zolmitriptan was administered to pregnant rabbits during the period of organogenesis at oral doses of 3, 10, and 30 mg/kg/day (plasma AUCs ≈1, 11, and 42 times the human AUC at the MRHD), there were increases in embryolethality and in fetal malformations and variations. The no-effect dose for adverse effects on embryofetal development was associated with a plasma AUC similar to that in humans at the MRHD. When female rats were given zolmitriptan during gestation, parturition, and lactation at oral doses of 25, 100, and 400 mg/kg/day (plasma AUCs ≈70, 280, and 1100 times that in human at the MRHD), an increased incidence of hydronephrosis was found in the offspring. The no-effect dose was associated with a plasma AUC ≈280 times that in humans at the MRHD. 8.2 Lactation Risk Summary There are no data on the presence of zolmitriptan or its metabolites in human milk, the effects on the breastfed infant, or the effects of zolmitriptan and its metabolites on milk production. In rats, oral dosing with zolmitriptan resulted in levels in milk up to 4 times that in maternal plasma. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZOMIG and any potential adverse effects on the breastfed infant from ZOMIG or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness in pediatric patients have not been established. Therefore, ZOMIG is not recommended for use in patients under 18 years of age. One randomized, placebo-controlled clinical trial of ZOMIG tablets (2.5, 5 and 10 mg) evaluated 696 pediatric patients (aged 12 to 17 years) with migraines. This study did not demonstrate the efficacy of ZOMIG compared to placebo in the treatment of migraine in adolescents. Adverse reactions in the adolescent patients treated with ZOMIG were similar in nature and frequency to those reported in clinical trials in adults treated with ZOMIG. ZOMIG has not been studied in pediatric patients less than 12 years old. In the postmarketing experience with triptans, including ZOMIG, there were no additional adverse reactions seen in pediatric patients that were not seen in adults. 8.5 Geriatric Use Clinical studies of ZOMIG did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease) prior to receiving ZOMIG [see Warnings and Precautions (5.1)] . The pharmacokinetics of zolmitriptan were similar in geriatric patients (aged > 65 years) compared to younger patients [see Clinical Pharmacology (12.3)] . 8.6 Patients with Hepatic Impairment After oral ZOMIG administration, zolmitriptan blood levels were increased in patients with moderate to severe hepatic impairment, and significant elevation in blood pressure was observed in some of these patients [see Warnings and Precautions (5.8)] . Therefore, adjust the ZOMIG dose and administer with caution in patients with moderate or severe hepatic impairment [see Dosage and Administration (2.3) and Clinical Pharmacology (12)] .

Pregnancy

8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of ZOMIG in pregnant women. In reproductive toxicity studies in rats and rabbits, oral administration of zolmitriptan to pregnant animals resulted in embryolethality and fetal abnormalities (malformations and variations) at clinically relevant exposures (see Data). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The estimated rates of major birth defects (2.2%-2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data have suggested that women with migraine may be at increased risk of preeclampsia during pregnancy. Data Animal Data When zolmitriptan was administered to pregnant rats during the period of organogenesis at oral doses of 100, 400, and 1200 mg/kg/day (plasma exposures (AUCs) ≈280, 1100, and 5000 times the human AUC at the maximum recommended human dose (MRHD) of 10 mg/day), there was a dose-related increase in embryolethality. A no-effect dose for embryolethality was not established. When zolmitriptan was administered to pregnant rabbits during the period of organogenesis at oral doses of 3, 10, and 30 mg/kg/day (plasma AUCs ≈1, 11, and 42 times the human AUC at the MRHD), there were increases in embryolethality and in fetal malformations and variations. The no-effect dose for adverse effects on embryofetal development was associated with a plasma AUC similar to that in humans at the MRHD. When female rats were given zolmitriptan during gestation, parturition, and lactation at oral doses of 25, 100, and 400 mg/kg/day (plasma AUCs ≈70, 280, and 1100 times that in human at the MRHD), an increased incidence of hydronephrosis was found in the offspring. The no-effect dose was associated with a plasma AUC ≈280 times that in humans at the MRHD.

Pediatric use

8.4 Pediatric Use The safety and effectiveness in pediatric patients have not been established. Therefore, ZOMIG is not recommended for use in patients under 18 years of age. One randomized, placebo-controlled clinical trial of ZOMIG tablets (2.5, 5 and 10 mg) evaluated 696 pediatric patients (aged 12 to 17 years) with migraines. This study did not demonstrate the efficacy of ZOMIG compared to placebo in the treatment of migraine in adolescents. Adverse reactions in the adolescent patients treated with ZOMIG were similar in nature and frequency to those reported in clinical trials in adults treated with ZOMIG. ZOMIG has not been studied in pediatric patients less than 12 years old. In the postmarketing experience with triptans, including ZOMIG, there were no additional adverse reactions seen in pediatric patients that were not seen in adults.

Geriatric use

8.5 Geriatric Use Clinical studies of ZOMIG did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease) prior to receiving ZOMIG [see Warnings and Precautions (5.1)] . The pharmacokinetics of zolmitriptan were similar in geriatric patients (aged > 65 years) compared to younger patients [see Clinical Pharmacology (12.3)] .

Overdosage

There is no experience with acute overdose of ZOMIG. Clinical study subjects who received single 50 mg oral doses of ZOMIG commonly experienced sedation. There is no specific antidote to ZOMIG. In cases of severe intoxication, intensive care procedures are recommended, including establishing and maintaining a patent airway, ensuring adequate oxygenation and ventilation, and monitoring and support of the cardiovascular system. The elimination half-life of ZOMIG is 3 hours [see Clinical Pharmacology (12.1)] ;therefore, monitor patients after overdose with ZOMIG for at least 15 hours or until symptoms or signs resolve. It is unknown what effect hemodialysis or peritoneal dialysis has on the plasma concentrations of zolmitriptan.

Description

11 DESCRIPTION ZOMIG ® (zolmitriptan) tablets contain zolmitriptan, which is a selective 5‑hydroxytryptamine 1B/1D (5-HT 1B/1D ) receptor agonist. Zolmitriptan is chemically designated as (S)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl]-2-oxazolidinone and has the following chemical structure: The empirical formula is C 16 H 21 N 3 O 2 , representing a molecular weight of 287.36. Zolmitriptan is a white to almost white powder that is readily soluble in water. ZOMIG tablets are available as 2.5 mg (yellow) and 5 mg (pink) film-coated tablets for oral administration. The film-coated tablets contain anhydrous lactose, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, colloidal silicon dioxide, titanium dioxide, polyvinyl alcohol, polyethylene glycol, talc, yellow iron oxide (2.5 mg tablet), and red iron oxide (5 mg tablet). structural figure

Mechanism of action

12.1 Mechanism of Action Zolmitriptan binds with high affinity to human recombinant 5-HT 1D and 5‑HT 1B receptors, and moderate affinity for 5-HT 1A receptors. The N-desmethyl metabolite also has high affinity for 5‑HT 1B/1D and moderate affinity for 5‑HT 1A receptors. Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (vasoactive intestinal peptide, substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system. The therapeutic activity of ZOMIG for the treatment of migraine headache is thought to be due to the agonist effects at the 5‑HT 1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

How supplied

2.5 mg Tablets – Yellow colored, round, biconvex film-coated tablets, debossed with 101 on one side and deep breakline on other side and are supplied in carton of 6 (1 x 6) unit-dose tablets (NDC 60846-130-30). 5 mg Tablets – Pink colored, round, biconvex film-coated tablets, debossed with 102 on one side and plain on the other side and are supplied in carton of 3 (1 x 3) unit-dose tablets (NDC 60846-133-60). Store ZOMIG Tablets between 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature]. Protect from light and moisture.

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information). Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospastic Reactions, and Cerebrovascular Events Inform patients that ZOMIG may cause serious cardiovascular adverse reactions such as myocardial infarction or stroke, which may result in hospitalization and even death. Although serious cardiovascular reactions can occur without warning symptoms, instruct patients to be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and instruct them to ask for medical advice when observing any indicative sign or symptoms. Instruct patients to seek medical advice if they have symptoms of other vasospastic reactions [see Warnings and Precautions (5.1, 5.2, 5.4, 5.5)] . Medication Overuse Headache Inform patients that use of drugs to treat acute migraines for 10 or more days per month may lead to an exacerbation of headache, and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)] . Serotonin Syndrome Inform patients about the risk of serotonin syndrome with the use of ZOMIG or other triptans, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) [see Warnings and Precautions (5.7)] . Pregnancy Advise patients to notify their healthcare provider if they are pregnant or plan to become pregnant. Lactation Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2)] .

Label text from the FDA structured product label by Amneal Pharmaceuticals LLC (revised Feb 14, 2024). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Zolmitriptan in 2 products

Zomig NDC products (2)

NDC	Strength & form	Labeler	Type
60846-130	Zolmitriptan 2.5 mg/1 Tablet, Film Coated	Amneal Pharmaceuticals LLC	ANDA
60846-133	Zolmitriptan 5 mg/1 Tablet, Film Coated	Amneal Pharmaceuticals LLC	ANDA

Frequently asked questions

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Zomig is listed by 1 labeler in the FDA NDC directory, including Amneal Pharmaceuticals LLC.