*ZOMIG is indicated for the acute treatment of migraine with or without aura in adults.
* 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.
<!--Off-Label Use and Dosage (Adult)-->
<!--Guideline-Supported Use (Adult)-->
|offLabelAdultGuideSupport=
=====Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Pediatric Indications and Dosage-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
<!--Off-Label Use and Dosage (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport=
=====Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Contraindications-->
|contraindications=
*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.
*Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.
*History of stroke, transient ischemic attack (TIA), or history of hemiplegic or basilar migraine because these patients are at a higher risk of stroke.
*Peripheral vascular disease (PVD).
*Ischemic bowel disease.
*Uncontrolled hypertension.
*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).
*Concurrent administration of a monoamine oxidase (MAO)-A inhibitor or recent use of a MAO-A inhibitor (that is within 2 weeks).
*Known hypersensitivity to ZOMIG or ZOMIG ZMT (angioedema and anaphylaxis seen).
<!--Warnings-->
|warnings=
====Precautions====
*Myocardial Ischemia, Myocardial Infarction, and Prinzmetal 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-HT1 agonists including ZOMIG may cause coronary artery vasospasm (Prinzmetal 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 administrating 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.
*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-HT1 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)].
*Chest, Throat, Neck and Jaw Pain/Tightness/Pressure
:*As with other 5-HT1 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-HT1 agonists including ZOMIG are contraindicated in patients with CAD or Prinzmetal’s variant angina [see Contraindications (4)].
*Cerebrovascular Events
:*Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 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)].
*Other Vasospasm Reactions
:*5-HT1 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-HT1 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-HT1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 agonists have not been clearly established.
*Medication Overuse Headache
:*Overuse of acute migraine drugs (e.g. ergotamine, triptans, opioids, or a combination of drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.
*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. 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.
*Increase in Blood Pressure
:*Significant elevations in systemic blood pressure have been reported in patients treated with 5-HT1 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.
:*As with all triptans, blood pressure should be monitored in ZOMIG-treated patients. ZOMIG is contraindicated in patients with uncontrolled hypertension [see Contraindications (4)].
*Risks in Patients with Phenylketonuria
:*Phenylalanine can be harmful to patients with phenylketonuria (PKU). ZOMIG-ZMT orally disintegrating tablets contain phenylalanine (a component of aspartame). Each 2.5 mg and 5 mg orally disintegrating tablet contains 2.81 and 5.62 mg of phenylalanine, respectively. ZOMIG tablets do not contain phenylalanine.
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
|clinicalTrials=
*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.
T1
*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.
*Adverse Reactions with ZOMIG-ZMT Oral Disintegrating Tablets
:*The adverse reaction profile seen with ZOMIG-ZMT oral disintegrating tablets was similar to that seen with ZOMIG tablets.
<!--Postmarketing Experience-->
|postmarketing=
*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‑HT1B/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-->
|drugInteractions=
*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.
*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.
*5-HT1B/1D agonists
:*Concomitant use of other 5-HT1B/1D agonists (including triptans) within 24 hours of ZOMIG treatment is contraindicated because the risk of [[vasospastic]] reactions may be additive.
*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).
*Cimetidine
:*Following administration of [[cimetidine]], the half-life and blood levels of zolmitriptan and its active N-desmethyl metabolite were approximately doubled. 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.
<!--Use in Specific Populations-->
|useInPregnancyFDA=
* '''Pregnancy Category C'''
*There are no adequate and well- controlled studies in pregnant women; therefore, ZOMIG should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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.
*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 embryo-fetal 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.
|useInPregnancyAUS=
* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=
There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=
*It is not known whether zolmitriptan is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ZOMIG, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. In rats, oral dosing with zolmitriptan resulted in levels in milk up to 4 times higher than in plasma.
|useInPed=
*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 12-17 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.
|useInGeri=
*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)].
|useInGender=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=
*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)].
|useInReproPotential=
There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=
There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
<!--Administration and Monitoring-->
|administration=
* Oral
* Intravenous
|monitoring=
There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
* Description
<!--IV Compatibility-->
|IVCompat=
There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
<!--Overdosage-->
|overdose=
===Acute Overdose===
====Signs and Symptoms====
* Description
====Management====
* Description
===Chronic Overdose===
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
<!--Pharmacology-->
<!--Drug box 2-->
|drugBox=
<!--Mechanism of Action-->
|mechAction=
*
<!--Structure-->
|structure=
*
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
<!--Pharmacodynamics-->
|PD=
There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
<!--Pharmacokinetics-->
|PK=
There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
<!--Nonclinical Toxicology-->
|nonClinToxic=
'''''For patient information about Zolmitriptan tablet, click [[Zolmitriptan Oral (patient information)|here]].'''''
There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
{{SB}} ZOLMIPTRIPTAN
<!--Clinical Studies-->
==Overview==
|clinicalStudies=
'''Zolmitriptan''' is an oral, selective [[Serotonin receptor agonist]], of the [[serotonin receptor]] 1B/1D (5-HT<sub>1B</sub>/<sub>1D</sub>). It is a second-generation [[triptan]], used in the acute treatment of [[migraine]] attacks with or without [[aura (symptom)|aura]] and [[cluster headache]]s.
There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
Zolmitriptan is marketed by [[AstraZeneca]] with the brand names '''Zomig''', '''Zomigon''' (Greece & Argentina), '''AscoTop''' (Germany) and '''Zomigoro''' (France). In 2005, AstraZeneca generated $352 million in sales with Zomig.
'''| [[Zolmitriptan labels and packages|Labels and Packages]]'''
==Description==
<!--Precautions with Alcohol-->
Zolmitriptan is a synthetic [[tryptamine]] derivative and appears as a white powder that is readily soluble in water.
|alcohol=
==Indications==
* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Zolmitriptan is used for the acute treatment of migraines with or without aura in adults. Zolmitriptan is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine.
<!--Brand Names-->
Zolmitriptan comes in both a swallowable and oral disintegrating tablet. People who get migraines from aspartame should not use the disintegrating tablet (Zomig ZMT), which contains aspartame.
|brandNames=
==Contraindications and Precautions==
* ®<ref>{{Cite web | title = | url = }}</ref>
Zolmitriptan should not be given to patients with ischemic heart disease ([[angina pectoris]], history of [[myocardial infarction]], or documented silent ischemia) or to patients who have symptoms or findings consistent with ischemic heart disease, [[coronary artery vasospasm]], including [[Prinzmetal's angina]], or other significant underlying cardiovascular disease.
<!--Look-Alike Drug Names-->
Zolmitriptan may increase [[blood pressure]], it should not be given to patients with uncontrolled hypertension, should not be used within 24 hours of treatment with another 5-HT1 agonist, or an ergotamine-containing or ergot-type medication like [[dihydroergotamine]] or [[methysergide]], and should not be administered to patients with hemiplegic or basilar migraine.
|lookAlike=
Concurrent administration of [[MAOI]] or use of zolmitriptan within 2 weeks of discontinuation of MAO-A inhibitor therapy is contraindicated.
* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
==Adverse Reactions==
<!--Drug Shortage Status-->
The Zomig ZMT dissolvable pill contains aspartame, and should be avoided by anyone sensitive to that ingredient.
|drugShortage=
}}
Serious cardiac events, including [[myocardial infarction]], have been associated with zolmitriptan. These are, however, rare.
<!--Pill Image-->
Reported minor [[adverse drug reaction|adverse reaction]]s include: [[hypesthesia]], [[paresthesia]] (all types), warm and cold sensations, [[chest pain]], throat and jaw tightness, dry mouth, [[dyspepsia]], [[dysphagia]], [[nausea]], [[somnolence]], [[Vertigo (medical)|vertigo]], [[asthenia]], [[myalgia]], [[myasthenia]] and [[sweating]].
{{PillImage
|fileName=No image.jpg|This image is provided by the National Library of Medicine.
|drugName=
|NDC=
|drugAuthor=
|ingredients=
|pillImprint=
|dosageValue=
|dosageUnit=
|pillColor=
|pillShape=
|pillSize=
|pillScore=
}}
==Mechanism of Action==
<!--Label Display Image-->
Zolmitriptan is a selective agonist for [[serotonin]] (5-HT1B and 5-HT1D receptors) in cerebral arteries and trigeminal sensory nerves. It causes [[vasoconstriction]] and reduces [[inflammation]] associated with antidromic neuronal transmission and has been used in the management of acute [[migraine]] attacks.
{{LabelImage
|fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
}}
==References==
{{LabelImage
|fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
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Overview
Zolmitriptan (oral) is a serotonin (5-HT)1B/1D receptor agonist that is FDA approved for the {{{indicationType}}} of migraine with or without aura. Common adverse reactions include neck/throat/jaw pain/tightness/pressure, dizziness, paresthesia, asthenia, somnolence, warm/cold sensation, nausea, heaviness sensation, and dry mouth.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Migraine
ZOMIG is indicated for the acute treatment of migraine with or without aura in adults.
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.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Zolmitriptan (oral) in adult patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Zolmitriptan (oral) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Zolmitriptan (oral) in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Zolmitriptan (oral) in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Zolmitriptan (oral) in pediatric patients.
Contraindications
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.
Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.
History of stroke, transient ischemic attack (TIA), or history of hemiplegic or basilar migraine because these patients are at a higher risk of stroke.
Peripheral vascular disease (PVD).
Ischemic bowel disease.
Uncontrolled hypertension.
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).
Concurrent administration of a monoamine oxidase (MAO)-A inhibitor or recent use of a MAO-A inhibitor (that is within 2 weeks).
Known hypersensitivity to ZOMIG or ZOMIG ZMT (angioedema and anaphylaxis seen).
Warnings
Precautions
Myocardial Ischemia, Myocardial Infarction, and Prinzmetal 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-HT1 agonists including ZOMIG may cause coronary artery vasospasm (Prinzmetal 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 administrating 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.
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-HT1 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)].
Chest, Throat, Neck and Jaw Pain/Tightness/Pressure
As with other 5-HT1 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-HT1 agonists including ZOMIG are contraindicated in patients with CAD or Prinzmetal’s variant angina [see Contraindications (4)].
Cerebrovascular Events
Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 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)].
Other Vasospasm Reactions
5-HT1 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-HT1 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-HT1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 agonists have not been clearly established.
Medication Overuse Headache
Overuse of acute migraine drugs (e.g. ergotamine, triptans, opioids, or a combination of drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.
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. 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.
Increase in Blood Pressure
Significant elevations in systemic blood pressure have been reported in patients treated with 5-HT1 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.
As with all triptans, blood pressure should be monitored in ZOMIG-treated patients. ZOMIG is contraindicated in patients with uncontrolled hypertension [see Contraindications (4)].
Risks in Patients with Phenylketonuria
Phenylalanine can be harmful to patients with phenylketonuria (PKU). ZOMIG-ZMT orally disintegrating tablets contain phenylalanine (a component of aspartame). Each 2.5 mg and 5 mg orally disintegrating tablet contains 2.81 and 5.62 mg of phenylalanine, respectively. ZOMIG tablets do not contain phenylalanine.
Adverse Reactions
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.
T1
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.
Adverse Reactions with ZOMIG-ZMT Oral Disintegrating Tablets
The adverse reaction profile seen with ZOMIG-ZMT oral disintegrating tablets was similar to that seen with ZOMIG tablets.
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‑HT1B/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
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.
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.
5-HT1B/1D agonists
Concomitant use of other 5-HT1B/1D agonists (including triptans) within 24 hours of ZOMIG treatment is contraindicated because the risk of vasospastic reactions may be additive.
Selective Serotonin Reuptake Inhibitors and Serotonin Norepinephrine Reuptake Inhibitors
Following administration of cimetidine, the half-life and blood levels of zolmitriptan and its active N-desmethyl metabolite were approximately doubled. 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.
There are no adequate and well- controlled studies in pregnant women; therefore, ZOMIG should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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.
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 embryo-fetal 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.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Zolmitriptan (oral) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Zolmitriptan (oral) during labor and delivery.
Nursing Mothers
It is not known whether zolmitriptan is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ZOMIG, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. In rats, oral dosing with zolmitriptan resulted in levels in milk up to 4 times higher than in plasma.
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 12-17 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.
Geriatic 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)].
Gender
There is no FDA guidance on the use of Zolmitriptan (oral) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Zolmitriptan (oral) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Zolmitriptan (oral) in patients with renal impairment.
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)].
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Zolmitriptan (oral) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Zolmitriptan (oral) in patients who are immunocompromised.
Administration and Monitoring
Administration
Oral
Intravenous
Monitoring
There is limited information regarding Monitoring of Zolmitriptan (oral) in the drug label.
Description
IV Compatibility
There is limited information regarding IV Compatibility of Zolmitriptan (oral) in the drug label.
Overdosage
Acute Overdose
Signs and Symptoms
Description
Management
Description
Chronic Overdose
There is limited information regarding Chronic Overdose of Zolmitriptan (oral) in the drug label.
Pharmacology
There is limited information regarding Zolmitriptan (oral) Pharmacology in the drug label.
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