Zolmitriptan tablet, orally disintegrating
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1 indications and usage
Zolmitriptan orally disintegrating tablets are a serotonin (5-HT) 1B/1Dreceptor agonist (triptan) indicated for the acute treatment of migraine with or without aura in adults ( 1)
Limitations of Use:
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Zolmitriptan orally disintegrating tablets are indicated for the acute treatment of migraine with or without aura in adults.
Limitations of Use
- Only use zolmitriptan if a clear diagnosis of migraine has been established. If a patient has no response to zolmitriptan treatment for the first migraine attack, reconsider the diagnosis of migraine before zolmitriptan is administered to treat any subsequent attacks.
- Zolmitriptan orally disintegrating tablets are not indicated for the prevention of migraine attacks.
- Safety and effectiveness of zolmitriptan have not been established for cluster headache.
2 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)
- Do not break zolmitriptan orally disintegrating tablets ( 2.2)
- Moderate or Severe Hepatic Impairment: 1.25 mg recommended ( 2.3, 8.6)
3 dosage forms and strengths
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2.5 mg tablets are white/mottled white to cream white, round, flat-faced uncoated tablet, debossed with '715' on one side and plain on other the side.
5 mg tablets are white/mottled white to cream white round, biconvex, beveled, uncoated tablet, debossed with '717' on one side and plain on the other side.
- 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 1agonist (e.g., another triptan), or an ergotamine-containing medication ( 4)
- Monoamine oxidase (MAO)-A inhibitor used in past 2 weeks ( 4)
- Known hypersensitivity to zolmitriptan ( 4)
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Zolmitriptan orally disintegrating tablets are 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), Clinical Pharmacology ( 12.3)].
- Known hypersensitivity to zolmitriptan (angioedema and anaphylaxis seen) [see Adverse Reactions ( 6.2)].
5 warnings and precautions
- Myocardial Ischemia/Infarction, and Prinzmetal Angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors ( 5.1)
- Arrhythmias: Discontinue zolmitriptan 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: Disc33ontinue zolmitriptan if occurs ( 5.4)
- Gastrointestinal Ischemic Reactions and Peripheral Vasospastic Reactions: Discontinue zolmitriptan if occurs ( 5.5)
- Medication Overuse Headache: Detoxification may be necessary ( 5.6)
- Serotonin Syndrome: Discontinue zolmitriptan if occurs ( 5.7, 7.4)
- Patients with Phenylketonuria: Zolmitriptan orally disintegrating tablets contain phenylalanine ( 5.9)
6 adverse reactions
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 Zydus Pharmaceuticals(USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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The following adverse reactions are described elsewhere in other sections of the prescribing information:
- Myocardial Ischemia, Myocardial Infarction, and Prinzmetal Angina [see Warnings and Precautions ( 5.1)].
- Arrthymias [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)].
- Risks in Patients with Phenylketonuria [see Warnings and Precautions ( 5.9)].
7 drug interactions
8 use in specific populations
There are no adequate data on the developmental risk associated with the use of zolmitriptan 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.
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.
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.
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 zolmitriptan and any potential adverse effects on the breastfed infant from zolmitriptan or from the underlying maternal condition.
8.4 pediatric use
The safety and effectiveness in pediatric patients have not been established. Therefore, zolmitriptan is not recommended for use in patients under 18 years of age.
One randomized, placebo-controlled clinical trial of zolmitriptan 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 zolmitriptan compared to placebo in the treatment of migraine in adolescents. Adverse reactions in the adolescent patients treated with zolmitriptan were similar in nature and frequency to those reported in clinical trials in adults treated with zolmitriptan. Zolmitriptan has not been studied in pediatric patients less than 12 years old.
In the postmarketing experience with triptans, including zolmitriptan, there were no additional adverse reactions seen in pediatric patients that were not seen in adults.
8.5 geriatric use
Clinical studies of zolmitriptan 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 zolmitriptan [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)].
There is no experience with acute overdose of zolmitriptan. Clinical study subjects who received single 50 mg oral doses of zolmitriptan commonly experienced sedation.
There is no specific antidote to zolmitriptan. 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 zolmitriptan is 3 hours [see Clinical Pharmacology ( 12.1)]; therefore, monitor patients after overdose with zolmitriptan 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.
Zolmitriptan orally disintegrating 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 molecular formula is C 16H 21N 3O 2, representing a molecular weight of 287.36.
Zolmitriptan, USP is white to off-white crystalline powder that is freely soluble to soluble in methanol and soluble in water, sparingly soluble in dichloromethane, practically insoluble in toluene.
Each zolmitriptan orally disintegrating tablet USP, intended for oral administration,contains 2.5 mg or 5 mg of zolmitriptan USP. In addition, each tablet contains the following inactive ingredients: anhydrous citric acid, aspartame, colloidal silicon dioxide, crospovidone, gelatin, magnesium stearate,mannitol, microcrystalline cellulose, orange flavor, polacrilin potassium and sodium stearyl fumarate.
12 clinical pharmacology
12.1 mechanism of action
Zolmitriptan binds with high affinity to human recombinant 5-HT 1Dand 5-HT 1Breceptors, and moderate affinity for 5-HT 1Areceptors. The N-desmethyl metabolite also has high affinity for 5-HT 1B/1Dand moderate affinity for 5-HT 1Areceptors.
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 zolmitriptan for the treatment of migraine headache is thought to be due to the agonist effects at the 5-HT 1B/1Dreceptors on intracranial blood vessels (including the arteriovenous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.
Absorption, Distribution, Metabolism, and Excretion
Zolmitriptan is well absorbed after oral administration for both zolmitriptan tablet s and the zolmitriptan orally disintegrating tablets. Zolmitriptan displays linear kinetics over the dose range of 2.5 to 50 mg.
The AUC and C maxof zolmitriptan are similar following administration of zolmitriptan tablets and zolmitriptan orally disintegrating tablets, but the T maxis somewhat later with zolmitriptan orally disintegrating tablets, with a median T maxof 3 hours for zolmitriptan orally disintegrating tablet compared with 1.5 hours for the zolmitriptan tablet. The AUC, C max, and T maxfor the active N-desmethyl metabolite are similar for the two formulations.
During a moderate to severe migraine attack, mean AUC 0-4and C maxfor zolmitriptan, dosed as a zolmitriptan tablet, were decreased by 40% and 25%, respectively, and mean T maxwas delayed by one-half hour compared to the same patients during a migraine free period.
Food has no significant effect on the bioavailability of zolmitriptan. No accumulation occurred on multiple dosing.
Mean absolute bioavailability is approximately 40%. The mean apparent volume of distribution is 7 L/kg. Plasma protein binding of zolmitriptan is 25% over the concentration range of 10 to 1000 ng/mL.
Zolmitriptan is converted to an active N-desmethyl metabolite; the metabolite concentrations are about two-thirds that of zolmitriptan. Because the 5-HT 1B/1Dpotency of the metabolite is 2 to 6 times that of the parent compound, the metabolite may contribute a substantial portion of the overall effect after zolmitriptan administration.
Total radioactivity recovered in urine and feces was 65% and 30% of the administered dose, respectively. About 8% of the dose was recovered in the urine as unchanged zolmitriptan. Indole acetic acid metabolite accounted for 31% of the dose, followed by N-oxide (7%) and N-desmethyl (4%) metabolites. The indole acetic acid and N-oxide metabolites are inactive.
Mean total plasma clearance is 31.5 mL/min/kg, of which one-sixth is renal clearance.The renal clearance is greater than the glomerular filtration rate suggesting renal tubular secretion.
In patients with severe hepatic impairment, the mean C max, T max, and AUC 0-of zolmitriptan were increased 1.5-fold, 2-fold (2 vs. 4 hours), and 3-fold, respectively, compared to subjects with normal hepatic function. Seven out of 27 patients experienced 20 to 80 mmHg elevations in systolic and/or diastolic blood pressure after a 10 mg zolmitriptan dose. Adjust the zolmitriptan dose in patients with moderate or severe hepatic impairment [see Dosage and Administration ( 2.3), Use in Specific Populations ( 8.6)].
Clearance of zolmitriptan was reduced by 25% in patients with severe renal impairment (Cl cr >5 <25 mL/min) compared to subjects with normal renal function (Cl cr> = 70 mL/min); no significant change in clearance was observed in patients with moderate renal impairment (Cl cr >26 <50 mL/min).
Zolmitriptan pharmacokinetics in healthy elderly non-migraineur volunteers (age 65 to 76 years) was similar to those in younger non-migraineur volunteers (age 18 to 39 years).
Mean plasma concentrations of zolmitriptan were up to 1.5-fold higher in females than males.
Retrospective analysis of pharmacokinetic data between Japanese and Caucasians revealed no significant differences.
No differences in the pharmacokinetics of zolmitriptan or its effects on blood pressure were seen in mild to moderate hypertensive volunteers compared with normotensive controls.
Drug Interaction Studies
All drug interaction studies were performed in healthy volunteers using a single 10 mg dose of zolmitriptan and a single dose of the other drug except where otherwise noted.
Following one week of administration of moclobemide (150 mg twice daily), a specific MAO-A inhibitor, there was an increase of about 25% in both C maxand AUC for zolmitriptan and a 3-fold increase in the C maxand AUC of the active N-desmethyl metabolite of zolmitriptan. MAO inhibitors are contraindicated in zolmitriptan-treated patients [see Contraindications ( 4), Warnings and Precautions ( 5.7), Drug Interactions ( 7.2, 7.4)].
Selegiline, a selective MAO-B inhibitor, at a dose of 10 mg/day for 1 week, had no effect on the pharmacokinetics of zolmitriptan and its metabolite.
Following the administration of cimetidine, the half-life and AUC of zolmitriptan (5 mg dose), and its active metabolite, were approximately doubled [see Dosage and Administration ( 2.4), Drug Interactions ( 7.5)].
The pharmacokinetics of zolmitriptan, as well as its effect on blood pressure, were unaffected by 4 weeks of pretreatment with oral fluoxetine (20 mg/day).
C maxand AUC of zolmitriptan were increased 1.5-fold after one week of dosing with propranolol (160 mg/day). C maxand AUC of the N-desmethyl metabolite were reduced by 30% and 15%, respectively. There were no changes in blood pressure or pulse rate following administration of propranolol with zolmitriptan.
A single 1 gram dose of acetaminophen did not alter the pharmacokinetics of zolmitriptan and its N-desmethyl metabolite. However, zolmitriptan administration delayed the T maxof acetaminophen by one hour.
A single 10 mg dose of metoclopramide had no effect on the pharmacokinetics of zolmitriptan or its metabolites.
Retrospective analysis of pharmacokinetic data across studies indicated that mean C maxand AUC of zolmitriptan were increased by 30% and 50%, respectively, and T maxwas delayed by one-half hour in women taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied.
13 nonclinical toxicology
14 clinical studies
The efficacy of zolmitriptan tablets in the acute treatment of migraine headaches was demonstrated in five randomized, double-blind, placebo-controlled studies (Studies 1, 2, 3, 4, and 5), of which two utilized the 1 mg dose, two utilized the 2.5 mg dose and four utilized the 5 mg dose. In Study 1, patients treated their headaches in a clinic setting. In the other studies, patients treated their headaches as outpatients. In Study 4, patients who had previously used sumatriptan were excluded, whereas in the other studies no such exclusion was applied.
Patients enrolled in these 5 studies were predominantly female (82%) and Caucasian (97%) with a mean age of 40 years (range 12 to 65). Patients were instructed to treat a moderate to severe headache. Headache response, defined as a reduction in headache severity from moderate or severe pain to mild or no pain, was assessed at 1, 2, and, in most studies, 4 hours after dosing. Associated symptoms such as nausea, photophobia, and phonophobia were also assessed. Maintenance of response was assessed for up to 24 hours post-dose. A second dose of zolmitriptan tablets or other medication was allowed 2 to 24 hours after the initial treatment for persistent and recurrent headache. The frequency and time to use of these additional treatments were also recorded. In all studies, the effect of zolmitriptan was compared to placebo in the treatment of a single migraine attack.
In all five studies, the percentage of patients achieving headache response 2 hours after treatment was significantly greater among patients who received zolmitriptan tablets at all doses (except for the 1 mg dose in the smallest study) compared to those who received placebo. In Studies 1 and 3, there was a statistically significant greater percentage of patients with headache response at 2 hours in the higher dose groups (2.5 and/or 5 mg) compared to the 1 mg dose group. There were no statistically significant differences between the 2.5 and 5 mg dose groups (or of doses up to 20 mg) for the primary end point of headache response at 2 hours in any study. The results of these controlled clinical studies are summarized in Table 2.
*Study 1 was the only study in which patients treated the headache in a clinic setting.
n = number of patients randomized
NA = not applicable
P<0.05 in comparison with placebo.
P<0.05 in comparison with 1 mg.
#Study 4 was the only study where patients were excluded who had previously used sumatriptan.
The estimated probability of achieving an initial headache response by 4 hours following treatment in pooled Studies 2, 3, and 5 is depicted in Figure 1.
Estimated Probability of Achieving Initial Headache Response (Reduction in Headache Severity from Moderate or Severe Pain to Mild or No Headache) Within 4 Hours of Treatment in Pooled Studies 2, 3, and 5*
* In this Kaplan-Meier plot, the averages displayed are based on pooled data from 3 placebo controlled, outpatient trials. Patients not achieving headache response or taking additional treatment prior to 4 hours were censored at 4 hours.
For patients with migraine associated photophobia, phonophobia, and nausea at baseline, there was a decreased incidence of these symptoms following administration of zolmitriptan tablets as compared with placebo.
Two to 24 hours following the initial dose of study treatment, patients were allowed to use additional treatment for pain relief in the form of a second dose of study treatment or other medication. The estimated probability of patients taking a second dose or other medication for migraine over the 24 hours following the initial dose of study treatment is summarized in Figure 2.
The Estimated Probability of Patients Taking a Second Dose or Other Medication for Migraines over the 24 Hours Following the Initial Dose of Study Treatment in Pooled Studies 2, 3, and 5*
*In this Kaplan-Meier plot, patients not using additional treatments were censored at 24 hours. The plot includes both patients who had headache response at 2 hours and those who had no response to the initial dose. The studies did not allow taking additional doses of study medication within 2 hours post-dose.
The efficacy of zolmitriptan was unaffected by presence of aura; duration of headache prior to treatment; relationship to menses; gender, age, or weight of the patient; pre-treatment nausea or concomitant use of common migraine prophylactic drugs.
Zolmitriptan Orally Disintegrating Tablets
The efficacy of zolmitriptan 2.5 mg orally disintegrating tablets was demonstrated in a randomized, placebo-controlled trial (Study 6) that was similar in design to the trials of zolmitriptan tablets. Patients were instructed to treat a moderate to severe headache. Of the 471 patients treated in Study 6, 87% were female and 97% were Caucasian, with a mean age of 41 years (range 18-62).
At 2 hours post-dosing, there was a statistically significant greater percentage of patients treated with zolmitriptan 2.5 mg orally disintegrating tablets with a headache response (reduction in headache severity from moderate or severe pain to mild or no headache) compared to patients treated with placebo (63% vs. 22%). The estimated probability of achieving an initial headache response by 2 hours following treatment with zolmitriptan orally disintegrating tablets is depicted in Figure 3.
Estimated Probability of Achieving Initial Headache Response (Reduction in Headache Severity from Moderate or Severe Pain to Mild or No Headache) Within 2 Hours in Study 6*
*In this Kaplan-Meier plot, patients taking additional treatment or not achieving headache response prior to 2 hours were censored at 2 hours.
For patients with migraine-associated photophobia, phonophobia and nausea at baseline, there was a decreased incidence of these symptoms following administration of zolmitriptan as compared to placebo.
Two to 24 hours following the initial dose of study treatment, patients were allowed to use additional treatment in the form of a second dose of study treatment or other medication. The estimated probability of patients taking a second dose or other medication for migraine over the 24 hours following the initial dose of study treatment in Study 6 is summarized in Figure 4.
The Estimated Probability of Patients Taking a Second Dose or Other Medication for Migraines over the 24 Hours Following the Initial Dose of Study Treatment in Study 6*
*In this Kaplan-Meier plot, patients not taking additional treatments were censored at 24 hours. The plot includes both patients who had headache response at 2 hours and those who had no response to the initial dose. Taking another dose of study medication was allowed 2 hours post-dose in Study 6. In contrast to studies of zolmitriptan tablets (Studies 1, 2, 3, 4, and 5), Study 6 allowed re-dosing of zolmitriptan oral disintegrating tablets prior to 4 hours.
16 how supplied/storage and handling
Zolmitriptan Orally Disintegrating Tablets USP, 2.5 mg are white/mottled white to cream white, round, flat-faced, uncoated tablet, debossed with '715' on one side and plain on the other side and are supplied as follows:
NDC 68382-715-06 in bottle of 30 tablets
NDC 68382-715-16 in bottle of 90 tablets
NDC 68382-715-01 in bottle of 100 tablets
NDC 68382-715-10 in bottle of 1000 tablets
NDC 68382-715-86 in unit-dose blister cartons of 6 (1 x 6) unit dose tablets
NDC 68382-715-77 in unit-dose blister cartons of 100 (10 x 10) unit dose tablets
Zolmitriptan Orally Disintegrating Tablets USP, 5 mg are white/mottled white to cream white, round, biconvex, beveled, uncoated tablet, debossed with '717' on one side and plain on the other side and are supplied as follows:
NDC 68382-717-06 in bottle of 30 tablets
NDC 68382-717-16 in bottle of 90 tablets
NDC 68382-717-01 in bottle of 100 tablets
NDC 68382-717-10 in bottle of 1000 tablets
NDC 68382-717-82 in unit-dose blister cartons of 3 (1 x 3) unit dose tablets
NDC 68382-717-77 in unit-dose blister cartons of 100 (10 x 10) unit dose tablets
Storage and Handling
Store at 20 to 25C (68 to 77F) [See USP Controlled Room Temperature].
Protect from light and moisture.
Dispense in a tight, light-resistant closed container.
17 patient counseling 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 zolmitriptan 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)].
Inform patients about the risk of serotonin syndrome with the use of zolmitriptan 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)].
Advise patients to notify their healthcare provider if they are pregnant or plan to become pregnant.
Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [ see Use in Specific Populations ( 8.2)].
Handling of Zolmitriptan Orally Disintegrating Tablets
Inform patients not to break zolmitriptan orally disintegrating tablets. Inform patients that the orally disintegrating tablet is packaged in a blister. Instruct patients not to remove the oral disintegrating tablet from the blister until just prior to dosing. Instruct patients that prior to dosing, peel open the blister pack and place the orally disintegrating tablet on the tongue, where it will dissolve and be swallowed with the saliva [see Dosage and Administration ( 2.2)].
Patients with Phenylketonuria
Inform patients with phenylketonuria (PKU) that zolmitriptan orally disintegrating tablets contains phenylalanine (a component of aspartame) [see Warnings and Precautions ( 5.9)].
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Cadila Healthcare Ltd.
Zydus Pharmaceuticals (USA) Inc.
Pennington, NJ 08534
Spl patient package insert section
Zolmitriptan (zole'' mi trip' tan) Orally Disintegrating Tablets, USP
Please read this information before you start taking zolmitriptan and each time you renew your prescription just in case anything has changed. Remember, this summary does not take the place of discussions with your doctor. You and your doctor should discuss zolmitriptan when you start taking your medication and at regular checkups.
Phenylketonurics is a component of aspartame. Each 2.5 mg zolmitriptan orally disintegrating tablet contains 2.51 mg phenylalanine. Each 5 mg zolmitriptan orally disintegrating tablet contains 5.01 mg phenylalanine.
What is zolmitriptan?
Zolmitriptan is a prescription medication used to treat migraine headaches in adults. Zolmitriptan is not for other types of headaches. The safety and efficacy of zolmitriptan in patients under 18 have not been established.
What is a Migraine Headache?
Migraine is an intense, throbbing headache. You may have pain on one or both sides of your head. You may have nausea and vomiting, and be sensitive to light and noise. The pain and symptoms of a migraine headache can be worse than a common headache. Some women get migraines around the time of their menstrual period. Some people have visual symptoms before the headache, such as flashing lights or wavy lines, called an aura.
How does zolmitriptan work?
Treatment with zolmitriptan reduces swelling of blood vessels surrounding the brain. This swelling is associated with the headache pain of a migraine attack. Zolmitriptan blocks the release of substances from nerve endings that cause more pain and other symptoms like nausea, and sensitivity to light and sound. It is thought that these actions contribute to relief of your symptoms by zolmitriptan.
Who should not take zolmitriptan?
Do not take zolmitriptan if you:
- Have heart disease or a history of heart disease Have uncontrolled high blood pressure
- Have hemiplegic or basilar migraine (if you are not sure about this, ask your doctor)
- Have or had a stroke or problems with your blood circulation
- Have serious liver problems
- Have taken any of the following medicines in the last 24 hours: other "triptans" like almotriptan (AXERT ®*), eletriptan (RELPAX ®*), frovatriptan (FROVA ®*), naratriptan (AMERGE ®*), rizatriptan (MAXALT ®*), sumatriptan (IMITREX ®*), sumatriptan/naproxen (TREXIMET ®*); ergotamines like BELLERGAL-S ®*, CAFERGOT ®* , ERGOMAR ®* , WIGRAINE ®*; dihydroergotamine like D.H.E. 45 ®*or MIGRANAL ®*; or methysergide (SANSERT ®*). These medications have side effects similar to zolmitriptan.
- Have taken monoamine oxidase (MAO) inhibitors such as phenelzine sulfate (NARDIL ®*) or tranylcypromine sulfate (PARNATE ®*) for depression or other conditions within the last 2 weeks.
- Are allergic to zolmitriptan or any of its ingredients. The active ingredient is zolmitriptan. The inactive ingredients are listed at the end of this leaflet.
Tell your doctor about all the medicines you take or plan to take, including prescription and non-prescription medicines, supplements, and herbal remedies.
Tell your doctor if you are sensitive to phenylalanine, which can be found in the artificial sweetener aspartame. Zolmitriptan orally disintegrating tablets contain phenylalanine.
Tell your doctor if you are taking selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs), two types of drugs for depression or other disorders. Common SSRIs are CELEXA ®*(citalopram HBr), LEXAPRO ®*(escitalopram oxalate), PAXIL ®*(paroxetine), PROZAC ®*(fluoxetine), SYMBYAX ®*(olanzapine/fluoxetine), ZOLOFT ®*(sertraline), SARAFEM ®*(fluoxetine) and LUVOX ®*(fluvoxamine). Common SNRIs are CYMBALTA ®*(duloxetine) and EFFEXOR ®*(venlafaxine). Your doctor will decide if you can take zolmitriptan with your other medicines.
Tell your doctor if you know that you have any of the following: risk factors for heart disease like high cholesterol, diabetes, smoking, obesity (overweight), menopause, or a family history of heart disease or stroke.
Tell your doctor if you are pregnant or plan to become pregnant. It is not known if zolmitriptan orally disintegrating tablets will harm your unborn baby. Tell your doctor if you are breast feeding or plan to breast feed. It is not known if zolmitriptan passes into your breast milk.
Talk to your doctor about the best way to feed your baby while using zolmitriptan orally disintegrating tablets.
How should I take zolmitriptan?
- Take zolmitriptan exactly as your doctor tells you to take it. Your doctor will tell you how much zolmitriptan to take and when to take it.
- If you take zolmitriptan oral disintegrating tablets, do not remove the tablet from the blister pack until you are ready to take your medicine.
- You do not need to take any liquids with your zolmitriptan oral disintegrating tablets.
- Take zolmitriptan orally disintegrating tablets whole.
- Place zolmitriptan oral disintegrating tablets on your tongue, where it will dissolve.
- Safely throw away any unused tablets or pieces of tablets that have been removed from the blister packaging.
- If your headache comes back after your first dose, you may take a second dose anytime after 2 hours of taking the first dose. For any attack where the first dose did not work, do not take a second dose without talking with your doctor. Do not take more than a total of 10 mg of zolmitriptan (tablets or spray combined in any 24 hour period. If you take too much medicine, contact your doctor, hospital emergency department, or poison control center right away.
What are the possible side effects of zolmitriptan?
Zolmitriptan is generally well tolerated. As with any medicine, people taking zolmitriptan may have side effects. The side effects are usually mild and do not last long.
The most common side effects of zolmitriptan are:
- pain, pressure or tightness in the neck, throat or jaw
- tingling or other abnormal sensations
- feeling warm or cold
- feeling of tightness or heaviness in other areas of the body
- dry mouth
In very rare cases, patients taking triptans may experience serious side effects, such as heart attacks, high blood pressure, stroke, or serious allergic reactions. Extremely rarely, patients have died. Call your doctor right away if you have any of the following problems after taking zolmitriptan:
- severe tightness, pain, pressure or heaviness in your chest, throat, neck, or jaw
- shortness of breath or wheezing
- sudden or severe stomach pain
- hives; tongue, mouth, or throat swelling
- problems seeing
- unusual weakness or numbness
Some people may have a reaction called serotonin syndrome, which can be life-threatening, when they use zolmitriptan. In particular, this reaction may occur when they use zolmitriptan together with certain types of antidepressants known as SSRIs or SNRIs. Symptoms may include mental changes (hallucinations, agitation, coma), fast heartbeat, changes in blood pressure, high body temperature or sweating, tight muscles, trouble walking, nausea, vomiting, and diarrhea. Call your doctor immediately if you have any of these symptoms after taking zolmitriptan.
This is not a complete list of side effects. Talk to your doctor if you develop any symptoms that concern you.
What to do in case of an overdose?
Call your doctor or poison control center or go to the nearest hospital emergency room.
General advice about zolmitriptan
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use zolmitriptan for a condition for which it was not prescribed. Do not give zolmitriptan to other people, even if they have the same symptoms as you. People may be harmed if they take medicines that have not been prescribed for them.
This leaflet summarizes the most important information about zolmitriptan. If you would like more information about zolmitriptan, talk to your doctor. You can ask your doctor or pharmacist for information on zolmitriptan that is written for healthcare professionals.
Please address medical inquiries to MedicalAffairs@zydususa.com or Tel.: 1-877-993-8779.
What are the Ingredients in zolmitriptan orally disintegrating tablets?
Active ingredient: zolmitriptan, USP
Inactive ingredients: anhydrous citric acid, aspartame, colloidal silicon dioxide, crospovidone, gelatin, magnesium stearate, mannitol, microcrystalline cellulose, orange flavor, polacrilin potassium and sodium stearyl fumarate.
Store zolmitriptan orally disintegrating tablets at 20 to 25C (68 to 77F) [See USP Controlled Room Temperature] and away from children. Protect from light and moisture. Discard when expired.
*Other brands mentioned are trademarks of their respective owners.
Cadila Healthcare Ltd.
Zydus Pharmaceuticals USA Inc.
Pennington, NJ 08534
Ingredients and appearance - Product information
Zolmitriptan tablet, orally disintegrating- Zolmitriptan
|Product Type||HUMAN PRESCRIPTION DRUG LABEL||Item Code (Source)||NDC: 68382-715|
|Route of Administration||Oral|
|Zolmitriptan ( UNII: 2FS66TH3YW)( Zolmitriptan - UNII: 2FS66TH3YW )||2.5 mgin 1|
|Anhydrous citric acid||( UNII: XF417D3PSL)|
|Aspartame||( UNII: Z0H242BBR1)|
|Silicon dioxide||( UNII: ETJ7Z6XBU4)|
|Gelatin||( UNII: 2G86QN327L)|
|Magnesium stearate||( UNII: 70097M6I30)|
|Mannitol||( UNII: 3OWL53L36A)|
|Cellulose, microcrystalline||( UNII: OP1R32D61U)|
|Orange||( UNII: 5EVU04N5QU)|
|Polacrilin potassium||( UNII: 0BZ5A00FQU)|
|Sodium stearyl fumarate||( UNII: 7CV7WJK4UI)|
|Crospovidone||( UNII: 2S7830E561)|
|Color||WHITE (WHITE/MOTTLED WHITE TO CREAM WHITE)||Flavor||ORANGE (ORANGE)|
|Shape||ROUND (ROUND)||Size||6 mm|
|Marketing Category||Application Number or Monograph Citation||Territorial Authority||Marketing Start Date|
Labeler - Zydus Pharmaceuticals (USA) Inc.( 156861945)
|Zydus Pharmaceuticals (USA) Inc.||156861945||ANALYSIS( 68382-715, 68382-717), MANUFACTURE( 68382-715, 68382-717)|
Package label.principal display panel
Zolmitriptan Orally Disintegrating Tablets USP, 2.5 mg
Zolmitriptan Orally Disintegrating Tablets USP, 2.5 mg
Zolmitriptan Orally Disintegrating Tablets USP, 2.5 mg
6 (16) Unit-dose tablets
Package label.principal display panel
Zolmitriptan Orally Disintegrating Tablets USP, 5 mg
Zolmitriptan Orally Disintegrating Tablets USP, 5 mg
Zolmitriptan Orally Disintegrating Tablets USP, 5 mg
3 (13) Unit-dose tablets