zolmitriptan 5 mg odt (generic zomig zmt)

Cautions

Contraindications

Ischemic heart disease (e.g., angina pectoris, myocardial infarction, silent ischemia), coronary vasospasm (e.g., Prinzmetal variant angina), Wolff-Parkinson-White syndrome or cardiac arrhythmias associated with other accessory pathway conduction disorders, uncontrolled hypertension, other serious underlying cardiovascular disease, history of stroke or transient ischemic attack, peripheral vascular disease, or ischemic bowel disease. Basilar or hemiplegic migraine. Treatment within the previous 24 hours with another 5-HT₁ receptor agonist or with an ergot alkaloid (e.g., ergotamine, dihydroergotamine, methysergide [no longer commercially available in the US]). Concurrent or recent (within 2 weeks) treatment with a monoamine oxidase-A (MAO-A) inhibitor. Known hypersensitivity to zolmitriptan or any ingredient in the formulation.

Warnings/Precautions

Careful Diagnosis of Migraine

Zolmitriptan should be used only in patients in whom a clear diagnosis of migraine has been established. If the first attack of migraine treated with zolmitriptan fails to respond to the drug, the diagnosis of migraine should be reconsidered before zolmitriptan is administered to treat subsequent attacks. Care should be taken to exclude other potentially serious neurologic disorders before zolmitriptan is administered to patients not previously diagnosed with migraine or to patients who present with atypical symptoms.

Cardiac Effects

Serious cardiac events, including acute myocardial infarction and fatal or life-threatening cardiac rhythm disturbances (e.g., ventricular tachycardia or fibrillation), have occurred within a few hours following administration of 5-HT₁ receptor agonists. Myocardial ischemia/infarction or coronary vasospasm (e.g., Prinzmetal variant angina) may occur even in patients without a history of coronary artery disease. Use of zolmitriptan is contraindicated in patients with ischemic or vasospastic heart disease. The drug should be discontinued if disturbances in cardiac rhythm occur.(See Cautions: Contraindications.)

Although sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw occur frequently following administration of 5-HT₁ receptor agonists, these sensations usually are noncardiac in origin. However, the manufacturer states that a cardiovascular evaluation should be performed if the patient is at high cardiac risk.

Patients with multiple cardiovascular risk factors (e.g., postmenopausal women; men older than 40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, or family history of coronary artery disease) who have not previously received therapy with a 5-HT₁ receptor agonist should undergo cardiovascular evaluation prior to initiation of 5-HT₁ receptor agonist therapy. If the evaluation provides evidence of coronary artery disease or coronary artery vasospasm, the drug should not be administered. For patients with a satisfactory cardiovascular evaluation, the manufacturer states that consideration should be given to administration of the first dose in a medically supervised setting with electrocardiographic monitoring performed immediately following administration of the dose. Periodic cardiovascular evaluation is recommended for patients with risk factors for coronary artery disease who are receiving intermittent long-term therapy with 5-HT₁ receptor agonists.

For further information on the systematic approach to administering 5-HT₁ receptor agonists in patients with risk factors for the development of coronary artery disease,

Cerebrovascular Effects

Cerebral or subarachnoid hemorrhage and stroke, sometimes fatal, have occurred in patients receiving 5-HT₁ receptor agonists. In a number of cases, it appears possible that the cerebrovascular event was the primary event, and the 5-HT₁ receptor agonist was administered in the mistaken belief that the patient's symptoms were caused by a migraine attack. Patients with migraine may be at increased risk for certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack). Therapy with 5-HT₁ receptor agonists should be discontinued in patients experiencing a cerebrovascular event.(See Cautions: Contraindications.)

Other Cardiovascular or Vasospastic Effects

Noncoronary vasospastic reactions, including peripheral vascular ischemia, GI ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud's syndrome, have been reported in patients receiving 5-HT₁ receptor agonists, including zolmitriptan.(See Cautions: Contraindications.) Transient or permanent blindness and partial vision loss also have been reported very rarely in patients receiving 5-HT₁ receptor agonists, although visual disorders may occur as manifestations of migraine attacks. Patients experiencing signs or symptoms suggestive of vasospastic reactions following administration of any 5-HT₁ receptor agonist should be evaluated to rule out vasospastic reactions before receiving additional doses of zolmitriptan.

Substantial increases in blood pressure, including hypertensive crisis with acute impairment of organ systems, have been reported rarely following administration of 5-HT₁ receptor agonists in patients with or without a history of hypertension.(See Cautions: Contraindications.) Blood pressure should be monitored in all patients receiving zolmitriptan. In healthy individuals receiving zolmitriptan 5 mg, increases in systolic and diastolic blood pressure of 1 and 5 mm Hg, respectively, were observed. However, substantial increases in blood pressure have been observed in patients with moderate to severe hepatic disease.(See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

Increases in mean pulmonary arterial pressure have been observed following administration of another 5-HT₁ receptor agonist to patients with suspected coronary artery disease who were undergoing cardiac catheterization.

Serotonin Syndrome

Potentially life-threatening serotonin syndrome has been reported in patients receiving 5-HT₁ receptor agonists, particularly in those receiving concomitant therapy with selective serotonin-reuptake inhibitors (SSRIs) or selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs). Serotonin syndrome also may occur in patients receiving 5-HT₁ receptor agonists concomitantly with MAO inhibitors or tricyclic antidepressants. Symptoms of serotonin syndrome 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 GI symptoms (e.g., nausea, vomiting, diarrhea). If concurrent therapy with a 5-HT₁ receptor agonist and an SSRI or SNRI is clinically warranted, the patient should be observed carefully, particularly during initiation of therapy, when dosage is increased, or when another serotonergic agent is initiated. If manifestations of serotonin syndrome occur, treatment with zolmitriptan and any concurrently administered serotonergic agents should be discontinued and supportive and symptomatic treatment should be initiated.

Medication Overuse Headache

Excessive use of drugs indicated for the management of acute migraine attacks (e.g., use of 5-HT₁ receptor agonists, ergotamine, opiates, or certain analgesic combinations on a regular basis for 10 or more days per month) may result in migraine-like daily headaches or a marked increase in the frequency of migraine attacks. Detoxification, including withdrawal of the overused drugs; treatment of withdrawal symptoms (which often include transient worsening of headaches); and consideration of prophylactic therapy for migraine attacks may be necessary.

Sensitivity Reactions

Hypersensitivity reactions (e.g., angioedema, anaphylaxis) have been reported in patients receiving zolmitriptan.

Ocular Effects

Accumulation of zolmitriptan and/or its metabolites in melanin-rich tissues (such as the eye) may occur over time, resulting in potential toxicity in these tissues with extended use.

Phenylketonuria

Individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that each zolmitriptan 2.5- or 5-mg orally disintegrating tablet contains aspartame, which is metabolized in the GI tract to provide 2.81 or 5.62 mg of phenylalanine, respectively, following oral administration. Zolmitriptan conventional tablets do not contain aspartame.

Specific Populations

Pregnancy

Category C.

Lactation

Zolmitriptan is distributed into milk in rats. It is not known whether zolmitriptan is distributed into milk in humans. A decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

Pediatric Use

Safety and efficacy of zolmitriptan have not been established in children younger than 18 years of age. Randomized, placebo-controlled studies in adolescents 12-17 years of age with migraine headaches failed to demonstrate efficacy of the drug. Adverse effects reported in adolescents were similar to those reported in adults. Serious adverse events have been reported during postmarketing experience in a limited number of pediatric patients receiving 5-HT₁ receptor agonists, including zolmitriptan. Zolmitriptan has not been studied in children younger than 12 years of age,

Geriatric Use

Experience in patients 65 years of age and older is insufficient to determine whether they respond differently than younger adults; dosage in geriatric patients should be selected with caution.

Pharmacokinetic profile of zolmitriptan in geriatric patients is similar to that in younger adults.

Hepatic Impairment

Peak plasma concentrations, time to achieve peak plasma concentrations, and area under the plasma concentration-time curve (AUC) of zolmitriptan reportedly were 1.5-, 2-, and 3-fold higher, respectively, in patients with severe hepatic impairment receiving orally administered zolmitriptan compared with healthy individuals. The effect of hepatic impairment on the pharmacokinetics of intranasally administered zolmitriptan has not been evaluated. Substantial elevation of blood pressure (increase in systolic and/or diastolic blood pressure of 20-80 mm Hg) was observed in some patients with moderate to severe hepatic impairment following a 10-mg dose of zolmitriptan. The drug should be used with caution in patients with moderate to severe hepatic impairment; dosage adjustment is recommended in such patients.(See Dosage and Administration: Special Populations.)

Renal Impairment

Clearance of zolmitriptan reportedly was reduced by 25% in patients with severe renal impairment (creatinine clearance of 5-25 mL/minute) receiving orally administered zolmitriptan; no substantial change in clearance was observed in patients with moderate renal impairment (creatinine clearance of 26-50 mL/minute). The effect of renal impairment on the pharmacokinetics of intranasally administered zolmitriptan has not been evaluated.

Common Adverse Effects

Adverse effects occurring in 2% or more of patients receiving orally administered zolmitriptan and more frequently (by at least 2 percentage points) with zolmitriptan than with placebo include dizziness, paresthesia, neck/throat/jaw/chest symptoms (e.g., pain, tightness, pressure, heaviness), other sensations of heaviness/pressure/tightness, nausea, somnolence, warm or cold sensation, asthenia, dry mouth, dyspepsia, dysphagia, vertigo, and sweating.

Adverse effects occurring in 2% or more of patients receiving intranasal zolmitriptan and more frequently with zolmitriptan than with placebo include paresthesia, hyperesthesia, unusual taste, throat pain, pain of specified location, nausea, somnolence, disorder or discomfort of the nasal cavity, asthenia, tightness of the throat, and dry mouth.