Zolmitriptan

5 mg or 5 mg in the controlled clinical trial, approximately 3% noted local irritation or soreness at the site of administration. Adverse reactions of any kind, perceived in the nasopharynx (which may include systemic effects of triptans) were severe in about 1% of patients and approximately 57% resolved in 1 hour.

Nasopharyngeal examinations, in a subset of patients participating in two long term trials of up to one-year duration, failed to demonstrate any clinically significant changes with repeated use of zolmitriptan nasal spray. All nasopharyngeal adverse reactions with an incidence of ≥ 2% of patients in any zolmitriptan nasal spray dose groups are included in Table 1.

Other Adverse Reactions:

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 zolmitriptan in their causation cannot be reliably determined.

, limit the value of the quantitative frequency estimates provided. Reaction frequencies are calculated as the number of patients who used zolmitriptan nasal spray and reported a reaction divided by the total number of patients exposed to zolmitriptan nasal spray (n=3059).

All reported reactions are included except those already listed in the previous table, those too general to be informative, and those not reasonably associated with the use of the drug. Reactions are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients and rare adverse reactions are those occurring in fewer than 1/1,000 patients.

General:

Infrequent: allergic reactions.

Cardiovascular:

Infrequent: arrhythmias, hypertension, syncope and tachycardia. Rare: angina pectoris and myocardial infarct.

Digestive:

Rare: stomatitis.

Neurological:

Infrequent: agitation, amnesia, anxiety, depression, insomnia, and nervousness. Rare: convulsions.

Respiratory:

Infrequent: bronchitis, increased cough, dyspnea, epistaxis, laryngeal edema, pharyngitis, rhinitis, and sinusitis.

Skin:

Infrequent: pruritus, rash, and urticaria.

Urogenital:

Infrequent: polyuria and urinary urgency. Rare: urinary frequency.

Special senses:

Infrequent: tinnitus. Rare: conjunctivitis, dry eye, and visual field defect. The adverse reaction profile seen with zolmitriptan nasal spray is similar to that seen with zolmitriptan tablets and zolmitriptan orally disintegrating tablets except for the occurrence of local adverse reactions from the nasal spray (see zolmitriptan tablet/zolmitriptan oral disintegrating tablet Prescribing Information) .

2) ] . 5 mg and 5 mg zolmitriptan nasal spray and numerically greater than placebo) after a single dose are summarized in Table 2. Dysgeusia (unusual taste) was the most common adverse reaction, with a numerically greater incidence for patients receiving zolmitriptan compared to placebo (10% vs.

2%). Other common adverse reactions were nasal discomfort, dizziness, oropharyngeal pain, and nausea. 5 mg or 5 mg zolmitriptan dose groups and with an incidence greater than placebo. 5 mg (N=81) Zolmitriptan 5 mg (N=431) Unusual taste 2% 6% 10% Nasal discomfort 1% 3% 3% Dizziness 1% 0% 2% Oropharyngeal pain 2% 0% 2% Nausea 1% 1% 2% The adverse reaction profile was similar across gender.

There were insufficient data to assess the impact of race on the incidence of adverse reactions. 2 Postmarketing Experience The following adverse reactions were identified during post approval use of zolmitriptan. 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:

There have been reports of anaphylaxis, anaphylactoid, and hypersensitivity reactions including angioedema in patients receiving zolmitriptan. Zolmitriptan is contraindicated in patients with a history of hypersensitivity reaction to zolmitriptan.

However, if a cardiac origin is suspected, patients should be evaluated. Patients shown to have CAD and those with Prinzmetal's variant angina should not receive 5-HT 1 agonists [see Contraindications (4) ] . 4 Cerebrovascular Events Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT 1 agonists, and some have resulted in fatalities.

In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT 1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not.

Discontinue zolmitriptan if a cerebrovascular event occurs. 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, other potentially serious neurological conditions should be excluded.

Zolmitriptan should not be administered to patients with a history of stroke or transient ischemic attack [see Contraindications (4) ] . 5 Other Vasospasm Reactions 5-HT 1 agonists, including zolmitriptan, 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 vasospasm reaction following the use of any 5-HT 1 agonist, the suspected vasospasm reaction should be ruled out before receiving additional zolmitriptan doses [see Contraindications (4) ] .

Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT 1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT 1 agonists have not been clearly established.

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. 5) ] . , 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.

5) and Patient Counseling Information (17) ] . 8 Increase in Blood Pressure Significant elevations in systemic blood pressure have been reported in patients treated with 5-HT 1 agonists including patients without a history of hypertension.

Very rarely these increases in blood pressure have been associated with significant clinical events. In healthy subjects treated with 5 mg of zolmitriptan oral tablet, 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 zolmitriptan oral tablet. As with all triptans, blood pressure should be monitored in zolmitriptan-treated patients.

Zolmitriptan is contraindicated in patients with uncontrolled hypertension [see Contraindications (4) ] .