Clinical Studies 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.

Serious cardiac reactions, including myocardial infarction, have occurred following the use of ZOMIG (zolmitriptan nasal spray) Tablets. These reactions are extremely rare and most have been reported in patients with risk factors predictive of CAD. Reactions reported, in association with triptans, have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation [see CONTRAINDICATIONS, and WARNINGS AND PRECAUTIONS].

Incidence in Controlled Clinical Trials

Among 464 adult patients treating single attacks with zolmitriptan nasal spray in a blinded placebo controlled trial, there was a low withdrawal rate related to adverse reactions: 5 mg (1.3%), and placebo (0.4%). None of the withdrawals were due to a serious reaction. One patient was withdrawn due to abnormal ECG changes from baseline that was incidentally found 23 days after the last dose of ZOMIG (zolmitriptan nasal spray) Nasal Spray. The most common adverse reactions in clinical trials for ZOMIG (zolmitriptan nasal spray) Nasal Spray were: unusual taste, paresthesia, hyperesthesia, and dizziness.

Table 1 lists the adverse reactions that occurred in ≥ 2% of the 236 patients in the 5 mg dose group of the controlled clinical trial.

Table 1: Adverse reactions with an incidence of ≥ 2% of patients in the zolmitriptan 5 mg nasal spray treatment group by body system and greater than placebo.

Adverse clinical reactions occurring in ≥ 1% and < 2% of patients in all attacks of the controlled clinical trial were pain abdominal, pressure throat, vomiting, headache, tightness chest, dysphagia, insomnia, palpitation and reaction aggravation.

The incidence of adverse reactions in controlled clinical trials was not affected by gender, weight, or age of the patients (18-39 vs. 40-65 years of age), or presence of aura. There were insufficient data to assess the impact of race on the incidence of adverse reactions.

Local Adverse Reactions

Among 922 patients using the zolmitriptan nasal spray to treat 2311 attacks in the controlled clinical study who were exposed, across all doses (0.5 to 5 mg), 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 60% 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 ZOMIG (zolmitriptan nasal spray) Nasal Spray.

All nasopharyngeal adverse reactions with an incidence of ≥ 2% of patients in any zolmitriptan nasal spray dose groups are included in ADVERSE REACTIONS 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 ZOMIG (zolmitriptan nasal spray) 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. Reaction frequencies are calculated as the number of patients who used ZOMIG (zolmitriptan nasal spray) Nasal Spray and reported a reaction divided by the total number of patients exposed to ZOMIG (zolmitriptan nasal spray) 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.

Body: Infrequent: allergic reaction, back pain, chills, cyst, flu syndrome, infection, jaw pain, pressure other, jaw tightening, edema of the face, abnormal laboratory test, neck pain, neoplasm, and neck tightness, chest heaviness, chest pain, and chest pressure Rare: cellulitis, fever, jaw pressure, and neck heaviness

Cardiovascular: Infrequent: arrhythmias, hypertension, syncope, thrombophlebitis, and tachycardia

Rare: angina pectoris, bradycardia, atrial fibrillation, myocardial infarct, vasodilation, and vascular disorder

Digestive: Infrequent: diarrhea, dyspepsia, tongue edema, gastrointestinal disorder, increased saliva, and thirst Rare: increased appetite, colitis, constipation, eructation, gastritis, gastrointestinal carcinoma, gingivitis, hepatic neoplasia, intestinal obstruction, jaundice, sialadenitis, and stomatitis

Endocrine System: Rare: hyperthyroidism and thyroid edema

Hemic: Infrequent: cyanosis

Rare: ecchymosis, lymphadenopathy and leukopenia

Metabolic Nutritional: Rare: increased weight, dehydration, and peripheral edema

Musculoskeletal: Infrequent: arthralgia, joint disorder, and myalgia Rare: bone pain, osteoporosis, tenosynovitis and twitching

Nervous System: Infrequent: agitation, amnesia, anxiety, ataxia, abnormal coordination, confusion, depersonalization, depression, hypertonia, insomnia, nervousness, speech disorder, abnormal thinking, tremor, vertigo, and circumoral paresthesia Rare: apathy, convulsions, abnormal dreams, euphoria, hypertonia, irritability, tardive dyskinesia, manic reaction, neuropathy, and psychosis

Respiratory: Infrequent: bronchitis, increased cough, dyspnea, epistaxis, laryngeal edema, pharyngitis, rhinitis, sinusitis, throat discomfort, and voice alteration Rare: hiccup, hyperventilation, laryngitis, pneumonia, increased sputum, and yawning

Skin: Infrequent: pruritus, rash, skin disorder, and sweating

Rare: eczema, erythema, erythema multiform, hair disorder, and neoplasm

Special Senses: Infrequent: amblyopia, disorder of lacrimation, ear pain, eye pain, parosmia and tinnitus Rare: conjunctivitis, dry eye, photophobia, and visual field defect

Urogenital: Infrequent: polyuria and menorrhagia

Rare: breast carcinoma, dysmenorrhea, metrorrhagia, breast neoplasm, unintended pregnancy, suspicious PAP smear, uterine disorder, enlarged uterine fibroids, fibrocytic breast, vaginitis, urogenital neoplasm, cystitis, urinary tract infection, kidney pain, pyelonephritis, urinary frequency, urine impaired, and urinary tract disorder The adverse experience profile seen with ZOMIG (zolmitriptan nasal spray) Nasal Spray is similar to that seen with ZOMIG (zolmitriptan nasal spray) tablets and ZOMIG (zolmitriptan nasal spray) -ZMT tablets except for the occurrence of local adverse reactions from the nasal spray (see ZOMIG (zolmitriptan nasal spray) Tablet Prescribing Information).

Postmarketing Experience with ZOMIG (zolmitriptan nasal spray) Tablets

The following adverse reactions were identified during post approval use of ZOMIG (zolmitriptan nasal spray) . 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 following section enumerates potentially important adverse reactions that have occurred in clinical practice and which have been reported spontaneously to various surveillance systems. The reactions enumerated represent reports arising from both domestic and nondomestic use of oral zolmitriptan. The reactions enumerated include all except those already listed in the ADVERSE REACTIONS section above or those too general to be informative. Because the reports cite reactions reported spontaneously from worldwide postmarketing experience, frequency of reactions and the role of zolmitriptan in their causation cannot be reliably determined.

Cardiovascular

Coronary artery vasospasm, transient myocardial ischemia, angina pectoris, and myocardial infarction.

Digestive

Very rare gastrointestinal ischemic reactions including splenic infarction, ischemic colitis and gastrointestinal infarction or necrosis have been reported; these may present as bloody diarrhea or abdominal pain [see WARNINGS AND PRECAUTIONS].

General

As with other 5-HT_1B/1D agonists, there have been very rare reports of anaphylaxis or anaphylactoid reactions in patients receiving ZOMIG (zolmitriptan nasal spray) . There have been rare reports of hypersensitivity reactions, including angioedema.

Serotonin syndrome has also been reported during the postmarketing period [see WARNINGS AND PRECAUTIONS].

Neurological

As with other acute migraine treatments including other 5-HT₁ agonists, there have been rare reports of headache.

Read the Zomig Nasal Spray (zolmitriptan nasal spray) Side Effects Center for a complete guide to possible side effects »

Ergot-containing drugs

Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because there is a theoretical basis that these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and zolmitriptan within 24 hours of each other should be avoided [see CONTRAINDICATIONS].

MAO-A Inhibitors

MAO-A inhibitors increase the systemic exposure of zolmitriptan. Therefore, the use of zolmitriptan in patients receiving MAO-A inhibitors is contraindicated [see CLINICAL PHARMACOLOGY and CONTRAINDICATIONS].

5-HT_1B/1D agonists (e.g. triptans)

Concomitant use of other 5-HT_1B/1D agonists within 24 hours of ZOMIG treatment is not recommended [see CONTRAINDICATIONS].

Cimetidine

Following administration of cimetidine, the half-life and AUC of zolmitriptan and its active metabolites were approximately doubled [see CLINICAL PHARMACOLOGY].

Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome

Cases of life-threatening serotonin syndrome have been reported during combined use of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) and triptans [see WARNINGS AND PRECAUTIONS ].

Drug abuse and dependence

The abuse potential of ZOMIG has not been assessed in clinical trials.

Last reviewed on RxList: 12/22/2008
This monograph has been modified to include the generic and brand name in many instances.