SIDE EFFECTS

Serious cardiac events, including some that have been fatal, have occurred following the use of IMITREX Injection or Tablets. These events are extremely rare and most have been reported in patients with risk factors predictive of CAD. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS).

Significant hypertensive episodes, including hypertensive crises, have been reported on rare occasions in patients with or without a history of hypertension (see WARNINGS).

Incidence in Controlled Clinical Trials

Table 2 lists adverse events that occurred in placebo-controlled clinical trials in patients who took at least 1 dose of study drug. Only events that occurred at a frequency of 2% or more in any group treated with IMITREX Tablets and were more frequent in that group than in the placebo group are included in Table 2. The events cited reflect experience gained under closely monitored conditions of clinical trials in a highly selected patient population. In actual clinical practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ.

Table 2: Treatment-Emergent Adverse Events Reported by at Least 2% of Patients in Controlled Migraine Trials^a

Other events that occurred in more than 1% of patients receiving IMITREX Tablets and at least as often on placebo included nausea and/or vomiting, migraine, headache, hyposalivation, dizziness, and drowsiness/sleepiness.

IMITREX Tablets are generally well tolerated. Across all doses, most adverse reactions were mild and transient and did not lead to long-lasting effects. The incidence of adverse events in controlled clinical trials was not affected by gender or age of the patients. There were insufficient data to assess the impact of race on the incidence of adverse events.

Other Events Observed in Association With the Administration of IMITREX Tablets

In the paragraphs that follow, the frequencies of less commonly reported adverse clinical events are presented. Because the reports include events observed in open and uncontrolled studies, the role of IMITREX Tablets in their causation cannot be reliably determined. Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, etc., limit the value of quantitative frequency estimates provided. Event frequencies are calculated as the number of patients who used IMITREX Tablets (25, 50, or 100 mg) and reported an event divided by the total number of patients (N = 6,348)exposed to IMITREX Tablets. All reported events 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. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in at least 1/100 patients, infrequent adverse events are those occurring in 1/100 to 1/1,000 patients, and rare adverse events are those occurring in fewer than 1/1,000 patients.

Atypical Sensations: Frequent were burning sensation and numbness. Infrequent was tight feeling in head. Rare were dysesthesia.

Cardiovascular: Frequent were palpitations, syncope, decreased blood pressure, and increased blood pressure. Infrequent were arrhythmia, changes in ECG, hypertension, hypotension, pallor, pulsating sensations, and tachycardia. Rare were angina, atherosclerosis, bradycardia, cerebral ischemia, cerebrovascular lesion, heart block, peripheral cyanosis, thrombosis, transient myocardial ischemia, and vasodilation.

Ear, Nose, and Throat: Frequent were sinusitis, tinnitus; allergic rhinitis; upper respiratory inflammation; ear, nose, and throat hemorrhage; external otitis; hearing loss; nasal inflammation; and sensitivity to noise. Infrequent were hearing disturbances and otalgia. Rare was feeling of fullness in the ear(s).

Endocrine and Metabolic: Infrequent was thirst. Rare were elevated thyrotropin stimulating hormone (TSH) levels; galactorrhea; hyperglycemia; hypoglycemia; hypothyroidism; polydipsia; weight gain; weight loss; endocrine cysts, lumps, and masses; and fluid disturbances.

Eye: Rare were disorders of sclera, mydriasis, blindness and low vision, visual disturbances, eye edema and swelling, eye irritation and itching, accommodation disorders, external ocular muscle disorders, eye hemorrhage, eye pain, and keratitis and conjunctivitis.

Gastrointestinal: Frequent were diarrhea and gastric symptoms. Infrequent were constipation, dysphagia, and gastroesophageal reflux. Rare were gastrointestinal bleeding, hematemesis, melena, peptic ulcer, gastrointestinal pain, dyspeptic symptoms, dental pain, feelings of gastrointestinal pressure, gastritis, gastroenteritis, hypersalivation, abdominal distention, oral itching and irritation, salivary gland swelling, and swallowing disorders.

Hematological Disorders: Rare was anemia.

Musculoskeletal: Frequent was myalgia. Infrequent was muscle cramps. Rare were tetany; muscle atrophy, weakness, and tiredness; arthralgia and articular rheumatitis; acquired musculoskeletal deformity; muscle stiffness, tightness, and rigidity; and musculoskeletal inflammation.

Neurological: Frequent were phonophobia and photophobia. Infrequent were confusion, depression, difficulty concentrating, disturbance of smell, dysarthria, euphoria, facial pain, heat sensitivity, incoordination, lacrimation, monoplegia, sleep disturbance, shivering, syncope, and tremor. Rare were aggressiveness, apathy, bradylogia, cluster headache, convulsions, decreased appetite, drug abuse, dystonic reaction, facial paralysis, hallucinations, hunger, hyperesthesia, hysteria, increased alertness, memory disturbance, neuralgia, paralysis, personality change, phobia, radiculopathy, rigidity, suicide, twitching, agitation, anxiety, depressive disorders, detachment, motor dysfunction, neurotic disorders, psychomotor disorders, taste disturbances, and raised intracranial pressure.

Respiratory: Frequent was dyspnea. Infrequent was asthma. Rare were hiccoughs, breathing disorders, cough, and bronchitis.

Skin: Frequent was sweating. Infrequent were erythema, pruritus, rash, and skin tenderness. Rare were dry/scaly skin, tightness of skin, wrinkling of skin, eczema, seborrheic dermatitis, and skin nodules.

Breasts: Infrequent was tenderness. Rare were nipple discharge; breast swelling; cysts, lumps, and masses of breasts; and primary malignant breast neoplasm.

Urogenital: Infrequent were dysmenorrhea, increased urination, and intermenstrual bleeding. Rare were abortion and hematuria, urinary frequency, bladder inflammation, micturition disorders, urethritis, urinary infections, menstruation symptoms, abnormal menstrual cycle, inflammation of fallopian tubes, and menstrual cycle symptoms.

Miscellaneous: Frequent was hypersensitivity. Infrequent were fever, fluid retention, and overdose. Rare were edema, hematoma, lymphadenopathy, speech disturbance, voice disturbances, contusions.

Other Events Observed in the Clinical Development of IMITREX

The following adverse events occurred in clinical trials with IMITREX Injection and IMITREX Nasal Spray. Because the reports include events observed in open and uncontrolled studies, the role of IMITREX in their causation cannot be reliably determined. All reported events are included except those already listed, those too general to be informative, and those not reasonably associated with the use of the drug.

Atypical Sensations: Feeling strange, prickling sensation, tingling, and hot sensation.

Cardiovascular: Abdominal aortic aneurysm, abnormal pulse, flushing, phlebitis, Raynaud syndrome, and various transient ECG changes (nonspecific ST or T wave changes, prolongation of PR or QTc intervals, sinus arrhythmia, nonsustained ventricular premature beats, isolated junctional ectopic beats, atrial ectopic beats, delayed activation of the right ventricle).

Chest Symptoms: Chest discomfort.

Endocrine and Metabolic: Dehydration.

Ear, Nose, and Throat: Disorder/discomfort nasal cavity and sinuses, ear infection, Meniere disease, and throat discomfort.

Eye: Vision alterations.

Gastrointestinal: Abdominal discomfort, colitis, disturbance of liver function tests, flatulence/eructation, gallstones, intestinal obstruction, pancreatitis, and retching.

Injection Site Reaction

Miscellaneous: Difficulty in walking, hypersensitivity to various agents, jaw discomfort, miscellaneous laboratory abnormalities, “serotonin agonist effect,” swelling of the extremities, and swelling of the face.

Mouth and Teeth: Disorder of mouth and tongue (e.g., burning of tongue, numbness of tongue, dry mouth).

Musculoskeletal: Arthritis, backache, intervertebral disc disorder, neck pain/stiffness, need to flex calf muscles, and various joint disturbances (pain, stiffness, swelling, ache).

Neurological: Bad/unusual taste, chills, diplegia, disturbance of emotions, sedation, globus hystericus, intoxication, myoclonia, neoplasm of pituitary, relaxation, sensation of lightness, simultaneous hot and cold sensations, stinging sensations, stress, tickling sensations, transient hemiplegia, and yawning.

Respiratory: Influenza and diseases of the lower respiratory tract and lower respiratory tract infection.

Skin: Skin eruption, herpes, and peeling of the skin.

Urogenital: Disorder of breasts, endometriosis, and renal calculus.

Postmarketing Experience (Reports for Subcutaneous or Oral Sumatriptan)

Thefollowing section enumerates potentially important adverse events that have occurred in clinical practice and that have been reported spontaneously to various surveillance systems. The events enumerated represent reports arising from both domestic and nondomestic use of oral or subcutaneous dosage forms of sumatriptan. The events enumerated include all except those already listed in the ADVERSE REACTIONS section above or those too general to be informative. Because the reports cite events reported spontaneously from worldwide postmarketing experience, frequency of events and the role of sumatriptan in their causation cannot be reliably determined. It is assumed, however, that systemic reactions following sumatriptan use are likely to be similar regardless of route of administration.

Blood: Hemolytic anemia, pancytopenia, thrombocytopenia.

Cardiovascular: Atrial fibrillation, cardiomyopathy, colonic ischemia (see WARNINGS), Prinzmetal variant angina, pulmonary embolism, shock, thrombophlebitis.

Ear, Nose, and Throat: Deafness.

Eye: Ischemic optic neuropathy, retinal artery occlusion, retinal vein thrombosis, loss of vision.

Gastrointestinal: Ischemic colitis with rectal bleeding (see WARNINGS), xerostomia.

Hepatic: Elevated liver function tests.

Neurological: Central nervous system vasculitis, cerebrovascular accident, dysphasia, serotonin syndrome, subarachnoid hemorrhage.

Non-Site Specific: Angioneurotic edema, cyanosis, death (see WARNINGS), temporal arteritis.

Psychiatry: Panic disorder.

Respiratory: Bronchospasm in patients with and without a history of asthma.

Skin: Exacerbation of sunburn, hypersensitivity reactions (allergic vasculitis, erythema, pruritus, rash, shortness of breath, urticaria; in addition, severe anaphylaxis/anaphylactoid reactions have been reported [see WARNINGS]), photosensitivity.

Urogenital: Acute renal failure.

Drug Abuse And Dependence

One clinical study with IMITREX Injection enrolling 12 patients with a history of substance abuse failed to induce subjective behavior and/or physiologic response ordinarily associated with drugs that have an established potential for abuse.

Read the entire FDA prescribing information for Imitrex (Sumatriptan Succinate) »