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,
Significant hypertensive episodes, including hypertensive crises, have been
reported on rare occasions in patients with or without a history of hypertension
Incidence in Controlled Clinical Trials: Among 3,653 patients treated
with IMITREX Nasal Spray (sumatriptan nasal spray) in active- and placebo-controlled clinical trials,
less than 0.4% of patients withdrew for reasons related to adverse events. Table
2 lists adverse events that occurred in worldwide placebo-controlled clinical
trials in 3,419 migraineurs. 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.
Only events that occurred at a frequency of 1% or more in the IMITREX Nasal Spray (sumatriptan nasal spray) 20-mg treatment group and were more frequent in that group than in the placebo group are included in Table 2.
Table 2. Treatment-Emergent Adverse Events Reported by at
Least 1% of Patients in Controlled Migraine Trials
|Adverse Event Type
|| Percent of Patients Reporting
(n = 704)
| IMITREX5 mg
(n = 496)
| IMITREX10 mg
(n = 1,007)
| IMITREX20 mg
(n = 1,212)
|Atypical sensations Burning sensation
|Ear, nose, and throat Disorder/discomfort of nasal cavity/sinuses
| Throat discomfort
|Gastrointestinal Nausea and/or vomiting
|Neurological Bad/unusual taste
Phonophobia also occurred in more than 1% of patients but was more frequent on placebo.
IMITREX Nasal Spray (sumatriptan nasal spray) is 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, weight, or age of the patients; use of prophylactic medications; or presence of aura. 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 Nasal
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 Nasal Spray (sumatriptan nasal spray) 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 the quantitative frequency estimates provided. Event frequencies
are calculated as the number of patients who used IMITREX Nasal Spray (sumatriptan nasal spray) (5, 10,
or 20 mg in controlled and uncontrolled trials) and reported an event divided
by the total number of patients (N = 3,711) exposed to IMITREX Nasal Spray (sumatriptan nasal spray) .
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:
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: Infrequent were tingling, warm/hot sensation,
numbness, pressure sensation, feeling strange, feeling of heaviness, feeling
of tightness, paresthesia, cold sensation, and tight feeling in head. Rare were
dysesthesia and prickling sensation.
Cardiovascular: Infrequent were flushing and hypertension (see
WARNINGS), palpitations, tachycardia, changes in ECG, and arrhythmia
(see WARNINGS and PRECAUTIONS). Rare were abdominal aortic aneurysm,
hypotension, bradycardia, pallor, and phlebitis.
Chest Symptoms: Infrequent were chest tightness, chest discomfort,
and chest pressure/heaviness (see PRECAUTIONS:
Ear, Nose, and Throat: Infrequent were disturbance of hearing
and ear infection. Rare were otalgia and Meniere disease.
Endocrine and Metabolic: Infrequent was thirst. Rare were galactorrhea,
hypothyroidism, and weight loss.
Eye: Infrequent were irritation of eyes and visual disturbance.
Gastrointestinal: Infrequent were abdominal discomfort, diarrhea,
dysphagia, and gastroesophageal reflux. Rare were constipation, flatulence/eructation,
hematemesis, intestinal obstruction, melena, gastroenteritis, colitis, hemorrhage
of gastrointestinal tract, and pancreatitis.
Mouth and Teeth: Infrequent was disorder of mouth and tongue
(e.g., burning of tongue, numbness of tongue, dry mouth).
Musculoskeletal: Infrequent were neck pain/stiffness, backache,
weakness, joint symptoms, arthritis, and myalgia. Rare were muscle cramps, tetany,
intervertebral disc disorder, and muscle stiffness.
Neurological: Infrequent were drowsiness/sedation, anxiety, sleep
disturbances, tremors, syncope, shivers, chills, depression, agitation, sensation
of lightness, and mental confusion. Rare were difficulty concentrating, hunger,
lacrimation, memory disturbances, monoplegia/diplegia, apathy, disturbance of
smell, disturbance of emotions, dysarthria, facial pain, intoxication, stress,
decreased appetite, difficulty coordinating, euphoria, and neoplasm of pituitary.
Respiratory: Infrequent were dyspnea and lower respiratory tract
infection. Rare was asthma.
Skin: Infrequent were rash/skin eruption, pruritus, and erythema.
Rare were herpes, swelling of face, sweating, and peeling of skin.
Urogenital: Infrequent were dysuria, disorder of breasts, and
dysmenorrhea. Rare were endometriosis and increased urination.
Miscellaneous: Infrequent were cough, edema, and fever. Rare
were hypersensitivity, swelling of extremities, voice disturbances, difficulty
in walking, and lymphadenopathy.
Other Events Observed in the Clinical Development of IMITREX
The following adverse events occurred in clinical trials with IMITREX Injection
and IMITREX Tablets. 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.
Breasts: Breast swelling; cysts, lumps, and masses of breasts;
nipple discharge; primary malignant breast neoplasm; and tenderness.
Cardiovascular:Abnormal pulse, angina, atherosclerosis, cerebral
ischemia, cerebrovascular lesion, heart block, peripheral cyanosis, pulsating
sensations, Raynaud syndrome, thrombosis, transient myocardial ischemia, 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), and vasodilation.
Ear, Nose, and Throat: Allergic rhinitis; ear, nose, and throat
hemorrhage; external otitis; feeling of fullness in the ear(s); hearing disturbances;
hearing loss; nasal inflammation; sensitivity to noise; sinusitis; tinnitus;
and upper respiratory inflammation.
Endocrine and Metabolic:Dehydration; endocrine cysts, lumps,
and masses; elevated thyrotropin stimulating hormone (TSH) levels; fluid disturbances;
hyperglycemia; hypoglycemia; polydipsia; and weight gain.
Eye: Accommodation disorders, blindness and low vision, conjunctivitis,
disorders of sclera, external ocular muscle disorders, eye edema and swelling,
eye itching, eye hemorrhage, eye pain, keratitis, mydriasis, and vision alterations.
Gastrointestinal: Abdominal distention, dental pain, disturbances
of liver function tests, dyspeptic symptoms, feelings of gastrointestinal pressure,
gallstones, gastric symptoms, gastritis, gastrointestinal pain, hypersalivation,
hyposalivation, oral itching and irritation, peptic ulcer, retching, salivary
gland swelling, and swallowing disorders.
Injection Site Reaction
Miscellaneous: Contusions, fluid retention, hematoma, hypersensitivity
to various agents, jaw discomfort, miscellaneous laboratory abnormalities, overdose,
“serotonin agonist effect,” and speech disturbance.
Musculoskeletal: Acquired musculoskeletal deformity, arthralgia
and articular rheumatitis, muscle atrophy, muscle tiredness, musculoskeletal
inflammation, need to flex calf muscles, rigidity, tightness, and various joint
disturbances (pain, stiffness, swelling, ache).
Neurological: Aggressiveness, bradylogia, cluster headache, convulsions,
detachment, disturbances of taste, drug abuse, dystonia, facial paralysis, globus
hystericus, hallucinations, headache, heat sensitivity, hyperesthesia, hysteria,
increased alertness, malaise/fatigue, migraine, motor dysfunction, myoclonia,
neuralgia, neurotic disorders, paralysis, personality change, phobia, photophobia,
psychomotor disorders, radiculopathy, raised intracranial pressure, relaxation,
stinging sensations, transient hemiplegia, simultaneous hot and cold sensations,
suicide, tickling sensations, twitching, and yawning.
Pain and Other Pressure Sensations:Chest pain, neck tightness/pressure,
throat/jaw pain/tightness/pressure, and pain (location specified).
Respiratory:Breathing disorders, bronchitis, diseases of the
lower respiratory tract, hiccoughs, and influenza.
Skin: Dry/scaly skin, eczema, seborrheic dermatitis, skin nodules,
skin tenderness, tightness of skin, and wrinkling of skin.
Urogenital:Abortion, abnormal menstrual cycle, bladder inflammation,
hematuria, inflammation of fallopian tubes, intermenstrual bleeding, menstruation
symptoms, micturition disorders, renal calculus, urethritis, urinary frequency,
and urinary infections.
Postmarketing Experience (Reports for Subcutaneous or Oral Sumatriptan)
The following 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,
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
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
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]),
Urogenital: Acute renal failure.
Drug Abuse And Dependence
One clinical study with IMITREX (sumatriptan succinate) 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.