ADVERSE REACTIONS
Serious cardiac events, including some that have been fatal, have occurred following the use of 5-HT1 agonists including RELPAX. 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).
Incidence in Controlled Clinical Trials
Among 4,597 patients who treated the first migraine headache with RELPAX in short-term placebo-controlled trials, the most common adverse events reported with treatment with RELPAX were asthenia, nausea, dizziness, and somnolence. These events appear to be dose-related.
In long-term open-label studies where patients were allowed to treat multiple migraine attacks for up to 1 year, 128 (8.3%) out of 1,544 patients discontinued treatment due to adverse events.
Table 2 lists adverse events that occurred in the subset of 5,125 migraineurs who received eletriptan doses of 20 mg, 40 mg and 80 mg or placebo in worldwide placebo-controlled clinical trials. 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, those frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ.
Only adverse events that were more frequent in a RELPAX treatment group compared to the placebo group with an incidence greater than or equal to 2% are included in Table 2.
Table 2: Adverse Experience Incidence in Placebo-Controlled Migraine Clinical Trials: Events Reported by ≥ 2% Patients Treated with RELPAX and More Than Placebo | Adverse Event Type | Placebo
(n=988) | RELPAX
20 mg
(n=431) | RELPAX
40 mg
(n=1774) | RELPAX
80 mg
(n=1932) |
|---|
|
|---|
| ATYPICAL SENSATIONS | | | | |
| Paresthesia | 2% | 3% | 3% | 4% |
| Flushing/feeling of warmth | 2% | 2% | 2% | 2% |
| PAIN AND PRESSURE SENSATIONS | | | | |
Chest –
tightness/pain/pressure | 1% | 1% | 2% | 4% |
Abdominal –
pain/discomfort/stomach pain/cramps/pressure | 1% | 1% | 2% | 2% |
| DIGESTIVE | | | | |
| Dry mouth | 2% | 2% | 3% | 4% |
| Dyspepsia | 1% | 1% | 2% | 2% |
Dysphagia –
throat tightness/difficulty swallowing | 0.2% | 1% | 2% | 2% |
| Nausea | 5% | 4% | 5% | 8% |
| NEUROLOGICAL | | | | |
| Dizziness | 3% | 3% | 6% | 7% |
| Somnolence | 4% | 3% | 6% | 7% |
| Headache | 3% | 4% | 3% | 4% |
| OTHER | | | | |
| Asthenia | 3% | 4% | 5% | 10% |
RELPAX is generally well tolerated. Across all doses, most adverse reactions were mild and transient. The frequency of adverse events in clinical trials did not increase when up to 2 doses of RELPAX were taken within 24 hours. The incidence of adverse events in controlled clinical trials was not affected by gender, age, or race of the patients. Adverse event frequencies were also unchanged by concomitant use of drugs commonly taken for migraine prophylaxis (e.g., SSRIs, beta blockers, calcium channel blockers, tricyclic antidepressants), estrogen replacement therapy and oral contraceptives.
Other Events Observed in Association With the Administration of RELPAX 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 studies, the role of RELPAX 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 the quantitative frequency estimates provided. Event frequencies are calculated as the number of patients reporting an event divided by the total number of patients (N=4,719) exposed to RELPAX. All reported events are included except those already listed in Table 2, 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 those occurring in at least 1/100 patients, infrequent adverse events are those occurring in 1/100 to 1/1000 patients and rare adverse events are those occurring in fewer than 1/1000 patients.
General: Frequent were back pain, chills and pain. Infrequent were face edema and malaise. Rare were abdomen enlarged, abscess, accidental injury, allergic reaction, fever, flu syndrome, halitosis, hernia, hypothermia, lab test abnormal, moniliasis, rheumatoid arthritis and shock.
Cardiovascular: Frequent was palpitation. Infrequent were hypertension, migraine, peripheral vascular disorder and tachycardia. Rare were angina pectoris, arrhythmia, atrial fibrillation, AV block, bradycardia, hypotension, syncope, thrombophlebitis, cerebrovascular disorder, vasospasm and ventricular arrhythmia.
Digestive: Infrequent were anorexia, constipation, diarrhea, eructation, esophagitis, flatulence, gastritis, gastrointestinal disorder, glossitis, increased salivation and liver function tests abnormal. Rare were gingivitis, hematemesis, increased appetite, rectal disorder, stomatitis, tongue disorder, tongue edema and tooth disorder.
Endocrine: Rare were goiter, thyroid adenoma and thyroiditis.
Hemic and Lymphatic: Rare were anemia, cyanosis, leukopenia, lymphadenopathy, monocytosis and purpura.
Metabolic: Infrequent were creatine phosphokinase increased, edema, peripheral edema and thirst. Rare were alkaline phosphatase increased, bilirubinemia, hyperglycemia, weight gain and weight loss.
Musculoskeletal: Infrequent were arthralgia, arthritis, arthrosis, bone pain, myalgia and myasthenia. Rare were bone neoplasm, joint disorder, myopathy and tenosynovitis.
Neurological: Frequent were hypertonia, hypesthesia and vertigo. Infrequent were abnormal dreams, agitation, anxiety, apathy, ataxia, confusion, depersonalization, depression, emotional lability, euphoria, hyperesthesia, hyperkinesia, incoordination, insomnia, nervousness, speech disorder, stupor, thinking abnormal and tremor. Rare were abnormal gait, amnesia, aphasia, catatonic reaction, dementia, diplopia, dystonia, hallucinations, hemiplegia, hyperalgesia, hypokinesia, hysteria, manic reaction, neuropathy, neurosis, oculogyric crisis, paralysis, psychotic depression, sleep disorder and twitching.
Respiratory: Frequent was pharyngitis. Infrequent were asthma, dyspnea, respiratory disorder, respiratory tract infection, rhinitis, voice alteration and yawn. Rare were bronchitis, choking sensation, cough increased, epistaxis, hiccup, hyperventilation, laryngitis, sinusitis and sputum increased.
Skin and Appendages: Frequent was sweating. Infrequent were pruritus, rash and skin disorder. Rare were alopecia, dry skin, eczema, exfoliative dermatitis, maculopapular rash, psoriasis, skin discoloration, skin hypertrophy and urticaria.
Special Senses: Infrequent was abnormal vision, conjunctivitis, ear pain, eye pain, lacrimation disorder, photophobia, taste perversion and tinnitus. Rare were abnormality of accommodation, dry eyes, ear disorder, eye hemorrhage, otitis media, parosmia and ptosis.
Urogenital: Infrequent were impotence, polyuria, urinary frequency and urinary tract disorder. Rare were breast pain, kidney pain, leukorrhea, menorrhagia, menstrual disorder and vaginitis.
Other Events Observed During Post-Marketing Use
The following adverse reaction(s) have been identified during postapproval use of RELPAX. 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.
Neurological: seizure
Digestive: vomiting
|
