ADVERSE REACTIONS
Serious cardiac events, including some that have been fatal, have occurred following use of 5-HT1 agonists. 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: Adverse experiences to rizatriptan were assessed in controlled clinical trials that included over 3700 patients who received single or multiple doses of MAXALT Tablets. The most common adverse events during treatment with MAXALT were asthenia/fatigue, somnolence, pain/pressure sensation and dizziness. These events appeared to be dose related. In long term extension studies where patients were allowed to treat multiple attacks for up to 1 year, 4% (59 out of 1525 patients) withdrew because of adverse experiences.
Table 3 lists the adverse events regardless of drug relationship (incidence ≥ 2% and greater than placebo) after a single dose of MAXALT. 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 3: Incidence (≥ 2% and Greater than Placebo) of Adverse Experiences After a Single Dose of MAXALT Tablets or Placebo
| |
% of Patients |
Adverse Experiences |
MAXALT
5 mg
(N=977) |
MAXALT
10 mg
(N=1167) |
Placebo
(N=627) |
|
Atypical Sensations
|
4 |
5 |
4 |
| Paresthesia |
3 |
4 |
<2 |
Pain and other Pressure Sensations
|
6 |
9 |
3 |
Chest Pain:
tightness/pressure and/or heaviness |
<2 |
3 |
1 |
Neck/throat/jaw:
pain/tightness/pressure |
<2 |
2 |
1 |
Regional Pain:
tightness/pressure/heaviness |
<1 |
2 |
0 |
| Pain, location unspecified |
3 |
3 |
<2 |
Digestive
|
9 |
13 |
8 |
| Dry Mouth |
3 |
3 |
1 |
| Nausea |
4 |
6 |
4 |
Neurological
|
14 |
20 |
11 |
| Dizziness |
4 |
9 |
5 |
| Headache |
<2 |
2 |
<1 |
| Somnolence |
4 |
8 |
4 |
Other
Asthenia/fatigue |
4 |
7 |
2 |
MAXALT was generally well-tolerated. Adverse experiences were typically mild in intensity and were transient. The frequencies of adverse experiences in clinical trials did not increase when up to three doses were taken within 24 hours. Adverse event frequencies were also unchanged by concomitant use of drugs commonly taken for migraine prophylaxis (including propranolol), oral contraceptives, or analgesics. The incidences of adverse experiences were not affected by age or gender. 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 MAXALT: In the section that follows, the frequencies of less commonly reported adverse clinical events are presented. Because the reports include events observed in open studies, the role of MAXALT 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 MAXALT (N=3716) and reported an event divided by the total number of patients exposed to MAXALT. 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 those defined as those occurring in at least (>)1/100 patients; infrequent adverse experiences are those occurring in 1/100 to 1/1000 patients; and rare adverse experiences are those occurring in fewer than 1/1000 patients.
General: Infrequent were chills, heat sensitivity, facial edema, hangover effect, and abdominal distention. Rare were fever, orthostatic effects, syncope and edema/swelling.
Atypical Sensations: Frequent were warm/cold sensations.
Cardiovascular: Frequent was palpitation. Infrequent were tachycardia, cold extremities, hypertension, arrhythmia, and bradycardia. Rare was angina pectoris.
Digestive: Frequent were diarrhea and vomiting. Infrequent were dyspepsia, thirst, acid regurgitation, dysphagia, constipation, flatulence, and tongue edema. Rare were anorexia, appetite increase, gastritis, paralysis (tongue), and eructation.
Metabolic: Infrequent was dehydration.
Musculoskeletal: Infrequent were muscle weakness, stiffness, myalgia, muscle cramp, musculoskeletal pain, arthralgia, and muscle spasm.
Neurological/Psychiatric: Frequent were hypesthesia, mental acuity decreased, euphoria and tremor. Infrequent were nervousness, vertigo, insomnia, anxiety, depression, disorientation, ataxia, dysarthria, confusion, dream abnormality, gait abnormality, irritability, memory impairment, agitation and hyperesthesia. Rare were: dysesthesia, depersonalization, akinesia/bradykinesia, apprehension, hyperkinesia, hypersomnia, and hyporeflexia.
Respiratory: Frequent was dyspnea. Infrequent were pharyngitis, irritation (nasal), congestion (nasal), dry throat, upper respiratory infection, yawning, respiratory congestion (nasal), dry nose, epistaxis, and sinus disorder. Rare were cough, hiccups, hoarseness, rhinorrhea, sneezing, tachypnea, and pharyngeal edema.
Special Senses: Infrequent were blurred vision, tinnitus, dry eyes, burning eye, eye pain, eye irritation, ear pain, and tearing. Rare were hyperacusis, smell perversion, photophobia, photopsia, itching eye, and eye swelling.
Skin and Skin Appendage: Frequent was flushing. Infrequent were sweating, pruritus, rash, and urticaria. Rare were erythema, acne, and photosensitivity.
Urogenital System: Frequent was hot flashes. Infrequent were urinary frequency, polyuria, and menstruation disorder. Rare was dysuria.
The adverse experience profile seen with MAXALT-MLT Orally Disintegrating Tablets was similar to that seen with MAXALT Tablets.
Postmarketing Experience
The following section enumerates potentially important adverse events that have occurred in clinical practice and which have been reported spontaneously to various surveillance systems. The events enumerated represent reports arising from both domestic and non-domestic use of rizatriptan. 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 rizatriptan in their causation cannot be reliably determined.
Cardiovascular: Myocardial ischemia, myocardial infarction, peripheral vascular ischemia (see WARNINGS).
Cerebrovascular: Stroke.
Neurological/Psychiatric: Serotonin syndrome (see WARNINGS), seizure.
Special Senses: Dysgeusia.
General: Hypersensitivity reaction, anaphylaxis/anaphylactoid reaction, angioedema (e.g., facial edema, tongue swelling, pharyngeal edema), wheezing, toxic epidermal necrolysis.
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