Can Almotriptan cause nightmare?

ADVERSE REACTIONS Serious cardiac reactions, including myocardial infarction, have occurred following the use of almotriptan (almotriptan malate) 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 (4.1) and Warnings and Precautions (5.1) ] . The following adverse reactions are discussed in more detail in other sections of the labeling: • Risk of Myocardial Ischemia and Infarction and Other Adverse Cardiac Events [see Warnings and Precautions (5.1) ] • Sensations of Pain, Tightness, Pressure in the Chest and/or Throat, Neck, and Jaw [see Warnings and Precautions (5.2) ] • Cerebrovascular Events and Fatalities [see Warnings and Precautions (5.3) ] • Other Vasospasm-Related Events, Including Peripheral Vascular Ischemia and Colonic Ischemia [see Warnings and Precautions (5.4) ] • Serotonin Syndrome [see Warnings and Precautions (5.5) ] • Increases in Blood Pressure [see Warnings and Precautions (5.7) ] Adverse events were assessed in controlled clinical trials that included 1840 adult patients who received one or two doses of almotriptan tablets and 386 adult patients who received placebo. The most common adverse reactions during treatment with almotriptan tablets were nausea, somnolence, headache, paresthesia, and dry mouth. In long-term open-label studies where patients were allowed to treat multiple attacks for up to 1 year, 5% (63 out of 1347 patients) withdrew due to adverse experiences. Adverse events were assessed in controlled clinical trials that included 362 adolescent patients who received almotriptan tablets and 172 adolescent patients who received placebo. The most common adverse reactions during treatment with almotriptan tablets were dizziness, somnolence, headache, paresthesia, nausea, and vomiting. In a long-term, open-label study where patients were allowed to treat multiple attacks for up to 1 year, 2% (10 out of 420 adolescent patients) withdrew due to adverse events. 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. The most common adverse reactions (≥ 1% and greater than placebo) are: • In adults: nausea, dry mouth and paresthesia ( 6.1 ) • In adolescents: dizziness, somnolence, headache, paresthesia, nausea and vomiting ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Almotriptan Tablet Clinical Trials Adults Table 1 lists the adverse events that occurred in at least 1% of the adult patients treated with almotriptan tablets, and at an incidence greater than in patients treated with placebo, regardless of drug relationship. Table 1. Incidence of Adverse Events in Controlled Clinical Trials (Reported in at Least 1% of Adult Patients Treated with Almotriptan Tablets, and at an Incidence Greater than Placebo) System/Organ Class Adverse Event Almotriptan Tablets 6.25 mg (n = 527) % Almotriptan Tablets 12.5 mg (n = 1313) % Placebo (n = 386) % Digestive Disorders Nausea 1 2 1 Dry Mouth 1 1 0.5 Nervous System Disorders Paresthesia 1 1 0.5 The incidence of adverse events in controlled clinical trials was not affected by gender, weight, age, presence of aura, or use of prophylactic medications or oral contraceptives. There were insufficient data to assess the effect of race on the incidence of adverse events. Adolescents Table 2 lists the adverse reactions reported by 1% or more of almotriptan tablet-treated adolescents age 12 to 17 years in one placebo-controlled, double-blind clinical trial. Table 2. Adverse Reactions Reported by ≥ 1% of Adolescent Patients Treated with Almotriptan Tablets in One Placebo-Controlled, Double-Blind Clinical Trial System/Organ Class Adverse Reaction Almotriptan Tablets 6.25 mg (n = 180) % Almotriptan Tablets 12.5 mg (n = 182) % Placebo (n = 172) % Nervous System Disorders Dizziness 4 3 2 Somnolence < 1 5 2 Headache 1 2 1 Paresthesia < 1 1 < 1 Gastrointestinal Disorders Nausea 1 3 0 Vomiting 2 0 < 1 6.2 Other Adverse Reactions Observed in Almotriptan Tablet Clinical Trials In the paragraphs that follow, the frequencies of less commonly reported adverse clinical reactions are presented. The reports include adverse reactions in five adult controlled studies and one adolescent controlled study. 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 almotriptan tablets and reported a reaction divided by the total number of patients exposed to almotriptan tablets (n = 3047, all doses). 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 system organ class and enumerated in order of decreasing frequency using the following definitions: frequent adverse reactions are those occurring in 1/100 or more patients, infrequent adverse reactions are those occurring in fewer than 1/100 to 1/1000 patients, and rare adverse reactions are those occurring in fewer than 1/1000 patients. Body: Frequent: Headache. Infrequent: Abdominal cramp or pain, Asthenia, Chills, Back pain, Chest pain, Neck pain, Fatigue, and Rigid neck. Rare: Fever and Photosensitivity reaction. Cardiovascular: Infrequent: Vasodilation, Palpitations, and Tachycardia. Rare: Hypertension and Syncope. Digestive: Infrequent: Diarrhea, Vomiting, Dyspepsia, Gastroenteritis, and Increased thirst. Rare: Colitis, Gastritis, Esophageal reflux, and Increased salivation. Metabolic: Infrequent: Hyperglycemia and Increased serum creatine phosphokinase. Rare: Increased gamma glutamyl transpeptidase and Hypercholesteremia. Musculoskeletal: Infrequent: Myalgia. Rare: Arthralgia, Arthritis, Myopathy, and Muscle weakness. Nervous: Frequent: Dizziness and Somnolence. Infrequent: Tremor, Vertigo, Anxiety, Hypoesthesia, Restlessness, CNS stimulation, and Shakiness. Rare: Change in dreams, Impaired concentration, Abnormal coordination, Depressive symptoms, Euphoria, Hyperreflexia, Hypertonia, Nervousness, Neuropathy, Nightmares, Nystagmus, and Insomnia. Respiratory: Infrequent: Pharyngitis, Rhinitis, Dyspnea, Laryngismus, Sinusitis, and Bronchitis. Rare: Hyperventilation, Laryngitis, Sneezing, and Epistaxis. Skin: Infrequent: Diaphoresis, Pruritus, and Rash. Rare: Dermatitis and Erythema. Special Senses: Infrequent: Ear pain and Tinnitus. Rare: Diplopia, Dry eyes, Eye pain, Otitis media, Parosmia, Scotoma, Conjunctivitis, Eye irritation, Hyperacusis, and Taste alteration. Urogenital: Infrequent: Dysmenorrhea. 6.3 Postmarketing Experience The following adverse reactions have been identified during postapproval use of almotriptan tablets. 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. Immune System Disorders: Hypersensitivity reactions (including angioedema, anaphylactic reactions and anaphylactic shock) Psychiatric Disorders: Confusional state, Restlessness Nervous System Disorders: Hemiplegia, Hypoesthesia, Seizures Eye Disorders: Blepharospasm, Visual impairment, Vision blurred Ear and Labyrinth Disorders: Vertigo Cardiac Disorders: Acute myocardial infarction, Coronary artery

WARNINGS AND PRECAUTIONS • Serious adverse cardiac events, including acute myocardial infarction and life-threatening disturbances of cardiac rhythm ( 5.1 ) • It is strongly recommended that almotriptan tablets not be given to patients in whom unrecognized coronary artery disease (CAD) is predicted by the presence of risk factors. In very rare cases, serious cardiovascular events have been reported in association with almotriptan tablet use in the absence of known cardiovascular disease. If almotriptan tablets are considered, patients should first have a cardiovascular evaluation. If the evaluation is satisfactory, first dose should take place in a physician’s office setting ( 5.1 ) • Sensations of pain, tightness, pressure, and heaviness in the chest, throat, neck, and jaw: generally not associated with myocardial ischemia, but patients with signs or symptoms suggestive of angina should be evaluated for the presence of CAD ( 5.2 ) • Cerebrovascular events, some fatal ( 5.3 ) • Gastrointestinal ischemic events and peripheral vasospastic reactions (e.g., Raynaud’s syndrome) ( 5.4 ) • Potentially life-threatening serotonin syndrome, particularly in combination with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). Monitor patients for neurologic changes and gastrointestinal symptoms if concomitant treatment is clinically warranted ( 5.5 , 7.3 ) • Medication overuse headache: Detoxification may be necessary ( 5.6 ) • Increase in blood pressure, very rarely associated with significant clinical events ( 4.4 , 5.7 ) • Use with caution in patients with a known hypersensitivity to sulfonamides ( 5.8 ) 5.1 Risk of Myocardial Ischemia and Infarction and Other Adverse Cardiac Events Cardiac Events and Fatalities with 5-HT 1 Agonists Serious adverse cardiac events, including acute myocardial infarction, have been reported within a few hours following administration of almotriptan tablets (almotriptan malate). Life-threatening disturbances of cardiac rhythm and death have been reported within a few hours following the administration of other triptans. Considering the extent of use of triptans in patients with migraine, the incidence of these events is extremely low. Almotriptan tablets can cause coronary vasospasm; at least one of these events occurred in a patient with no cardiac history and with documented absence of coronary artery disease. Because of the close proximity of the events to use of almotriptan tablets, a causal relationship cannot be excluded. Patients who experience signs or symptoms suggestive of angina following dosing should be evaluated for the presence of coronary artery disease (CAD) or a predisposition to Prinzmetal’s variant angina before receiving additional doses of medication, and should be monitored electrocardiographically if dosing is resumed and similar symptoms recur. Premarketing Experience with Almotriptan Tablets in Adults Among the 3865 subjects/patients who received almotriptan tablets in premarketing clinical trials, one patient was hospitalized for observation after a scheduled electrocardiogram (ECG) was found to be abnormal (negative T-waves on the left leads) 48 hours after taking a single 6.25 mg dose of almotriptan. The patient, a 48-year-old female, had previously taken three other doses for earlier migraine attacks. Myocardial enzymes at the time of the abnormal ECG were normal. The patient was diagnosed as having had myocardial ischemia and that she had a family history of coronary disease. An ECG performed 2 days later was normal, as was a follow-up coronary angiography. The patient recovered without incident. Postmarketing Experience with Almotriptan Tablets in Adults Serious cardiovascular events have been reported in association with the use of almotriptan tablets. The uncontrolled nature of postmarketing surveillance, however, makes it impossible to definitively determine the proportion of the reported cases that were actually caused by almotriptan or to reliably assess causation in individual cases [see Adverse Reactions (6.3) ] . Patients with Documented Coronary Artery Disease Because of the potential of this class of compound (5-HT 1 agonists) to cause coronary vasospasm, almotriptan tablets should not be given to patients with documented ischemic or vasospastic coronary artery disease [see Contraindications (4.1) ] . Patients with Risk Factors for CAD It is strongly recommended that almotriptan tablets not be given to patients in whom unrecognized CAD is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient’s medical history, electrocardiographic or other investigations reveal findings indicative of, or consistent with, coronary artery vasospasm or myocardial ischemia, almotriptan tablets should not be administered [see Contraindications (4.1) ] . For patients with risk factors predictive of CAD, who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of almotriptan tablets take place in the setting of a physician’s office or similar medically staffed and equipped facility unless the patient has previously received almotriptan tablets. Because cardiac ischemia can occur in the absence of clinical symptoms, consideration should be given to obtaining on the first occasion of use an ECG during the interval immediately following almotriptan tablets, in these patients with risk factors. It is recommended that patients who are intermittent long-term users of almotriptan tablets and who have or acquire risk factors predictive of CAD, as described above, undergo periodic interval cardiovascular evaluation as they continue to use almotriptan tablets. The systematic approach described above is intended to reduce the likelihood that patients with unrecognized cardiovascular disease will be inadvertently exposed to almotriptan tablets. The ability of cardiac diagnostic procedures to detect all cardiovascular diseases or predisposition to coronary artery vasospasm is modest at best. Cardiovascular events associated with triptan treatment have occurred in patients with no cardiac history and with documented absence of coronary artery disease. 5.2 Sensations of Pain, Tightness, Pressure in the Chest and/or Throat, Neck, and Jaw As with other 5-HT 1 agonists, sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw have been reported after treatment with almotriptan tablets. Because 5-HT 1 agonists may cause coronary vasospasm, patients who experience signs or symptoms suggestive of angina following dosing should be evaluated for the presence of CAD or a predisposition to Prinzmetal’s variant angina before receiving additional doses of medication, and should be monitored electrocardiographically if dosing is resumed and similar symptoms occur. Patients shown to have CAD and those with Prinzmetal’s variant angina should not receive 5-HT 1 agonists [see Contraindications (4.1) and Warnings and Precautions (5.1) ] . 5.3 Cerebrovascular Events and Fatalities Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with other triptans and some events have resulted in fatalities. In a number of cases, it appeared possible that the cerebrovascular events were primary, the triptan having been administered in the in