PRODUCT MONOGRAPH IMITREX DF IMITREX ... - GlaxoSmithKline

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Among approximately 4,000 patients with migraine who participated in premarketingcontrolled and uncontrolled clinical trials of IMITREX ® Nasal Spray, one patientexperienced an asymptomatic subendocardial infarction possibly subsequent to acoronary vasospastic event.Postmarketing Experience With IMITREX ® :Serious cardiovascular events, some resulting in death, have been reported in associationwith the use of IMITREX ® Injection or IMITREX ® Tablets. The uncontrolled nature ofpostmarketing surveillance, however, makes it impossible to determine definitively theproportion of the reported cases that were actually caused by IMITREX ® or to reliablyassess causation in individual cases. On clinical grounds, the longer the latency betweenthe administration of IMITREX ® and the onset of the clinical event, the less likely theassociation is to be causative. Accordingly, interest has focused on events beginningwithin 1 hour of the administration of IMITREX ® .Cardiac events that have been observed to have onset within 1 hour of IMITREX ®administration include: coronary artery vasospasm, transient ischemia, myocardialinfarction, ventricular tachycardia and ventricular fibrillation, cardiac arrest, and death.Some of these events occurred in patients who had no findings of CAD and appear torepresent consequences of coronary artery vasospasm. However, among reports from theUSA of serious cardiac events occurring within 1 hour of IMITREX ® administration,almost all of the patients had risk factors predictive of CAD and the presence ofsignificant underlying CAD was established in most cases (seeCONTRAINDICATIONS).Cerebrovascular Events and Fatalities with 5-HT 1 Agonists:Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular eventshave been reported in patients treated with oral or subcutaneous IMITREX ® , and somehave resulted in fatalities. The relationship of IMITREX ® to these events is uncertain. Ina number of cases, it appears possible that the cerebrovascular events were primary,IMITREX ® having been administered in the incorrect belief that the symptomsexperienced were a consequence of migraine when they were not. Before treatingmigraine headaches with IMITREX DF ® and IMITREX ® in patients not previouslydiagnosed as migraineurs, and in migraineurs who present with atypical symptoms, careshould be taken to exclude other potentially serious neurological conditions. If a patientdoes not respond to the first dose, the opportunity should be taken to review the diagnosisbefore a second dose is given. It should also be noted that patients with migraine may beat increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA).Special Cardiovascular Pharmacology Studies:In subjects (n=10) with suspected coronary artery disease undergoing angiography,a 5-HT 1 agonist at a subcutaneous dose of 1.5 mg produced an 8% increase in aorticblood pressure, an 18% increase in pulmonary artery blood pressure, and an 8% increasein systemic vascular resistance. In addition, mild chest pain or tightness was reported byfour subjects. Clinically significant increases in blood pressure were experienced byOctober 21, 2014Page 8 of 58
three of the subjects (two of whom also had chest pain/discomfort). Diagnosticangiogram results revealed that 9 subjects had normal coronary arteries and 1 hadinsignificant coronary artery disease.In an additional study with this same drug, migraine patients (n=35) free ofcardiovascular disease were subjected to assessments of myocardial perfusion by positronemission tomography while receiving a subcutaneous 1.5 mg dose in the absence of amigraine attack. Reduced coronary vasodilatory reserve (~10%), increase in coronaryresistance (~20%), and decrease in hyperemic myocardial blood flow (~10%) were noted.The relevance of these finding to the use of the recommended oral doses of this 5-HT 1agonist is not known.Similar studies have not been done with IMITREX DF ® or IMITREX ® . However, owingto the common pharmacodynamic actions of 5-HT 1 agonists, the possibility ofcardiovascular effects of the nature described above should be considered for any agentof this pharmacological class.Other Vasospasm-Related Events: 5-HT 1 agonists may cause vasospastic reactionsother than coronary artery vasospasm. Extensive post-market experience has shown theuse of IMITREX ® to be associated with rare occurrences of peripheral vascular ischemiaand colonic ischemia with abdominal pain and bloody diarrhea, and in isolated casesthere was no previous history or concomitant medications.Increase in Blood Pressure: Significant elevation in blood pressure, includinghypertensive crisis, has been reported on rare occasions in patients with and without ahistory of hypertension. IMITREX DF ® and IMITREX ® are contraindicated in patientswith uncontrolled or severe hypertension (see CONTRAINDICATIONS). In patientswith controlled hypertension, IMITREX DF ® or IMITREX ® should be administered withcaution, as transient increases in blood pressure and peripheral vascular resistance havebeen observed in a small portion of patients.ImmuneRare hypersensitivity (anaphylaxis/anaphylactoid) reactions may occur in patientsreceiving 5-HT 1 agonists such as IMITREX DF ® or IMITREX ® . Such reactions can belife-threatening or fatal. In general, hypersensitivity reactions to drugs are more likely tooccur in individuals with a history of sensitivity to multiple allergens (seeCONTRAINDICATIONS). Owing to the possibility of cross-reactive hypersensitivityreactions, IMITREX DF ® and IMITREX ® should not be used in patients having a historyof hypersensitivity to chemically related 5-HT 1 receptor agonists. There have beenreports of patients with known hypersensitivity to sulphonamides exhibiting an allergicreaction following administration of IMITREX ® . Reactions ranged from cutaneoushypersensitivity to anaphylaxis.October 21, 2014Page 9 of 58
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