PRODUCT MONOGRAPH IMITREX DF IMITREX ... - GlaxoSmithKline

The systematic approach described above is intended to reduce thelikelihood that patients with unrecognized cardiovascular disease will beinadvertently exposed to IMITREX DF ® or IMITREX ® .Discomfort in the chest, neck, throat and jaw (including pain, pressure, heaviness,tightness, dyspnea) has been reported after administration of IMITREX ® . Because5-HT1 agonists may cause coronary vasospasm, patients who experience signs orsymptoms suggestive of angina following IMITREX DF ® or IMITREX ® should beevaluated for the presence of CAD or a predisposition to variant angina beforereceiving additional doses, and should be monitored electrocardiographically ifdosing is resumed and similar symptoms recur. Similarly, patients who experienceother symptoms or signs suggestive of decreased arterial flow, such as ischemicbowel syndrome or Raynaud’s syndrome, following IMITREX DF ® or IMITREX ®should be evaluated for atherosclerosis or predisposition to vasospasm (seeCONTRAINDICATIONS and WARNINGS and PRECAUTIONS and ADVERSEDRUG REACTIONS, Clinical Trial Adverse Drug Reactions).Cardiac Events and Fatalities Associated with 5-HT 1 Agonists:IMITREX DF ® and IMITREX ® can cause coronary artery vasospasm. Serious adversecardiac events, including acute myocardial infarction, life-threatening disturbances ofcardiac rhythm, and death have been reported within a few hours following theadministration of 5-HT 1 agonists. Considering the extent of use of 5-HT 1 agonists inpatients with migraine, the incidence of these events is extremely low. The fact that someof these events have occurred in patients with no prior cardiac disease history and withdocumented absence of CAD, and the close proximity of the events to IMITREX ® usesupport the conclusion that some of these cases were caused by the drug. In many cases,however, where there has been known underlying coronary artery disease, therelationship is uncertain.Premarketing Experience With IMITREX ® :Of 6348 patients with migraine who participated in premarketing controlled anduncontrolled clinical trials of oral and IMITREX ® , two experienced clinical adverseevents shortly after receiving oral IMITREX ® that may have reflected coronaryvasospasm. Neither of these adverse events was associated with a serious clinicaloutcome.Among the more than 1900 patients with migraine who participated in premarketingcontrolled clinical trials of subcutaneous IMITREX ® , there were eight patients whosustained clinical events during or shortly after receiving IMITREX ® that may havereflected coronary artery vasospasm. Six of these eight patients had ECG changesconsistent with transient ischemia, but without accompanying clinical symptoms or signs.Of these eight patients, four had either findings suggestive of CAD or risk factorspredictive of CAD prior to study enrolment.October 21, 2014Page 7 of 58