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boxed warning
WARNING: PERIPHERAL ISCHEMIA FOLLOWING COADMINISTRATION WITH POTENT CYP3A4 INHIBITORS Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of DIHYDROERGOTAMINE with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP 3A4 inhibition elevates the serum levels of DIHYDROERGOTAMINE, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated. (See also CONTRAINDICATIONS and WARNINGS section)
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warnings
WARNINGS Dihydroergotamine mesylate nasal spray should only be used where a clear diagnosis of migraine headache has been established. CYP 3A4 Inhibitors (e.g., Macrolide Antibiotics and Protease Inhibitors) There have been rare reports of serious adverse events in connection with the coadministration of dihydroergotamine and potent CYP 3A4 inhibitors, such as protease inhibitors and macrolide antibiotics, resulting in vasospasm that led to cerebral ischemia and/or and ischemia of the extremities. The use of potent CYP 3A4 inhibitors with dihydroergotamine should therefore be avoided (see CONTRAINDICATIONS) . Examples of some of the more potent CYP 3A4 inhibitors include: antifungals ketoconazole and itraconazole, the protease inhibitors ritonavir, nelfinavir, and indinavir, and macrolide antibiotics erythromycin, clarithromycin, and troleandomycin. Other less potent CYP 3A4 inhibitors should be administered with caution. Less potent inhibitors include saquinavir, nefazodone, fluconazole, grapefruit juice, fluoxetine, fluvoxamine, zileuton, and clotrimazole. These lists are not exhaustive, and the prescriber should consider the effects on CYP 3A4 of other agents being considered for concomitant use with dihydroergotamine. Fibrotic Complications There have been reports of pleural and retroperitoneal fibrosis in patients following prolonged daily use of injectable dihydroergotamine mesylate. Rarely, prolonged daily use of other ergot alkaloid drugs has been associated with cardiac valvular fibrosis. Rare cases have also been reported in association with the use of injectable dihydroergotamine mesylate; however, in those cases, patients also received drugs known to be associated with cardiac valvular fibrosis. Administration of dihydroergotamine mesylate nasal spray, should not exceed the dosing guidelines and should not be used for chronic daily administration ( see DOSAGE AND ADMINISTRATION ). Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events: Dihydroergotamine mesylate nasal spray should not be used by patients with documented ischemic or vasospastic coronary artery disease (see CONTRAINDICATIONS). It is strongly recommended that dihydroergotamine mesylate nasal spray not be given to patients in whom unrecognized coronary artery disease (CAD) is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemi...
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adverse reactions
ADVERSE REACTIONS During clinical studies and the foreign postmarketing experience with dihydroergotamine mesylate nasal spray there have been no fatalities due to cardiac events. Serious cardiac events, including some that have been fatal, have occurred following use of the parenteral form of dihydroergotamine mesylate, but are extremely rare. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation ( see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS ). Fibrotic complications have been reported in association with long term use of injectable dihydroergotamine mesylate ( see WARNINGS: Fibrotic Complications ). Incidence in Controlled Clinical Trials Of the 1,796 patients and subjects treated with dihydroergotamine mesylate nasal spray doses 2 mg or less in U.S. and foreign clinical studies, 26 (1.4%) discontinued because of adverse events. The adverse events associated with discontinuation were, in decreasing order of frequency: rhinitis 13, dizziness 2, facial edema 2, and one each due to cold sweats, accidental trauma, depression, elective surgery, somnolence, allergy, vomiting, hypotension, and paraesthesia. The most commonly reported adverse events associated with the use of dihydroergotamine mesylate nasal spray during placebo-controlled, double-blind studies for the treatment of migraine headache and not reported at an equal incidence by placebo-treated patients were rhinitis, altered sense of taste, application site reactions, dizziness, nausea, and vomiting. 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. Dihydroergotamine mesylate nasal spray was generally well tolerated. In most instances these events were transient and self-limited and did not result in patient discontinuation from a study. The following table summarizes the incidence rates of adverse events reported by at least 1% of patients who received dihydroergotamine mesylate nasal spray for the treatment of migraine headaches during placebo-controlled, double-blind clinical studies and were more frequent th...
adverse reactions table
Table 3: Adverse Reactions Reported by at least 1% of theDihydroergotamine Mesylate Nasal Spray Treated Patients and Occurred MoreFrequently than in the Placebo-Group in the Migraine Placebo-Controlled TrialsDihydroergotamine mesylate N=597PlaceboN=631Respiratory SystemRhinitis26%7%Pharyngitis3%1%Sinusitis1%1%Gastrointestinal SystemNausea10%4%Vomiting4%1%Diarrhea2%<1%Special Senses, OtherAltered Sense of Taste8%1%Application SiteApplication Site Reaction6%2%Central and Peripheral Nervous SystemDizziness4%2%Somnolence3%2%Paraesthesia2%2%Body as a Whole, GeneralHot Flashes1%<1%Fatigue1%1%Asthenia1%0%Autonomic Nervous SystemMouth Dry1%1%Musculoskeletal SystemStiffness1%<1%