Dihydroergotamine Mesylate Injection, USP

<div class="Texte" id="TheTexte" lang="zxx"> <p><strong>Dihydroergotamine Mesylate Injection, USP</strong></p> <h3><strong>WARNING</strong></h3> <p><strong>Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP3A4 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.</strong></p> <p><strong>INDICATION AND IMPORTANT SAFETY INFORMATION</strong></p> <p>&nbsp;</p> <p><strong>INDICATIONS AND USAGE</strong></p> <p>Dihydroergotamine Mesylate Injection, USP is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes.</p> <p>Dihydroergotamine Mesylate Injection, USP should only be used where a clear diagnosis of migraine headache has been established. Dihydroergotamine Mesylate Injection, USP is not recommended for prolonged daily use.</p> <p>&nbsp;</p> <p><strong>CONTRAINDICATIONS</strong></p> <p>Dihydroergotamine Mesylate Injection, USP is contraindicated for:</p> <ul class="normal"> <li> <p>Use with potent CYP3A4 inhibitors (i.e., ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole).</p> </li> <li> <p>Patients with ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, or documented silent ischemia) or patients who have clinical symptoms or findings consistent with coronary artery vasospasm including Prinzmetal’s variant angina.</p> </li> <li> <p>Patients with uncontrolled hypertension.</p> </li> <li> <p>Patients with hemiplegic or basilar migraine.</p> </li> <li> <p>Patients with known peripheral arterial disease, sepsis, or following vascular surgery</p> </li> <li> <p>Patients with severely impaired hepatic or renal function.</p> </li> <li> <p>Patients who are or trying to become pregnant.</p> </li> <li> <p>Nursing mothers.</p> </li> <li> <p>Use with peripheral and central vasoconstrictors.</p> </li> <li> <p>Patients who have previously shown hypersensitivity to ergot alkaloids.</p> </li> <li> <p>Dihydroergotamine Mesylate Injection, USP, 5-HT agonists (e.g., sumatriptan), ergotamine containing or ergot-type medications or methysergide should not be used within 24 hours of each other.</p> </li> </ul> <p>&nbsp;</p> <p><strong>WARNINGS AND PRECAUTIONS</strong></p> <p>&nbsp;</p> <p><strong>CYP3A4 Inhibitors (e.g., Macrolide Antibiotics and Protease Inhibitors)</strong>: There have been rare reports of serious adverse events in connection with the coadministration of dihydroergotamine and potent CYP3A4 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 CYP3A4 inhibitors with Dihydroergotamine Mesylate Injection, USP should be avoided.</p> <p>&nbsp;</p> <p><strong>Fibrotic Complications:</strong>&nbsp;There have been reports of pleural and retroperitoneal fibrosis in patients following prolonged daily use of dihydroergotamine mesylate injection. Administration of Dihydroergotamine Mesylate Injection, USP, should not exceed the dosing guidelines and should not be used for chronic daily administration.</p> <p>&nbsp;</p> <p><strong>Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events</strong>: Dihydroergotamine Mesylate Injection, USP should not be used by patients with documented ischemic or vasospastic coronary artery disease. It is strongly recommended that Dihydroergotamine Mesylate Injection, USP not be given to patients in whom unrecognized coronary artery disease (CAD) is predicted by the presence of risk factors 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. 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 Dihydroergotamine Mesylate Injection, USP take place in the setting of a physician’s office or similar medically staffed and equipped facility unless the patient has previously received dihydroergotamine mesylate.</p> <p>&nbsp;</p> <p><strong>Cardiac Events and Fatalities</strong>: The potential for adverse cardiac events exists. Serious adverse cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and death have been reported to have occurred following the administration of dihydroergotamine mesylate injection.</p> <p>&nbsp;</p> <p><strong>Drug-Associated Cerebrovascular Events and Fatalities</strong>: Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with Dihydroergotamine Mesylate Injection, USP; and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, and the Dihydroergotamine Mesylate Injection, USP had been administered due to the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. It should be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack).</p> <p>&nbsp;</p> <p><strong>Other Vasospasm-Related Events</strong>: Myocardial, peripheral vascular, and colonic ischemia have been reported with Dihydroergotamine Mesylate Injection, USP. Dihydroergotamine Mesylate Injection, USP associated vasospastic phenomena may also cause muscle pains, numbness, coldness, pallor, and cyanosis of the digits. In patients with compromised circulation, persistent vasospasm may result in gangrene or death. Dihydroergotamine Mesylate Injection, USP should be discontinued immediately if signs or symptoms of vasoconstriction develop.</p> <p>&nbsp;</p> <p><strong>Increase in Blood Pressure</strong>: Significant elevation in blood pressure has been reported on rare occasions in patients with and without a history of hypertension treated with dihydroergotamine mesylate injection. Dihydroergotamine Mesylate Injection, USP is contraindicated in patients with uncontrolled hypertension.</p> <p>&nbsp;</p> <p><strong>ADVERSE REACTIONS</strong></p> <p>Serious cardiac events, including some that have been fatal, have occurred following use of Dihydroergotamine Mesylate Injection, USP. &nbsp;In post marketing experience, the following have been reported in patients receiving Dihydroergotamine Mesylate Injection, USP: vasospasm, paraesthesia, hypertension, dizziness, anxiety, dyspnea, headache, flushing, diarrhea, rash, increased sweating, and pleural and retroperitoneal fibrosis after long-term use of dihydroergotamine.</p> <p>&nbsp;</p> <p><strong>DRUG INTERACTIONS</strong></p> <p><strong>Vasoconstrictors:</strong>&nbsp;Dihydroergotamine Mesylate Injection, USP should not be used with peripheral vasoconstrictors because combination may cause synergistic elevation of blood pressure.</p> <p><strong>Sumatriptan:</strong>&nbsp;Sumatriptan has been reported to cause coronary artery vasospasm, and its effect could be additive with Dihydroergotamine Mesylate Injection, USP. Sumatriptan and Dihydroergotamine Mesylate Injection, USP should not be taken within 24 hours of each other.</p> <p><strong>Beta Blockers:</strong>&nbsp;There have been reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.</p> <p><strong>Nicotine:</strong>&nbsp;Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy.</p> <p><strong>CYP3A4 Inhibitors:</strong>&nbsp;The use of potent CYP3A4 inhibitors with Dihydroergotamine Mesylate Injection, USP should be avoided.</p> <p><strong>SSRIs:</strong>&nbsp;Weakness, hyperreflexia, and incoordination have been reported rarely when 5-HT agonists have been co-administered with SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline).</p> <p><strong>Oral Contraceptives</strong>: The effect of oral contraceptives on the pharmacokinetics of Dihydroergotamine Mesylate Injection, USP has not been studied.</p> <p>&nbsp;</p> <p><strong>IMPORTANT ADMINISTRATION INSTRUCTIONS</strong></p> <p>Dihydroergotamine Mesylate Injection, USP should be administered in a dose of 1 mL intravenously, intramuscularly or subcutaneously. The dose can be repeated, as needed, at 1-hour intervals to a total dose of 3 mL for intramuscular or subcutaneous delivery or 2 mL for intravenous delivery in a 24-hour period. Total weekly dosage should not exceed 6mL.</p> <p>&nbsp;</p> <p><strong>USE IN SPECIFIC POPULATIONS</strong></p> <p><strong>Pregnancy</strong>&nbsp;<u>Risk Summary</u>:&nbsp;<strong>Contraindicated</strong>. Dihydroergotamine Mesylate Injection, USP may cause fetal harm when administered to a pregnant woman. Dihydroergotamine possesses oxytocic properties and should not be administered during pregnancy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.</p> <p><strong>Lactation</strong>&nbsp;<u>Risk Summary</u>:&nbsp;<strong>Contraindicated</strong>. Nursing should be avoided with the use ofDihydroergotamine Mesylate Injection, USP. Ergot drugs are known to inhibit prolactin. It is likely that Dihydroergotamine Mesylate Injection, USP is excreted in human milk, but there are no data on the concentration in human milk. It is known that ergotamine is excreted in breast milk and may cause vomiting, diarrhea, weak pulse, and unstable blood pressure in nursing infants.</p> <p><strong>Pediatric Use:</strong>&nbsp;Safety and effectiveness in pediatric patients have not been established.</p> <p>&nbsp;</p> <p><strong>OVERDOSAGE</strong></p> <p>Excessive doses of dihydroergotamine may result in peripheral signs and symptoms of ergotism including nausea, vomiting, diarrhea, numbness, tingling, pain, peripheral cyanosis associated with diminished or absent peripheral pulses; respiratory depression; an increase and/or decrease in blood pressure; headache, confusion, delirium, convulsions, coma; and gangrene and death in patients with compromised circulation. Treatment includes discontinuance of the drug, local application of warmth to the affected area, the administration of vasodilators, and nursing care to prevent tissue damage.</p> <p><strong>For additional Safety Information, please see Full Prescribing Information.</strong></p> <p><strong>You are encouraged to report adverse drug events to Provepharm at 1-833-727-6556 or to the FDA by visiting www.fda.gov/medwatch or by calling 1-800-FDA-1088.</strong></p> </div>