Dihydroergotamine

Dihydroergotamine Mesylate Nasal Spray is indicated for the acute treatment of migraine headaches with or without aura. Dihydroergotamine Mesylate Nasal Spray is not intended for the prophylactic therapy of migraine or for the management of hemiplegic or basilar migraine.

Dihydroergotamine binds with high affinity to 5-HT 1Dα and 5-HT 1Dβ receptors. It also binds with high affinity to serotonin 5-HT 1A, 5-HT 2A, and 5-HT 2C receptors, noradrenaline α 2A, α 2B and α 1 receptors, and dopamine D 2L and D 3 receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT 1D receptors. Two current theories have been proposed to explain the efficacy of 5-HT 1D receptor agonists in migraine. One theory suggests that activation of 5-HT 1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. The alternative hypothesis suggests that activation of 5-HT 1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.

The solution used in Dihydroergotamine Mesylate Nasal Spray (4 mg/mL) is intended for intranasal use and must not be injected. In clinical trials, Dihydroergotamine Mesylate Nasal Spray has been effective for the acute treatment of migraine headaches with or without aura. One spray (0.5 mg) of Dihydroergotamine Mesylate Nasal Spray should be administered in each nostril. Fifteen minutes later, an additional one spray (0.5 mg) of Dihydroergotamine Mesylate Nasal Spray should be administered in each nostril, for a total dosage of four sprays (2 mg) of Dihydroergotamine Mesylate Nasal Spray. Studies have shown no additional benefit from acute doses greater than 2 mg for a single migraine administration. The safety of doses greater than 3 mg in a 24-hour period and 4 mg in a 7‑day period has not been established.

There have been a few reports of serious adverse events associated 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 ischemia of the extremities. The use of potent CYP 3A4 inhibitors (ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole) with dihydroergotamine is, therefore contraindicated.

Boxed 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. 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.

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 (D.H.E. 45 Injection), but are extremely rare. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation. Fibrotic complications have been reported in association with long term use of injectable dihydroergotamine mesylate. 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.

Vasoconstrictors Dihydroergotamine Mesylate Nasal Spray should not be used with peripheral vasoconstrictors because the combination may cause synergistic elevation of blood pressure. Sumatriptan Sumatriptan has been reported to cause coronary artery vasospasm, and its effect could be additive with Dihydroergotamine Mesylate Nasal Spray. Sumatriptan and Dihydroergotamine Mesylate Nasal Spray should not be taken within 24 hours of each other. Beta-Blockers Although the results of a clinical study did not indicate a safety problem associated with the administration of Dihydroergotamine Mesylate Nasal Spray to subjects already receiving propranolol, there have been reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.

Store below 25°C (77°F). Do not refrigerate or freeze. * Trademark of PDR Network, LLC Distributed by: Oceanside Pharmaceuticals, a division of Bausch Health US, LLC Bridgewater, NJ 08807 USA Manufactured by: Mipharm, S.p.A.