indication

For the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes.

pharmacology

Dihydroergotamine is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes. Dihydroergotamine binds with high affinity to 5-HT_1Da and 5-HT_1Db receptors. It also binds with high affinity to serotonin 5-HT_1A, 5-HT_2A, and 5-HT_2C receptors, noradrenaline a2A, a2B and a receptors, and dopamine D2L and D3 receptors. The therapeutic activity of Dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT_1D receptors.

mechanism of action

Two theories have been proposed to explain the efficacy of 5-HT_1D receptor agonists in migraine: 1) 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 and 2) activation of 5-HT_1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.

toxicity

Side effects include abdominal pain, abnormal speech, coma, confusion, convulsions, hallucinations, increase and/or decrease in blood pressure, nausea, numbness, tingling, pain, and a bluish color of your fingersand toes, slowed breathing, vomiting

biotransformation

Hepatic

absorption

Interpatient variable and may be dependent on the administration technique

half life

9 hours

route of elimination

The major excretory route of dihydroergotamine is via the bile in the feces. Only 6%-7% of unchanged dihydroergotamine is excreted in the urine after intramuscular injection.

drug interactions

Acebutolol: Ischemia with risk of gangrene

Almotriptan: Possible severe and prolonged vasoconstriction

Amprenavir: Amprenavir may increase the serum concentration of dihydroergotamine. Concomitant therapy is contraindicated.

Amyl Nitrite: Possible antagonism of action

Atazanavir: Atazanavir may increase the therapeutic and adverse effects of dihydroergotamine.

Atenolol: Ischemia with risk of gangrene

Betaxolol: Ischemia with risk of gangrene

Bevantolol: Ischemia with risk of gangrene

Bisoprolol: Ischemia with risk of gangrene

Carteolol: Ischemia with risk of gangrene

Carvedilol: Ischemia with risk of gangrene

Clarithromycin: Risk of ergotism and severe ischemia with this association

Delavirdine: Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of dihydroergotamine by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dihydroergotamine if delavirdine is initiated, discontinued or dose changed.

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Efavirenz: Efavirenze may increase the adverse/toxic effects of dihydroergotamine. Concomitant therapy is contraindicated.

Eletriptan: Possible severe and prolonged vasoconstriction

Erythrityl Tetranitrate: Possible antagonism of action

Erythromycin: Possible ergotism and severe ischemia with this combination

Esmolol: Ischemia with risk of gangrene

Fluconazole: Possible ergotism and severe ischemia with this combination

Fluoxetine: Possible ergotism and severe ischemia with this combination

Fluvoxamine: Possible ergotism and severe ischemia with this combination

Fosamprenavir: Amprenavir increases the effect and toxicity of ergot derivative

Frovatriptan: Possible severe and prolonged vasoconstriction

Indinavir: Indinavir may increase the serum concentration of dihydroergotamine. Concomitant therapy is contraindicated.

Isosorbide Dinitrate: Possible antagonism of action

Isosorbide Mononitrate: Possible antagonism of action

Itraconazole: Possible ergotism and severe ischemia with this combination

Josamycin: Possible ergotism and severe ischemia with this combination

Ketoconazole: Possible ergotism and severe ischemia with this combination

Labetalol: Ischemia with risk of gangrene

Metoprolol: Ischemia with risk of gangrene

Nadolol: Ischemia with risk of gangrene.

Naratriptan: Naratriptan, a serotonin 5-HT1D receptor agonists, may increase the vasoconstricting effect of dihydroergotamine. Concomitant use of these two agents within 24 hours is contraindicated.

Nefazodone: Possible ergotism and severe ischemia with this combination

Nelfinavir: Nelfinavir increases the effect and toxicity of ergot derivative

Nitroglycerin: Possible antagonism of action

Oxprenolol: Ischemia with risk of gangrene

Penbutolol: Ischemia with risk of gangrene

Pindolol: Ischemia with risk of gangrene

Posaconazole: Contraindicated co-administration

Practolol: Ischemia with risk of gangrene

Propranolol: Ischemia with risk of gangrene

Ritonavir: The protease inhibitor, ritonavir, may increase the effect and toxicity of the ergot derivative, dihydroergotamine.

Rizatriptan: Possible severe and prolonged vasoconstriction

Saquinavir: The protease inhibitor, saquinavir, may increase the effect and toxicity of the ergot derivative, dihydroergotamine.

Sibutramine: Possible serotoninergic syndrome with this combination

Sotalol: Ischemia with risk of gangrene

Sumatriptan: Possible severe and prolonged vasoconstriction

Telithromycin: Telithromycin may reduce clearance of Dihydroergotamine. Concomitant therapy is contraindicated.

Timolol: Ischemia with risk of gangrene

Tipranavir: Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Dihydroergotamine. Concomitant therapy is contraindicated.

Tramadol: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Tranylcypromine: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Troleandomycin: Possible ergotism and severe ischemia with this combination

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of dihydroergotamine by decreasing its metabolism. Concomitant therapy is contraindicated.

Zileuton: Possible ergotism and severe ischemia with this combination

Zolmitriptan: Concomitant use of the serotonin 5-HT1D receptor agonist, zolmitriptan, and the ergot derivative, dihydroergotamine, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.