10-dihydroergotamine

Uses

10-dihydroergotamine is an ergot alkaloid used in the acute treatment of migraine headache and cluster headache.

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

10-dihydroergotamine is also used to associated treatment for these conditions: Cluster Headache, Deep vein thrombosis postoperative, Migraine, Pulmonary Embolism

How 10-dihydroergotamine works

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

Food Interaction

• Avoid grapefruit products. Grapefruit inhibits the metabolism of dihydroergotamine through the CYP3A4 pathway and, therefore, may increase serum levels of dihydroergotamine. Use caution if co-administering.

[Moderate] MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability).

In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.

Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4.

Grapefruit and grapefruit juice should be avoided if an interaction is suspected.

Orange juice is not expected to interact with these drugs.

10-dihydroergotamine Hypertension interaction

[Major] The use of ergot alkaloids is contraindicated in patients with conditions predisposing them to vasospastic reactions, including, ischemic heart disease (angina, history of myocardial infarction, silent ischemia), peripheral vascular disease, sepsis, shock, vascular surgery, uncontrolled hypertension, and severely impaired hepatic or renal function.

The vasoconstriction produced be ergot alkaloids may exacerbate these conditions.

Ergot alkaloids may cause vasospastic reactions other than coronary artery vasospasm such as peripheral vascular reactions, and colonic ischemia, causing muscle pains, numbness, coldness, pallor, and cyanosis of the digits.

In patients with compromised circulation, persistent vasospasm may result in gangrene or death.

Nitroprusside and heparin have been used to treat ergotamine- induced severe vasoconstriction.

10-dihydroergotamine Drug Interaction

Major: duloxetine, duloxetineModerate: acetaminophen / butalbital / caffeine, acetaminophen / butalbital / caffeineUnknown: erenumab, erenumab, diphenhydramine, diphenhydramine, montelukast, montelukast, topiramate, topiramate, ubrogepant, ubrogepant, cholecalciferol, cholecalciferol, alprazolam, alprazolam, ondansetron, ondansetron

10-dihydroergotamine Disease Interaction

Major: vasospastic reactions

Volume of Distribution

• 800 L

Elimination Route

Interpatient variable and may be dependent on the administration technique

Half Life

9 hours

Clearance

• 1.5 L/min

Elimination Route

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.

Innovators Monograph

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