Dihydroergotamine Data - Uses, Dosage, Drug class, Brand name, Warnings, etc

Pharmacology	Dihydroergotamine (DHE) is a semisynthetic ergot alkaloid that is hypothesized to exert its antimigraine effect via its agonist activity at the serotonin 5-HT1D receptor, resulting in vasoconstriction of intracranial blood vessels and inhibition of inflammatory neuropeptide release. The drug also binds with high affinity to adrenergic and dopamine receptors; however, the antimigraine effect of these events is unknown. Compared with ergotamine, DHE is a weaker vasoconstrictor, is less active as an emetic, and is less oxytocic.
Administration and Adult Dosage	For migraine treatment: - IM: 1 mg initially, then 1 mg every 1 hr as needed, to a maximum of 3 mg/day or 6 mg/week - IV (for rapid effect): 0.5–1 mg, may repeat in 1 hr to a maximum of 2 mg/day or 6 mg/week - Consider administering metoclopramide 10 mg IV before DHE to treat nausea due to migraine and prevent nausea due to the drug - Intranasal: One spray (0.5 mg) into each nostril; may repeat in 15 min to a maximum of 2 mg over 24 hr
Special Populations - Pediatric Dosage	Safety and efficacy not established.
Special Populations - Geriatric Dosage	Same as adult dosage.
Dosage Forms	- Injection: 1 mg/mL - Nasal Spray: 4 mg/mL
Patient Instructions	- This drug can cause numbness and tingling in fingers, toes, or face - Notify your physician if you are pregnant or have heart disease or high blood pressure - Do not exceed the maximum dosage - The nasal spray can cause local irritation. Do not reuse the applicator; use the solution right after opening - Review training materials with your health care provider and report the use of all cold or allergy medications and all over-the-counter medications
Pharmacokinetics - Onset and Duration	- IV: Onset under 5 min - IM or Intranasal: Onset within 15–30 min - Duration: 3–4 hr - Intranasal: 50–70% of patients respond in 4 hr
Pharmacokinetics - Fate	- The drug is absorbed directly into the systemic circulation when administered intranasally, but it undergoes extensive first-pass metabolism if given orally - Bioavailability: Nasal spray 38 ± 16%, variable depending on self-administration technique - Protein Binding: 93% - Peak Levels (1 mg dose): • Intranasal: 1 ± 0.4 µg/L at 0.9 ± 0.6 hr • IM: 4.4 µg/L at 0.4 ± 0.3 hr - Distribution: Vc = 12 ± 4 L/kg, Vd = 33 ± 0.2 L/kg, suggesting distribution into deep tissue compartments - Clearance: Cl = 1.6 ± 0.17 L/hr/kg - Metabolism: Metabolized to at least 5 metabolites, 3 of which are active - Excretion: Major route for DHE and its metabolites is in the feces via the bile
Pharmacokinetics - t¹⁄₂	- α phase: • Intranasal: 1 ± 0.5 hr • IM: 0.9 ± 0.3 hr - β phase: • Intranasal: 7.9 ± 4 hr • IM: 7.2 ± 2.2 hr
Adverse Reactions & Side Effects	Frequent (intranasal): - Rhinitis, pharyngitis, altered sense of taste, application site reactions, nausea, vomiting, dizziness Frequent (all routes): - Nausea, vomiting, diarrhea, localized edema Occasional: - Numbness and tingling of fingers and toes, muscle pain in extremities, weakness in legs, pruritus, rash, infection Rare (with prolonged use): - Pleural and retroperitoneal fibrosis
Contraindications	- Pregnancy and lactation - Peripheral vascular disease - Coronary artery disease - Ischemic heart disease - Hemiplegic or basilar migraine - Sepsis - Recent history of vascular surgery - Severely impaired hepatic or renal function - Hypersensitivity to ergot alkaloids
Precautions & Warnings	- Use caution to avoid overuse by patients with chronic vascular headaches - Patients with risk factors for coronary artery disease should undergo periodic cardiovascular evaluation
Drug Interactions	- DHE can antagonize the antianginal effects of nitrates - The risk of bleeding with warfarin (e.g., wound hematoma, anemia, hematuria) is worsened with co-administration of DHE - Macrolides including erythromycin can increase the risk of ergot toxicity - Sumatriptan can exacerbate coronary artery vasospasm and should not be taken within 24 hr of DHE - SSRIs can cause weakness, hyperreflexia, or incoordination
Class and Drug Brand Name	- Class: Analgesic and Anti-Inflammatory Drugs - Brand Names: D.H.E. 45, Migranal
Notes	- IV DHE is used when oral agents have failed to abort migraine and for terminating cluster or migraine headache in an emergency setting - It is not intended for prophylaxis or the management of hemiplegic or basilar migraine - The intranasal preparation is a noninvasive option for outpatients - Intranasal administration results in improved bioavailability over the oral form because it does not undergo a first-pass effect in the liver - DHE does not cause physical dependence and is associated with a more favorable side effect profile than ergotamine, especially with regard to GI and peripheral vascular effects - In one study, subcutaneously administered sumatriptan appeared to be more effective than DHE nasal spray; however, DHE was better tolerated

References

Hand of Clinical Drug Data