DIHYDROERGOTAMINE MESYLATE

DIHYDROERGOTAMINE MESYLATE (dye-hye-droe-er-got'a-meen) D.H.E. 45, Migranal Classifications: alpha-adrenergic antagonist; ergot alkaloid; Therapeutic: antimigraine; ergot alkaloid Prototype: Ergotamine Pregnancy Category: X

Availability

4 mg/mL nasal spray; 1 mg/mL injection

Action

Alpha-adrenergic blocking agent and dihydrogenated ergot alkaloid with direct constricting effect on smooth muscle of peripheral and cranial blood vessels. Additionally, its ergot properties act as selective serotonin agonists at the 5-HT₁ receptors located on intracranial blood vessels, which may also cause vasoconstriction of large intracranial conductance arteries; this correlates with relief of migraine headaches.

Therapeutic Effect

Reduces rate of serotonin-induced platelet aggregation. Has somewhat weaker vasoconstrictor action than ergotamine but greater adrenergic blocking activity, resulting in relief from migraine headaches.

Uses

To prevent or abort vascular headache (e.g., migraine or histaminic cephalalgia) when rapid control is desired or other routes are not feasible. With low-dose heparin therapy to prevent postoperative deep-vein thrombosis and pulmonary embolism.

Unlabeled Uses

To treat postural hypotension.

Contraindications

History of hypersensitivity to ergot preparations; peripheral vascular disease, coronary heart disease, MI, hypertension; peptic ulcer; severely impaired hepatic or renal function; sepsis; within 48 h of surgery; pregnancy (category X), lactation. Safe use in children <6 y is not established.

Cautious Use

Moderate or mild renal or hepatic impairment; obesity; diabetes mellitus; postmenopausal women; males >40 y; pulmonary heart disease; valvular heart disease; smokers.

Route & Dosage

Migraine Headache Adult: IV/IM/SC 1 mg, may be repeated at 1 h intervals to a total of 3 mg IM or 2 mg IV/SC (max: 6 mg/wk) Intranasal 1 spray (0.5 mg) in each nostril, may repeat with additional spray in 15 min if no relief (max: 4 sprays per  attack); wait 6–8 h before treating another attack (max: 8 sprays per 24 h, 24 sprays/wk)

Administration

Intranasal

• Give at first warning of migraine headache.
• Optimum results: Titrate the doses required to bring relief for several headaches to determine the minimal effective dose. Use the established dose for subsequent attacks.

Intramuscular/Subcutaneous

• Withdraw IM or SC dose directly from ampule. Do not dilute.
• Note: Onset of action is about 20 min; when rapid relief is required, the IV route is prescribed.

Intravenous PREPARE: Direct: Give undiluted.   ADMINISTER: Direct: Give at a rate of 1 mg/60 sec.

• Store at 15°–30° C (59°–86° F) unless otherwise directed.
• Protect ampules from heat and light; do not freeze.
• Discard ampule if solution appears discolored.

Adverse Effects (≥1%)

CV: Vasospasm: coldness, numbness and tingling in fingers and toes, muscle pains and weakness of legs, precordial distress and pain, transient tachycardia or bradycardia, hypertension (large doses). GI: Nausea, vomiting. Body as a Whole: Dizziness, dysphoria, localized edema and itching; ergotism (excessive doses).

Interactions

Drug: beta blockers, erythromycin increase peripheral vasoconstriction with risk of ischemia; increased ergotamine toxicity with drugs that inhibit CYP3A4 (e.g., protease inhibitors, amprenavir, ritonavir, nelfinavir, indinavir, saquinavir), macrolide antibiotics (erythromycin, azithromycin, clarithromycin), azole antifungals (ketoconazole, itraconazole, fluconazole, clotrimazole), nefazodone, fluoxetine, fluvoxamine. Food: Grapefruit juice may increase toxicity.

Pharmacokinetics

Onset: 15–30 min IM; <5 min IV. Duration: 3–4 h. Distribution: Probably distributed into breast milk. Metabolism: In liver by CYP3A4. Elimination: Primarily in urine; some in feces. Half-Life: 21–32 h.

Nursing Implications

Assessment & Drug Effects

• Monitor cardiac status, especially when large doses are given.
• Monitor for and report numbness and tingling of fingers and toes, extremity weakness, muscle pain, or intermittent claudication.

Patient & Family Education

• Take at first warning of migraine headache.
• Lie down in a quiet, darkened room for several hours after drug administration for best results.
• Report immediately if any of the following S&S develop: Chest pain, nausea, vomiting, change in heartbeat, numbness, tingling, pain or weakness of extremities, edema, or itching.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug