Dihydroergotamine (Dihydroergotamine Mesylate)


Novartis Pharmaceuticals

Dihydroergotamine Mesylate

Vascular Headache Therapy

Action And Clinical Pharmacology: Dihydroergotamine displays moderate to high affinity for various serotonergic receptor subtypes (5-HT1A, 5-HT1C, 5-HT1D, 5-HT2). The compound exerts agonistic activity at the 5-HT1D subtype and antagonistic activity at the 5-HT2 subtype. Dihydroergotamine also displays blocking actions at alpha adrenergic receptor level, with a direct stimulating effect on the smooth muscle of peripheral blood vessels. Its tonic effect on capacitance vessels (veins) is particularly pronounced, compared to its effects on resistance vessels (arterioles). In comparison to ergotamine, dihydroergotamine is more potent with regard to its adrenergic blocking actions, and less potent with regard to its vasconstrictive actions.

Dihydroergotamine is 93% bound to plasma proteins. Its apparent volume of distribution is about 30 L/kg. The total body clearance is about 1.5 L/min, reflecting mainly the hepatic clearance. Elimination from the plasma is biphasic with an phase of 1.5 hours and a b-phase of 15 hours. The major route of excretion is via the bile in the feces. Urinary excretion of parent substance and metabolites amounts to about 10% after i.v. administration.

Indications And Clinical Uses: As therapy to abort acute attacks of migraine, with and without aura, and related vascular headaches including cluster headaches, where rapid relief is desired.

Contra-Indications: In patients who have previously shown hypersensitivity to ergot alkaloids.

DHE is contraindicated in patients having conditions predisposing to vasospastic reactions such as peripheral occlusive vascular disease (thromboangiitis obliterans, luetic arteritis, severe arteriosclerosis, thrombophlebitis, Raynaud’s disease), coronary artery disease (in particular, unstable or vasospastic angina), angina pectoris, sepsis or other serious infectious states, shock, vascular surgery (especially arterial, recent or contemplated), inadequately controlled hypertension, severely impaired hepatic or renal functions, peptic ulcer, severe pruritus and malnutrition.

Pregnancy: DHE possesses oxytocic properties and, therefore, should not be administered during pregnancy.

Manufacturers’ Warnings In Clinical States: Intra-arterial injection of dihydroergotamine (DHE) must strictly be avoided. Should this occur by accident, an blocker such as phentolamine should be administered.

Caution should be exercised when DHE is administered to patients with severe renal disease, unless they are receiving dialysis. In such cases the dosage should be reduced.

If excessive or prolonged dosage is contemplated, patients should be closely monitored for peripheral vascular complications.

Lactation: It is not known whether dihydroergotamine is excreted in the breast milk. Consequently, DHE should not be used in nursing mothers.

Precautions: Children: Safety and effectiveness of DHE in children have not been established.

Drug Interactions: The concomitant use of erythromycin, troleandomycin or josamycin with DHE should be avoided since these antibiotics may increase the plasma level of dihydroergotamine.

Adverse Reactions: Nausea and vomiting (not migraine related) may occasionally occur but they are less frequent and less prolonged than with ergotamine tartrate. Numbness and tingling of fingers and toes, muscle pains in the extremities, weakness in the legs, precordial distress and pain, transient tachycardia or bradycardia, localized edema and itching have also been reported.

In a few patients who have taken oral dihydroergotamine continuously over years, development of fibrotic changes, in particular of the pleura and the retroperitoneum, has been observed.

Symptoms And Treatment Of Overdose: Symptoms: Nausea, vomiting; drowsiness; confusion; tachycardia; dizziness; numbness, tingling and pain in the extremities due to ischemia; coma.

Treatment: Symptomatic under close monitoring of the patient.

The treatment includes discontinuation of the drug, local application of warmth to the affected area and nursing care to prevent tissue damage. In case of severe vasospasm, vasodilators such as nitroprusside sodium should be administered.

Dosage And Administration: Optimal results are obtained by titrating the dose for several headaches to find the minimal effective dose for each patient and this dose should then be employed at onset of subsequent attacks.

Onset of action occurs in 15 to 30 minutes following i.m. administration and persists for 3 to 4 hours. Repeated dosage at 1 hour intervals up to a total of 3 mL may be required to obtain maximal effect.

The total weekly dosage should not exceed 6 mL (6 mg).

Pretreatment with an antiemetic may be considered when DHE is administered by the i.v. route.

Acute Migraine Attack: 1 mL (1 mg) by i.m. or s.c. injection at the first sign of headache; in refractory cases, a further 1 mL may be administered after 30 to 60 minutes.

Do not exceed a total of 3 mL per attack or per day.

When more rapid effect is desired, the i.v. route may be employed: 1 mL (1 mg) by slow i.v. injection at the onset of the attack, followed in an hour by 1 mL (1 mg), if necessary. Do not exceed a total of 2 mL (2 mg) per migraine attack.

Cluster Headache (Horton Syndrome): 0.5 mL (0.5 mg) by slow i.v. injection.

Availability And Storage: Each mL of injectable solution contains: dihydroergotamine mesylate 1 mg. Also contains ethanol 47 mg/mL and glycerol 150 mg. Ampuls of 1 mL, boxes of 5. Protect ampuls from light. Store below 25°C. If the solution becomes discolored, do not use.

DIHYDROERGOTAMINE (DHE) Novartis Pharmaceuticals Dihydroergotamine Mesylate Vascular Headache Therapy

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