D.H.E. 45® (dihydroergotamine mesylate) Injection, USP

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

Dihydroergotamine Mesylate (UNII: 81AXN7R2QT) (Dihydroergotamine - UNII:436O5HM03C)

Available from:

Bausch Health US, LLC

INN (International Name):

Dihydroergotamine Mesylate

Composition:

Dihydroergotamine Mesylate 1 mg in 1 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

D.H.E. 45 (dihydroergotamine mesylate) Injection, USP is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes. There have been a few reports of serious adverse events associated with the coadministration of dihydroergotamine and potent CYP3A4 inhibitors, such as protease inhibitors and macrolide antibiotics, resulting in vasospasm that led to cerebral ischemia and/or ischemia of the extremities. The use of potent CYP3A4 inhibitors (i.e., ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole) with dihydroergotamine is, therefore, contraindicated (see WARNINGS, CYP3A4 Inhibitors ). D.H.E. 45 (dihydroergotamine mesylate) Injection, USP should not be given to patients with ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have clinical symptoms or findings consistent with coronary artery vasospasm includi

Product summary:

Available as a clear, colorless, sterile solution in single 1 mL sterile ampuls containing 1 mg of dihydroergotamine mesylate per mL, in packages of 10 (NDC 66490-041-01). Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Use carton to protect contents from light until used. Do not refrigerate or freeze. To assure constant potency, protect the ampuls from light and heat. Administer only if clear and colorless.

Authorization status:

New Drug Application

Summary of Product characteristics

D.H.E. 45- DIHYDROERGOTAMINE MESYLATE INJECTION, SOLUTION
BAUSCH HEALTH US, LLC
----------
D.H.E. 45®
(DIHYDROERGOTAMINE MESYLATE)
INJECTION, USP
WARNING: PERIPHERAL ISCHEMIA FOLLOWING COADMINISTRATION
WITH POTENT CYP3A4 INHIBITORS
DESCRIPTION
D.H.E. 45 is ergotamine hydrogenated in the 9, 10 position as the
mesylate salt. D.H.E.
45 is known chemically as
ergotaman-3´,6´,18-trione,9,10-dihydro-12´-hydroxy-2´-
methyl-5´-(phenylmethyl)-,(5´α)-, monomethanesulfonate. Its
molecular weight is
679.80 and its empirical formula is C
H
N O •CH O S.
The chemical structure is:
Dihydroergotamine mesylate
C
H
N O •CH O S Mol. Wt. 679.80
D.H.E. 45 (dihydroergotamine mesylate) Injection, USP is a clear,
colorless solution
supplied in sterile ampuls for intravenous, intramuscular, or
subcutaneous
administration. Each mL contains 1 mg Dihydroergotamine Mesylate, USP;
Alcohol, USP
6.1% by volume; Glycerin, USP 15% by weight; Water for Injection, USP;
Methanesulfonic Acid and/or Sodium Hydroxide for pH adjustment (pH
range is 3.4 to
4.9).
CLINICAL PHARMACOLOGY
MECHANISM OF ACTION
Dihydroergotamine binds with high affinity to 5-HT
α and 5-HT
β receptors. It also
binds with high affinity to serotonin 5-HT
, 5-HT
, and 5-HT
receptors, noradrenaline
α
, α
and α receptors, and dopamine D and D receptors.
33
37
5
5
4
3
33
37
5
5
4
3
1D
1D
1A
2A
2C
2A
2B
1
2L
3
The therapeutic activity of dihydroergotamine in migraine is generally
attributed to the
agonist effect at 5-HT
receptors. Two current theories have been proposed to explain
the efficacy of 5-HT
receptor agonists in migraine. One theory suggests that
activation of 5-HT
receptors located on intracranial blood vessels, including those on
arteriovenous anastomoses, leads to vasoconstriction, which correlates
with the relief of
migraine headache. The alternative hypothesis suggests that activation
of 5-HT
receptors on sensory nerve endings of the trigeminal system results in
the inhibition of
pro-inflammatory neuropeptide release.
In addition, dihydroergotamine possess