D.H.E. 45- dihydroergotamine mesylate injection, solution
Valeant Pharmaceuticals North America
Rx only
Prescribing Information
WARNING
Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of DIHYDROERGOTAMINE with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP 3A4 inhibition elevates the serum levels of DIHYDROERGOTAMINE, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated. (See also CONTRAINDICATIONS and WARNINGS section)
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�?)-, monomethanesulfonate. Its molecular weight is 679.80 and its empirical formula is C33 H37 N5 O5 �CH4 O3 S.
The chemical structure is
Chemical Structure
(click image for full-size original)
Dihydroergotamine mesylate
C33 H37 N5 O5 �CH4 O3 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 � 4.9.
CLINICAL PHARMACOLOGY
Mechanism of Action
Dihydroergotamine binds with high affinity to 5-HT1D ? and 5-HT1D ? receptors. It also binds with high affinity to serotonin 5-HT1A , 5-HT2A , and 5-HT2C receptors, noradrenaline ?2A , ?2B and ?1 receptors, and dopamine D2L and D3 receptors.
The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT1D receptors. Two current theories have been proposed to explain the efficacy of 5-HT1D receptor agonists in migraine. One theory suggests that activation of 5-HT1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. The alternative hypothesis suggests that activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.
In addition, dihydroergotamine possesses oxytocic properties. (See CONTRAINDICATIONS.)
