Dihydroergotamine Mesylate (dihydroergotamine mesylate)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Dihydroergotamine is a semisynthetic ergot alkaloid that is structurally and pharmacologically related to ergotamine.
Dihydroergotamine is a semisynthetic ergot alkaloid that is structurally and pharmacologically related to ergotamine. The mechanism of action of dihydroergotamine in the acute management of migraine headaches generally is attributed to the agonist effect at serotonin (5-hydroxytryptamine; 5-HT) type 1D receptors. Some clinicians suggest that activation of 5-HT1D receptors located on intracranial blood vessels, including those on arteriovenous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache.
Alternatively, other clinicians have suggested that activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of proinflammatory neuropeptide release. Dihydroergotamine also exhibits oxytocic activity.
Dihydroergotamine has poor oral bioavailability. Following intranasal administration, mean bioavailability is 32% relative to parenteral administration; absorption is variable, reflecting both intersubject differences in absorption and technique used for self-administration. Absolute bioavailability for subcutaneous and IM routes has not been determined, however, no difference was observed in bioavailability from IM and subcutaneous doses.
The median time to maximum plasma concentration is 0.4 hours after subcutaneous administration and 0.5 hours after intranasal administration. Dihydroergotamine is 93% plasma protein bound. Dihydroergotamine is extensively metabolized in the liver by cytochrome P-450 3A4; the major metabolite (8'-beta-hydroxydihydroergotamine) exhibits affinity for adrenergic and serotonergic receptors similar to the parent drug.
Dihydroergotamine is eliminated principally in the feces via the bile; 6--7% is excreted unchanged in the urine after IM injection. The decline of plasma dihydroergotamine after IM or IV injection is multi-exponential with a terminal half life of ~9 hours. The decline of plasma dihydroergotamine after intranasal administration is biphasic with a terminal half-life of ~10 hours.
No studies have been performed on the effect of renal or hepatic impairment, gender, race, or ethnicity on the pharmacokinetics of dihydroergotamine.
USES: Dihydroergotamine is used to treat migraine headaches and cluster headaches. It is not recommended for migraines that affect only one side of the brain (hemiplegic migraine) or the base of the brain/neck area (basilar migraine), or to prevent migraines from occurring. Dihydroergotamine is an ergot medication that helps narrow widened blood vessels in the head, thereby reducing the throbbing effects of these headaches.
Generic name: dihydroergotamine mesylate
Pronunciation: (dye-HI-dro-er-GOT-uh-meen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Dihydroergotamine Mesylate
Indications
The following indications are listed for Dihydroergotamine Mesylate:
- Cluster Headache
- Migraine
Dosing
Available as dihydroergotamine mesylate; dosage expressed in terms of the salt.
Administer dihydroergotamine intranasally or by IM, IV, or subcutaneous injection for acute treatment of migraine. Administer by direct IV injection or continuous IV infusion+ for the acute treatment of intractable migraines in an inpatient setting.
Administer dihydroergotamine by IM, IV, or subcutaneous injection for acute treatment of cluster headaches.
If the drug is being self-administered, the patient should be counseled on proper use and administration technique.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Concomitant therapy with strong inhibitors of the cytochrome P-450 (CYP) 3A4 isoenzyme (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole, nelfinavir, ritonavir).
*Known or suspected ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, documented silent ischemia) or clinical symptoms or findings consistent with coronary artery vasospasm (including Prinzmetal's variant angina).
*Uncontrolled hypertension.
*Recent use (i.e., within 24 hours) of a 5-HT1 receptor agonist (e.g., sumatriptan), ergotamine-containing or ergot-type medication or methysergide.
*Basilar or hemiplegic migraine.
*Known peripheral arterial disease, sepsis, severe renal or hepatic impairment, or following vascular surgery.
*Known hypersensitivity to ergot alkaloids. For the dihydroergotamine subcutaneous autoinjector, known hypersensitivity to dihydroergotamine, ergot alkaloids, latex, or any excipients in the formulation.
*Concomitant use of peripheral and central vasoconstrictors.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects of dihydroergotamine injection include vasospasm, paresthesia, hypertension, dizziness, anxiety, dyspnea, headache, flushing, diarrhea, rash, increased sweating, and pleural and retroperitoneal fibrosis after long-term use.
The most common adverse effects of dihydroergotamine nasal spray and powder (>1% of patients) include rhinitis, nausea, altered sense of taste, application site reactions, dizziness, vomiting, somnolence, pharyngitis, and diarrhea.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of dihydroergotamine not established in children.
Available data from published literature indicate an increased risk of preterm delivery associated with dihydroergotamine use during pregnancy. Data collected over decades have found no increased risk of major birth defects or miscarriage. In animal reproduction studies, adverse developmental effects were observed in rats and rabbits following intranasal administration of dihydroergotamine during pregnancy (decreased fetal body weight and/or skeletal ossification) and lactation (decreased body weight and impaired reproductive function in offspring) at doses not associated with maternal toxicity. Dihydroergotamine-induced intrauterine growth retardation has been attributed to reduced uteroplacental blood flow resulting from prolonged vasoconstriction of the uterine vessels and/or increased myometrial tone.
Avoid use of dihydroergotamine during pregnancy.
There are no data on the presence of dihydroergotamine in human milk; however, ergotamine is present in human milk. Vomiting, diarrhea, weak pulse, and unstable blood pressure have been reported in breast-fed infants exposed to ergotamine. Ergot alkaloids inhibit prolactin secretion, which may reduce milk supply. Because of the potential for reduced milk supply and serious adverse effects in the breast-fed infant, advise patients not to breast-feed during treatment with dihydroergotamine and for 3 days after the last dose. Breast milk supply during this time should be pumped and discarded.
The manufacturers make no specific dosage recommendations for geriatric patients. In general, dose selection should be cautious, starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
Experience with intranasal dihydroergotamine in patients 65 years of age and older is insufficient to determine whether they respond differently than younger adults. In general, dose selection should be cautious, starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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