Overview
A 9,10alpha-dihydro derivative of ergotamine. Dihydroergotamine is used as an abortive therapy for migraines. Its use has largely been supplanted by triptans in current therapy due to the class's greater selectivity and more favourable side effect profile. Recent improvements have been made in the design of intranasal delivery devices allowing for greater delivery of dihydroergotamine solution to the vasculature-rich upper nasal cavity. The recently approved Precision Olfactory Delivery technology developed by Impel Neuropharma technology has correlated with an increase of 3-fold in Cmax and 4-fold in AUC despite the solution formulated at 75% of the strength of the existing intranasal product.
Indication
Dihydroergotamine (DHE) in all formulations is indicated for the acute treatment of migraine with or without aura in adults. As an injection, DHE is also indicated for the acute treatment of cluster headache episodes. DHE is not indicated for migraine prevention or the management of hemiplegic or basilar migraine.
Associated Conditions
- Cluster Headache
- Migraine Headache, With or Without Aura
Research Report
Dihydroergotamine: A Comprehensive Pharmacological and Clinical Monograph
Executive Summary
Dihydroergotamine (DHE) is a semi-synthetic ergot alkaloid that has been a component of the therapeutic armamentarium for acute headache for over 70 years. Identified by DrugBank ID DB00320 and CAS Number 511-12-6, this small molecule is a derivative of ergotamine, engineered to possess a distinct pharmacological profile characterized by potent, broad-spectrum receptor activity and reduced arterioconstrictor effects compared to its parent compound. This monograph provides an exhaustive analysis of Dihydroergotamine, integrating molecular data, complex pharmacology, clinical evidence, and the global regulatory landscape to present a nuanced understanding of its contemporary role in medicine.
The central thesis of this report is that Dihydroergotamine, a legacy molecule, is undergoing a significant revitalization driven by modern pharmaceutical innovation. Its enduring clinical utility is rooted in a unique, multi-receptor mechanism of action that engages serotonergic, adrenergic, and dopaminergic pathways, offering a powerful therapeutic option for severe and refractory headache disorders, including intractable migraine (status migrainosus) and medication overuse headache, where more selective agents may fail. Historically, its use has been limited by a challenging pharmacokinetic profile—notably poor oral bioavailability and variable absorption from early nasal formulations—and a side-effect profile dominated by nausea.
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2022/04/28 | Phase 1 | Completed | |||
2022/04/20 | Phase 1 | Completed | |||
2021/06/25 | Phase 3 | Completed | |||
2020/05/28 | Phase 3 | Completed | |||
2019/04/03 | Phase 3 | Completed | |||
2019/03/21 | Phase 2 | Terminated | Kimberly S Jones | ||
2019/03/14 | Phase 1 | Completed | |||
2018/01/17 | Phase 1 | Completed | Impel Pharmaceuticals | ||
2011/11/09 | Phase 1 | Completed | |||
2010/09/13 | Phase 1 | Completed |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
|---|---|---|---|---|---|
| Cipla USA Inc. | 69097-503 | NASAL | 4 mg in 1 mL | 1/24/2024 | |
| Padagis US LLC | 0574-0850 | SUBCUTANEOUS, INTRAMUSCULAR, INTRAVENOUS | 1 mg in 1 mL | 8/20/2018 | |
| Bausch Health US, LLC | 0187-0245 | NASAL | 4 mg in 1 mL | 9/1/2022 | |
| Advagen Pharma Ltd | 72888-096 | NASAL | 4 mg in 1 mL | 7/5/2023 | |
| Hikma Pharmaceuticals USA Inc. | 24201-463 | NASAL | 4 mg in 1 mL | 4/24/2023 | |
| Gland Pharma Limited | 68083-466 | INTRAVENOUS, INTRAMUSCULAR, SUBCUTANEOUS | 1 mg in 1 mL | 8/22/2023 | |
| Sagent Pharmaceuticals | 25021-609 | INTRAVENOUS, INTRAMUSCULAR, SUBCUTANEOUS | 1 mg in 1 mL | 5/2/2022 | |
| Exelan Pharmaceuticals, Inc. | 76282-680 | NASAL | 4 mg in 1 mL | 12/10/2020 | |
| Hikma Pharmaceuticals USA Inc. | 0143-9151 | INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS | 1 mg in 1 mL | 3/17/2023 | |
| Provepharm Inc. | 81284-411 | INTRAVENOUS, INTRAMUSCULAR, SUBCUTANEOUS | 1 mg in 1 mL | 8/24/2021 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
|---|---|---|---|
| No EMA approvals found for this drug. | |||
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No HSA approvals found for this drug. | |||||
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
|---|---|---|---|---|---|
| No NMPA approvals found for this drug. | |||||
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
|---|---|---|---|---|---|
| No PPB approvals found for this drug. | |||||
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
|---|---|---|---|---|---|
| No TGA approvals found for this drug. | |||||
Health Canada Drug Approvals
Approved Product | Company | DIN | Dosage Form | Strength | Market Date |
|---|---|---|---|---|---|
| DIHYDROERGOTAMINE (DHE), 1MG/ML | Sterimax Inc | 00027243 | Liquid - Intramuscular
,
Intravenous
,
Subcutaneous | 1 MG / ML | 12/31/1946 |
| DIHYDROERGOTAMINE MESYLATE INJECTION USP | 02241163 | Liquid - Subcutaneous
,
Intramuscular
,
Intravenous | 1 MG / ML | 12/23/1999 | |
| MIGRANAL NASAL SPRAY 4MG/ML | Sterimax Inc | 02228947 | Liquid - Nasal | 0.5 MG / ACT | 11/5/1996 |
| PMS-DIHYDROERGOTAMINE | 02242411 | Liquid - Nasal | 4 MG / ML | N/A | |
| PMS-DIHYDROERGOTAMINE | 02242457 | Liquid - Intramuscular
,
Intravenous
,
Subcutaneous | 1 MG / ML | N/A |
CIMA AEMPS Drug Approvals
Approved Product | Company | Registration Number | Pharmaceutical Form | Prescription Type | Status |
|---|---|---|---|---|---|
| No CIMA AEMPS (Spain) approvals found for this drug. | |||||
Philippines FDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Philippines FDA approvals found for this drug. | |||||
Saudi SFDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Saudi SFDA approvals found for this drug. | |||||
Malaysia NPRA Drug Approvals
Approved Product | Company | Registration Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Malaysia NPRA approvals found for this drug. | |||||
UK EMC Drug Information
Medicine Name | MA Holder | MA Number | Pharmaceutical Form | Active Ingredient | Authorization Date |
|---|---|---|---|---|---|
| No UK EMC drug information found for this drug. | |||||
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