Orally inhaled dihydroergotamine: A novel ergot delivery method for the treatment of migraine

February 1, 2012

Orally inhaled dihydroergotamine (DHE) is a newly developed formulation of DHE for the treatment of acute migraine attack and is undergoing FDA review.

Key Points


Orally inhaled dihydroergotamine (DHE) is a newly developed formulation of DHE for the treatment of acute migraine attack and is undergoing FDA review. This new agent provides an alternative to nonsteroidal anti-inflammatory drugs and triptans. In clinical trials, orally inhaled DHE was effective compared with placebo in relieving headache, nausea, phonophobia, and photophobia. No serious adverse events were documented; mild adverse effects included poor taste, nausea, coughing, and vomiting. Orally inhaled DHE has not yet been approved for use, so final dosing and cost information is not available. No head-to-head trials have been conducted to compare orally inhaled DHE with other medications to treat acute migraine attacks, so further studies may be necessary to determine comparative efficacy. Orally inhaled DHE may provide an effective option for patients with moderate to severe acute migraine attack. (Formulary. 2012;47:54-57)

Migraine is a chronic and debilitating neurologic disorder characterized by severe headaches, nausea, vomiting, photophobia, and phonophobia.1 Migraines vary greatly in frequency, duration, and level of disability in affected patients.1

Dihydroergotamine (DHE) has been used intravenously, subcutaneously, and intranasally for the treatment of migraines.1 These formulations are effective and are reasonable choices in patients with moderate to severe migraine and in those whose mild to moderate headaches have failed to respond to other migraine treatments. A major limitation to the currently available DHE formulations is that the delivery route may be inconvenient for the patient. Orally inhaled DHE (Levedex, MAP Pharmaceuticals Inc) is under investigation for treatment of migraine.


DHE interacts with adrenergic, dopaminergic, and serotonergic 5-hydroxytryptamine (5-HT) receptors. The affected 5-HT subtypes include 5-HT1A, 1B, 1D, 1F, 2A, 2C, 3, and 4.2 5-HT1B agonism leads to intracranial extracerebral blood vessel constriction within the meninges, which is thought to be responsible for producing pain.2 The primary effect of DHE occurs in the brainstem, where its serotonergic effects work to reverse vasodilation, reduce pain signal transmission, and halt other ascending pathways to the cortex that are related to photophobia and phonophobia.2


Orally inhaled DHE is rapidly and completely absorbed in the plasma. In healthy volunteers administered a 0.88-mg systemic equivalent dose, tmax was 12 minutes, half-life was 11 hours, and Cmax was 3648 pg/mL.3 When orally inhaled DHE was evaluated in patients with asthma, tmax was 9.6 minutes, half-life was 9.5 hours, and Cmax was 4097 pg/mL with a 1-mg systemic equivalent dose.4