Dihydroergotamine mesylate nasal spray: an acute treatment option for migraine in adults

ABSTRACT

Introduction

Although the landscape of migraine symptomatic treatment has been enriched by novel effective drugs, it is mandatory to critically reappraise older molecules to ascertain whether they could still represent reliable alternatives in specific endophenotypes of patients or migraine attacks. Among these, dihydroergotamine (DHE) nasal spray has been shown to be effective and is characterized by greater tolerability and manageability than the parenteral DHE formulation.

Areas covered

In this narrative review, the authors describe the pharmacodynamic and pharmacokinetic properties of DHE nasal spray and explore the results of the trials which explored its efficacy, safety and tolerability as migraine symptomatic treatment. They also discuss the limitations of the classically used device and the attempts that several companies are carrying out to generate devices warranting a more reproducible drug absorption.

Expert opinion

DHE nasal spray could be considered as rescue treatment in patients who have failed other symptomatic therapeutic strategies. Nevertheless, in the perspective of tailored therapy, the intranasal route of administration and the consequent rapid onset of action may represent benefits putatively making DHE a treatment of choice for challenging migraine attacks such as those with nocturnal onset or quickly reaching the climax of both headache and neurovegetative associated symptoms.

KEYWORDS:

• Ergotamine
• nasal spray
• dihydroergotamine
• migraine
• symptomatic treatment

Article highlights

• DHE, although characterized by a better tolerability profile than ergotamine, is burdened by adverse effects as nausea and emesis when administered intravenously, to avoid which a nasal formulation has been developed.

• Although burdened by some bias, the study results place DHE nasal spray as an effective symptomatic strategy in patients with migraine with previous unsatisfactory response to triptans.

• DHE nasal spray, when compared to ergotamine or to parenteral DHE, seems to be characterized by favorable safety and tolerability profile.

• The nasal route of drug administration, unlike oral administration, has the potential to bypass the blood-brain-barrier entering the central nervous system along the olfactory and trigeminal pathways.

• Balancing pros and cons, DHE nasal spray could represent an acute treatment to be considered in those patients who have failed or have not tolerated other symptomatic therapeutic strategies.

Declaration of interest

M Silvestro has received speaker’s honoraria from Novartis, Pfizer Inc, Teva Pharmaceuticals, Eli Lilly and Company. A Russo has received speaker’s honoraria from Allergan, Pfizer Inc, Eli Lilly and Company, Novartis and Teva Pharmaceuticals. A Tessitore has received speaker’s honoraria from Novartis, Schwarz Pharma/UCB, Lundbeck A/S, AbbVie and GlaxoSmithKline. G Tedeschi has received speaker’s honoraria from Sanofi, Merck Serono, Bayer Schering, Novartis, Biogen-Dompe, AG, Teva Pharmaceuticals and Eli Lilly and Company. He has also received funding for travel from Bayer Schering, Biogen-Dompe AG, Merck Serono, Novartis and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One reviewer declares that, over the past 36 months, they have received institutional support for serving as an investigator from Teva Pharmaceuticals, AbbVie, Trillen, Thermaquil Inc, and Ipsen. They also declare receiving consultancy fees from Salvia, Pfizer, AbbVie, Cerenovus have received and royalties from Cambridge University Press and MedLink. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.