Breath-powered sumatriptan dry nasal powder: an intranasal medication delivery system for acute treatment of migraine

Abstract

There is a need for fast-acting, non-oral medication options for migraine because some attacks develop rapidly and some are accompanied by nausea, vomiting, and gastroparesis, which can hinder oral medication uptake and absorption. The most commonly prescribed migraine medications are oral triptans, with sumatriptan as the most common. However, oral triptans are associated with adverse events (AEs) of atypical sensations that may be problematic for patients. Subcutaneous (SC) injectable sumatriptan and conventional liquid triptan nasal spray formulations are also available, but the frequency of atypical sensations is the highest with SC sumatriptan, and the intense bitter taste of conventional liquid triptan nasal spray discourages use. AVP-825 (ONZETRA® Xsail®) is an intranasal medication delivery system containing 22 mg sumatriptan nasal powder that is now available in the USA for the acute treatment of migraine with or without aura in adults. The objective of this review is to summarize the development of AVP-825, which utilizes unique features of nasal anatomy to achieve efficient absorption and reduced systemic exposure. Literature searches for “sumatriptan nasal powder”, “AVP-825”, and “sumatriptan intranasal” were conducted. Review articles and pharmacokinetic, Phase II and Phase III studies were evaluated. AVP-825 demonstrates an earlier onset of efficacy and lower rate of atypical sensations than the oral standard of care, which can be attributed to its fast absorption and low systemic exposure. AEs of abnormal taste are predominantly mild. These results confirm the initial design concept for AVP-825, which aligned pharmacokinetics, anatomy, and drug presentation in a novel device to achieve optimal outcomes for the acute treatment of migraine.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Tolerability, and Safety of Celecoxib Oral Solution (ELYXYB) in Acute Treatment of Episodic Migraine With or Without Aura

“…Liquid triptan nasal sprays are more rapid-acting than oral triptans, but conventional intranasal spray pumps deposit only a limited amount of drug to the upper posterior nasal cavity; a substantial amount of the dose is swallowed. Once swallowed, the triptan effectively becomes an orally administered medication subject to the previously noted disadvantages [12]. Sumatriptan subcutaneous injections have a more rapid onset of action than oral triptans, but also have lower tolerability and patient acceptance [13,14].…”

Nose-to-Brain Delivery

“…There are limitations to the use of the nose-to-brain route, and these must be acknowledged when developing new therapeutics to be administered via this route. There is a limitation on the dose volume for liquids of 100-250 ml (Davis, 1999;Djupesland et al, 2014;Santos-Morales et al, 2017) and powders 20-50 mg (depending on the bulk density of the powder) (Davis, 1999;Tepper and Johnstone, 2018;Shrewsbury et al, 2019), making the route only possible for potent drugs. Drugs that are metabolized by nasal cavity enzymes will also need to be protected from degradation, and drug formulations must be non-irritant to the nasal cavity.…”

Transmucosal drug administration as an alternative route in palliative and end-of-life care during the COVID-19 pandemic

“…It also allows prolonged mucosal contact time which enhances drug absorption [ 75 ]. There are a few intranasal powder formulations available in the market, including sumatriptan for the treatment of migraine [ 76 , 77 ] and glucagon for use in hypoglycemic emergency [ 78 ]. Both these demonstrate good safety profile, fast absorption and rapid onset of action.…”