The Food and Drug Administration (FDA) has approved Atzumi™ (dihydroergotamine) nasal powder for the acute treatment of migraine with or without aura in adults.

Atzumi is a drug-device combination consisting of dihydroergotamine (DHE), an ergotamine derivative. The safety and efficacy of Atzumi was based on data from 2 clinical trials: a phase 1 pharmacokinetics study (ClinicalTrials.gov Identifier: NCT03874832) and the phase 3 ASCEND trial (ClinicalTrials.gov Identifier: NCT04406649), which evaluated the long term safety and tolerability of the product.

Pharmacokinetic findings showed fast absorption with Atzumi, with rapid and sustained achievement of effective DHE plasma concentrations. Compared with dihydroergotamine mesylate nasal spray, DHE plasma concentrations were found to be higher with the nasal powder. In the ASCEND trial, results showed long term, repeated, as-needed use of Atzumi was safe and beneficial, resulting in rapid freedom from pain and most bothersome symptoms associated with migraine.

The most common adverse reactions reported were rhinitis, nausea, altered sense of taste, application site reactions, dizziness, vomiting, somnolence, pharyngitis, and diarrhea. As with other DHE products, the labeling for Atzumi includes a Boxed Warning regarding the risk of peripheral ischemia following coadministration with strong CYP3A4 inhibitors. 

Concomitant use of strong CYP3A4 inhibitors is contraindicated, as is use in patients with ischemic heart disease, coronary artery vasospasm, uncontrolled hypertension, peripheral arterial disease, sepsis, severe hepatic or renal impairment, and following vascular surgery. Concomitant use of other 5-HT1 agonists, ergotamine-containing or ergot-type drugs within 24 hours, or use of peripheral and central vasoconstrictors should also be avoided.

The recommended dose of Atzumi is 5.2mg, the contents of 1 nasal device, administered into 1 nostril. The dose may be repeated, if needed, a minimum of 1 hour after the first dose; the maximum dose in a 24 hour period is 10.4mg (2 doses). 

The nasal device does not need to be primed; patients should insert the nozzle into 1 nostril and then squeeze the air pump 3 separate times into the nostril while inhaling. Fast, complete, pulse-like squeezes (the air pump should expand back to its original shape between squeezes) are needed to deliver the complete dose.

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