ATZUMI (Dihydroergotamine) Nasal Powder

ATZUMI (dihydroergotamine) is an ergotamine derivative formulated as a nasal powder and supplied in a single-dose intranasal delivery device.

NDA 217901 (Atzumi [dihydroergotamine] nasal powder) was submitted and approved under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The applicant is Satsuma Pharmaceuticals, Inc., and the application was approved on April 30, 2025. The product is a nasal powder supplied at a strength of 5.2 mg dihydroergotamine in a single-dose nasal device, administered intranasally. Atzumi is indicated for the acute treatment of migraine with or without aura in adults; it is not indicated for the preventive treatment of migraine or for the management of hemiplegic migraine or migraine with brainstem aura.

Dihydroergotamine mesylate had been approved in prior NDAs for the same active ingredient before the current NDA 217901. NDA 005929 (D.H.E. 45, dihydroergotamine mesylate injection, USP) is an injectable solution containing 1 mg per mL for intravenous, intramuscular, or subcutaneous administration. NDA 020148 (Migranal, dihydroergotamine mesylate nasal spray) is an intranasal solution supplied in an ampul containing 4 mg dihydroergotamine mesylate, indicated for the acute treatment of migraine headaches with or without aura. NDA 213436 (Trudhesa, dihydroergotamine mesylate nasal spray) is an intranasal spray delivering 0.725 mg per spray, indicated for the acute treatment of migraine with or without aura in adults. The current NDA 217901 differs from these prior products in dosage form and formulation: it is a dry nasal powder delivered from a single-dose device at a 5.2 mg dihydroergotamine strength, rather than an injectable solution or a liquid nasal spray.

Per the prescribing information, the pharmacokinetics of dihydroergotamine were characterized following administration of the nasal powder, and a drug interaction study was conducted in which coadministration with itraconazole increased dihydroergotamine exposure (approximately 14% for Cmax and 19% for AUC). The prescribing information also describes an open-label trial that allowed repeated use of the nasal powder for up to 12 months, in which local irritative symptoms were reported in 29% of treated patients; this study supports the product's safety characterization. The prescribing information notes that the placebo-controlled efficacy and adverse-reaction data presented in the label were generated with dihydroergotamine mesylate nasal spray, not with the current nasal powder, and that adverse reactions with the powder are expected to be similar to those of the nasal spray.

The Orange Book lists three-year exclusivity for the current NDA 217901.

ATZUMI is indicated for the following:

• Acute treatment of migraine with or without aura in adults.

ATZUMI is not indicated for the preventive treatment of migraine, nor for the management of hemiplegic migraine or migraine with brainstem aura.

ATZUMI is supplied as a nasal powder containing 5.2 mg dihydroergotamine (equivalent to 6.0 mg dihydroergotamine mesylate) per single-dose nasal device.

Per device: Dihydroergotamine 5.2 mg (equivalent to 6.0 mg dihydroergotamine mesylate).

Hypromellose, mannitol, and microcrystalline cellulose.

ATZUMI is administered by the nasal route only, into one nostril. The dose for a migraine attack is 5.2 mg (the full contents of one nasal device). A second dose may be administered no sooner than 1 hour after the first if needed; the maximum dose is 10.4 mg in any 24-hour period. The safety of more than 4 doses in 7 days or more than 12 doses in 30 days has not been established.

Priming is not required prior to use. To administer, remove the round blue tab and insert the blue nozzle into one nostril. Squeeze the white air pump three separate times while inhaling through the nose; each squeeze should be fast, complete, and pulse-like—do not squeeze slowly, partially, or with hesitation. Allow the air pump to fully re-expand between squeezes. If any loose powder remains in the device after delivery, repeat the process into the same nostril until no loose powder remains.

A cardiovascular evaluation is recommended prior to initiating treatment. For patients with coronary artery disease risk factors who receive a satisfactory cardiovascular evaluation, administration of the first dose in a medically equipped healthcare facility is strongly recommended.

ATZUMI is supplied as a single-dose nasal device containing white powder. Each device is individually packaged in a protective foil pouch; cartons contain 8 nasal devices.

Store at controlled room temperature, 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C and 30°C (59°F to 86°F). The approved expiry dating period is 30 months from the date of manufacture when stored at the recommended temperature.

The content below is an abbreviated summary drawn from the full prescribing information. It is meant to give a directional overview and should not be relied upon as comprehensive. Consult the full label for complete details.

Pharmacokinetic parameters below reflect dihydroergotamine following nasal administration of ATZUMI. Median time to peak concentration (Tₐₘₐₓ) is approximately 0.5 hours. Dihydroergotamine is 93% bound to plasma proteins, with an apparent steady-state volume of distribution of approximately 800 L and a mean apparent half-life of approximately 13 hours.

The primary route of excretion is biliary elimination in feces. Total body clearance is approximately 1.5 L/min, reflecting predominantly hepatic clearance. Renal clearance is approximately 0.1 L/min and is described as unaffected by route of administration, based on data from other dihydroergotamine products.

The efficacy basis for ATZUMI is grounded in a relative bioavailability comparison of ATZUMI nasal powder to dihydroergotamine mesylate nasal spray. Specific study design details, the evaluated patient population, and the pharmacokinetic metrics assessed are not provided in the Clinical Studies section of the reviewed prescribing information.

The content below is an abbreviated summary drawn from the full prescribing information. It is meant to give a directional overview and should not be relied upon as comprehensive. Consult the full label for complete details.

No placebo-controlled efficacy trials were conducted with ATZUMI nasal powder for the current NDA. The labeling describes four randomized, double-blind, placebo-controlled U.S. efficacy trials. In these trials, adults treated a single moderate-to-severe migraine attack. As stated in the prescribing information, these trials were conducted with dihydroergotamine mesylate nasal spray, not with the current NDA product. Adverse reactions with the nasal powder are expected to be similar to those with the nasal spray. Efficacy for the approved indication therefore rests on the established evidence base for dihydroergotamine mesylate, bridged to ATZUMI through relative bioavailability.

The clinical program specific to the current NDA was limited to two studies. The first was a Phase 1 pharmacokinetic study. The second was an open-label, long-term safety study (ASCEND) that allowed repeated as-needed use of the nasal powder for up to 12 months. In that study, local irritative symptoms were reported in 29% of treated patients. These studies characterized the pharmacokinetics, safety, and tolerability of the nasal powder. They were not placebo-controlled efficacy trials.