General Information

Trudhesa (dihydroergotamine mesylate) is a nasal spray using Impel’s proprietary Precision Olfactory Delivery (POD) Technology. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effects at 5-HT1D receptors.

Trudhesa is specifically indicated for the acute treatment of migraine with or without aura in adults.

The recommended dose of Trudhesa  is 1.45 mg administered as two metered sprays into the nose (one spray of 0.725 mg into each nostril). The dose may be repeated, if needed, a minimum of 1 hour after the first dose. Do not use more than 2 doses of Trudhesa  within a 24-hour period or 3 doses within a 7-day period.

Assessment Prior to First Dose:

• Prior to initiation of Trudhesa, a cardiovascular evaluation is recommended. See Side Effects below. For patients with risk factors predictive of coronary artery disease who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of Trudhesa  take place in the setting of an equipped healthcare facility.

Mechanism of Action

Trudhesa (dihydroergotamine mesylate) is a nasal spray using Impel’s proprietary Precision Olfactory Delivery (POD) Technology. Dihydroergotamine mesylate (DHE) binds with high affinity to 5-HT1Dα and 5-HT1Dβ receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effects at 5-HT1D receptors. Trudhesa is designed to deliver DHE quickly to the bloodstream through the vascular-rich upper nasal space. Trudhesa bypasses the gut and potential absorption issues, offering the potential for rapid, sustained, and consistent relief without injection or infusion, even when administered hours after the start of a migraine attack.

Side Effects

Adverse effects associated with the use of Trudhesa may include, but are not limited to, the following:

• rhinitis
• nausea
• altered sense of taste
• application site reactions
• dizziness
• vomiting
• somnolence
• pharyngitis
• diarrhea

The Trudhesa drug label comes with the following Black Box Warning: Serious and/or life-threatening peripheral ischemia has been associated with the co-administration of dihydroergotamine with strong CYP3A4 inhibitors. Because CYP3A4 inhibition elevates the serum levels of dihydroergotamine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of Tudhesa with strong CYP3A4 inhibitors is contraindicated.

Clinical Trial Results

FDA approval was based on the results of the Phase 3, open-label, pivotal safety study, STOP 301. More than 5,650 migraine attacks were treated over 24 or 52 weeks during the study. The primary objective of the study was to assess the safety and tolerability of Trudhesa. Exploratory objectives included efficacy assessments of migraine measures and a patient acceptability questionnaire. In the STOP 301 study, patient-reported exploratory efficacy findings reported that more than a third of patients (38%) had pain freedom, two-thirds (66%) had pain relief, and more than half (52%) had freedom from their most bothersome migraine symptom at two hours after their first dose of Trudhesa. For one in six patients (16%), pain relief started as early as 15 minutes. Of patients who were pain free at two hours, 93 percent were still pain free at 24 hours, and 86 percent were still pain free through two days.