TRUDHESA (dihydroergotamine mesylate)

AbsorptionThe mean time from dosing to maximum plasma concentration following TRUDHESA administration was approximately 0.5 hours.

DistributionDihydroergotamine mesylate is 93% plasma protein bound. The apparent steady-state volume of distribution is approximately 800 liters.

Elimination

MetabolismFour dihydroergotamine mesylate metabolites have been identified in human plasma following oral administration. The major metabolite, 8'-β-hydroxy dihydroergotamine, exhibits affinity equivalent to ...

The efficacy of TRUDHESA is based on the relative bioavailability of TRUDHESA nasal spray compared to dihydroergotamine mesylate nasal spray in healthy subjects . The clinical studies described below were conducted using dihydroergotamine mesylate nasal spray. The efficacy of dihydroergotamine mesylate nasal spray for the acute treatment of migraine headaches was evaluated in four randomized, double-blind, placebo controlled studies in the U.S. The patient population for the trials was predominantly female (87%) and Caucasian (95%) with a mean age of 39 years (range 18 to 65 years). Patients t...

The following clinically significant adverse reactions are described elsewhere in the labeling: Peripheral Ischemia Following Coadministration with Strong CYP3A4 Inhibitors [see Boxed Warning and Warnings and Precautions (5.1) ] Myocardial Ischemia and/or Infarction, Other Adverse Cardiac Events, and Fatalities [see Warnings and Precautions (5.2) ] Cerebrovascular Adverse Reactions and Fatalities [see Warnings and Precautions (5.3) ] Other Vasospasm Related Adverse Reactions [see Warnings and Pr...

TRUDHESA is contraindicated in patients: with concomitant use of strong CYP3A4 inhibitors, such as protease inhibitors (e.g., ritonavir, nelfinavir, or indinavir), macrolide antibiotics (e.g., erythromycin or clarithromycin), and antifungals (ketoconazole or itraconazole) [see Warnings and Precautions (5.1) and Drug Interactions (7.1) ] with ischemic heart disease (angina pectoris, history of myoc...

Myocardial Ischemia and/or Infarction, Other Cardiac Adverse Reactions, and Fatalities: In patients with risk factors, consider 1 st dose administration under medical supervision with electrocardiogram. ( 2.2 , 5.2 ) Cerebrovascular Adverse Reactions and Fatalities: Cerebral hemorrhage, subarachnoid hemorrhage and stroke have been reported; discontinue TRUDHESA if suspected. ( 5.3 ) Other Vasospasm Related Adverse Reactions: TRUDHESA may cause vasospasm or elevation in blood pressure. Discontinu...

7 DRUG INTERACTIONS Beta Blockers/Nicotine: May potentiate/provoke vasoconstriction ( 7.3 , 7.5 ) Selective Serotonin Reuptake Inhibitors: Weakness, hyperreflexia, and incoordination may occur with coadministration. ( 7.6 ) 7.1 CYP3A4 Inhibitors There have been rare reports of serious adverse events in connection with the coadministration of intravenous administration of dihydroergotamine and stro...