Trudhesa

— THERAPEUTIC CATEGORIES —
  • Migraine and headache
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Trudhesa Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Dihydroergotamine mesylate 4mg/mL (0.725mg/spray); nasal spray; contains caffeine.

    Pharmacological Class

    Ergot alkaloid.

    How Supplied

    Nasal spray—4 single-dose units (vial + device)

    Storage

    Store in the original packaging at 20°C to 25°C (68°F to 77°F), with excursions allowed between 15°C to 30°C (59°F to 86°F). 

    Do not refrigerate or freeze.

    Manufacturer

    Impel NeuroPharma Inc.

    Generic Availability

    NO

    Trudhesa Indications

    Indications

    Acute treatment of migraine with or without aura.

    Limitations of Use

    Not for the preventative treatment of migraine. Not for the management of hemiplegic or basilar migraine.

    Trudhesa Dosage and Administration

    Prior to Treatment Evaluations

    Cardiovascular evaluation prior to starting Trudhesa is recommended.

    Adult

    2 sprays into the nose (1 spray of 0.725mg in each nostril), may repeat at least 1hr later if needed; max 2 doses (4 sprays) within 24hrs or 3 doses (6 sprays) within 7 days.

    Children

    Not established.

    Trudhesa Contraindications

    Contraindications

    Ischemic heart disease. Coronary artery vasospasm (eg, Prinzmetal's angina). Uncontrolled hypertension. Peripheral artery disease. Sepsis. Post-vascular surgery. Severe hepatic or renal impairment. Concomitant strong CYP3A4 inhibitors (eg, ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, ketoconazole, itraconazole) or other vasoconstrictors. Within 24 hours of other ergot-type drugs or 5-HT1 agonists (eg, sumatriptan).

    Trudhesa Boxed Warnings

    Boxed Warning

    Peripheral ischemia following coadministration with strong CYP3A4 inhibitors.

    Trudhesa Warnings/Precautions

    Warnings/Precautions

    Increased risk of serious peripheral ischemia with concomitant strong CYP3A4 inhibitors. Perform cardiovascular evaluation prior to initiation. Exclude underlying cardiovascular disease, supervise 1st dose, and consider monitoring ECG in patients with risk factors of coronary artery disease (eg, postmenopausal women, men over age 40, hypercholesterolemia, hypertension, obesity, diabetes, smokers, strong family history). Cerebrovascular events (eg, stroke, hemorrhage, transient ischemic attack). Compromised circulation. Withhold therapy if severe local irritation event occurs; permanently discontinue if the event does not resolve or recurs with re-challenge. Elderly. Pregnancy: may cause preterm labor; avoid. Nursing mothers: not recommended (during and for 3 days after the last dose).

    Warnings/Precautions

    Peripheral Ischemia Following Coadministration With Strong CYP3A4 Inhibitors

    • CYP3A4 inhibition elevates the serum levels of dihydroergotamine.
    • This increases the risk of vasospasm leading to cerebral ischemia and/or ischemia of the extremities. 
    • Concomitant use of Trudhesa and strong CYP3A4 inhibitors is contraindicated.

    Myocardial Ischemia and/or Infarction, Other Cardiac Adverse Reactions, and Fatalities

    • Serious adverse cardiac events (eg, acute myocardial infarction, ventricular tachycardia, ventricular fibrillation, coronary artery vasospasm, transient myocardial ischemia), including fatalities, have occurred following use of dihydroergotamine mesylate.
    • Cardiovascular evaluation is recommended before initiating treatment with Trudehsa.
    • If findings are consistent with coronary artery vasospasm or myocardial ischemia, do not administer Trudhesa.
    • Patients with risk factors predictive of coronary artery disease who are determined to have a satisfactory cardiovascular evaluation: Administer first dose in the setting of an equipped health care facility, unless the patient has previously received dihydroergotamine mesylate.
    • Immediately following the first dose, an electrocardiogram is recommended for patients with risk factors as ischemia can occur in the absence of clinical symptoms.

    Cerebrovascular Adverse Reactions and Fatalities

    • Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported with dihydroergotamine mesylate.
    • In some cases, dihydroergotamine mesylate may have been administered in the incorrect belief that the symptoms were a consequence of migraine, when they were actually not.
    • If a cerebrovascular event is suspected, discontinue Trudhesa.

    Other Vasospasm Related Adverse Reactions

    • Myocardial, peripheral vascular, and colonic ischemia have been reported with dihydroergotamine mesylate.
    • Discontinue immediately if signs/symptoms of vasoconstriction develop.
    • Evaluate if signs/symptoms of decreased arterial flow (eg, ischemic bowel syndrome, Raynaud syndrome) develop after 5-HT agonist use.

    Increase in Blood Pressure

    • On rare occasions, significant elevation in blood pressure has been reported with dihydroergotamine mesylate in patients with and without a history of hypertension.
    • Trudesa is contraindicated in patients with uncontrolled hypertension.

    Medication Overuse Headache

    • Overuse of acute migraine medications may lead to exacerbation of headache.
    • Detoxification including withdrawal of the overused drugs and treatment of withdrawal symptoms may be necessary.

    Fibrotic Complications

    • Pleural and retroperitoneal fibrosis following prolonged daily use of dihydroergotamine mesylate has been reported.
    • Administration of Trudhesa should not exceed dosing guidelines; chronic daily use is not advised.

    Local Irritation

    • The most common local irritative symptoms (at least 1% of patients) were nasopharyngitis (21%), rhinitis (19%), nasal discomfort (7%), product taste abnormal/dysgeusia (6%), sinusitis (5%), sinus discomfort (4%), olfactory test abnormal (4%), epistaxis (3%), pharyngitis (3%), nasal mucosal disorder (2%), change in smell (1%), ear discomfort (1%), and rhinorrhea (1%).
    • Temporarily suspend Trudhesa if severe local irritation occurs.
    • Discontinue permanently if severe reaction recurs with rechallenge.

    Pregnancy Considerations

    Trudehsa may cause preterm labor; avoid use during pregnancy.

    No increased risk of major birth defects or miscarriage has been observed with the use of dihydroergotamine mesylate during pregnancy based on data collected over decades.

    Nursing Mother Considerations

    No data on the presence of dihydroergotamine in human milk; however, ergotamine has been shown to be present in human milk.

    Adverse effects reported in breastfed infants exposed to ergotamine included diarrhea, vomiting, weak pulse, and unstable blood pressure.

    Trudhesa may reduce milk supply because it may decrease prolactin levels.

    Patients should be advised not to breastfeed during treatment with Trudhesa and for 3 days after the last dose. Breast milk during this time should be pumped and discarded.

    Pediatric Considerations

    Safety and effectiveness in pediatric patients have not been established. 

    Geriatric Considerations

    Clinical studies did not include a sufficient number of patients 65 years of age and older to determine a response difference. Dose selection should be cautious for elderly patients.

    Other Considerations for Specific Populations

    Abuse/Dependence

    • Currently available data have not demonstrated drug abuse with dihydroergotamine, though cases of abuse have been reported with other ergot therapies.
    • Currently available data have not demonstrated physical or psychological dependence with dihydroergotamine, though cases of dependence have been reported with other ergot therapies.

    Trudhesa Pharmacokinetics

    Absorption

    Mean time from dosing to max plasma concentration was approximately 0.5 hours.

    Distribution

    Dihydroergotamine mesylate is 93% plasma protein bound.

    Elimination

    The major excretory route of dihydroergotamine is via the bile in the feces.

    The mean apparent half-life of Trudhesa nasal administration in healthy subjects is approximately 12 hours.

    Trudhesa Interactions

    Interactions

    Other ergots, 5-HT1 agonists, strong CYP3A4 inhibitors, other vasoconstrictors: see Contraindications. Potentiated by moderate CYP3A4 inhibitors (eg, saquinavir, nefazodone, fluconazole, fluoxetine, fluvoxamine, grapefruit juice, zileuton, clotrimazole); use caution. May be potentiated by propranolol, nicotine. Rarely: may cause weakness, hyperreflexia, and incoordination with concomitant SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline).

    Trudhesa Adverse Reactions

    Adverse Reactions

    Rhinitis, nausea, altered sense of taste, application site reactions, dizziness, vomiting, somnolence, pharyngitis, diarrhea; myocardial and peripheral ischemia, vasoconstriction, local irritation; rare: fibrotic complications.

    Trudhesa Clinical Trials

    Clinical Trials

    The approval of Trudhesa is supported by data from the open-label phase 3 STOP 301 study (ClinicalTrials.gov Identifier: NCT03557333), which evaluated the safety and tolerability of Trudhesa in 354 adults who had a documented diagnosis of migraine with or without aura, including at least 2 attacks per month for the previous 6 months.

    Patients who received at least 1 dose of Trudhesa comprised the full safety set (n=354), and patients who took at least 2 doses of Trudhesa per 28-day period during the 24-week treatment period comprised the primary safety set (n=185).

    The primary safety endpoints included serious and non-serious treatment emergent adverse events as well as changes in nasal mucosa and olfactory function. 

    Results showed that the study met its primary endpoints with no new safety signals. Additional exploratory efficacy data in the full safety set showed that after the first dose, 66.3% of patients achieved pain relief, 38% of patients had pain freedom, and 52% had freedom from their most bothersome migraine symptom at 2 hours. Among patients who were pain free at 2 hours, 93% remained pain free at 24 hours, and 86% remained pain free through day 2.

    Trudhesa Note

    Not Applicable

    Trudhesa Patient Counseling

    Patient Counseling

    Coadministration with CYP3A4 inhibitors such as macrolide antibiotics and protease inhibitors can lead to serious and/or life-threatening reactions (cerebral ischemia and/or ischemia of the extremities).

    Serious cardiac, cerebrovascular, and other vasospasm related events have been associated with Trudhesa; alert a health care provider if any risk factors or symptoms develop during treatment. Nicotine may provoke vasoconstriction predisposing to a greater ischemic response.

    Using drugs to treat 10 or more migraine attacks per month may lead to an exacerbation of headache. Keep a headache diary to record headache frequency and drug use.

    Local irritation may occur; bothersome reactions should be reported to a health care provider.

    Alert a health care provider regarding any new prescription or OTC medications.

    There is a risk of preterm; use should be avoided during pregnancy. Additionally, breastfeeding should be avoided during treatment.

    Trudhesa must be assembled before use and should be primed (pumped 4 times) prior to administration. Discard the product within 8 hours once the vial has been opened or the product has been assembled.

    Cost Savings Program

    Trudhesa Savings Program

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