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Trudhesa Dihydroergotamine mesylate 4 mg/mL Spray, Metered, 4 vials — NDC 77530-0725-04 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Trudhesa Dihydroergotamine mesylate 4 mg/mL Spray, Metered, 4 vials — NDC 77530-725-04 (Billing 77530-0725-04)

by Impel Pharmaceuticals LLC · 4 VIAL, GLASS in 1 CARTON / 1 mL in 1 VIAL, GLASS

This is a package of 4 vials of Trudhesa Dihydroergotamine mesylate 4 mg/mL Spray, Metered from Impel Pharmaceuticals LLC, marketed since Sep 2021 and currently FDA-listed.

NDC 77530-0725-04
🏷️ FDA NDC (as labeled) 77530-725-04 billing pads the product segment with a zero
This package
Contains4 vials Pack sizes3 compare ↓
Also priced by: Part D plans $1,284.25/unit — full pricing hub ↓
Product page 77530-0725-00 Also comes in: 1 mL 77530-725-00 6 vials 77530-725-06
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Sep 17, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 77530-725-04 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
77530 labeler · 725 product · 04 package
Package marketed since
Sep 24, 2021
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Barcode (UPC-A, from the NDC)
3 7753072504 9
FDA record last changed
Sep 17, 2026
⚠️
Other active recalls for Dihydroergotamine Mesylate (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Nov 22, 2024 — Discoloration (Provepharm Inc.) · FDA recall D-0150-2025
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 77530-725-04
Product NDC 77530-725
11-digit billing NDC 77530072504
NCPDP billing unit ML — per mL (volume)
RxCUI 2569836, 2569842
UNII 81AXN7R2QT
Application # NDA213436
SPL Set ID b81397b0-910d-4eb4-8fee-a9a3c9d94d63
Established class (EPC) Ergotamine Derivative
Chemical class Ergotamines
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2021-09-24
Route NASAL
Dosage form SPRAY, METERED
Substance DIHYDROERGOTAMINE MESYLATE

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GCN Seq No 082656
GCN 50931
HICL code 000155
Ingredient (HICL) Dihydroergotamine Mesylate
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H3
Therapeutic class — intermediate (HIC2) Analgesics
HIC3 code H3F
Therapeutic class — specific (HIC3) Antimigraine Preparations
AHFS code 12:16.04.04
AHFS class Non-Sel.alpha-Adrenergic Blocking Agents
FDB label name TRUDHESA NASAL SPRAY
FDB brand name Trudhesa
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 082656
  • GCN: 50931
  • HICL (First Databank): 000155
  • AHFS class code: 12:16.04.04
  • RxCUI (RxNorm): 2569836
Why two NDCs? The FDA registers this code as 77530-725-04 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 77530-0725-04. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Ergotamine Derivative class.

Pharmacologic class Ergotamine Derivative
Drug family (ATC) Ergot alkaloids
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name TRUDHESA NASAL SPRAY Ingredient Dihydroergotamine Mesylate
📖 What it is MedlinePlus · NLM

Dihydroergotamine nasal spray is used to treat migraine headaches (severe, throbbing headaches that sometimes are accompanied by nausea and sensitivity to sound and light). Dihydroergotamine is in a class of medications called ergot alkaloids. It works by tightening blood vessels in the brain and by stopping the release of natural substances in the brain that cause swelling.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It treats migraine attacks after they start. It is not for preventing migraines. It should not be used for hemiplegic or basilar migraine.
  • It goes in the nose only. With Atzumi, you squeeze the pump three fast, full squeezes into one nostril. Follow your prescriber's directions on repeating a dose and the daily limits...
  • Nose and throat irritation, a stuffy nose, an odd taste, nausea, and dizziness are the most common. These are usually mild and short-lived.
  • Get help for chest pain, stroke symptoms, or cold, numb, pale, or bluish fingers or toes. These can be signs of blocked blood flow. Stop the medicine and seek care.
📖 Read our full Dihydroergotamine Nasal Spray guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $1,284.25 $5,137.00 / 4 ml
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
77530-0725-00 77530-725-00 Main listing 1 VIAL, GLASS in 1 CARTON / 1 mL in 1 VIAL, GLASS Sample 2021-09-24 — Active
77530-0725-04 You're viewing this 4 VIAL, GLASS in 1 CARTON / 1 mL in 1 VIAL, GLASS 2021-09-24 — Active
77530-0725-06 77530-725-06 6 VIAL, GLASS in 1 CARTON / 1 mL in 1 VIAL, GLASS Sample 2026-09-01 — Active

Pack size FAQ

What quantity is in this package?
This package contains 4 vials — 4 vial, glass in 1 carton / 1 ml in 1 vial, glass.
How does this package differ from NDC 77530-0725-00?
Both are Trudhesa Dihydroergotamine mesylate 4 mg/mL Spray, Metered — the drug itself is identical. This page's package is the 4 vials one, while NDC 77530-0725-00 is the 1 vial package.
What NDC number is used to bill for this package of Trudhesa Dihydroergotamine mesylate 4 mg/mL Spray, Metered?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Dihydroergotamine Mesylate 4 mg/mL 70069-0880-08 Somerset 1 kit $29.436 AB Availability likely —
Dihydroergotamine mesylate 4 mg/mL 73352-0096-19 Trifluent 8 kits $29.436 AB Availability likely —
Dihydroergotamine mesylate 4 mg/mL 72888-0096-19 Advagen 8 kits $29.436 AB Availability likely —
Dihydroergotamine Mesylate 4 mg/mL 68682-0357-10 Oceanside 8 vials $34.212 AB FDA listed —
Dihydroergotamine Mesylate 4 mg/mL 24201-0463-01 Hikma 1 vial $49.630 AB Availability likely —
Trudhesa 4 mg/mLthis 77530-0725-04 Impel 4 vials — — FDA listed —
About this product: this is the brand-name version. FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2021
First FDA approval
Sep 2021
📍
2026
Currently FDA-listed
5 years listed
🛡️
2039
Latest patent/protection listed
not a guaranteed launch date
✅Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Jan 2039. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Sep 2, 2021 RLD RS ⏳ ~12.3 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 11185497 — method of use (U-3218)
US 9919117 — method of use (U-3218)
US 10940278 — drug product
US 9550036 — drug product
US 10507295 — drug product
US 11266799 — drug product
2021 2023 2025 2027 2029 2031 2033 2035 2037 2039
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (6)
PatentTypeUse codeExpires
US 11185497 ↗ Method of use U-3218 Jan 4, 2039
US 9919117 ↗ Method of use U-3218 Mar 17, 2033
US 10940278 ↗ Drug product — Jan 23, 2033
US 9550036 ↗ Drug product — Sep 5, 2032
US 10507295 ↗ Drug product — Dec 25, 2032
US 11266799 ↗ Drug product — Nov 5, 2036
Common questions
Is there a generic version of TRUDHESA NASAL SPRAY?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for TRUDHESA NASAL SPRAY. See the alternatives section for substitutable, lower-cost products.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

🧪 Avoiding an ingredient? See Dihydroergotamine Nasal Spray inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 5SL0G7R0OK
    A simple sugar made from corn or other plants, used in medicines as a filler and sweetener. It helps create the right texture and taste in tablets, powders, and liquid formulations.
  • UNII 3G6A5W338E
    Caffeine is a natural stimulant compound commonly extracted from coffee beans and tea leaves. In medicines, it serves as an active booster in pain relievers and cold products to enhance alertness and improve the effectiveness of other ingredients.
  • UNII 142M471B3J
    Carbon dioxide is a colorless gas used in medicines as a propellant in pressurized inhalers and aerosol sprays to help deliver the active medication to where it's needed.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

4 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerImpel Pharmaceuticals LLC
Application holderIMPEL PHARMACEUTICALS LLC
FDA applicationNDA213436 (NDA)
Labeler code77530
First marketedSep 2021
Product typeHuman Prescription Drug
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🔒 Drug Abuse and Dependence 🔒 Controlled Substance 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📖 Instructions for Use 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 151 words ▾

WARNING: PERIPHERAL ISCHEMIA FOLLOWING COADMINISTRATION WITH STRONG CYP3A4 INHIBITORS Serious and/or life-threatening peripheral ischemia has been associated with the coadministration 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 TRUDHESA with strong CYP3A4 inhibitors is contraindicated [see Contraindications (4) , Warnings and Precautions (5.1) , and Drug Interactions (7.1) ].

WARNING: PERIPHERAL ISCHEMIA FOLLOWING COADMINISTRATION WITH POTENT CYP3A4 INHIBITORS See full prescribing information for complete boxed warning. Serious and/or life-threatening peripheral ischemia has been associated with the coadministration 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 TRUDHESA with strong CYP3A4 inhibitors is contraindicated. ( 4 , 5.1 , 7.1 )

🎯 Indications and Usage 90 words ▾

1 INDICATIONS AND USAGE TRUDHESA is indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use TRUDHESA is not indicated for the preventive treatment of migraine. TRUDHESA is not indicated for the management of hemiplegic or basilar migraine.

TRUDHESA is an ergotamine derivative indicated for the acute treatment of migraine with or without aura in adults. ( 1 ) Limitations of Use: TRUDHESA is not indicated for the preventive treatment of migraine or for the management of hemiplegic or basilar migraine. ( 1 )

⏱️ Dosage and Administration ~1 min read ▾

2 DOSAGE AND ADMINISTRATION The recommended dose of TRUDHESA is 1.45 mg (administered as one metered spray of 0.725 mg into each nostril). ( 2.1 ) The dose may be repeated, if needed, a minimum of 1 hour after the first dose. Do not use more than 2 doses within a 24-hour period or 3 doses within 7 days.

( 2.1 ) Prior to initiation, a cardiovascular evaluation is recommended. ( 2.2 ) TRUDHESA is for nasal administration only. ( 2.3 ) Assemble and prime (i.e., pumped 4 times) before use.

( 2.3 ) Use TRUDHESA immediately after priming and then discard. ( 2.3 )

2.1Dosing Information 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.

2.2Assessment Prior to First Dose Prior to initiation of TRUDHESA, a cardiovascular evaluation is recommended [see Warnings and Precautions (5.2) ] . 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.

2.3Important Administration Instructions TRUDHESA is for nasal administration only and must not be injected. TRUDHESA must be assembled prior to use (see Instructions for Use ). Use or discard TRUDHESA within 8 hours once the vial has been opened or the product has been assembled.

Prime the assembled TRUDHESA before initial use by releasing 4 sprays. Use TRUDHESA immediately after priming. Discard TRUDHESA immediately after use.

Open and prepare a new TRUDHESA if an additional dose is needed.

💊 Dosage Forms and Strengths 55 words ▾

3 DOSAGE FORMS AND STRENGTHS TRUDHESA (dihydroergotamine mesylate) nasal spray is a single-dose, drug-device combination product containing a vial of dihydroergotamine mesylate with a clear and colorless to faintly yellow solution and an intranasal delivery device. Each spray delivers 0.725 mg of dihydroergotamine mesylate. Nasal spray: 0.725 mg dihydroergotamine mesylate per spray. ( 3 )

⛔ Contraindications ~1 min read ▾

4 CONTRAINDICATIONS 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 myocardial infarction, or documented silent ischemia) or patients who have clinical symptoms or findings consistent with coronary artery vasospasm, including Prinzmetal's variant angina [see Warnings and Precautions (5.4) ] with uncontrolled hypertension [see Warnings and Precautions (5.5) ] with peripheral arterial disease with sepsis following vascular surgery with severe hepatic impairment with severe renal impairment with known hypersensitivity to ergot alkaloids with recent use (i.e., within 24 hours) of other 5-HT 1 agonists (e.g., sumatriptan) or ergotamine-containing or ergot-type medications [see Drug Interactions (7.2) ] with concomitant use of peripheral and central vasoconstrictors because the combination may result in additive or synergistic elevation of blood pressure [see Warnings and Precautions (5.5) ] Concomitant use of strong CYP3A4 inhibitors ( 4 ) Patients with ischemic heart disease or coronary artery vasospasm ( 4 ) Patients with uncontrolled hypertension, peripheral arterial diseases, sepsis, following vascular surgery, or severe hepatic or renal impairment ( 4 ) Patients with hypersensitivity to ergot alkaloids ( 4 ) Concomitant use of other 5-HT 1 agonists (e.g., sumatriptan) or ergotamine-containing or ergot-type medications within 24 hours ( 4 ) Concomitant use of peripheral and central vasoconstrictors ( 4 )

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS 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.

Discontinue if signs or symptoms of vasoconstriction develop. ( 5.4 , 5.5 ) Medication Overuse Headache: Detoxification may be necessary. ( 5.6 ) Preterm Labor: Advise pregnant women of the risk.

( 5.7 , 8.1 ) Fibrotic Complications: Pleural and retroperitoneal fibrosis have been reported following prolonged daily use of dihydroergotamine mesylate. Administration of TRUDHESA should not exceed the dosing guidelines or be used for chronic daily administration. ( 5.8 ) Local Irritation: If severe local irritation occurs for no other attributable reasons, suspend TRUDHESA until resolution.

( 5.9 )

5.1Peripheral Ischemia Following Coadministration with Strong CYP3A4 Inhibitors Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with strong CYP3A4 inhibitors, including protease inhibitors, macrolide antibiotics, and antifungals. 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 TRUDHESA with strong CYP3A4 inhibitors is contraindicated [see Contraindications (4) and Drug Interactions (7.1) ].

5.2Myocardial Ischemia and/or Infarction, Other Cardiac Adverse Reactions, and Fatalities The potential for adverse cardiac adverse reactions exists with TRUDHESA treatment. Serious adverse cardiac events, including some that have been fatal, have occurred following use of dihydroergotamine mesylate. These events have included acute myocardial infarction, life-threatening disturbances of cardiac rhythm (e.g., ventricular tachycardia and ventricular fibrillation), coronary artery vasospasm, and transient myocardial ischemia.

Prior to initiation of TRUDHESA, a cardiovascular evaluation is recommended to determine if the patient is free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. If, during the cardiovascular evaluation, the patient's medical history (including risk factors), or electrocardiographic investigation, findings are consistent with coronary artery vasospasm or myocardial ischemia, TRUDHESA should not be administered [see Contraindications (4) ]. For patients with risk factors predictive of coronary artery disease (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of coronary artery disease, females who are surgically or physiologically postmenopausal, or males who are over 40 years of age) 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, unless the patient has previously received dihydroergotamine mesylate.

During the interval immediately following the first use of TRUDHESA, an electrocardiogram is recommended in those patients with risk factors because ischemia can occur in the absence of clinical symptoms.

5.3Cerebrovascular Adverse Reactions and Fatalities The potential for adverse cerebrovascular adverse reactions exists with TRUDHESA treatment. Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with dihydroergotamine mesylate; and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the dihydroergotamine mesyl… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS 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 Precautions (5.4) ] Increase in Blood Pressure [see Warnings and Precautions (5.5) ] Medication Overuse Headache [see Warnings and Precautions (5.6) ] Preterm Labor [see Warnings and Precautions (5.7) ] Fibrotic Complications [see Warnings and Precautions (5.8) ] Local Irritation [see Warnings and Precautions (5.9) ] Most common adverse reactions (greater than 1%) were rhinitis, nausea, altered sense of taste, application site reactions, dizziness, vomiting, somnolence, pharyngitis, and diarrhea.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Impel Pharmaceuticals LLC at 1-833-878-3437 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Placebo-Controlled Trials with Dihydroergotamine (DHE) Mesylate Nasal Spray [see Clinical Studies (14) ] Of the 1,796 patients and subjects treated with DHE nasal spray doses 2 mg or less in U.S. and foreign clinical studies, 26 (1.4%) discontinued because of adverse events.

The adverse events associated with discontinuation were, in decreasing order of frequency: rhinitis (13), dizziness (2), facial edema (2), and one patient each due to cold sweats, accidental trauma, depression, elective surgery, somnolence, allergy, vomiting, hypotension, and paraesthesia. Table 1 summarizes the incidence rates of adverse reactions reported by at least 1% of patients who received DHE nasal spray for the treatment of migraine during placebo-controlled, double-blind clinical studies and were more frequent than in those patients receiving placebo.

The most commonly reported adverse reactions (greater than 1% of patients who received DHE nasal spray) were rhinitis, nausea, altered sense of taste, application site reactions, dizziness, vomiting, somnolence, pharyngitis, and diarrhea. In most instances these events were transient and self-limited and did not result in patient discontinuation from a study. Table 1 Adverse Reactions Reported by at Least 1% of the DHE Nasal Spray Treated Patients and Occurred more Frequently than in the Placebo-Group in the Migraine Placebo-Controlled Trials DHE Nasal Spray N=597 % Placebo N=631 % Respiratory System Rhinitis 26 7 Pharyngitis 3 1 Gastrointestinal System Nausea 10 4 Vomiting 4 1 Diarrhea 2 <1 Special Senses, Other Altered Sense of Taste 8 1 Application Site Application Site Reaction 6 2 Central and Peripheral Nervous System Dizziness 4 2 Somnolence 3 2 Body as a Whole, General Hot Flashes 1 <1 Asthenia 1 0 Musculoskeletal System Stiffness 1 <1 Adverse Reactions in Studies with TRUDHESA An open-label study in adults (18 to 66 years of age) was conducted to evaluate the safety and tolerability of TRUDHESA, repeated use of TRUDHESA was allowed over the course of 6 to 12 months.

A total of 354 patients with migraine received at least one dose of TRUDHESA. One hundred and eighty-five patients treated on average at least two migraines per month for 6 months, and 55 patients treated on average at least two migraines per month for 12 months. Of the patients who received at least one dose of TRUDHESA, 185 (52.3%) patients experienced local irritative symptoms.

Of these, the most common local irritative symptoms were nasopharyngitis, rhinitis, nasal dis… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

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 )

7.1CYP3A4 Inhibitors There have been rare reports of serious adverse events in connection with the coadministration of intravenous administration of dihydroergotamine and strong CYP3A4 inhibitors, such as protease inhibitors (e.g., ritonavir, nelfinavir, indinavir), macrolide antibiotics (e.g., erythromycin, clarithromycin), and antifungals (e.g., ketoconazole, itraconazole), resulting in vasospasm that led to cerebral ischemia and/or ischemia of the extremities [see Warnings and Precautions (5.1) ]. The use of strong CYP3A4 inhibitors with dihydroergotamine is contraindicated [see Contraindications (4) ] .

Administer moderate CYP3A4 inhibitors (e.g., saquinavir, nefazodone, fluconazole, grapefruit juice, fluoxetine, fluvoxamine, zileuton, clotrimazole) with caution.

7.2Triptans Triptans (serotonin [5-HT] 1B/1D receptor agonists) have been reported to cause coronary artery vasospasm, and its effect could be additive with TRUDHESA. Therefore, triptans and TRUDHESA should not be taken within 24 hours of each other [see Contraindications (4) ].

7.3Beta Blockers There have been reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.

7.4Vasoconstrictors TRUDHESA is contraindicated for use with peripheral and central vasoconstrictors because the combination may cause synergistic elevation of blood pressure [see Warnings and Precautions (5.5) ].

7.5Nicotine Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy [see Warnings and Precautions (5.1 , 5.5) ].

7.6Selective Serotonin Reuptake Inhibitors Weakness, hyperreflexia, and incoordination have been reported rarely when 5-HT 1 agonists have been coadministered with selective serotonin reuptake inhibitors (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline).

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ) Lactation: Advise not to use during breastfeeding. ( 8.2 )

8.1Pregnancy Risk Summary Available data from published literature indicate an increased risk of preterm delivery with TRUDHESA use during pregnancy. Avoid use of TRUDHESA during pregnancy [see Warnings and Precautions (5.7) ]. Data collected over decades have shown no increased risk of major birth defects or miscarriage with use of dihydroergotamine mesylate during pregnancy.

In animal studies, adverse effects on embryofetal development were observed following administration of dihydroergotamine mesylate during pregnancy (decreased fetal body weight and/or skeletal ossification) in rats and rabbits or during pregnancy and lactation in rats (decreased body weight and impaired reproductive function in the offspring) in rats at doses less than those used clinically and which were not associated with maternal toxicity (see Data ). The estimated rate of major birth defects (2.2% to 2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Intranasal administration of dihydroergotamine mesylate to pregnant rats throughout the period of organogenesis resulted in decreased fetal body weight and/or skeletal ossification at doses of 0.16 mg/day (associated with plasma exposures [AUC] less than that in humans at the maximum recommended human dose [MRHD] of 2.9 mg) or greater.

A no-effect level for embryofetal toxicity was not identified in rats. Intranasal administration of dihydroergotamine mesylate to pregnant rabbits throughout organogenesis resulted in decreased skeletal ossification at 3.6 mg/day. At the no-effect dose (1.2 mg/day) for adverse effects on embryofetal development in rabbits, plasma exposures (AUC) were less than that in humans at the MRHD.

Intranasal administration of dihydroergotamine mesylate to female rats throughout pregnancy and lactation resulted in decreased body weight and impaired reproductive function (decreased mating indices) were observed in the offspring at doses of 0.16 mg/day or greater. A no-effect dose for adverse developmental effects in rats was not established. Effects on development occurred at doses below those that produced evidence of significant maternal toxicity in these studies.

Dihydroergotamine-induced intrauterine growth retardation has been attributed to reduced uteroplacental blood flow resulting from prolonged vasoconstriction of the uterine vessels and/or increased myometrial tone.

8.2Lactation Risk Summary There are no data on the presence of dihydroergotamine in human milk; however, ergotamine, a related drug, is present in human milk. There are reports of diarrhea, vomiting, weak pulse, and unstable blood pressure in breastfed infants exposed to ergotamine. TRUDHESA may reduce milk supply because it may decrease prolactin levels.

Because of the potential for reduced milk supply and serious adverse events in the breastfed infant, including diarrhea, vomiting, weak pulse, and unstable blood pressure, advise patients not to breastfeed during treatment with TRUDHESA and for 3 days after the last dose. Breast milk supply during this time should be pumped and discarded.

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

8.5Geriatric Use Clinical studies of TRUDHESA and other dihydroergotamine mesylate products did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of th… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary Available data from published literature indicate an increased risk of preterm delivery with TRUDHESA use during pregnancy. Avoid use of TRUDHESA during pregnancy [see Warnings and Precautions (5.7) ]. Data collected over decades have shown no increased risk of major birth defects or miscarriage with use of dihydroergotamine mesylate during pregnancy.

In animal studies, adverse effects on embryofetal development were observed following administration of dihydroergotamine mesylate during pregnancy (decreased fetal body weight and/or skeletal ossification) in rats and rabbits or during pregnancy and lactation in rats (decreased body weight and impaired reproductive function in the offspring) in rats at doses less than those used clinically and which were not associated with maternal toxicity (see Data ). The estimated rate of major birth defects (2.2% to 2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Intranasal administration of dihydroergotamine mesylate to pregnant rats throughout the period of organogenesis resulted in decreased fetal body weight and/or skeletal ossification at doses of 0.16 mg/day (associated with plasma exposures [AUC] less than that in humans at the maximum recommended human dose [MRHD] of 2.9 mg) or greater.

A no-effect level for embryofetal toxicity was not identified in rats. Intranasal administration of dihydroergotamine mesylate to pregnant rabbits throughout organogenesis resulted in decreased skeletal ossification at 3.6 mg/day. At the no-effect dose (1.2 mg/day) for adverse effects on embryofetal development in rabbits, plasma exposures (AUC) were less than that in humans at the MRHD.

Intranasal administration of dihydroergotamine mesylate to female rats throughout pregnancy and lactation resulted in decreased body weight and impaired reproductive function (decreased mating indices) were observed in the offspring at doses of 0.16 mg/day or greater. A no-effect dose for adverse developmental effects in rats was not established. Effects on development occurred at doses below those that produced evidence of significant maternal toxicity in these studies.

Dihydroergotamine-induced intrauterine growth retardation has been attributed to reduced uteroplacental blood flow resulting from prolonged vasoconstriction of the uterine vessels and/or increased myometrial tone.

🧒 Pediatric Use 13 words ▾

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

🧓 Geriatric Use 72 words ▾

8.5Geriatric Use Clinical studies of TRUDHESA and other dihydroergotamine mesylate products did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

🆘 Overdosage 166 words ▾

10 OVERDOSAGE

10.1Symptoms Excessive doses of dihydroergotamine may result in peripheral signs and symptoms of ergotism. In general, the symptoms of an acute TRUDHESA overdose are similar to those of an ergotamine overdose, although there may be less pronounced nausea and vomiting with TRUDHESA. The symptoms of an ergotamine overdose include the following: numbness, tingling, pain, and cyanosis of the extremities associated with diminished or absent peripheral pulses; respiratory depression; an increase and/or decrease in blood pressure, usually in that order; confusion, delirium, convulsions, and coma; and/or some degree of nausea, vomiting, and abdominal pain.

In laboratory animals, dihydroergotamine was lethal when given at intravenous doses of 44 mg/kg in mice, 130 mg/kg in rats, and 37 mg/kg in rabbits.

10.2Treatment Treatment includes discontinuance of the drug, local application of warmth to the affected area, the administration of vasodilators, and nursing care to prevent tissue damage. Up-to-date information about the treatment of overdosage can often be obtained from a certified Regional Poison Control Center.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Dihydroergotamine binds with high affinity to 5-HT 1Dα and 5-HT 1Dβ receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effects at 5-HT 1D receptors.

12.2Pharmacodynamics Significant elevation in blood pressure has been reported in patients with and without a history of hypertension [see Warnings and Precautions (5.5) ]. Dihydroergotamine possesses oxytocic properties [see Warnings and Precautions (5.7) ].

12.3Pharmacokinetics Absorption The mean time from dosing to maximum plasma concentration following TRUDHESA administration was approximately 0.5 hours. Distribution Dihydroergotamine mesylate is 93% plasma protein bound. The apparent steady-state volume of distribution is approximately 800 liters.

Elimination Metabolism Four dihydroergotamine mesylate metabolites have been identified in human plasma following oral administration. The major metabolite, 8'-β-hydroxy dihydroergotamine, exhibits affinity equivalent to its parent for adrenergic and 5-HT receptors and demonstrates equivalent potency in several venoconstrictor activity models, in vivo and in vitro. The other metabolites, i.e., dihydrolysergic acid, dihydrolysergic amide, and a metabolite formed by oxidative opening of the proline ring, are of minor importance.

Following nasal administration, total metabolites represent only 20% to 30% of plasma AUC. The systemic clearance of dihydroergotamine mesylate following intravenous and intramuscular administration is

1.5L/min. Quantitative pharmacokinetic characterization of the four metabolites has not been performed. Excretion The major excretory route of dihydroergotamine is via the bile in the feces. The total body clearance is

1.5L/min, which reflects mainly hepatic clearance. Only 6% to 7% of unchanged dihydroergotamine is excreted in the urine after intramuscular injection. The renal clearance (0.1 L/min) is unaffected by the route of dihydroergotamine administration.

The mean apparent half-life of TRUDHESA nasal administration in healthy subjects is approximately 12 hours. Specific Populations No studies have been conducted on the effect of renal or hepatic impairment, gender, race, ethnicity, or pregnancy on dihydroergotamine pharmacokinetics [see Contraindications (4) , Use in Specific Populations (8.1) ]. Drug Interaction Studies CYP3A4 Inhibitors Rare reports of ergotism have been obtained from patients treated with dihydroergotamine and macrolide antibiotics (e.g., clarithromycin, erythromycin) and from patients treated with dihydroergotamine and protease inhibitors (e.g., ritonavir), presumably due to inhibition of CYP3A metabolism of ergotamine [see Contraindications (4) ].

Other Drugs The pharmacokinetics of dihydroergotamine did not appear to be significantly affected by the concomitant use of a local vasoconstrictor. Multiple oral doses of the β-adrenoceptor antagonist propranolol, used for migraine prophylaxis, had no significant influence on the C max , t max , or AUC of dihydroergotamine doses up to 4 mg. However, propranolol may potentiate the vasoconstrictive action of ergotamine [see Drug Interactions (7.3) ].

The effect of oral contraceptives on the pharmacokinetics of TRUDHESA has not been studied.

🧬 Mechanism of Action 34 words ▾

12.1Mechanism of Action Dihydroergotamine binds with high affinity to 5-HT 1Dα and 5-HT 1Dβ receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effects at 5-HT 1D receptors.

📦 How Supplied / Storage and Handling 100 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied TRUDHESA (dihydroergotamine mesylate) nasal spray (0.725 mg per spray) is supplied as a package of 4 single-dose units (NDC 77530-725-04), or 6 single-dose units (NDC 77530-725-06). One amber glass vial (NDC 77530-725-01) containing 4 mg dihydroergotamine mesylate in a 1 mL clear and colorless to faintly yellow solution. The stopper is not made with natural rubber latex. One nasal spray device.

16.2Storage and Handling Store TRUDHESA at controlled room temperature, 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.

📦 Storage and Handling 31 words ▾

16.2Storage and Handling Store TRUDHESA at controlled room temperature, 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.

📋 Description 147 words ▾

11 DESCRIPTION TRUDHESA (dihydroergotamine mesylate) nasal spray is a single-dose, drug-device combination product containing a dihydroergotamine mesylate drug constituent and a nasal spray device constituent. The chemical name for dihydroergotamine mesylate is ergotaman-3', 6', 18-trione, 9,10-dihydro-12'-hydroxy-2'-methyl-5'- (phenylmethyl)-, (5'α)-, monomethanesulfonate. Its molecular weight is 679.78, and its molecular formula is C 33 H 37 N 5 O 5 ∙CH 4 O 3 S.

The chemical structure is: The drug constituent is a dihydroergotamine mesylate solution. Each milliliter (mL) of solution contains dihydroergotamine mesylate 4.0 mg (equivalent to 3.43 mg dihydroergotamine), and the following inactive ingredients: caffeine (10.0 mg), carbon dioxide (q.s.), dextrose (50.0 mg), and water (q.s. to 1.0 mL). TRUDHESA nasal spray, after assembly and priming, delivers 0.725 mg dihydroergotamine mesylate per spray.

A total dose of 1.45 mg of dihydroergotamine mesylate is delivered in 2 sprays. The nasal spray device contains hydrofluoroalkane-134a (HFA) propellant. Chemical Structure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Serious and/or Life-Threatening Reactions with Coadministration of CYP3A4 Inhibitors Inform patients that serious and/or life-threatening peripheral ischemia (cerebral ischemia and/or ischemia of the extremities) has been associated with the coadministration of dihydroergotamine mesylate and strong CYP3A4 inhibitors, such as macrolide antibiotics and protease inhibitors [see Contraindications (4) , Warnings and Precautions (5.1) , and Drug Interactions (7.1) ].

Myocardial Ischemia and/or Infarction, Other Cardiac Events, Cerebrovascular Events, and Fatalities Inform patients of the risk for serious cardiac, cerebrovascular, and other vasospasm related events. Advise patients to notify their healthcare provider if they develop any risk factors or symptoms while taking TRUDHESA. Inform patients that nicotine may provoke vasoconstriction predisposing to a greater ischemic response [see Warnings and Precautions (5.2 , 5.3 , 5.4) ].

Medication Overuse Headache Inform patients that use of drugs to treat migraine attacks for 10 or more days per month may lead to an exacerbation of headache, and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6) ]. Local Irritation Advise patients to notify their healthcare provider if they have bothersome local irritation [see Warnings and Precautions (5.9) ]. Drug Interactions Advise patients to inform their healthcare providers if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions [see Drug Interactions (7) ].

Pregnancy Advise patients of the risk for preterm birth. Advise women to inform their healthcare provider if they are pregnant or intend to become pregnant [see Warnings and Precautions (5.7) , Use in Specific Populations (8.1) ]. Lactation Advise patients not to breastfeed during treatment with TRUDHESA [see Use In Specific Populations (8.2) ].

Important Administration Instructions Advise patients that TRUDHESA must be assembled prior to use and that, prior to administration, the device must be primed (i.e., pumped 4 times). Instruct patients to use or discard TRUDHESA within 8 hours once the vial has been opened or the product has been assembled.

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE TRUDHESA ® (true - deh - sa) (dihydroergotamine mesylate) nasal spray This Medication Guide has been approved by the U.S. Food and Drug Administration Issued: 5/2026 What is the most important information I should know about TRUDHESA? TRUDHESA can cause serious side effects, including: Serious problems with blood circulation to your legs and feet (peripheral ischemia).

TRUDHESA can cause peripheral ischemia when you take it with certain medicines known as CYP3A4 inhibitors. Peripheral ischemia may lead to a stroke and death. Stop taking TRUDHESA and get emergency medical help right away if you have any of the following symptoms: cramping and pain in your legs or hips feeling of heaviness or tightness in your leg muscles burning or aching pain in your feet or toes while resting numbness, tingling, or weakness in your legs cold feeling or color changes in 1 or both legs or feet slurred speech sudden weakness Do not take medicines known as strong CYP3A4 inhibitors, such as: ritonavir nelfinavir erythromycin clarithromycin ketoconazole itraconazole These are not all of the medicines that could affect how TRUDHESA works.

Your healthcare provider can tell you if it is safe to take TRUDHESA with other medicines. What is TRUDHESA? TRUDHESA is a prescription medicine used for the acute treatment of migraine with or without aura in adults.

TRUDHESA is not used to prevent migraine. TRUDHESA is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines. It is not known if TRUDHESA is safe and effective in children.

Do not take TRUDHESA if you: are taking medicines known as strong CYP3A4 inhibitors. have heart problems or a history of heart problems. have uncontrolled high blood pressure. have narrowing of blood vessels in your legs, arms, stomach, or kidneys (peripheral vascular disease). have sepsis. have had vascular surgery. have severe liver problems. have severe kidney problems. are allergic to dihydroergotamine mesylate, ergot alkaloids, or any ingredients in TRUDHESA. See the end of this Medication Guide for a complete list of ingredients. have taken any of the following medicines in the last 24 hours: sumatriptan almotriptan eletriptan frovatriptan naratriptan rizatriptan ergotamine or ergotamine-type medicines have taken any medicines that constrict your blood vessels or raise your blood pressure.

Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take TRUDHESA with other medicines. Before you take TRUDHESA, tell your healthcare provider about all of your medical conditions, including if you: have high blood pressure. have liver problems. have kidney problems. smoke. are pregnant or plan to become pregnant.

TRUDHESA may cause preterm labor. TRUDHESA should be avoided during pregnancy. Talk to your healthcare provider right away if you are pregnant or want to become pregnant. are breastfeeding or plan to breastfeed.

TRUDHESA may reduce breast milk supply and pass into your breast milk. TRUDHESA may be harmful to your baby. Do not breastfeed your baby while taking TRUDHESA and for 3 days after you use TRUDHESA.

Talk with your healthcare provider about the best way to feed your baby if you take TRUDHESA. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. Your healthcare provider will decide if you can take TRUDHESA with your other medicines.

Especially tell your healthcare provider if you take: sumatriptan ergot-type medicine saquinavir nefazodone fluconazole grapefruit juice zileuton nicotine propranolol or other medicines that can lower your heart rate any medicines that can increase your blood pressure selective serotonin reuptake inhibitors These are not all of the medicines that could affect how TRUDHESA… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~2 min read ▾

12.3Pharmacokinetics Absorption The mean time from dosing to maximum plasma concentration following TRUDHESA administration was approximately 0.5 hours. Distribution Dihydroergotamine mesylate is 93% plasma protein bound. The apparent steady-state volume of distribution is approximately 800 liters.

Elimination Metabolism Four dihydroergotamine mesylate metabolites have been identified in human plasma following oral administration. The major metabolite, 8'-β-hydroxy dihydroergotamine, exhibits affinity equivalent to its parent for adrenergic and 5-HT receptors and demonstrates equivalent potency in several venoconstrictor activity models, in vivo and in vitro. The other metabolites, i.e., dihydrolysergic acid, dihydrolysergic amide, and a metabolite formed by oxidative opening of the proline ring, are of minor importance.

Following nasal administration, total metabolites represent only 20% to 30% of plasma AUC. The systemic clearance of dihydroergotamine mesylate following intravenous and intramuscular administration is

1.5L/min. Quantitative pharmacokinetic characterization of the four metabolites has not been performed. Excretion The major excretory route of dihydroergotamine is via the bile in the feces. The total body clearance is

1.5L/min, which reflects mainly hepatic clearance. Only 6% to 7% of unchanged dihydroergotamine is excreted in the urine after intramuscular injection. The renal clearance (0.1 L/min) is unaffected by the route of dihydroergotamine administration.

The mean apparent half-life of TRUDHESA nasal administration in healthy subjects is approximately 12 hours. Specific Populations No studies have been conducted on the effect of renal or hepatic impairment, gender, race, ethnicity, or pregnancy on dihydroergotamine pharmacokinetics [see Contraindications (4) , Use in Specific Populations (8.1) ]. Drug Interaction Studies CYP3A4 Inhibitors Rare reports of ergotism have been obtained from patients treated with dihydroergotamine and macrolide antibiotics (e.g., clarithromycin, erythromycin) and from patients treated with dihydroergotamine and protease inhibitors (e.g., ritonavir), presumably due to inhibition of CYP3A metabolism of ergotamine [see Contraindications (4) ].

Other Drugs The pharmacokinetics of dihydroergotamine did not appear to be significantly affected by the concomitant use of a local vasoconstrictor. Multiple oral doses of the β-adrenoceptor antagonist propranolol, used for migraine prophylaxis, had no significant influence on the C max , t max , or AUC of dihydroergotamine doses up to 4 mg. However, propranolol may potentiate the vasoconstrictive action of ergotamine [see Drug Interactions (7.3) ].

The effect of oral contraceptives on the pharmacokinetics of TRUDHESA has not been studied.

🧬 Pharmacodynamics 35 words ▾

12.2Pharmacodynamics Significant elevation in blood pressure has been reported in patients with and without a history of hypertension [see Warnings and Precautions (5.5) ]. Dihydroergotamine possesses oxytocic properties [see Warnings and Precautions (5.7) ].

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES 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 treated a single moderate to severe migraine headache with a single dose of study medication and assessed pain severity over the 24 hours following treatment. Headache response was determined 0.5, 1, 2, 3 and 4 hours after dosing and was defined as a reduction in headache severity to mild or no pain.

In studies 1 and 2, a four-point pain intensity scale was utilized; in studies 3 and 4, a five-point scale was used to record pain response. Although rescue medication was allowed in all four studies, patients were instructed not to use them during the four hour observation period. In studies 3 and 4, a total dose of 2 mg was compared to placebo.

In studies 1 and 2, doses of 2 and 3 mg were evaluated, and showed no advantage of the higher dose for a single treatment. In all studies, patients received a regimen consisting of 0.5 mg in each nostril, repeated in 15 minutes (and again in another 15 minutes for the 3 mg dose in studies 1 and 2). The percentage of patients achieving headache response 4 hours after treatment was significantly greater in patients receiving 2 mg doses of dihydroergotamine mesylate nasal spray compared to those receiving placebo in 3 of the 4 studies (see Table 2 and Table 3 and Figure 1 and Figure 2 ).

Table 2 Studies 1 and 2: Percentage of Patients with Headache Response Headache response was defined as a reduction in headache severity to mild or no pain. Headache response was based on pain intensity as interpreted by the patient using a four-point pain intensity scale. 2 and 4 Hours Following a Single Treatment of Study Medication (Dihydroergotamine Mesylate Nasal Spray or Placebo) N 2 hours 4 hours Study 1 Dihydroergotamine mesylate nasal spray 105 61% p value < 0.001 70% Placebo 98 23% 28% Difference from Placebo 37% 42% Study 2 Dihydroergotamine mesylate nasal spray 103 47% 56% p value <

0.01Placebo 102 33% 35% Difference from Placebo 14% 21% Table 3 Studies 3 and 4: Percentage of Patients with Headache Response Headache response was defined as a reduction in headache severity to mild or no pain. Headache response was evaluated on a five-point scale that included pain response. 2 and 4 Hours Following a Single Treatment of Study Medication (Dihydroergotamine Mesylate Nasal Spray or Placebo) N 2 hours 4 hours Study 3 Dihydroergotamine mesylate nasal spray 50 32% 48% p value <

0.01Placebo 50 20% 22% Difference from Placebo 12% 26% Study 4 Dihydroergotamine mesylate nasal spray 47 30% 47% Placebo 50 20% 30% Difference from Placebo 10% 17% The Kaplan-Meier plots below (Figure 1 and Figure 2) provide an estimate of the probability that a patient will have responded to a single 2 mg dose of dihydroergotamine mesylate nasal spray as a function of the time elapsed since initiation of treatment. Figure 1 Estimated Probability of a Patient Responding During the Four Hours Following a Single 2 mg Dose of Dihydroergotamine Mesylate Nasal Spray as a Function of the Time Elapsed Since Initiation of Treatment The figure shows the probability over time of obtaining a response following treatment with dihydroergotamine mesylate nasal spray.

Headache response was based on pain intensity as interpreted by the patient using a four-point pain intensity scale. Patients not achieving response within 4 hours were censored to 4 hours. Figure 2 Estimated Probability of a Patient Responding to Dihydroergotamine Mesylate… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence 133 words ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance TRUDHESA contains dihydroergotamine (as the mesylate salt), which is not a controlled substance.

9.2Abuse Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Currently available data have not demonstrated drug abuse with dihydroergotamine. However, cases of drug abuse in patients on other forms of ergot therapy have been reported.

9.3Dependence Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Currently available data have not demonstrated physical or psychological dependence with dihydroergotamine. However, cases of psychological dependence in patients on other forms of ergot therapy have been reported.

🔒 Controlled Substance 16 words ▾

9.1Controlled Substance TRUDHESA contains dihydroergotamine (as the mesylate salt), which is not a controlled substance.

🧪 Nonclinical Toxicology 116 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Assessment of the carcinogenic potential of dihydroergotamine mesylate in mice and rats has not been assessed. Mutagenesis Dihydroergotamine mesylate was negative in an in vitro mutagenicity (Ames) assay and positive in in vitro chromosomal aberration (V79 Chinese hamster cell assay with metabolic activation, and human peripheral blood lymphocyte) assays. Dihydroergotamine was negative in in vivo micronucleus assays in mouse and hamster.

Impairment of Fertility There was no evidence of impairment of fertility in rats given intranasal doses of dihydroergotamine mesylate up to 1.6 mg/day, which was associated with plasma exposures (AUC) approximately 3 times that in humans at the maximum recommended human dose of 2.9 mg/day.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 113 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Assessment of the carcinogenic potential of dihydroergotamine mesylate in mice and rats has not been assessed. Mutagenesis Dihydroergotamine mesylate was negative in an in vitro mutagenicity (Ames) assay and positive in in vitro chromosomal aberration (V79 Chinese hamster cell assay with metabolic activation, and human peripheral blood lymphocyte) assays. Dihydroergotamine was negative in in vivo micronucleus assays in mouse and hamster.

Impairment of Fertility There was no evidence of impairment of fertility in rats given intranasal doses of dihydroergotamine mesylate up to 1.6 mg/day, which was associated with plasma exposures (AUC) approximately 3 times that in humans at the maximum recommended human dose of 2.9 mg/day.

📖 Instructions for Use ~3 min read ▾

INSTRUCTIONS FOR USE Trudhesa™ (true-deh-sa) (dihydroergotamine mesylate) nasal spray For Nasal Use Only 622344 Remove and Follow When Dosing This Instructions for Use contains information on how to deliver Trudhesa. Introduction Read this Instructions for Use before you start to use Trudhesa and each time you get a prescription refill. There may be new information.

This information does not take the place of talking with your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about Trudhesa when you start taking it and at regular checkups. It is important to follow these directions accurately in order to receive the correct dose.

Contact your healthcare provider if you have any questions about how to use this product. Nasal Spray Device Parts Glass Vial Parts Important Information You Need To Know Before Dosing with Trudhesa For nasal use only. Always prime the nasal spray device before dosing by pumping the finger grips and glass vial together exactly 4 times.

The purpose of priming is to bring the medicine to the tip of the spray nozzle. You may or may not see liquid or spray come out of the nozzle during each priming action. During priming, make sure to aim the spray nozzle away from your face and anything that you do not want coming into contact with the spray of medicine.

A complete dose is 2 sprays; 1 spray in each nostril. Do not take more than 2 doses within a 24-hour period. Do not take more than 3 doses in a 7-day period.

Always hold the nasal spray device perfectly upright when priming and when dosing. Sniffing while dosing is not necessary. However, sniffing will not hurt you nor make the medicine less effective.

This nasal spray device product is single-dose (for one complete dose only) and should be thrown away (discarded) after use. You will need a new kit for each dose. Keep the product in the case until ready to use.

After a TRUDHESA vial has been opened, it must be thrown away after 8 hours. Do not open the glass vial and expose to air until ready to use. Store at room temperature in a clean, dry area.

Do not use if product is damaged. Do not use if product is expired. Each glass vial and nasal spray device can only be used 1 time.

Throw away the entire nasal spray device after dosing, without removing the glass vial. You can take another complete dose at least 1 hour after your first dose if your symptoms persist Storing Trudhesa Store Trudhesa at room temperature between 68 °F to 77°F (20 °C to 25°C). Store Trudhesa in the original packaging in a clean, dry area away from heat and light (Figure A).

Keep Trudhesa in the original packaging until you are ready to use. Do not refrigerate or freeze Trudhesa. Keep Trudhesa and all medicines out of the reach of children.

Figure A Preparing to Dose with Trudhesa Step 1: Gather and Check Supplies

1.1Check to make sure you are using the right medicine for your migraine (see Figure B ). Figure B

1.2Check to make sure Trudhesa is not expired (EXP) (see Figure C ). If expired, throw away and get a new glass vial. Figure C

1.3Check to make sure that the glass vial and blue plastic cover do not look damaged. Step 2: Remove Blue Plastic Cover, Metal Foil and Grey Rubber Stopper from Glass Vial

2.1Remove (flip up) the blue plastic cover from the glass vial (see Figure D ).

2.2Use the blue plastic cover to slowly peel away all the metal foil from the grey rubber stopper in a circular motion (see Figure E ). NOTE: The metal foil may come off in 2 or more pieces. Make sure to remove all of the metal foil. Figure D Figure E

2.3Pull the grey rubber stopper up and out of the glass vial (Figure F and Figure G). Figure F Figure G

2.4Throw away (discard) cover, foil and grey rubber stopper into the trash. Step 3: Remove the Clear Plastic Cover from the Nasal Spray Device

3.1Hold the nasal spray device upright.

3.2Pull down on the clear plastic cover and remove it from the nasal spray device (Figure H). Throw away the… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 141 words ▾

PRINCIPAL DISPLAY PANEL - 0.725 mg Vial Carton Trudhesa™ (dihydroergotamine mesylate) nasal spray 0.725 mg per spray Recommended Dosage: See Prescribing Information Contains: 4 Nasal Spray Devices, 4 Trudhesa Vials, Instructions for Use and Prescribing Information NOT FOR INDIVIDUAL SALE Contents are disposable; discard used nasal spray device and vial after use. For nasal use only. RX ONLY 622338 PRINCIPAL DISPLAY PANEL - 0.725 mg Vial Carton

PRINCIPAL DISPLAY PANEL - 0.725 mg Vial Carton - NDC 77530-725-06 RX ONLY Trudhesa ® (dihydroergotamine mesylate) nasal spray 0.725 mg per spray Recommended Dosage: See Prescribing Information Contains: 6 Nasal Spray Devices, 6 Trudhesa Vials, Instructions for Use and Prescribing Information NOT FOR INDIVIDUAL SALE Contents are disposable; discard used nasal spray device and vial after use. For nasal use only. 622338-01-N PRINCIPAL DISPLAY PANEL - 0.725 mg Vial Carton - NDC 77530-725-06

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Trudhesa — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Trudhesa. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$2.03M
Claims incl. refills
234
Beneficiaries
135
Spend / beneficiary
$15,004.12
Spend / claim
$8,656.22
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Impel Pharmaceuticals LLC. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 2 other package presentations of this same product, including 1 vial (77530-0725-00), 6 vials (77530-0725-06). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Impel Pharmaceuticals LLC is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 77462-0012-01 · SORA 77556-0580-01 · Astera →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.