HomeNDC LookupIngredientsDihydroergotamine Mesylate › 81284-0411-05
Dihydroergotamine Mesylate 1 mg/mL Injection, Solution, 5 ampules — NDC 81284-0411-05 package photo

Dihydroergotamine Mesylate 1 mg/mL Injection, Solution, 5 ampules

by Provepharm Inc. · 5 AMPULE in 1 CARTON (81284-411-05) / 1 mL in 1 AMPULE (81284-411-00)
NDC 81284-0411-05
🏷️ FDA NDC (as labeled) 81284-411-05 billing pads the product segment with a zero
This package
Contains5 ampules Medicaid pays$76.98 / unit · 12 mo Per package$384.88 / 5 ml · Medicaid Pack sizes2 compare ↓
Also comes in: 10 ampules 81284-0411-10
Rx only Generic On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →
🚨
Active recall for this product.
Class II · Nov 22, 2024 — Discoloration (Provepharm Inc.) · FDA recall D-0150-2025
Check your lot/expiration against the official notice — look up the recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 81284-411-05
Product NDC 81284-411
11-digit billing NDC 81284041105
NCPDP billing unit ML — per mL (volume)
RxCUI 861672
UNII 81AXN7R2QT
UPC 0381284411059
Application # ANDA212046
SPL Set ID 40b9ba9e-436e-444e-b078-01b12bb57ea7
Established class (EPC) Ergotamine Derivative
Chemical class Ergotamines
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2021-09-30
Route INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS
Dosage form INJECTION, SOLUTION
Substance DIHYDROERGOTAMINE MESYLATE
GPI-14 67000030102005
GPI class Dihydroergotamine Mesylate
GCN Seq No 004504
GCN 01590
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 DIHYDROERGOTAMINE 1 MG/ML AMP
FDB brand name Dihydroergotamine Mesylate
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AP · RLD · RS
Why two NDCs? The FDA registers this code as 81284-411-05 — 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 → 81284-0411-05. 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.

🏭 Manufacturer & labeler

LabelerProvepharm Inc.
Application holderMILLA PHARMACEUTICALS INC
FDA applicationANDA212046 (ANDA)
Labeler code81284
First marketedSep 2021
Product typeHuman Prescription Drug
Portfolio13 products on file
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.

🩺 Clinical

Label name DIHYDROERGOTAMINE 1 MG/ML AMP Ingredient Dihydroergotamine Mesylate
📖 What it is MedlinePlus · NLM

Dihydroergotamine injection is used to treat migraine headaches (severe, throbbing headaches that sometimes are accompanied by nausea and sensitivity to sound and light) and cluster headaches (severe headaches usually on one side of the head or around one eye). 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 works by activating certain serotonin receptors in the brain, which helps shrink swollen blood vessels and block pain signals from your trigeminal nerve — the nerve network resp...
  • What exactly does this injection do for my migraine?
  • Brekiya is injected just under the skin of your middle thigh. Remove the red needle cap, press the device firmly against a clean area of skin, then push and release the gray activa...
  • How do I use the Brekiya autoinjector at home?
📖 Read our full Dihydroergotamine Injection 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.

🧪 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.

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

  • UNII 3K9958V90M
    A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
  • UNII PDC6A3C0OX
    Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
  • UNII 12EH9M7279
    Methanesulfonic acid is a strong organic acid used in medicines as a pH buffer and stabilizer. It helps maintain the correct acidity level and keeps active ingredients stable during storage.
  • UNII 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
  • 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.

5 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 DailyMedingredient 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.

💲 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 $76.98 $384.88 / 5 ml
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J1110 $54.978 / J1110 unit
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.

🧾 Billing & reimbursement

FDA NDC (as labeled)81284-411-05
11-digit billing NDC81284-0411-05
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ1110
DescriptorINJECTION, DIHYDROERGOTAMINE MESYLATE, PER 1 MG
Billing units / pkg1 units
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Dihydroergotamine Mesylate 1 mg/mL 00143-9151-10 Hikma 10 vials AP FDA listed
Dihydroergotamine Mesylate 1 mg/mL 00143-9273-10 Hikma 10 ampules AP FDA listed
dihydroergotamine mesylate 1 mg/mL 36000-0300-10 Baxter 10 ampules FDA listed
Dihydroergotamine Mesylate 1 mg/mL 68083-0466-10 Gland 10 ampules AP FDA listed
Dihydroergotamine Mesylate 1 mg/mL 71357-0013-05 Milla 5 ampules AP FDA listed
Dihydroergotamine Mesylate 1 mg/mLthis 81284-0411-05 Provepharm 5 ampules AP FDA listed
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
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
On the market since
Sep 2021
📍
2026
Currently FDA-listed
5 years listed
🔓
·
Generic on the market
this product is a generic
This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

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.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 81284-0411-05, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q4 2025 · 4 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
30
Units reimbursed last 4 qtrs
191
Gross reimbursed last 4 qtrs
$14.7K
Avg / prescription
$490.08
Avg / unit
$76.9766
Latest quarter Q4 2025
30Rx
Fee-for-service vs managed care
43% FFS 57% MCO
Fee-for-service · 13 Rx Managed care · 17 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: 50 units · 0.9 per 100k residents MN Wisconsin: no data reported WI Michigan: no data reported MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: no data reported CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: 141 units · 3.9 per 100k residents CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
0.93.9
gray = no data reported
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Connecticut 3.9 /100k
2 Minnesota 0.9 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

💊 Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
Drug total (last 4 qtrs): 61 Rx · 241 units · $16,693 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

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

Medicare Part D (outpatient prescription) spending for Dihydroergotamine Mesylate — the program that covers self-administered drugs. 7 manufacturers.
⚠️ 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 Dihydroergotamine Mesylate. 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
$2.55M
Claims incl. refills
3.5K
Beneficiaries
1.5K
Spend / beneficiary
$1,672.11
Spend / claim
$729.25
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.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Dihydroergotamine Mesylate — the ingredient across all brands.

Top reported reactions

Nausea365
Hyperhidrosis323
Nightmare308
Sedation308
Nephrolithiasis222
Migraine105
Dyspnoea87

Age at onset

Child1
Adolescent2
Adult100
Elderly6

Reporter sex

1,268 reports
Male · 39%
Female · 60%
Unknown · 0%

Serious outcomes

Life-threatening14
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 67 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
81284-0411-05 You're viewing this 5 AMPULE in 1 CARTON (81284-411-05) / 1 mL in 1 AMPULE (81284-411-00) 2021-09-30 Active
81284-0411-10 10 AMPULE in 1 CARTON (81284-411-10) / 1 mL in 1 AMPULE (81284-411-00) 2021-09-30 Active

Pack size FAQ

What quantity is in NDC 81284-0411-05?
NDC 81284-0411-05 contains 5 ampules — 5 ampule in 1 carton / 1 ml in 1 ampule.
What is the difference between NDC 81284-0411-05 and NDC 81284-0411-10?
Both are Dihydroergotamine Mesylate 1 mg/mL Injection, Solution — the drug itself is identical. NDC 81284-0411-05 is the 5 ampules package, while NDC 81284-0411-10 is the 10 ampules package.
What NDC number is used to bill for this package of Dihydroergotamine Mesylate 1 mg/mL Injection, Solution?
Bill NDC 81284-0411-05 — the 11-digit billing format is 81284041105. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 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 ✓ Available
Medicaid utilization (CMS SDUD) ✓ Available
“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 FDA registers it as 81284-411-05, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 81284-0411-05, written without dashes as 81284041105. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 81284-0411-05, the first segment (81284) is the labeler code FDA assigned to Provepharm Inc.; the middle segment (0411) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (05) identifies this exact package size and type. Together they name one specific package of one specific product.
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 Provepharm Inc.. 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 1 other package presentation of this same product, including 10 ampules (81284-0411-10). 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?
Provepharm Inc. 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.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J1110 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
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.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 70 words

WARNING: PERIPHERAL ISCHEMIA FOLLOWING COADMINISTRATION WITH POTENT CYP3A4 INHIBITORS Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics. 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 these medications is contraindicated (see also CONTRAINDICATIONS and WARNINGS ).

🎯 Indications and Usage 28 words

INDICATIONS AND USAGE Dihydroergotamine Mesylate Injection, USP is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes.

⏱️ Dosage and Administration 73 words

DOSAGE AND ADMINISTRATION Dihydroergotamine Mesylate Injection, USP should be administered in a dose of 1 mL intravenously, intramuscularly or subcutaneously. The dose can be repeated, as needed, at 1-hour intervals to a total dose of 3 mL for intramuscular or subcutaneous delivery or 2 mL for intravenous delivery in a 24-hour period. The total weekly dosage should not exceed 6 mL.

Dihydroergotamine Mesylate Injection, USP should not be used for chronic daily administration.

Contraindications ~1 min read

CONTRAINDICATIONS There have been a few reports of serious adverse events associated with the coadministration of dihydroergotamine and potent CYP3A4 inhibitors, such as protease inhibitors and macrolide antibiotics, resulting in vasospasm that led to cerebral ischemia and/or ischemia of the extremities. The use of potent CYP3A4 inhibitors (i.e., ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole) with dihydroergotamine is, therefore, contraindicated (see WARNINGS, CYP3A4 Inhibitors ).

Dihydroergotamine Mesylate Injection, USP should not be given to patients with ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have clinical symptoms or findings consistent with coronary artery vasospasm including Prinzmetal's variant angina (see WARNINGS ). Because Dihydroergotamine Mesylate Injection, USP may increase blood pressure, it should not be given to patients with uncontrolled hypertension. Dihydroergotamine Mesylate Injection, USP, 5-HT 1 agonists (e.g., sumatriptan), ergotamine-containing or ergot-type medications or methysergide should not be used within 24 hours of each other.

Dihydroergotamine Mesylate Injection, USP should not be administered to patients with hemiplegic or basilar migraine. In addition to those conditions mentioned above, Dihydroergotamine Mesylate Injection, USP is also contraindicated in patients with known peripheral arterial disease, sepsis, following vascular surgery and severely impaired hepatic or renal function. Dihydroergotamine Mesylate Injection, USP is contraindicated in patients who have previously shown hypersensitivity to ergot alkaloids.

Dihydroergotamine mesylate should not be used with peripheral and central vasoconstrictors because the combination may result in additive or synergistic elevation of blood pressure.

⚠️ Warnings ~2 min read

WARNINGS Dihydroergotamine Mesylate Injection, USP should only be used where a clear diagnosis of migraine headache has been established. CYP3A4 Inhibitors (e.g., Macrolide Antibiotics and Protease Inhibitors) There have been rare reports of serious adverse events in connection with the coadministration of dihydroergotamine and potent CYPA4 inhibitors, such as protease inhibitors and macrolide antibiotics, resulting in vasospasm that led to cerebral ischemia and/or and ischemia of the extremities. The use of potent CYP3A4 inhibitors with dihydroergotamine should therefore be avoided (see CONTRAINDICATIONS ).

Examples of some of the more potent CYP3A4 inhibitors include: antifungals ketoconazole and itraconazole, the protease inhibitors ritonavir, nelfinavir, and indinavir, and macrolide antibiotics erythromycin, clarithromycin, and troleandomycin. Other less potent CYP3A4 inhibitors should be administered with caution. Less potent inhibitors include saquinavir, nefazodone, fluconazole, grapefruit juice, fluoxetine, fluvoxamine, zileuton, and clotrimazole.

These lists are not exhaustive, and the prescriber should consider the effects on CYP3A4 of other agents being considered for concomitant use with dihydroergotamine. Fibrotic Complications There have been reports of pleural and retroperitoneal fibrosis in patients following prolonged daily use of injectable dihydroergotamine mesylate. Rarely, prolonged daily use of other ergot alkaloid drugs has been associated with cardiac valvular fibrosis.

Rare cases have also been reported in association with the use of injectable dihydroergotamine mesylate; however, in those cases, patients also received drugs known to be associated with cardiac valvular fibrosis. Administration of Dihydroergotamine Mesylate Injection, USP, should not exceed the dosing guidelines and should not be used for chronic daily administration (see DOSAGE AND ADMINISTRATION ). Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events Dihydroergotamine Mesylate Injection, USP should not be used by patients with documented ischemic or vasospastic coronary artery disease (see CONTRAINDICATIONS ).

It is strongly recommended that Dihydroergotamine Mesylate Injection, USP not be given to patients in whom unrecognized coronary artery disease (CAD) is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, females who are surgically or physiologically postmenopausal, or males who are over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease.

The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient's medical history or electrocardiographic investigations reveal findings indicative of or consistent with coronary artery vasospasm or myocardial ischemia, Dihydroergotamine Mesylate Injection, USP should not be administered (see CONTRAINDICATIONS ). For patients with risk factors predictive of CAD who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of Dihydroergotamine Mesylate Injection, USP take place in the setting of a physician's office or similar medically staffed and equipped facility unless the patient has previously received dihydroergotamine mesylate.

Because cardiac ischemia can occur in the absence of clinical symptoms, consideration should be given to obtaining on the first occasion of use, an electrocardiogram (ECG) during the interval immediately following Dihydroergotamine Mesylate Injection, USP in those patients with risk factors. It is recommended that patients who are intermittent long-term users of D…

🤒 Adverse Reactions 163 words

ADVERSE REACTIONS Serious cardiac events, including some that have been fatal, have occurred following use of Dihydroergotamine Mesylate Injection, USP, but are extremely rare. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation (see CONTRAINDICATIONS , WARNINGS , and PRECAUTIONS ). Fibrotic complications have been reported in association with long term use of injectable dihydroergotamine mesylate (see WARNINGS, Fibrotic Complications ).

Post-introduction Reports The following events derived from postmarketing experience have been occasionally reported in patients receiving Dihydroergotamine Mesylate Injection, USP: vasospasm, paraesthesia, hypertension, dizziness, anxiety, dyspnea, headache, flushing, diarrhea, rash, increased sweating, and pleural and retroperitoneal fibrosis after long-term use of dihydroergotamine. Extremely rare cases of myocardial infarction and stroke have been reported. A causal relationship has not been established.

Dihydroergotamine Mesylate Injection, USP is not recommended for prolonged daily use (see DOSAGE AND ADMINISTRATION ). To report SUSPECTED ADVERSE REACTIONS, contact Provepharm Inc., at 1–833-727-6556 or [email protected] or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

🔄 Drug Interactions 204 words

Drug Interactions Vasoconstrictors Dihydroergotamine Mesylate Injection, USP should not be used with peripheral vasoconstrictors because the combination may cause synergistic elevation of blood pressure. Sumatriptan Sumatriptan has been reported to cause coronary artery vasospasm, and its effect could be additive with Dihydroergotamine Mesylate Injection, USP. Sumatriptan and Dihydroergotamine Mesylate Injection, USP should not be taken within 24 hours of each other (see CONTRAINDICATIONS ).

Beta Blockers Although the results of a clinical study did not indicate a safety problem associated with the administration of Dihydroergotamine Mesylate Injection, USP to subjects already receiving propranolol, there have been reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine. Nicotine Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy. CYP3A4 Inhibitors (e.g., Macrolide Antibiotics and Protease Inhibitors) (see CONTRAINDICATIONS and WARNINGS ) SSRI's Weakness, hyperreflexia, and incoordination have been reported rarely when 5-HT 1 agonists have been co-administered with SSRI's (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline).

There have been no reported cases from spontaneous reports of drug interaction between SSRI's and Dihydroergotamine Mesylate Injection, USP. Oral Contraceptives The effect of oral contraceptives on the pharmacokinetics of Dihydroergotamine Mesylate Injection, USP has not been studied.

🤰 Pregnancy ~2 min read

Pregnancy Risk Summary Available data from published literature indicated an increased risk of preterm delivery with Dihydroergotamine Mesylate Injection, USP use during pregnancy. Avoid use of Dihydroergotamine Mesylate Injection, USP during pregnancy (see WARNINGS ) . Data collected over decades have shown no increased risk of major birth defects or miscarriage with the use of dihydroergotamine mesylate during pregnancy.

In animal reproduction studies, adverse effects on development were observed following intranasal 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) at doses that 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 and greater.

A no-effect level for adverse effects on embryofetal development was not identified in rats. Intranasal administration of dihydroergotamine mesylate to pregnant rabbits throughout organogenesis resulted in decreased skeletal ossification of 3.6 mg/day. The no-effect dose for adverse effects on embryofetal development in rabbits was 1.2 mg/day.

Intranasal administration of dihydroergotamine mesylate to female rats throughout pregnancy and lactation resulted in decreased body weight and impaired reproductive function (decreased mating indices) in the offspring at doses of 0.16 mg/day or greater. A no-effect dose for adverse effects on pre- and postnatal development in rats was not established. Effects on offspring development occurred at doses below those that produced evidence of 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 12 words

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

🆘 Overdosage 218 words

OVERDOSAGE To date, there have been no reports of acute overdosage with this drug. Due to the risk of vascular spasm, exceeding the recommended dosages of Dihydroergotamine Mesylate Injection, USP is to be avoided. Excessive doses of dihydroergotamine may result in peripheral signs and symptoms of ergotism.

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. In general, the symptoms of an acute Dihydroergotamine Mesylate Injection, USP overdose are similar to those of an ergotamine overdose, although there is less pronounced nausea and vomiting with Dihydroergotamine Mesylate Injection, USP. 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, significant lethality occurs when dihydroergotamine is given at I.V. doses of 44 mg/kg in mice, 130 mg/kg in rats, and 37 mg/kg in rabbits. Up-to-date information about the treatment of overdosage can often be obtained from a certified Regional Poison Control Center. Telephone numbers of certified Poison Control Centers are listed in the Physician's Desk Reference (PDR) * .

🧬 Clinical Pharmacology ~2 min read

CLINICAL PHARMACOLOGY Mechanism of Action Dihydroergotamine binds with high affinity to 5-HT 1D α and 5-HT 1D β receptors. It also binds with high affinity to serotonin 5-HT 1A , 5-HT 2A , and 5-HT 2C receptors, noradrenaline α 2A , α 2B and α 1 receptors, and dopamine D 2L and D 3 receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT 1D receptors.

Two current theories have been proposed to explain the efficacy of 5-HT 1D receptor agonists in migraine. One theory suggests that activation of 5-HT 1D receptors located on intracranial blood vessels, including those on arteriovenous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. The alternative hypothesis suggests that activation of 5-HT 1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.

In addition, dihydroergotamine possesses oxytocic properties. Pharmacokinetics Absorption Absolute bioavailability for the subcutaneous and intramuscular route have not been determined; however, no difference was observed in dihydroergotamine bioavailability from intramuscular and subcutaneous doses. Dihydroergotamine mesylate is poorly bioavailable following oral administration.

Distribution Dihydroergotamine mesylate is 93% plasma protein bound. The apparent steady-state volume of distribution is approximately 800 liters. Metabolism Four dihydroergotamine mesylate metabolites have been identified in human plasma following oral administration.

The major metabolite, 8´-β-hydroxydihydroergotamine, 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.

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 decline of plasma dihydroergotamine after intramuscular or intravenous administration is multi-exponential with a terminal half-life of about 9 hours. Subpopulations No studies have been conducted on the effect of renal or hepatic impairment, gender, race, or ethnicity on dihydroergotamine pharmacokinetics. Dihydroergotamine Mesylate Injection, USP is contraindicated in patients with severely impaired hepatic or renal function (see CONTRAINDICATIONS ).

Interactions Pharmacokinetic interactions have been reported in patients treated orally with other ergot alkaloids (e.g., increased levels of ergotamine) and macrolide antibiotics, principally troleandomycin, presumably due to inhibition of cytochrome P4503A metabolism of the alkaloids by troleandomycin. Dihydroergotamine has also been shown to be an inhibitor of cytochrome P4503A catalyzed reactions and rare reports of ergotism have been obtained from patients treated with dihydroergotamine and macrolide antibiotics (e.g., troleandomycin, clarithromycin, erythromycin), and in patients treated with dihydroergotamine and protease inhibitors (e.g., ritonavir), presumably due to inhibition of cytochrome P4503A metabolism of ergotamine (see CONTRAINDICATIONS ).

No pharmacokinetic interactions involving other cytochrome P450 isoenzymes are known.

🧬 Mechanism of Action 150 words

Mechanism of Action Dihydroergotamine binds with high affinity to 5-HT 1D α and 5-HT 1D β receptors. It also binds with high affinity to serotonin 5-HT 1A , 5-HT 2A , and 5-HT 2C receptors, noradrenaline α 2A , α 2B and α 1 receptors, and dopamine D 2L and D 3 receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT 1D receptors.

Two current theories have been proposed to explain the efficacy of 5-HT 1D receptor agonists in migraine. One theory suggests that activation of 5-HT 1D receptors located on intracranial blood vessels, including those on arteriovenous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. The alternative hypothesis suggests that activation of 5-HT 1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.

In addition, dihydroergotamine possesses oxytocic properties.

📦 How Supplied / Storage and Handling 113 words

HOW SUPPLIED/STORAGE AND HANDLING Dihydroergotamine Mesylate Injection, USP Available as a clear, colorless, sterile solution in single 1 mL sterile ampules containing 1 mg of dihydroergotamine mesylate per mL, in packages of 5 (NDC 81284-411-05) and 10 (NDC 81284-411-10). Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Use carton to protect contents from light until used.

Do not refrigerate or freeze. To assure constant potency, protect the ampules from light and heat. Administer only if clear and colorless. *Trademark of PDR Network, LLC Manufactured for: Provepharm SAS Distributed by: Provepharm, Inc.

Collegeville, PA 19426 Made in France Revised: 11/2022

📦 Storage and Handling 74 words

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Use carton to protect contents from light until used. Do not refrigerate or freeze.

To assure constant potency, protect the ampules from light and heat. Administer only if clear and colorless. *Trademark of PDR Network, LLC Manufactured for: Provepharm SAS Distributed by: Provepharm, Inc. Collegeville, PA 19426 Made in France Revised: 11/2022

📋 Description 129 words

DESCRIPTION Dihydroergotamine Mesylate Injection, USP is ergotamine hydrogenated in the 9, 10 position as the mesylate salt. Dihydroergotamine Mesylate Injection, USP is known chemically as ergotaman-3´,6´,18-trione,9,10-dihydro-12´-hydroxy-2´-methyl-5´-(phenylmethyl)-,(5´α)-, monomethanesulfonate. Its molecular weight is 679.80 and its empirical formula is C 33 H 37 N 5 O 5 •CH 4 O 3 S.

The chemical structure is: Dihydroergotamine mesylate C 33 H 37 N 5 O 5 •CH 4 O 3 S Mol. Wt. 679.80 Dihydroergotamine Mesylate Injection, USP is a clear, colorless solution supplied in sterile ampules for intravenous, intramuscular, or subcutaneous administration.

Each mL contains 1 mg Dihydroergotamine Mesylate, USP; Alcohol, USP 6.1% by volume; Glycerin, USP 15% by weight; Water for Injection, USP; Methanesulfonic Acid and/or Sodium Hydroxide for pH adjustment (pH range is 3.4 to 4.9). Chemical Structure

💬 Information for Patients 154 words

Information for Patients The text of a patient information sheet is printed at the end of this insert. To assure safe and effective use of Dihydroergotamine Mesylate Injection, USP, the information and instructions provided in the patient information sheet should be discussed with patients. Patients should be advised to report to the physician immediately any of the following: numbness or tingling in the fingers and toes, muscle pain in the arms and legs, weakness in the legs, pain in the chest, temporary speeding or slowing of the heart rate, swelling, or itching.

Prior to the initial use of the product by a patient, the prescriber should take steps to ensure that the patient understands how to use the product as provided (see Patient Information Sheet and product packaging). Administration of Dihydroergotamine Mesylate Injection, USP should not exceed the dosing guidelines and should not be used for chronic daily administration (see DOSAGE AND ADMINISTRATION ).

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