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EVOMELA Melphalan 50 mg/10mL Injection, Powder, Lyophilized, For Solution — NDC 72893-0001-01 package photo

EVOMELA Melphalan 50 mg/10mL Injection, Powder, Lyophilized, For Solution

by Acrotech Biopharma Inc · 1 VIAL in 1 CARTON (72893-001-01) / 20 mL in 1 VIAL
NDC 72893-0001-01
🏷️ FDA NDC (as labeled) 72893-001-01 billing pads the product segment with a zero
Rx only Brand 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 →

This page is curated, coded, and maintained by

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

🆔 Identity & classification

FDA NDC (as labeled) 72893-001-01
Product NDC 72893-001
11-digit billing NDC 72893000101
NCPDP billing unit EA — each (per item)
RxCUI 311487, 1745090
UNII 1VXP4V453T
Application # NDA207155
SPL Set ID 69f55869-dc11-408e-8fc7-47634269a52c
Established class (EPC) Alkylating Drug
Mechanism of action Alkylating Activity
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2016-03-31
Route INTRAVENOUS
Dosage form INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Substance MELPHALAN HYDROCHLORIDE
GPI-14 21101040102115
GPI class Evomela
GCN Seq No 076651
GCN 42355
HICL code 043793
Ingredient (HICL) Melphalan Hcl/Betadex Sbes
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1A
Therapeutic class — specific (HIC3) Antineoplastic - Alkylating Agents
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name EVOMELA 50 MG VIAL
FDB brand name Evomela
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 72893-001-01 — 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 → 72893-0001-01. 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 Alkylating Drug class.

Pharmacologic class Alkylating Drug
Drug family (ATC) Nitrogen mustard analogues
How it works Alkylating Activity
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

LabelerAcrotech Biopharma Inc
Application holderACROTECH BIOPHARMA INC
FDA applicationNDA207155 (NDA)
Labeler code72893
First marketedMar 2016
Product typeHuman Prescription Drug
Portfolio8 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 EVOMELA 50 MG VIAL Ingredient Melphalan Hcl/Betadex Sbes
📗 Our plain-language guide HelloPharmacist
  • Melphalan injection is a chemotherapy drug used to treat multiple myeloma, a cancer of the plasma cells in the bone marrow. Evomela, one of the brand-name forms, is specifically ap...
  • What exactly is melphalan injection used for?
  • Most people receiving melphalan injection experience nausea, diarrhea, fatigue, and mouth sores — your team will give you medications to help manage these. Your blood cell counts w...
  • What side effects should I expect, and which ones should make me call the doctor?
📖 Read our full Melphalan Injection guide →
1
Nutrient depletion considerations

Melphalan may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Melphalan nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
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.

  • 2700 mg / 10 mL UNII 2PP9364507
    A modified form of beta-cyclodextrin, a natural sugar-like molecule. It helps dissolve and stabilize drugs in liquid medicines and improves how well the body absorbs certain medications.

1 inactive ingredient 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.

💲 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 · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J9246 $18.044 / J9246 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)72893-001-01
11-digit billing NDC72893-0001-01
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ9246
DescriptorInjection, melphalan (evomela), 1 mg
Billing units / pkg50 units
Crosswalk sourceCMS ASP NDC-HCPCS Crosswalk
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
Melphalan hydrochloride 23155-0355-41 Heritage 1 kit — AP FDA listed —
Melphalan Hydrochloride 25021-0258-61 Sagent 1 kit — AP FDA listed —
Melphalan Hydrochloride 31722-0362-31 Camber 1 kit — AP FDA listed —
Melphalan Hydrochloride 43598-0392-48 Dr.Reddy's 1 kit — AP FDA listed —
Melphalan hydrochloride 54288-0109-02 BPI 1 kit — AP FDA listed —
Melphalan 63323-0760-20 Fresenius 1 kit — AP FDA listed —
Melphalan Hydrochloride 67184-0618-02 Qilu 1 kit — AP FDA listed —
Melphalan Hydrochloride 67457-0195-01 Mylan 1 kit — AP FDA listed —
Melphalan hydrochloride 68083-0259-01 Gland 1 kit — AP FDA listed —
Melphalan hydrochloride 71288-0132-90 Meitheal 1 kit — AP FDA listed —
Melphalan hydrochloride 72266-0128-01 Fosun 1 kit — AP FDA listed —
Evomela 50 mg/10mLthis 72893-0001-01 Acrotech 1 vial — — FDA listed —
Hepzato Kit 75833-0601-01 Delcath 1 kit — — FDA listed —
Melphalan Hydrochloride 75907-0112-11 Dr.Reddy's 1 kit — AP FDA listed —
Melphalan Hydrochloride 83634-0202-61 Avenacy 1 kit — AP FDA listed —
Melphalan Hydrochloride 84679-0001-01 Arthur 1 kit — AP FDA listed —
About this product: this is the brand-name version. Some generic versions are approved by the FDA, but we could not confirm current pharmacy availability from our pricing/market data.
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

🏛️
2016
First FDA approval
Mar 2016
📍
2026
Currently FDA-listed
10 years listed
🛡️
2034
Latest patent/protection listed
not a guaranteed launch date
🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Jan 2034. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Mar 10, 2016 RLD RS ⏳ ~7.4 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 10940128 — method of use (U-3086)
US 11020363 — drug product
US 10864183 — drug product
US 10040872 — drug product
US 9200088 — drug product
US 9493582 — drug product
US 8410077 — drug product
2016 2018 2020 2022 2024 2026 2028 2030 2032 2034
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 (7)
PatentTypeUse codeExpires
US 10940128 ↗ Method of use U-3086 Jun 14, 2030
US 11020363 ↗ Drug product — May 28, 2030
US 10864183 ↗ Drug product — May 28, 2030
US 10040872 ↗ Drug product — Jan 30, 2034
US 9200088 ↗ Drug product — Mar 13, 2029
US 9493582 ↗ Drug product — Feb 27, 2033
US 8410077 ↗ Drug product — Mar 13, 2029
Common questions
Is there a generic version of EVOMELA 50 MG VIAL?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for EVOMELA 50 MG VIAL. 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.

🔬 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 EVOMELA (this brand).

Top reported reactions

Plasma Cell Myeloma1,274
Febrile Neutropenia1,217
Neutropenia1,114
Mucosal Inflammation1,097
Pyrexia1,060
Pneumonia1,055
Thrombocytopenia1,043

Age at onset

Neonate34
Infant153
Child671
Adolescent187
Adult2,015
Elderly1,127

Reporter sex

22,618 reports
Male · 56%
Female · 42%
Unknown · 2%

Serious outcomes

Hospitalization6,500
Death5,186
Life-threatening1,862
Disabling356
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 1,961 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
72893-0001-01 You're viewing this 1 VIAL in 1 CARTON (72893-001-01) / 20 mL in 1 VIAL 2016-03-31 Active

🧭 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) — 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 FDA registers it as 72893-001-01, 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: 72893-0001-01, written without dashes as 72893000101. 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 72893-0001-01, the first segment (72893) is the labeler code FDA assigned to Acrotech Biopharma Inc; the middle segment (0001) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (01) 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 Acrotech Biopharma Inc. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Acrotech Biopharma 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 J9246 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 🎯 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 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🚨 Boxed Warning 205 words ▾

WARNING: SEVERE BONE MARROW SUPPRESSION, HYPERSENSITIVITY, and LEUKEMOGENICITY Severe bone marrow suppression with resulting infection or bleeding may occur. Controlled trials comparing intravenous (IV) melphalan to oral melphalan have shown more myelosuppression with the IV formulation. Monitor hematologic laboratory parameters. [see Warnings and Precautions ( 5.1 )] Hypersensitivity reactions, including anaphylaxis, have occurred in approximately 2% of patients who received the IV formulation of melphalan.

Discontinue treatment with Evomela for serious hypersensitivity reactions. [see Warnings and Precautions ( 5.4 )] Melphalan produces chromosomal aberrations in vitro and in vivo. Evomela should be considered potentially leukemogenic in humans. [see Warnings and Precautions ( 5.5 )] WARNING: SEVERE BONE MARROW SUPPRESSION, HYPERSENSITIVITY, AND LEUKEMOGENICITY See full prescribing information for complete boxed warning. Severe bone marrow suppression with resulting infection or bleeding may occur.

Controlled trials comparing intravenous (IV) melphalan to oral melphalan have shown more myelosuppression with the IV formulation. Monitor hematologic laboratory parameters. ( 5.1 ) Hypersensitivity reactions, including anaphylaxis, have occurred in approximately 2% of patients who received the IV formulation of melphalan.

Discontinue treatment with Evomela for serious hypersensitivity reactions. ( 5.4 ) Melphalan produces chromosomal aberrations in vitro and in vivo . Evomela should be considered potentially leukemogenic in humans.

( 5.5 )

🎯 Indications and Usage 58 words ▾

1 INDICATIONS AND USAGE Evomela is an alkylating drug indicated for use as a high-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation in patients with multiple myeloma. ( 1.1 )

1.1Multiple Myeloma-Conditioning Treatment Evomela is indicated for use as a high-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation in patients with multiple myeloma.

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION For Conditioning Treatment , the recommended dose of Evomela is 100 mg/m 2 /day administered over 30 minutes by intravenous infusion for 2 consecutive days (Day -3 and Day -2) prior to autologous stem cell transplantation (ASCT, Day 0). ( 2.1 )

2.1Recommended Dosage for Conditioning Treatment The recommended dose of Evomela for conditioning treatment is 100 mg/m 2 /day administered over 30 minutes by intravenous infusion for 2 consecutive days (Day -3 and Day -2) prior to autologous stem cell transplantation (ASCT, Day 0). For patients who weigh more than 130% of their ideal body weight, body surface area should be calculated based on adjusted ideal body weight. Administer prophylactic antiemetics [see Warnings and Precautions ( 5.2 )] .

2.2Preparation and Administration Evomela is a hazardous drug. Follow applicable special handling and disposal procedures 1 . Evomela is light sensitive.

Retain in original carton until use. Do not mix Evomela with other melphalan hydrochloride for injection drug products. Reconstitution and Infusion Instructions: 1.

Use 0.9% Sodium Chloride Injection, USP (8.6 mL as directed) to reconstitute Evomela and make a 50 mg/10 mL (5 mg/ mL) nominal concentration of melphalan. The reconstituted Evomela drug product is stable for 24 hours at refrigerated temperature (5 o C) without any precipitation due to the high solubility. The reconstituted Evomela drug product is stable for 1 hour at room temperature.

2. Calculate the required volume of Evomela needed for a patient’s dose and withdraw that volume from the vial(s). 3.

Add the required volume of Evomela to the appropriate volume of 0.9% Sodium Chloride Injection, USP to a final concentration of 0.45 mg/mL. The Evomela admixture solution is stable for 4 hours at room temperature in addition to the 1 hour following reconstitution. 4.

Infuse over 30 minutes via an injection port or central venous catheter. Evomela may cause local tissue damage should extravasation occur. Do not administer by direct injection into a peripheral vein.

Administer Evomela by injecting slowly into a fast-running IV infusion via a central venous access line. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

💊 Dosage Forms and Strengths 61 words ▾

3 DOSAGE FORMS AND STRENGTHS For injection: 50 mg, white to off-white lyophilized powder in single-dose vial for reconstitution (after reconstitution the solution is clear and colorless to light yellow). Each vial contains 50 mg melphalan free base equivalent to 56 mg melphalan hydrochloride. For Injection: 50 mg per vial, lyophilized powder in a single-dose vial for reconstitution. ( 3 )

⛔ Contraindications 16 words ▾

4 CONTRAINDICATIONS History of serious allergic reaction to melphalan. History of serious allergic reaction to melphalan

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS Gastrointestinal toxicity: Nausea, vomiting, diarrhea or oral mucositis may occur; provide supportive care using antiemetic and antidiarrheal medications as needed. ( 2.1 , 5.2 ) Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus and to use effective contraception.

( 5.6 , 8.1 , 8.3 ) Infertility: Melphalan may cause ovarian function suppression or testicular suppression. ( 5.7 )

5.1Bone Marrow Suppression For patients receiving Evomela as part of a conditioning regimen, myeloablation occurs in all patients. Do not begin the conditioning regimen if a stem cell product is not available for rescue. Monitor complete blood counts, provide supportive care for infections, anemia and thrombocytopenia until there is adequate hematopoietic recovery.

5.2Gastrointestinal Toxicity For patients receiving Evomela as part of a conditioning regimen, nausea, vomiting, mucositis, and diarrhea may occur in over 50% of patients. Use prophylactic antiemetic medication. Provide supportive care for nausea, vomiting, diarrhea, and mucositis.

The frequency of grade 3/4 mucositis in clinical studies was 13%. Provide nutritional support and analgesics for patients with severe mucositis. [see Dosage and Administration ( 2.1 ) and Adverse Reactions ( 6.1 )] .

5.3Hepatotoxicity Hepatic disorders ranging from abnormal liver function tests to clinical manifestations such as hepatitis and jaundice have been reported after treatment with melphalan. Hepatic veno-occlusive disease has also been reported. Monitor liver chemistries.

5.4Hypersensitivity Acute hypersensitivity reactions, including anaphylaxis, have occurred in approximately 2% of patients who received an intravenous formulation of melphalan. Symptoms may include urticaria, pruritus, edema, and skin rashes and, in some patients, tachycardia, bronchospasm, dyspnea, and hypotension. Discontinue treatment with Evomela for serious hypersensitivity reactions.

5.5Secondary Malignancies Melphalan has been shown to cause chromatid or chromosome damage in humans. Secondary malignancies such as myeloproliferative syndrome or acute leukemia have been reported in multiple myeloma patients treated with melphalan-containing chemotherapy regimens. The potential benefit of Evomela therapy must be considered against the possible risk of the induction of a secondary malignancy.

5.6Embryo-Fetal Toxicity Based on its mechanism of action, Evomela can cause fetal harm when administered to a pregnant woman. Melphalan is genotoxic, targets actively dividing cells, and was embryolethal and teratogenic in rats. Advise pregnant women of the potential risk to a fetus.

Advise females of reproductive potential to use effective contraception during treatment with Evomela and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Evomela and for 3 months after the last dose [see Use in Specific Populations ( 8.1 , 8.3 )] .

5.7Infertility Melphalan-based chemotherapy regimens have been reported to cause suppression of ovarian function in premenopausal women, resulting in persistent amenorrhea in approximately 9% of patients. Reversible or irreversible testicular suppression has also been reported [see Use in Specific Populations ( 8.3 )].

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS Most common adverse reactions observed in at least 50% of patients treated with Evomela are neutrophil count decreased, white blood cell count decreased, lymphocyte count decreased, platelet count decreased, diarrhea, nausea, fatigue, hypokalemia, anemia, and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Acrotech Biopharma Inc. at 1-888-292-9617 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch The following serious adverse reactions are described in more detail in other sections of the prescribing information. • Bone Marrow Suppression [see Warnings and Precautions ( 5.1 )] • Gastrointestinal Toxicity [see Warnings and Precautions ( 5.2 )] • Hepatotoxicity [see Warnings and Precautions ( 5.3 )] • Hypersensitivity [see Warnings and Precautions ( 5.4 )] • Secondary Malignancies [see Warnings and Precautions ( 5.5 )]

6.1Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of Evomela may not reflect the rates observed in practice. The most common adverse reactions observed in at least 50% of patients with multiple myeloma treated with Evomela were neutrophil count decreased, white blood cell count decreased, lymphocyte count decreased, platelet count decreased, diarrhea, nausea, fatigue, hypokalemia, anemia, and vomiting. Myeloablative Conditioning in Multiple Myeloma Patients Undergoing ASCT The safety of Evomela was evaluated in 61 patients with multiple myeloma in a single arm clinical trial in which patients were administered Evomela at a dosage of 100 mg/m 2 /day administered over ~30 minutes (range: 24-48 minutes) by intravenous (IV) infusion for 2 consecutive days (Day -3 and Day -2) prior to autologous stem cell transplant (ASCT, Day 0). [see Clinical Studies ( 14.1 )].

Table 1 summarizes the adverse reactions from the single-arm trial in patients with multiple myeloma. Severe myelosuppression is expected and these adverse reactions are not listed below. Table 1 Non-hematologic Adverse Reactions in≥ 25% of Patients with Multiple Myeloma Who Received Evomela Conditioning for ASCT Adverse Reactions Number (%) of Patients (N=61) All Grades Grade 3or 4 All Adverse Reactions 61 61 Diarrhea 57 (93%) 2 (3%) Nausea 55 (90%) 1 (2%) Fatigue 47 (77%) 1 (2%) Hypokalemia 45 (74%) 17 (28%) Vomiting 39 (64%) 0 (0%) Hypophosphatemia 30 (49%) 29 (2%) Decreased Appetite 30 (49%) 0 (0%) Pyrexia 29 (48%) 2 (3%) Constipation 29 (48%) 0 (0%) Febrile Neutropenia 25 (41%) 17 (28%) Mucosal Inflammation 23 (38%) 6 (10%) Dizziness 23 (38%) 0 (0%) Edema Peripheral 20 (33%) 0 (0%) Stomatitis 17 (28%) 3 (5%) Abdominal Pain 17 (28%) 0 (0%) Dysgeusia 17 (28%) 0 (0%) Dyspepsia 16 (26%) 0 (0%) Serious Adverse Reactions Twelve (20%) patients experienced a treatment emergent serious adverse reaction while on study.

The most common serious adverse reactions (>1 patient, 1.6%) were pyrexia, hematochezia, febrile neutropenia, and renal failure. Treatment-related serious adverse reactions reported in >1 patient were pyrexia (n=2, 3%), febrile neutropenia (n=2, 3%), and hematochezia (n=2, 3%).

🔄 Drug Interactions 51 words ▾

7 DRUG INTERACTIONS No formal drug interaction studies have been conducted. The development of severe renal impairment has been reported in patients treated with a single dose of intravenous melphalan 140-250 mg/m 2 followed by standard oral doses of cyclosporine. Intravenous melphalan may also reduce the threshold for BCNU lung toxicity.

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed ( 8.2 )

8.1Pregnancy Risk Summary Based on its mechanism of action, Evomela can cause fetal harm when administered to a pregnant woman, including teratogenicity and/or embryo-fetal lethality [see Clinical Pharmacology ( 12.1 )] . Melphalan is a genotoxic drug and can cause chromatid or chromosome damage in humans [see Nonclinical Toxicology ( 13.1 )] . In animal studies, melphalan was embryolethal and teratogenic in rats at doses below the recommended clinical doses [see Data] .

Advise a pregnant woman of the potential risk to a fetus.. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.

Data Animal Data Adequate animal studies have not been conducted with intravenous melphalan. Melphalan was embryolethal and teratogenic in rats following oral administration of 6 to 18 mg/m 2 /day for 10 days (0.06 to 0.18 times the highest recommended clinical dose of 100 mg/m 2 /day) and intraperitoneal administration of 18 mg/m 2 (0.18 times the highest recommended clinical dose). Malformations resulting from melphalan administration included alterations of the brain (underdevelopment, deformation, meningocele, and encephalocele) and eye (anophthalmia and microphthalmos), reduction of the mandible and tail, and hepatocele (exomphaly).

8.2Lactation Risk Summary It is not known whether melphalan is present in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing children from melphalan, breastfeeding is not recommended during treatment with Evomela and for one week after the last dose.

8.3Females and Males of Reproductive Potential Evomela can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Contraception Females Advise females of reproductive potential to use effective contraception during treatment with Evomela and for 6 months after the last dose. Males Evomela administration may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities.

Advise males with female partners of reproductive potential to use effective contraception during treatment with Evomela and for 3 months after the last dose [ see Nonclinical Toxicology ( 13.1 )]. Infertility Females Melphalan causes suppression of ovarian function in premenopausal women, resulting in amenorrhea in a significant number of patients. Males Reversible and irreversible testicular suppression has been reported in male patients after administration of melphalan.

8.4Pediatric Use Pediatric patients were not included in clinical trials. Safety and effectiveness have not been established in pediatric patients.

8.5Geriatric Use Of the total number of subjects in the single-arm pivotal study of Evomela, 30% were 65 and over, but no patients were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. A greater incidence of engraftment syndrome was observed in older patients; 7% (3 of 43) of patients younger than 65 years old versus 28% (5 of 18) of patients 65 years old and over.

🤰 Pregnancy 214 words ▾

8.1Pregnancy Risk Summary Based on its mechanism of action, Evomela can cause fetal harm when administered to a pregnant woman, including teratogenicity and/or embryo-fetal lethality [see Clinical Pharmacology ( 12.1 )] . Melphalan is a genotoxic drug and can cause chromatid or chromosome damage in humans [see Nonclinical Toxicology ( 13.1 )] . In animal studies, melphalan was embryolethal and teratogenic in rats at doses below the recommended clinical doses [see Data] .

Advise a pregnant woman of the potential risk to a fetus.. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.

Data Animal Data Adequate animal studies have not been conducted with intravenous melphalan. Melphalan was embryolethal and teratogenic in rats following oral administration of 6 to 18 mg/m 2 /day for 10 days (0.06 to 0.18 times the highest recommended clinical dose of 100 mg/m 2 /day) and intraperitoneal administration of 18 mg/m 2 (0.18 times the highest recommended clinical dose). Malformations resulting from melphalan administration included alterations of the brain (underdevelopment, deformation, meningocele, and encephalocele) and eye (anophthalmia and microphthalmos), reduction of the mandible and tail, and hepatocele (exomphaly).

🧒 Pediatric Use 21 words ▾

8.4Pediatric Use Pediatric patients were not included in clinical trials. Safety and effectiveness have not been established in pediatric patients.

🆘 Overdosage 185 words ▾

10 OVERDOSAGE Overdoses resulting in death have been reported with melphalan. Overdoses, including doses up to 290 mg/m 2 , have produced the following symptoms: severe nausea and vomiting, decreased consciousness, convulsions, muscular paralysis, and cholinomimetic effects. Severe mucositis, stomatitis, colitis, diarrhea, and hemorrhage of the gastrointestinal tract occur at high doses (>100 mg/m 2 ).

Elevations in liver enzymes and veno-occlusive disease occur infrequently. Significant hyponatremia, caused by an associated inappropriate secretion of ADH syndrome, has been observed. Nephrotoxicity and adult respiratory distress syndrome have been reported rarely.

The principal toxic effect is bone marrow suppression leading to leucopenia, thrombocytopenia and anemia. Hematologic parameters should be closely followed for 3 to 6 weeks. An uncontrolled study suggests that administration of autologous bone marrow or hematopoietic growth factors (i.e., sargramostim, filgrastim) may shorten the period of pancytopenia.

General supportive measures together with appropriate blood transfusions and antibiotics should be instituted as deemed necessary by the physician. This drug is not removed from plasma to any significant degree by hemodialysis or hemoperfusion. A pediatric patient survived a 254 mg/m 2 overdose treated with standard supportive care.

🧬 Clinical Pharmacology ~1 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Melphalan is an alkylating agent of the bischloroethylamine type. As a result, its cytotoxicity appears to be related to the extent of its interstrand cross-linking with DNA, probably by binding at the N 7 position of guanine. Like other bifunctional alkylating agents, it is active against both resting and rapidly dividing tumor cells.

12.2Pharmacodynamics The peak mean heart rate increased 20 bpm from baseline following melphalan 100 mg/m 2 for 2 consecutive days in multiple myeloma patients undergoing autologous stem cell transplantation. Cardiac Electrophysiology No large mean increase in QTc (i.e. > 20 ms) was detected following melphalan 100 mg/m 2 .

12.3Pharmacokinetics Mean (± SD) peak plasma concentrations and AUC 0-inf were 5.8 ± 1.5 mcg/mL and 451 ± 109 mcg*min/mL, respectively, following administration of melphalan 100 mg/m 2 in multiple myeloma patients. Distribution The volume of distribution of melphalan ranges from approximately 35.5 to 185.7 L/m 2 . Melphalan penetrates into cerebrospinal fluid (CSF).

Protein binding of melphalan ranges from approximately 50% to 90%, primarily to serum albumin (40% to 60%) and to a lesser extent to α1-acid glycoprotein (20%). Approximately 30% of melphalan is (covalently) irreversibly bound to plasma proteins. Elimination Melphalan terminal elimination half-life is approximately 75 minutes.

Average total body clearance (CL) ranges from approximately 250 to 325 mL/min/m 2 . Metabolism Melphalan primarily undergoes chemical hydrolysis to inactive metabolites. Excretion Mean values of melphalan excreted in urine range from 5.8% to 21.3%.

Specific Populations Patient Body Weight Melphalan clearance changes with ideal body weight (IBW), which decreased by 28% and increased by 31% with IBW of 45 kg and 100 kg compared to 70 kg IBW, respectively. Renal Impairment A decrease in estimated creatinine CL from 100 mL/min to 30 mL/min results in 28.2% reduction in CL for a typical person with an IBW of 70 kg.

🧬 Mechanism of Action 57 words ▾

12.1Mechanism of Action Melphalan is an alkylating agent of the bischloroethylamine type. As a result, its cytotoxicity appears to be related to the extent of its interstrand cross-linking with DNA, probably by binding at the N 7 position of guanine. Like other bifunctional alkylating agents, it is active against both resting and rapidly dividing tumor cells.

📦 How Supplied / Storage and Handling 120 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Evomela is supplied in a single carton containing one (1) vial. Each 50 mg vial contains a white to off- white lyophilized powder in single-dose vial for reconstitution (after reconstitution the solution is clear and coloress to light yellow). Each vial contains 50 mg melphalan free base equivalent to 56 mg melphalan hydrochloride.

NDC 72893-001-01: Individual carton of Evomela single-dose vial containing 50 mg melphalan free base. Storage and Handling Store Evomela at room temperature 25°C (77°F). Temperature excursions are permitted between 15- 30°C (59-86°F). [see USP Controlled Room Temperature] Evomela is light sensitive.

Retain in original carton until use. Melphalan is a hazardous drug. Follow applicable special handling and disposal procedures.

1

📋 Description 136 words ▾

11 DESCRIPTION Evomela contains melphalan hydrochloride, an alkylating drug, as the active ingredient. The chemical name of melphalan hydrochloride is 4-[bis(2-chloroethyl)amino]-L-phenylalanine hydrochloride. Its molecular formula is C 13 H 18 Cl 2 N 2 O 2 • HCl and the molecular weight is 341.67.

The structural formula is: Melphalan hydrochloride is a white to off-white powder, with a melting range of 199°C − 201°C. It is practically insoluble in water, but freely soluble in 1N HCl and methanol. Evomela (melphalan) for injection is supplied as a sterile white to off-white lyophilized powder in a single-dose vial for intravenous use.

Each vial contains 50 mg melphalan free base equivalent to 56 mg melphalan hydrochloride and 2700 mg Betadex Sulfobutyl Ether Sodium, NF. Sodium hydroxide and if necessary, hydrochloric acid are added as a pH adjuster. melphalan structure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Advise patients or their caregivers of the following: Low Blood Cell Counts • To report any signs or symptoms of thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia. Inform patients of the need for routine blood counts [see Warnings and Precautions ( 5.1 )] .

Mucositis • Inform patients of the signs and symptoms of mucositis. Instruct patients on ways to reduce the risk of its development, and on ways to maintain nutrition and control discomfort if it occurs [see Warnings and Precautions ( 5.2 )] . Nausea, Vomiting and Diarrhea • To report symptoms of nausea, vomiting and diarrhea, so that appropriate antiemetic and/or antidiarrheal medications can be administered [see Warnings and Precautions ( 5.2 )] .

Allergic Reactions • To immediately report symptoms of hypersensitivity reactions including changes involving the skin, breathing or heart rate, so that antihistamine or corticosteroid therapy can be administered [see Warnings and Precautions ( 5.4 )] . Secondary cancers • To understand the potential long-term risks related to secondary malignancy [see Warnings and Precautions ( 5.5 )] . Embryo-Fetal Toxicity • Advise pregnant women of the potential risk to a fetus [see Warnings and Precautions ( 5.6 ) and Use in Specific Populations ( 8.1 )] . • Advise females of reproductive potential to use effective contraception during treatment with Evomela and for 6 months after the last dose.

Advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking Evomela [see Warnings and Precautions ( 5.6 ) and Use in Specific Populations ( 8.1 , 8.3 )] . • Inform both females and males of reproductive potential about the risk for infertility [see Warnings and Precautions ( 5.7 ) and Use in Specific Populations ( 8.3 )] . • Advise males with female partners of reproductive potential to use effective contraception during treatment with Evomela and for 3 months after the last dose [see Use in Specific Populations ( 8.3 )] .

Lactation • Advise women not to breastfeed during treatment with Evomela and for one week after the last dose [see Use in Specific Populations ( 8.2 )] . Manufacturer by: Cenexi Laboratories Thissen S.A Braine I’Alleud, 1420, Belgium or Manufactured by: Baxter Oncology GmbH Hale 33790 Germany Manufactured for: Acrotech Biopharma Inc. East Windsor, NJ 08520 1-888 -292-9617

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 72888-0510-01 · Advagen 72893-0002-01 · Acrotech →
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.