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IVRA melphalan HCl 90 mg/mL Injection, Solution — NDC 60505-6414-01 package photo

IVRA melphalan HCl 90 mg/mL Injection, Solution

by Apotex Corp · 1 VIAL, MULTI-DOSE in 1 CARTON (60505-6414-1) / 3 mL in 1 VIAL, MULTI-DOSE
NDC 60505-6414-01
🏷️ FDA NDC (as labeled) 60505-6414-1 billing pads the package segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced Sep 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) 60505-6414-1
Product NDC 60505-6414
11-digit billing NDC 60505641401
NCPDP billing unit ML — per mL (volume)
Application # NDA217110
SPL Set ID c23e868a-dc62-2181-5099-76c9226602b2
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 2025-05-09
Route INTRAVENOUS
Dosage form INJECTION, SOLUTION
Substance MELPHALAN HYDROCHLORIDE
GCN Seq No 085201
GCN 54621
HICL code 003895
Ingredient (HICL) Melphalan Hcl
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 IVRA 90 MG/ML VIAL
FDB brand name Ivra
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 60505-6414-1 — a 5-4-1 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 package segment → 60505-6414-01. 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.

🏭 Manufacturer & labeler

LabelerApotex Corp
Application holderAPOTEX INC
FDA applicationNDA217110 (NDA)
Labeler code60505
First marketedMay 2025
Product typeHuman Prescription Drug
Portfolio53 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 IVRA 90 MG/ML VIAL Ingredient Melphalan Hcl
📗 Our plain-language guide HelloPharmacist
  • Melphalan is a chemotherapy drug used specifically for multiple myeloma — a cancer of certain immune cells in the bone marrow. Depending on which product you're receiving, it may b...
  • What exactly is melphalan being used for in my case?
  • Melphalan works partly by suppressing your bone marrow — the place where your body makes blood cells. That means your white blood cells (which fight infection), platelets (which st...
  • Why do I need so many blood tests during treatment?
📖 Read our full Melphalan guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
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.

  • UNII QTT17582CB
    A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
  • 5 mg / 1 mL UNII AAO1P0WSXJ
    Monothioglycerol is a clear liquid derived from glycerin with a sulfur-containing group added. It works as an antioxidant and reducing agent in medicines, helping prevent degradation of active ingredients during storage.
  • UNII B697894SGQ
    Polyethylene glycol 400 is a clear, thick liquid made from petroleum-derived polymers. It acts as a solvent and humectant in medicines, helping dissolve active ingredients and retain moisture in the formulation.
  • 170 mg / 1 mL UNII 6DC9Q167V3
    Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
  • UNII 451W47IQ8X
    Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
  • 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.
  • 0.5 mg / 1 mL UNII 1HTE449DGZ
    A chelating agent derived from ethylenediamine tetraacetic acid (EDTA) chemistry, tetraxetan binds metal ions in formulations. It's used as a stabilizer to prevent oxidation and degradation of active ingredients.
  • 0.025 mg / 1 mL 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.

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

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

Inactive ingredient FAQ

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

💲 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.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Ivra 90 mg/mLthis 60505-6414-01 Apotex 1 vial — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
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

🏛️
2023
First FDA approval
Aug 2023
📍
2026
Currently FDA-listed
3 years listed
🛡️
2036
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Jun 2036. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Aug 18, 2023 RLD RS ⏳ ~9.8 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 10537520 — drug product
2023 2025 2027 2029 2031 2033 2035
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 (1)
PatentTypeUse codeExpires
US 10537520 ↗ Drug product — Jun 29, 2036
Common questions
Is there a generic version of IVRA 90 MG/ML VIAL?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for IVRA 90 MG/ML VIAL. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Jun 2036 — an estimate, not a guaranteed launch date.
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.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
60505-6414-01 You're viewing this 1 VIAL, MULTI-DOSE in 1 CARTON (60505-6414-1) / 3 mL in 1 VIAL, MULTI-DOSE 2025-05-09 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 — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 60505-6414-1, 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: 60505-6414-01, written without dashes as 60505641401. 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 60505-6414-01, the first segment (60505) is the labeler code FDA assigned to Apotex Corp; the middle segment (6414) 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 Apotex Corp. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Apotex Corp is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 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 🧓 Geriatric 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 melphalan to oral melphalan have shown more myelosuppression with the intravenous 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 intravenous formulation of melphalan. Discontinue treatment with IVRA for serious hypersensitivity reactions [see Warnings and Precautions ( 5.4 )] . Melphalan produces chromosomal aberrations in vitro and in vivo .

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

Discontinue treatment with IVRA for serious hypersensitivity reactions ( 5.4 ). Melphalan produces chromosomal aberrations in vitro and in vivo. IVRA should be considered potentially leukemogenic in humans ( 5.5 ).

🎯 Indications and Usage 50 words ▾

1 INDICATIONS AND USAGE Multiple Myeloma-Palliative Treatment IVRA is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate. IVRA is an alkylating drug indicated for palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate. ( 1 )

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION Recommended dosage is 16 mg/m 2 administered intravenously over 15 to 20 minutes at 2-week intervals for 4 doses, then, after adequate recovery from toxicity, at 4-week intervals. ( 2.2 ) See full prescribing information for preparation and administration instructions. ( 2.3 )

2.1Recommended Dosage The recommended dosage is 16 mg/m 2 intravenously over 15 to 20 minutes at 2-week intervals for 4 doses, then at 4-week intervals until unacceptable toxicity. Administer prophylactic antiemetics [see Warnings and Precautions ( 5.2 )].

2.2Dosage Modifications for Adverse Reactions See Table 1 for dosage modifications for adverse reactions related to bone marrow suppression [see Warnings and Precautions ( 5.1 )]. Table 1. Dosage Modifications for Adverse Reaction: Bone Marrow Suppression Parameter Dosing Recommendations White Blood Cell Count (WBC/mm 3 ) Platelet Count (Per mcL) Greater than or equal to 4,000 Greater than or equal to 100,000 Continue full IVRA dose Greater than or equal to 3,000 Greater than or equal to 75,000 Reduce IVRA to 75% of full dose Greater than or equal to 2,000 Greater than or equal to 50,000 Reduce IVRA to 50% of full dose Less than 2,000 Less than 50,000 Withold IVRA

2.3Dosage Modifications for Renal Impairment Consider a dosage reduction of up to 50% in patients with renal insufficiency (BUN ≥30 mg/dL) [see Use in Specific Populations ( 8.6 )] .

2.4Preparation and Administration Preparation IVRA is a hazardous drug. Follow applicable special handling and disposal procedures 1 . Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration whenever solution and container permit.

If either occurs, do not use this product. IVRA is light sensitive. After first use, store the partially used vial refrigerated at 2°C to 8°C [36°F to 46°F] in the original carton for use within 28 days and then discard the remaining contents.

Retain vial in original carton until contents are used. Do not mix IVRA with other melphalan hydrochloride drug products. Dilution Calculate the required volume of IVRA needed for a patient’s dose and withdraw that volume from the vial(s).

Add the required volume of IVRA to the appropriate volume of 0.9% Sodium Chloride Injection to obtain a solution with a concentration not greater than 0.45 mg/mL. Immediately mix the contents of infusion vigorously by manual rotation. The diluted product is stable for 1 hour at room temperature.

Administration Infuse over 15 to 20 minutes via an injection port or central venous catheter. Complete administration within 60 minutes of dilution. IVRA may cause local tissue damage should extravasation occur.

Administer IVRA only by injecting slowly into a fast-running intravenous infusion via an injection port or, central venous access line.

💊 Dosage Forms and Strengths 35 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 90 mg/mL melphalan as a clear colorless to yellow solution in a multiple-dose vial for dilution. Injection : 90 mg/mL of melphalan in a multiple-dose vial. ( 3 )

⛔ Contraindications 35 words ▾

4 CONTRAINDICATIONS IVRA is contraindicated in patients with a history of severe hypersensitivity to melphalan. Reactions have included anaphylaxis [see Warnings and Precautions ( 5.4 )]. History of severe hypersensitivity to melphalan. ( 4 )

⚠️ Warnings and Cautions ~3 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. ( 5.2 ) Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of potential risk to fetus and to use effective contraception.

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

5.1Bone Marrow Suppression IVRA causes bone marrow suppression in most patients. Obtain complete blood counts with differential at the start of therapy and prior to each subsequent dose of IVRA. Withhold treatment for grade 3 thrombocytopenia and/ or leukopenia until blood counts have returned to grade 2 [see Dosage and Administration ( 2.2 )] . Consider dose adjustment on the basis of blood counts at the nadir and day of treatment.

5.2Gastrointestinal Toxicity Gastrointestinal disturbances such as nausea and vomiting, diarrhea, and oral ulceration can occur with melphalan treatment. Severe mucositis, stomatitis, colitis, diarrhea, and hemorrhage of the gastrointestinal tract occur at high doses (greater than 100 mg/m 2 6 times the recommended approved dose). Use prophylactic antiemetics [see Dosage and Administration ( 2.1 )].

Provide supportive care for nausea, vomiting, diarrhea, and mucositis.

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

5.4Hypersensitivity Acute hypersensitivity reactions including anaphylaxis were reported in 2.4% of 425 patients receiving melphalan injection for myeloma. These reactions were characterized by urticaria, pruritus, edema, skin rashes, and in some patients, tachycardia, bronchospasm, dyspnea, and hypotension. These patients appeared to respond to antihistamine and corticosteroid therapy.

If a hypersensitivity reaction occurs, intravenous or oral melphalan should not be readministered since hypersensitivity reactions have also been reported with oral melphalan. Cardiac arrest has also been reported in association with such reports. Discontinue treatment with IVRA for serious hypersensitivity reactions.

5.5Secondary Malignancies Melphalan has been shown to cause chromatid or chromosome damage in humans. Secondary malignancies, including acute nonlymphocytic leukemia, myeloproliferative syndrome, and carcinoma, have been reported in patients with cancer treated with alkylating agents (including melphalan). Some patients also received other chemotherapeutic agents or radiation therapy.

The potential benefits from melphalan therapy must be weighed on an individual basis against the possible risk of the induction of a second malignancy.

5.6Embryo-Fetal Toxicity Based on its mechanism of action, IVRA can cause fetal harm when administered to a pregnant woman. Melphalan is genotoxic, targets actively dividing cells, and was embryolethal and teratogenic in rats. While adequate animal studies have not been conducted with intravenous melphalan, oral (6 to 18 mg/m 2 /day for 10 days) and IP (18 mg/m 2 ) administration in rats was embryolethal and teratogenic.

Malformations resulting from melphalan included alterations of the brain (underdevelopment, deformation, meningocele, and encephalocele) and eye (anophthalmia and microphthalmos), reduction of the mandible and tail, as well as hepatocele (exomphaly). If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, advise a pregnant woman of the of potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with IVRA and for 6 months after the last dose.

Advise males with female partners of reproductive potent…

🤒 Adverse Reactions ~1 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: 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 )] Most common adverse reactions (≥50%) 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 Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . ­

6.1Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of melphalan 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 melphalan were neutrophil count decreased, white blood cell count decreased, lymphocyte count decreased, platelet count decreased, diarrhea, nausea, fatigue, hypokalemia, anemia, and vomiting. Palliative Treatment of Patients with Multiple Myeloma The safety of melphalan was evaluated in 295 patients with multiple myeloma in the randomized clinical trial [see Clinical Studies ( 14 )].

One hundred and ninety-five patients were administered intravenous melphalan at a dosage of 16 mg/m 2 q 2 weeks x 4 (over 6 weeks) followed by the same dose every 4 weeks. One hundred patients were administered oral melphalan at a dosage of 0.15 mg/kg/day x 7 followed by 0.05 mg/kg/day when WBC counts began to rise. Severe myelotoxicity (WBC ≤1,000 and/or platelets ≤25,000) was more common in the intravenous melphalan arm (28%) than in the oral melphalan arm (11%).

🔄 Drug Interactions 115 words ▾

7 DRUG INTERACTIONS

7.1Effect of Other Drugs on IVRA Cisplatin Concomitant use with cisplatin may alter melphalan clearance by inducing renal dysfunction. Consider intravenous IVRA dosage reduction in patients with renal insufficiency following concomitant use with cisplatin [see Dosage and Administration ( 2.2 )] .

7.2Effect of IVRA on Other Drugs BCNU Concomitant use with BCNU may reduce the threshold for lung toxicity. Monitor for increased lung toxicity.

7.3Cyclosporine Concomitant use with cyclosporine may increase the risk of developing severe renal failure [see Clinical Pharmacology ( 12.3 ) ]. Consider intravenous IVRA dosage reduction in patients with renal insufficiency following concomitant use with cyclosporine [see Dosage and Administration ( 2.2 )] .

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) Renal insufficiency (BUN ≥30 mg/dL): Consider dosage reduction ( 2.2 , 8.6 )

8.1Pregnancy Risk Summary Based on its mechanism of action and findings from animal studies, IVRA can cause fetal harm when administered to a pregnant woman. There are no available data on IVRA use in pregnant women to evaluate for a drug-associated risk. In rats, melphalan was embryolethal and teratogenic at doses lower than the highest recommended clinical dose (see Data).

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to the fetus. The background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 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 There are no data on the presence of melphalan in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with IVRA and for 1 week following the last dose.

8.3Females and Males of Reproductive Potential IVRA 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 IVRA and for 6 months after the last dose. Males Melphalan 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 IVRA 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 The safety and effectiveness of IVRA in pediatric patients have not been established.

8.5Geriatric Use Clinical studies of melphalan did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8.6Renal Impairment Consider a dosage reduction in patients with renal insufficiency receiving intravenous IVRA [see Dosage and Administration ( 2.2 )] . In one trial, increased bone marrow suppression was observed in patients with elevated BUN [see Clinical Pharmacology ( 12.3 )] .

🤰 Pregnancy 207 words ▾

8.1Pregnancy Risk Summary Based on its mechanism of action and findings from animal studies, IVRA can cause fetal harm when administered to a pregnant woman. There are no available data on IVRA use in pregnant women to evaluate for a drug-associated risk. In rats, melphalan was embryolethal and teratogenic at doses lower than the highest recommended clinical dose (see Data).

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to the fetus. The background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 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 16 words ▾

8.4Pediatric Use The safety and effectiveness of IVRA in pediatric patients have not been established.

🧓 Geriatric Use 83 words ▾

8.5Geriatric Use Clinical studies of melphalan did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

🆘 Overdosage 152 words ▾

10 OVERDOSAGE Overdoses resulting in death have been reported. Overdoses, including doses up to 290 mg/m 2 (18 times the recommended dose), 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 (greater than 100 mg/m 2 6 times the recommended dose).

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

The principal toxic effect is bone marrow suppression. In the event of an overdosage, monitor hematologic parameters for 3 to 6 weeks. 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.

🧬 Clinical Pharmacology ~2 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 Due to lack of information, melphalan exposure-response relationships and the time course of pharmacodynamic response are unknown.

12.3Pharmacokinetics The mean ±SD melphalan peak plasma concentration is 1.2 ± 0.4 following an intravenous dosage of 10 mg/m 2 (0.62 times the approved recommended dosage) and 2.8 ± 1.9 mcg/mL following an intravenous dosage of 20 mg/m 2 (1.25 times the approved recommended dosage) in myeloma patients. Distribution The melphalan steady-state volume of distribution is

0.5L/kg. Melphalan penetration into cerebrospinal fluid (CSF) is low. The mean melphalan plasma protein binding ranges from 53% to 92% with approximately 30% irreversible (covalent).

Serum albumin accounts for approximately 40% to 60% and α 1 -acid glycoprotein approximately 20% of the plasma protein binding. Elimination The melphalan elimination half-life is approximately 75 minutes. Mean total body melphalan clearance varied among studies, but typical values of approximately 7 to 9 mL/min/kg (250 to 325 mL/min/m 2 ) were observed.

Metabolism Melphalan primarily metabolized by hydrolysis to monohydroxymelphalan and dihydroxymelphalan, which are inactive. Excretion Following a radiolabeled dose of intravenous melphalan in 9 patients with cancer, the mean (± SD) excretion of melphalan over 24 hours was 13% ± 5.4% of the total dose. Specific Populations Patients with renal Impairment Although melphalan renal clearance appears to be low, one study reported an increase in the occurrence of severe leukopenia in patients with BUN levels ≥30 mg/dL after 10 weeks of therapy.

A 50% reduction in the IV melphalan dosage decreased the incidence of severe bone marrow suppression in the latter portion of this study. Drug Interaction Studies Cyclosporine Patients treated with a single dose of intravenous melphalan followed by standard oral doses of cyclosporine were reported to develop severe renal failure. Immunoglobulins Interactions between melphalan and immunoglobulins are negligible.

🧬 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 73 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied IVRA (melphalan) injection is a clear colorless to yellow solution supplied in a carton containing one 90 mg/mL amber glass multiple-dose vial for dilution. (NDC 60505-6414-1). Storage and Handling Store IVRA refrigerated at 2°C to 8°C (36°F to 46°F). IVRA is light sensitive. Retain in original carton when not in use. IVRA is a hazardous drug 1 . Follow special handling and disposal procedures 1 .

📋 Description 171 words ▾

11 DESCRIPTION IVRA contains melphalan which is an alkylating drug. The chemical name of melphalan hydrochloride is 4-[bis(2-chloroethyl)amino]-L-phenylalanine hydrochloride. The 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 to 201°C. It is practically insoluble in water, but freely soluble in 1N HCl and methanol. IVRA is supplied as a sterile, clear colorless to yellow solution in a multiple-dose vial for intravenous use.

Each mL contains 90 mg melphalan free base equivalent to 100.75 mg melphalan hydrochloride, 170 mg propylene glycol, 5 mg monothioglycerol, 0.5 mg (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid dihydrate), and 0.025 mL water for injection in polyethylene glycol 400. May contain hydrochloric acid and/or sodium hydroxide for pH adjustment. The pH of the drug product solution after dilution with 0.9% sodium chloride ranges from 2.4 - 3.5.

Each mL contains 90 mg melphalan free base equivalent to 100.75 mg melphalan hydrochloride.

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Low Blood Cell Counts Advise patients 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 )]. Allergic Reactions Advise patients 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 Malignancies Advise patients of 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 and for 6 months after treatment with IVRA. Advise males with female partners of reproductive potential to use effective contraception during treatment with IVRA and for 3 months after the last dose.

Advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking IVRA [see Warnings and Precautions ( 5.6 ) and Use in Specific Populations ( 8.1 )]. Inform females of reproductive potential about the risk for infertility. Advise males that reversible and irreversible testicular suppression have been reported [see Warnings and Precautions ( 5.7 )].

Advise women not to breastfeed during treatment with IVRA and for 1 week following the last dose [see Use in Specific Populations ( 8.2 )]. Manufactured by: AqVida GmbH 23942 Dassow Germany Manufactured for: Apotex Corp. Weston, Florida, USA 33326 Rev 1

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 60505-6411-00 · Apotex 60505-6420-06 · Apotex →
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.