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Doxorubicin Hydrochloride 2 mg/mL Injection, Powder, Lyophilized, For Solution

by Mylan Institutional LLC · 1 VIAL in 1 CARTON (67457-436-50) / 25 mL in 1 VIAL
NDC 67457-0436-50
🏷️ FDA NDC (as labeled) 67457-436-50 billing pads the product segment with a zero
Rx only Generic On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

⚠️
Other active recalls for Doxorubicin Hydrochloride (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class I · May 12, 2026 — Presence of Particulate matter: Particulate matter identified as glass. (SUN PHARMACEUTICAL INDUSTRIES INC) · FDA recall D-0580-2026
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 67457-436-50
Product NDC 67457-436
11-digit billing NDC 67457043650
NCPDP billing unit EA — each (per item)
RxCUI 1790095, 1790103
UNII 82F2G7BL4E
UPC 0367457478104
Application # ANDA200170
SPL Set ID 5f71f79a-4f14-472d-b982-e28c3ce8f972
Established class (EPC) Anthracycline Topoisomerase Inhibitor
Mechanism of action Topoisomerase Inhibitors
Chemical class Anthracyclines
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2014-02-27
Route INTRAVENOUS
Dosage form INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Substance DOXORUBICIN HYDROCHLORIDE
GPI-14 21200040102115
GPI class DOXOrubicin HCl
GCN Seq No 008818
GCN 38591
HICL code 003916
Ingredient (HICL) Doxorubicin Hcl
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1D
Therapeutic class — specific (HIC3) Antibiotic Antineoplastics
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name DOXORUBICIN 50 MG VIAL
FDB brand name Doxorubicin Hcl
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 67457-436-50 — 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 → 67457-0436-50. 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 Anthracycline Topoisomerase Inhibitor class.

Pharmacologic class Anthracycline Topoisomerase Inhibitor
Drug family (ATC) Anthracyclines and related substances
How it works Topoisomerase Inhibitors
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

LabelerMylan Institutional LLC
Application holderMYLAN LABORATORIES LTD
FDA applicationANDA200170 (ANDA)
Labeler code67457
First marketedFeb 2014
Product typeHuman Prescription Drug
Portfolio167 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 DOXORUBICIN 50 MG VIAL Ingredient Doxorubicin Hcl
📖 What it is MedlinePlus · NLM

Doxorubicin is used in combination with other medications to treat certain types of bladder, breast, lung, stomach, and ovarian cancer; Hodgkin's lymphoma (Hodgkin's disease) and non-Hodgkin's lymphoma (cancer that begins in the cells of the immune system); and certain types of leukemia (cancer of the white blood cells), including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML, ANLL). Doxorubicin is also used alone and in combination with other medications to treat certain types of thyroid cancer and certain types of soft tissue or bone sarcomas (cancer that forms in muscle...

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Doxorubicin is well-known for its potential to damage the heart muscle over time — a condition called cardiomyopathy. The higher the total amount you receive over your lifetime, th...
  • Why is my doctor monitoring my heart so closely while I'm on this drug?
  • It's a real but uncommon risk. A small number of people who receive doxorubicin — especially when combined with other DNA-damaging chemotherapy drugs or radiation — have gone on to...
  • I've heard this drug can cause leukemia later. Should I be worried?
📖 Read our full Doxorubicin guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
1
Nutrient depletion considerations

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

🧪 Full Doxorubicin 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 EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.

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 · J9000 $2.710 / J9000 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)67457-436-50
11-digit billing NDC67457-0436-50
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ9000
DescriptorInjection, doxorubicin hydrochloride, 10 mg
Billing units / pkg5 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
Doxorubicin Hydrochloride 2 mg/mL 00143-9093-01 Hikma 1 vial — — FDA listed —
Doxorubicin Hydrochloride 2 mg/mLthis 67457-0436-50 Mylan 1 vial — — FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 70121-1219-01 Amneal 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 49315-0008-03 Zydus 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 49315-0009-07 Zydus 1 vial — AB FDA listed —
DOXOrubicin Hydrochloride 2 mg/mL 62756-0826-40 Sun 1 vial — AP FDA listed —
DOXOrubicin Hydrochloride 2 mg/mL 62756-0827-40 Sun 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 68001-0345-26 BluePoint 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 16714-0742-01 NorthStar 1 vial — AB Discontinued —
Doxorubicin Hydrochloride 2 mg/mL 16714-0856-01 NorthStar 1 vial — AB Discontinued —
Doxorubicin Hydrochloride 2 mg/mL 00069-0343-02 Pfizer 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00143-9085-01 Hikma 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 63323-0883-05 Fresenius 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 68001-0492-36 BluePoint 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 68001-0704-26 BluePoint 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00069-0277-02 Pfizer 1 vial — AP FDA listed —
Doxorubicin hydrochloride 2 mg/mL 45963-0733-55 Actavis 1 vial — AP FDA listed —
Doxil 2 mg/mL 00338-0063-01 Baxter 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 68083-0248-01 Gland 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00069-1442-04 Pfizer 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00069-3358-25 Pfizer 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00069-4031-12 Pfizer 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00143-9084-01 Hikma 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00143-9090-01 Hikma 1 vial — AP FDA listed —
doxorubicin hydrochloride 2 mg/mL 62332-0810-10 Alembic 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 68083-0249-01 Gland 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00069-1542-20 Pfizer 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 47335-0049-40 Sun 1 vial — AB FDA listed —
Doxil 2 mg/mL 00338-9665-01 Baxter 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 68001-0703-36 BluePoint 1 vial — AB FDA listed —
doxorubicin hydrochloride 2 mg/mL 75907-0363-01 Dr. 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00069-0358-20 Pfizer 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00069-4205-05 Pfizer 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00143-9092-01 Hikma 1 vial — — FDA listed —
doxorubicin hydrochloride 2 mg/mL 46708-0810-10 Alembic 1 vial — AB FDA listed —
doxorubicin hydrochloride 2 mg/mL 62332-0525-25 Alembic 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 68001-0493-26 BluePoint 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 68001-0629-26 BluePoint 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 70748-0340-01 Lupin 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00069-0255-10 Pfizer 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00143-9086-01 Hikma 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00143-9087-01 Hikma 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 72603-0103-01 NorthStar 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 72603-0200-01 NorthStar 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00143-9091-01 Hikma 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 70710-1531-01 Zydus 1 vial — AB FDA listed —
doxorubicin hydrochloride 2 mg/mL 75907-0364-01 Dr. 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00069-5629-05 Pfizer 1 vial — AP FDA listed —
Doxorubicin Hydrochloride Liposome 2 mg/mL 25021-0263-10 Sagent 1 vial — AB FDA listed —
doxorubicin hydrochloride 2 mg/mL 46708-0525-25 Alembic 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 68083-0250-01 Gland 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 47335-0050-40 Sun 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 63323-0101-61 Fresenius 1 vial — AP FDA listed —
doxorubicin hydrochloride 2 mg/mL 25021-0207-25 Sagent 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00143-9088-01 Hikma 1 vial — AP FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 00143-9089-01 Hikma 1 vial — AP FDA listed —
doxorubicin hydrochloride, Liposomal 2 mg/mL 00338-9581-02 Baxter 1 vial — — FDA listed —
Doxil 2 mg/mL 00338-9667-01 Baxter 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 70710-1530-01 Zydus 1 vial — AB FDA listed —
Doxorubicin Hydrochloride 2 mg/mL 70748-0339-01 Lupin 1 vial — AB FDA listed —
doxorubicin hydrochloride 2 mg/mL 68001-0706-36 BluePoint 1 vial — AB FDA listed —
doxorubicin hydrochloride 2 mg/mL 68001-0707-26 BluePoint 1 vial — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & generic status

🏛️
2014
On the market since
Feb 2014
📍
2026
Currently FDA-listed
12 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

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

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
67457-0436-50 You're viewing this 1 VIAL in 1 CARTON (67457-436-50) / 25 mL in 1 VIAL 2014-02-27 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 — Not published for this NDC No photo available yet for this listing.
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 — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
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 67457-436-50, 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: 67457-0436-50, written without dashes as 67457043650. 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 67457-0436-50, the first segment (67457) is the labeler code FDA assigned to Mylan Institutional LLC; the middle segment (0436) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (50) 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 Mylan Institutional LLC. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Mylan Institutional LLC is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J9000 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 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🚨 Boxed Warning ~2 min read ▾

WARNING: CARDIOMYOPATHY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS, and SEVERE MYELOSUPPRESSION See full prescribing information for complete boxed warning. • Cardiomyopathy: Myocardial damage can occur with doxorubicin hydrochloride with incidences from 1% to 20% for cumulative doses from 300 mg/m 2 to 500 mg/m 2 when doxorubicin hydrochloride is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess left ventricular ejection fraction (LVEF) before and regularly during and after treatment with doxorubicin hydrochloride.

( 5.1 ). • Secondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including doxorubicin hydrochloride. ( 5.2 ). • Extravasation and Tissue Necrosis: Extravasation of doxorubicin hydrochloride can result in severe local tissue injury and necrosis requiring wide excision and skin grafting. Immediately terminate the drug, and apply ice to the affected area.

( 5.3 ). • Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur. ( 5.4 ). WARNING: CARDIOMYOPATHY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS and SEVERE MYELOSUPPRESSION • Cardiomyopathy: Myocardial damage, including acute left ventricular failure can occur with doxorubicin hydrochloride.

The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 1% to 20% for cumulative doses ranging from 300 mg/m 2 to 500 mg/m 2 when doxorubicin hydrochloride is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess LVEF before and regularly during and after treatment with doxorubicin hydrochloride [see Warnings and Precautions (5.1) ]. • Secondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including doxorubicin hydrochloride [see Warnings and Precautions (5.2) ]. • Extravasation and Tissue Necrosis: Extravasation of doxorubicin hydrochloride can result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting.

Immediately terminate the drug and apply ice to the affected area [see Warnings and Precautions (5.3) ]. • Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur [see Warnings and Precautions (5.4) ].

🎯 Indications and Usage 196 words ▾

1. INDICATIONS AND USAGE Doxorubicin hydrochloride, USP is an anthracycline topoisomerase II inhibitor indicated: • as a component of multiagent adjuvant chemotherapy for treatment of women with axillary lymph node involvement following resection of primary breast cancer ( 1.1 ). • for the treatment of: acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin lymphoma, Non-Hodgkin lymphoma, metastatic breast cancer, metastatic Wilms' tumor, metastatic neuroblastoma, metastatic soft tissue sarcoma, metastatic bone sarcomas, metastatic ovarian carcinoma, metastatic transitional cell bladder carcinoma, metastatic thyroid carcinoma, metastatic gastric carcinoma, metastatic bronchogenic carcinoma ( 1.2 ).

1.1Adjuvant Breast Cancer Doxorubicin hydrochloride, USP is indicated as a component of multi-agent adjuvant chemotherapy for treatment of women with axillary lymph node involvement following resection of primary breast cancer [see Clinical Studies (14) ] .

1.2Other Cancers Doxorubicin hydrochloride, USP is indicated for the treatment of • acute lymphoblastic leukemia • acute myeloblastic leukemia • Hodgkin lymphoma • non-Hodgkin lymphoma (NHL) • metastatic breast cancer • metastatic Wilms' tumor • metastatic neuroblastoma • metastatic soft tissue sarcoma • metastatic bone sarcoma • metastatic ovarian carcinoma • metastatic transitional cell bladder carcinoma • metastatic thyroid carcinoma • metastatic gastric carcinoma • metastatic bronchogenic carcinoma

⏱️ Dosage and Administration ~3 min read ▾

2. DOSAGE AND ADMINISTRATION • Single agent: 60 to 75 mg/m 2 given intravenously every 21 days ( 2.1 ). • In combination therapy: 40 to 75 mg/m 2 given intravenously every 21 to 28 days ( 2.1 ). • Discontinue doxorubicin hydrochloride in patients who develop signs or symptoms of cardiomyopathy ( 2.2 ). • Reduce dose in patients with hepatic impairment ( 2.2 ).

2.1Recommended Dose Adjuvant Breast Cancer The recommended dose of doxorubicin hydrochloride, USP is 60 mg/m 2 administered as an intravenous bolus on day 1 of each 21-day treatment cycle, in combination with cyclophosphamide, for a total of four cycles [see Clinical Studies (14) ]. Metastatic Disease, Leukemia, or Lymphoma • The recommended dose of doxorubicin hydrochloride, USP when used as a single agent is 60 to 75 mg/m 2 intravenously every 21 days. • The recommended dose of doxorubicin hydrochloride, USP, when administered in combination with other chemotherapy drugs, is 40 to 75 mg/m 2 intravenously every 21 to 28 days. • Consider use of the lower doxorubicin dose in the recommended dose range or longer intervals between cycles for heavily pretreated patients, elderly patients, or obese patients. • Cumulative doses above 550 mg/m 2 are associated with an increased risk of cardiomyopathy [see Warnings and Precautions (5.1) ].

2.2Dose Modifications Cardiac Impairment Discontinue doxorubicin in patients who develop signs or symptoms of cardiomyopathy. Hepatic Impairment Doxorubicin hydrochloride, USP is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C or serum bilirubin >5.0 mg/dL) [see Contraindications (4) ]. Decrease the dose of doxorubicin hydrochloride, USP in patients with elevated serum total bilirubin concentrations as follows: Serum bilirubin concentration Doxorubicin hydrochloride, USP Dose reduction 1.2 to 3 mg/dL 50 % 3.1 to 5 mg/dL 75 % greater than 5 mg/dL Do not initiate doxorubicin hydrochloride, USP Discontinue doxorubicin hydrochloride, USP [see Warnings and Precautions (5.5) and Use in Specific Populations (8.7) ]

2.3Preparation and Administration Preparation of Doxorubicin Hydrochloride for injection, USP Reconstitute doxorubicin hydrochloride for injection, USP with 0.9% Sodium Chloride Injection, USP to obtain a final concentration of 2 mg per mL as follows: • 5 mL 0.9% Sodium Chloride Injection, USP to reconstitute 10 mg doxorubicin hydrochloride, USP vial. • 25 mL 0.9% Sodium Chloride Injection, USP to reconstitute 50 mg doxorubicin hydrochloride, USP vial. Gently shake vial until the contents have dissolved. Protect reconstituted solution from light.

Administration Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard if the solution is discolored, cloudy, or contains particulate matter. Storage of vials of Doxorubicin hydrochloride for injection, USP following reconstitution under refrigerated conditions can result in the formation of a gelled product.

Place gelled product at room temperature [15 0 to 30 0 C (59 0 to 86 0 F)] for 2 to 4 hours to return the product to a slightly viscous, mobile solution. Administration by Intravenous Injection: • Administer doxorubicin hydrochloride, USP as an intravenous injection through a central intravenous line or a secure and free-flowing peripheral venous line containing 0.9% Sodium Chloride Injection, USP, 0.45% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP. • Administer doxorubicin hydrochloride, USP intravenously over 3 to 10 minutes.

Decrease the rate of doxorubicin hydrochloride, USP administration if erythematous streaking along the vein proximal to the site of infusion or facial flushing occur. Administration by Continuous Intravenous Infusion: Infuse only through a central catheter. Decrease the rate of doxorubicin hydrochloride, USP administration if erythematous streaking along the vein proximal to the site of infusion or facial flushing occur.…

💊 Dosage Forms and Strengths 43 words ▾

3. DOSAGE FORMS AND STRENGTHS • Doxorubicin hydrochloride for injection: Vials contain 10 mg and 50 mg as a lyophilized powder ( 3 ) Doxorubicin hydrochloride for injection, USP: Vials contain 10 mg and 50 mg doxorubicin hydrochloride as a red-orange lyophilized powder.

⛔ Contraindications 121 words ▾

4. CONTRAINDICATIONS • Severe myocardial insufficiency ( 4 ) • Recent myocardial infarction ( 4 ) • Severe persistent drug-induced myelosuppression ( 4 ) • Severe hepatic impairment ( 4 ) • Hypersensitivity to doxorubicin hydrochloride ( 4 ) Doxorubicin hydrochloride is contraindicated in patients with: • Severe myocardial insufficiency [see Warnings and Precautions (5.1) ] • Recent (occurring within the past 4-6 weeks) myocardial infarction [see Warnings and Precautions (5.1) ] • Severe persistent drug-induced myelosuppression [see Warnings and Precautions (5.4) ] • Severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin level greater than 5 mg/dL) [see Warnings and Precautions (5.5) ] • Severe hypersensitivity reaction to doxorubicin hydrochloride including anaphylaxis [see Adverse Reactions (6.2) ]

⚠️ Warnings and Cautions ~3 min read ▾

5. WARNINGS AND PRECAUTIONS • Radiation-induced toxicity can be increased by the administration of doxorubicin hydrochloride. Radiation recall can occur in patients who receive doxorubicin hydrochloride after prior radiation therapy ( 5.7 ). • Embryofetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk to the fetus ( 5.8 ).

5.1Cardiomyopathy and Arrhythmias Cardiomyopathy Doxorubicin hydrochloride can result in myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy is generally proportional to the cumulative exposure. Include prior doses of other anthracyclines or anthracenediones in calculations of total cumulative dosage for doxorubicin hydrochloride.

Cardiomyopathy may develop during treatment or up to several years after completion of treatment and can include decrease in LVEF and signs and symptoms of congestive heart failure (CHF). The probability of developing cardiomyopathy is estimated to be 1 to 2% at a total cumulative dose of 300 mg/m 2 of doxorubicin hydrochloride, 3 to 5% at a dose of 400 mg/m 2 , 5 to 8% at a dose of 450 mg/m 2 , and 6 to 20% at a dose of 500 mg/m 2 , when doxorubicin hydrochloride is administered every 3 weeks. There is an additive or potentially synergistic increase in the risk of cardiomyopathy in patients who have received radiotherapy to the mediastinum or concomitant therapy with other known cardiotoxic agents such as cyclophosphamide and trastuzumab.

Pericarditis and myocarditis have also been reported during or following doxorubicin hydrochloride treatment. Assess left ventricular cardiac function (e.g., MUGA or echocardiogram) prior to initiation of doxorubicin hydrochloride, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity. Increase the frequency of assessments as the cumulative dose exceeds 300 mg/m 2 .

Use the same method of assessment of LVEF at all time points [see Use in Specific Populations (8.4) ]. Consider the use of dexrazoxane to reduce the incidence and severity of cardiomyopathy due to doxorubicin hydrochloride administration in patients who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m 2 and who will continue to receive doxorubicin hydrochloride. Arrhythmias Doxorubicin hydrochloride can result in arrhythmias, including life-threatening arrhythmias, during or within a few hours after doxorubicin hydrochloride administration and at any time point during treatment.

Tachyarrhythmias, including sinus tachycardia, premature ventricular contractions, and ventricular tachycardia, as well as bradycardia may occur. Electrocardiographic changes including non-specific ST-T wave changes, atrioventricular and bundle-branch block can also occur. These electrocardiographic changes may be transient and self-limited and may not require dose-modifications of doxorubicin hydrochloride.

5.2Secondary Malignancies The risk of developing secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) is increased following treatment with doxorubicin hydrochloride. Cumulative incidences ranged from 0.2% at five years to 1.5% at 10 years in two separate trials involving the adjuvant treatment of women with breast cancer. These leukemias generally occur within 1 to 3 years of treatment.

5.3Extravasation and Tissue Necrosis Extravasation of doxorubicin hydrochloride can result in severe local tissue injury manifesting as blistering, ulceration, and necrosis requiring wide excision of the affected area and skin grafting. When given via a peripheral venous line, infuse doxorubicin over 10 minutes or less to minimize the risk of thrombosis or perivenous extravasation. If signs or symptoms of extravasation occur, immediately terminate the injection or infusion [see Dosage and Administration (2.3) ] .

Extravasation may be present in patients who do not experience a stinging or burning sensation or when blood return is present on aspiration of t…

🤒 Adverse Reactions ~2 min read ▾

6. ADVERSE REACTIONS The most common (>10%) adverse drug reactions are alopecia, nausea and vomiting ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

The following adverse reactions are discussed in more detail in other sections of the labeling. • Cardiomyopathy and Arrhythmias [see Warnings and Precautions (5.1) ] • Secondary Malignancies [see Warnings and Precautions (5.2) ] • Extravasation and Tissue Necrosis [see Warnings and Precautions (5.3) ] • Severe Myelosuppression [see Warnings and Precautions (5.4) ] • Tumor Lysis Syndrome [see Warnings and Precautions (5.6) ] • Radiation Sensitization and Radiation Recall [see Warnings and Precautions (5.7) ]

6.1Clinical Trial Experience in Breast Cancer Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety data below were collected from 1492 women who received doxorubicin hydrochloride at a dose of 60 mg/m 2 and cyclophosphamide at a dose of 600 mg/m 2 (AC) every 3 weeks for 4 cycles for the adjuvant treatment of axillary lymph node positive breast cancer.

The median number of cycles received was 4. Selected adverse reactions reported in this study are provided in Table 1. No treatment-related deaths were reported in patients on either arm of the study.

Table 1. Selected Adverse Reactions in Patients with Early Breast Cancer Involving Axillary Lymph Nodes AC * Includes pooled data from patients who received either AC alone for 4 cycles, or who were treated with AC for 4 cycles followed by 3 cycles of CMF Conventional CMF N=1492 N=739 Adverse reactions, % of patients Leukopenia Grade 3 (1,000 to 1,999 /mm3) Grade 4 (<1000 /mm3) 3.4 0.3 9.4

0.3Thrombocytopenia Grade 3 (25,000 to 49,999 /mm3) 0 0.1 0.3 0 Grade 4 (<25,000 /mm3) Shock, sepsis 2 1 Systemic infection 2 1 Vomiting Vomiting≤12 hours Vomiting >12 hours Intractable 34 37 5 25 12 2 Alopecia 92 71 Cardiac dysfunction Asymptomatic Transient Symptomatic 0.2 0.1 0.1 0.1 0 0

6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of doxorubicin hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac – cardiogenic shock Cutaneous – Skin and nail hyperpigmentation, oncolysis, rash, itching, photosensitivity, urticaria, acral erythema, palmar plantar erythrodysesthesia Gastrointestinal – Nausea, mucositis, stomatitis, necrotizing colitis, typhlitis, gastric erosions, gastrointestinal tract bleeding, hematochezia, esophagitis, anorexia, abdominal pain, dehydration, diarrhea, hyperpigmentation of the oral mucosa Hypersensitivity – Anaphylaxis Laboratory Abnormalities – Increased alanine aminotransferase, increased aspartate aminotransferase Neurological – Peripheral sensory and motor neuropathy, seizures, coma Ocular – Conjunctivitis, keratitis, lacrimation Vascular – Phlebosclerosis, phlebitis/thrombophlebitis, hot flashes, thromboembolism Other – Malaise/asthenia, fever, chills, weight gain

🔄 Drug Interactions ~1 min read ▾

7. DRUG INTERACTIONS • Avoid concurrent use of doxorubicin hydrochloride with inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp ( 7.1 ). • Do not administer doxorubicin hydrochloride in combination with trastuzumab due to increased risk of cardiac dysfunction ( 5.1 , 7.2 ).

7.1Effect of CYP3A4 Inhibitors, Inducers and P-gp Doxorubicin is a major substrate of cytochrome P450 CYP3A4 and CYP2D6, and P-glycoprotein (P-gp). Clinically significant interactions have been reported with inhibitors of CYP3A4, CYP2D6, and/or P-gp (e.g., verapamil), resulting in increased concentration and clinical effect of doxorubicin. Inducers of CYP3A4 (e.g., phenobarbital, phenytoin, St.

John's Wort) and P-gp inducers may decrease the concentration of doxorubicin. Avoid concurrent use of doxorubicin hydrochloride with inhibitors and inducers of CYP3A4, CYP2D6, or P-gp.

7.2Trastuzumab Concurrent use of trastuzumab and doxorubicin hydrochloride results in an increased risk of cardiac dysfunction. Avoid concurrent administration of doxorubicin and trastuzumab. The appropriate interval for administering doxorubicin following trastuzumab therapy has not been determined [see Warnings and Precautions (5.1) ].

7.3Paclitaxel Paclitaxel, when given prior to doxorubicin hydrochloride, increases the plasma-concentrations of doxorubicin and its metabolites. Administer doxorubicin hydrochloride prior to paclitaxel if used concomitantly.

7.4Dexrazoxane Do not administer dexrazoxane as a cardioprotectant at the initiation of doxorubicin hydrochloride containing chemotherapy regimens. In a randomized trial in women with metastatic breast cancer, initiation of dexrazoxane with doxorubicin hydrochloride-based chemotherapy resulted in a significantly lower tumor response rate (48% vs. 63%; p=0.007) and shorter time to progression than in women who received doxorubicin hydrochloride-based chemotherapy alone.

7.56-Mercaptopurine Doxorubicin hydrochloride may potentiate 6-mercaptopurine-induced hepatotoxicity. In 11 patients with refractory leukemia treated with 6-mercaptopurine (500 mg/m 2 intravenously daily for 5 days per cycle every 2-3 weeks) and doxorubicin hydrochloride (50 mg/m 2 intravenous once per cycle every 2-3 weeks) alone or with vincristine and prednisone, all developed hepatic dysfunction manifested by elevations of total serum bilirubin, alkaline phosphatase and aspartate aminotransferase.

👥 Use in Specific Populations ~3 min read ▾

8. USE IN SPECIFIC POPULATIONS • Nursing Mothers: Discontinue drug or nursing taking into consideration importance of drug to mother ( 8.3 ). • Pediatric Use: Recommend long-term follow-up cardiac evaluations due to risk of delayed cardiotoxicity ( 8.4 ). • Females and Males of Reproductive Potential: May impair fertility.Counsel female and male patients on pregnancy planning and prevention ( 8.6 ).

8.1Pregnancy Pregnancy Category D Risk Summary Doxorubicin hydrochloride can cause fetal harm when administered to a pregnant woman. Doxorubicin hydrochloride was teratogenic and embryotoxic in rats and rabbits at doses approximately 0.07 times (based on body surface area) the recommended human dose of 60 mg/m 2 . If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus.

Animal Data Doxorubicin hydrochloride was teratogenic and embryotoxic at doses of 0.8 mg/kg/day (about 0.07 times the recommended human dose based on body surface area) when administered during the period of organogenesis in rats. Teratogenicity and embryotoxicity were also seen using discrete periods of treatment. The most susceptible was the 6- to 9-day gestation period at doses of 1.25 mg/kg/day and greater.

Characteristic malformations included esophageal and intestinal atresia, tracheo-esophageal fistula, hypoplasia of the urinary bladder, and cardiovascular anomalies. Doxorubicin hydrochloride was embryotoxic (increase in embryofetal deaths) and abortifacient at 0.4 mg/kg/day (about 0.07 times the recommended human dose based on body surface area) in rabbits when administered during the period of organogenesis.

8.3Nursing Mothers Doxorubicin has been detected in the milk of at least one lactating patient [see Clinical Pharmacology (12.3) ] . Because of the potential for serious adverse reactions in nursing infants from doxorubicin hydrochloride, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

8.4Pediatric Use Based on postmarketing reports, pediatric patients treated with doxorubicin hydrochloride are at risk for developing late cardiovascular dysfunction. Risk factors include young age at treatment (especially < 5 years), high cumulative doses and receipt of combined modality therapy. Long-term periodic cardiovascular monitoring is recommended for all pediatric patients who have received doxorubicin hydrochloride.

Doxorubicin hydrochloride, as a component of intensive chemotherapy regimens administered to pediatric patients, may contribute to prepubertal growth failure and may also contribute to gonadal impairment, which is usually temporary. There are no recommended dose adjustments based on age. Doxorubicin clearance was increased in patients aged 2 years to 20 years as compared to adults, while doxorubicin clearance was similar in children less than 2 years as compared to adults [see Clinical Pharmacology (12.3) ] .

8.5Geriatric Use Clinical experience in patients who were 65 years of age and older who received doxorubicin hydrochloride-based chemotherapy regimens for metastatic breast cancer showed no overall differences in safety and effectiveness compared with younger patients.

8.6Females and Males of Reproductive Potential Contraception Females Doxorubicin hydrochloride can cause fetal harm when administered during pregnancy. Advise female patients of reproductive potential to use highly effective contraception during treatment with doxorubicin hydrochloride and for 6 months after treatment. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking doxorubicin hydrochloride [see Use in Specific Populations (8.1) ] .

Males Doxorubicin hydrochloride may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities. Males with female sexual partners of reproductive pote…

🤰 Pregnancy 188 words ▾

8.1Pregnancy Pregnancy Category D Risk Summary Doxorubicin hydrochloride can cause fetal harm when administered to a pregnant woman. Doxorubicin hydrochloride was teratogenic and embryotoxic in rats and rabbits at doses approximately 0.07 times (based on body surface area) the recommended human dose of 60 mg/m 2 . If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus.

Animal Data Doxorubicin hydrochloride was teratogenic and embryotoxic at doses of 0.8 mg/kg/day (about 0.07 times the recommended human dose based on body surface area) when administered during the period of organogenesis in rats. Teratogenicity and embryotoxicity were also seen using discrete periods of treatment. The most susceptible was the 6- to 9-day gestation period at doses of 1.25 mg/kg/day and greater.

Characteristic malformations included esophageal and intestinal atresia, tracheo-esophageal fistula, hypoplasia of the urinary bladder, and cardiovascular anomalies. Doxorubicin hydrochloride was embryotoxic (increase in embryofetal deaths) and abortifacient at 0.4 mg/kg/day (about 0.07 times the recommended human dose based on body surface area) in rabbits when administered during the period of organogenesis.

🧒 Pediatric Use 132 words ▾

8.4Pediatric Use Based on postmarketing reports, pediatric patients treated with doxorubicin hydrochloride are at risk for developing late cardiovascular dysfunction. Risk factors include young age at treatment (especially < 5 years), high cumulative doses and receipt of combined modality therapy. Long-term periodic cardiovascular monitoring is recommended for all pediatric patients who have received doxorubicin hydrochloride.

Doxorubicin hydrochloride, as a component of intensive chemotherapy regimens administered to pediatric patients, may contribute to prepubertal growth failure and may also contribute to gonadal impairment, which is usually temporary. There are no recommended dose adjustments based on age. Doxorubicin clearance was increased in patients aged 2 years to 20 years as compared to adults, while doxorubicin clearance was similar in children less than 2 years as compared to adults [see Clinical Pharmacology (12.3) ] .

🧓 Geriatric Use 37 words ▾

8.5Geriatric Use Clinical experience in patients who were 65 years of age and older who received doxorubicin hydrochloride-based chemotherapy regimens for metastatic breast cancer showed no overall differences in safety and effectiveness compared with younger patients.

🆘 Overdosage 129 words ▾

10. OVERDOSAGE Few cases of overdose have been described. A 58-year-old man with acute lymphoblastic leukemia received 10-fold overdose of doxorubicin hydrochloride (300 mg/m 2 ) in one day.

He was treated with charcoal filtration, hemopoietic growth factor (G-CSF), proton pump inhibitor and antimicrobial prophylaxis. The patient suffered sinus tachycardia, grade 4 neutropenia and thrombocytopenia for 11 days, severe mucositis and sepsis. The patient recovered completely 26 days after the overdose.

A 17-year-old girl with osteogenic sarcoma received 150 mg of doxorubicin hydrochloride daily for 2 days (intended dose was 50 mg per day for 3 days). The patient developed severe mucositis on days 4-7 after the overdose and chills and pyrexia on day 7. The patient was treated with antibiotics and platelets and recovered 18 days after overdose.

🧬 Clinical Pharmacology ~3 min read ▾

12. CLINICAL PHARMACOLOGY

12.1Mechanism of Action The cytotoxic effect of doxorubicin hydrochloride on malignant cells and its toxic effects on various organs are thought to be related to nucleotide base intercalation and cell membrane lipid binding activities of doxorubicin. Intercalation inhibits nucleotide replication and action of DNA and RNA polymerases. The interaction of doxorubicin with topoisomerase II to form DNA-cleavable complexes appears to be an important mechanism of doxorubicin hydrochloride cytocidal activity.

12.3Pharmacokinetics Pharmacokinetic studies conducted in patients with various types of tumors have shown that doxorubicin follows multiphasic disposition after intravenous injection. The distribution half-life is approximately 5 minutes, while the terminal half-life is 20 to 48 hours. In four patients, doxorubicin demonstrated dose-independent pharmacokinetics across a dose range of 30 to 70 mg/m2.

Distribution Steady-state distribution volume ranges from 809 to 1214 L/m 2 . Binding of doxorubicin and its major metabolite, doxorubicinol, to plasma proteins is about 75% and is independent of plasma concentration of doxorubicin up to 1.1 mcg/mL. Doxorubicin was measured in the milk of one lactating patient after therapy with 70 mg/m 2 of doxorubicin hydrochloride given as a 15-minute intravenous infusion.

The peak milk concentration at 24 hours after treatment was 4.4-fold greater than the corresponding plasma concentration. Doxorubicin was detectable in the milk up to 72 hours. Doxorubicin does not cross the blood brain barrier.

Metabolism Enzymatic reduction at the 7 position and cleavage of the daunosamine sugar yields aglycones which are accompanied by free radical formation, the local production of which may contribute to the cardiotoxic activity of doxorubicin hydrochloride. Disposition of doxorubicinol in patients is formation rate limited, with the terminal half-life of doxorubicinol being similar to doxorubicin. The relative exposure of doxorubicinol, i.e., the ratio between the AUC of doxorubicinol and the AUC of doxorubicin is approximately 0.5.

Excretion Plasma clearance is in the range 324 to 809 mL/min/m 2 and is predominately by metabolism and biliary excretion. Approximately 40% of the dose appears in the bile in 5 days, while only 5 to 12% of the drug and its metabolites appear in the urine during the same time period. In urine, <3% of the dose was recovered as doxorubicinol over 7 days.

Systemic clearance of doxorubicin is significantly reduced in obese women with ideal body weight greater than 130%. There was a significant reduction in clearance without any change in volume of distribution in obese patients when compared with normal patients with less than 115% ideal body weight. Pediatric patients Following administration of doses ranging from 10 to 75 mg/m 2 of doxorubicin hydrochloride to 60 children and adolescents ranging from 2 months to 20 years of age, doxorubicin clearance averaged 1443 ± 114 mL/min/m2.

Further analysis demonstrated that clearance in 52 children greater than 2 years of age (1540 mL/min/m 2 ) was increased compared with adults. However, clearance in infants younger than 2 years of age (813 mL/min/m 2 ) was decreased compared with older children and approached the range of clearance values determined in adults [see Use in Specific Populations (8.4) ]. Patient Gender There is no recommended dose adjustment based on gender.

A published clinical study involving 6 men and 21 women with no prior anthracycline therapy reported a significantly higher median doxorubicin clearance in men compared to women (1088 mL/min/m 2 versus 433 mL/min/m 2 ). However, the terminal half-life of doxorubicin was longer in men compared to women (54 versus 35 hours). Patients with hepatic impairment The clearance of doxorubicin and doxorubicinol was reduced in patients with elevation in serum bilirubin [see Dosage and Administration (2.2) and Warnings and Precautions (5.5) ] .

🧬 Mechanism of Action 70 words ▾

12.1Mechanism of Action The cytotoxic effect of doxorubicin hydrochloride on malignant cells and its toxic effects on various organs are thought to be related to nucleotide base intercalation and cell membrane lipid binding activities of doxorubicin. Intercalation inhibits nucleotide replication and action of DNA and RNA polymerases. The interaction of doxorubicin with topoisomerase II to form DNA-cleavable complexes appears to be an important mechanism of doxorubicin hydrochloride cytocidal activity.

📦 How Supplied / Storage and Handling 168 words ▾

16. HOW SUPPLIED/STORAGE AND HANDLING Doxorubicin Hydrochloride for Injection, USP is supplied as a sterile red-orange lyophilized powder for intravenous use only, is available in single dose flip-top vials in the following package strengths: NDC 67457-478-10: 10 mg vial; individually boxed. NDC 67457-436-50: 50 mg vial; individually boxed.

Store unreconstituted vial at controlled room temperature, between 20°C to 25°C (68°F to 77°F). [See USP.] Protect vials from light. Retain in carton until time of use. Discard unused portion.

Reconstituted Solution Stability After adding the diluent, the vial should be shaken and the contents allowed to dissolve. The reconstituted solution is stable for 7 days at room temperature and under normal room light (100 foot-candles) and 15 days under refrigeration (2° to 8°C). It should be protected from exposure to sunlight.

Discard any unused solution from the 10 mg and 50 mg single dose vials. Handling and Disposal Handle and dispose of Doxorubicin Hydrochloride for Injection, USP consistent with recommendations for the handling and disposal of hazardous drugs. 1

📋 Description 110 words ▾

11. DESCRIPTION Doxorubicin hydrochloride, USP is a cytotoxic, anthracycline, topoisomerase II inhibitor isolated from cultures of Streptomyces peucetius var. caesius. Chemically, doxorubicin hydrochloride, USP is: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-α-L- lyx o-hexopyranosyl)oxy]-7,8,9,10 tetrahydro-6,8,11-trihydroxy-8-(hydroxylacetyl)-1-methoxy-, hydrochloride (8S- ci s)-.

The chemical structure of doxorubicin hydrochloride is: Doxorubicin Hydrochloride for Injection, USP is a sterile red-orange lyophilized powder, provided in single dose vial containing 10 mg, 50 mg doxorubicin HCl, USP. Doxorubicin Hydrochloride for Injection, USP Each 10 mg lyophilized vial contains 10 mg of Doxorubicin Hydrochloride, USP and 50 mg of Lactose Monohydrate, NF. Each 50 mg lyophilized vial contains 50 mg of Doxorubicin Hydrochloride, USP and 250 mg of Lactose Monohydrate, NF.

Chemical Structure

💬 Information for Patients ~2 min read ▾

17. PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (Patient Information). Inform patients of the following: • Doxorubicin hydrochloride can cause irreversible myocardial damage.

Advise patients to contact a healthcare provider for symptoms of heart failure during or after treatment with doxorubicin hydrochloride [see Warnings and Precautions (5.1) ] . • There is an increased risk of treatment-related leukemia from doxorubicin hydrochloride [see Warnings and Precautions (5.2) ] . • Doxorubicin hydrochloride can reduce the absolute neutrophil count resulting in an increased risk of infection. Advise patients to contact a healthcare provider for new onset fever or symptoms of infection [see Warnings and Precautions (5.4) ] . • Doxorubicin hydrochloride can cause fetal harm when administered during pregnancy.

Advise females of reproductive potential to use effective contraception during treatment with doxorubicin hydrochloride and for 6 months after treatment, and to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment with doxorubicin hydrochloride [see Warnings and Precautions (5.8) and Use in Specific Populations (8.6) ] . • Doxorubicin hydrochloride may induce chromosomal damage in sperm, which may lead to loss of fertility and offspring with birth defects. Advise patients to use effective contraception during and for 6 months after treatment [see Warnings and Precautions (5.8) and Use in Specific Populations (8.6) ] . • Doxorubicin hydrochloride can cause premature menopause in females and loss of fertility in males [see Use in Specific Populations (8.6) ] . • Discontinue nursing while receiving doxorubicin HCl [see Use in Specific Populations (8.3) ] . • Doxorubicin hydrochloride can cause nausea, vomiting, diarrhea, mouth/oral pain and sores.

Advise patients to contact a healthcare provider should they develop any severe symptoms that prevent them from eating and drinking [see Adverse Reactions (6) ] . • Doxorubicin hydrochloride causes alopecia [see Adverse Reactions (6.1) ] . • Doxorubicin hydrochloride can cause their urine to appear red for 1 to 2 days after administration. Manufactured for: Mylan Institutional LLC Morgantown, WV 26505 U.S.A. Manufactured by: Mylan Laboratories Limited Bangalore, India Code No.: KR/DRUGS/KTK/28/381/2008 1033608 JULY 2022

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