NDC 16714-001 Doxorubicin Hydrochloride

Doxorubicin Hydrochloride

NDC Product Code 16714-001

NDC CODE: 16714-001

Proprietary Name: Doxorubicin Hydrochloride What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Doxorubicin Hydrochloride What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Product Characteristics

Color(s):
RED (C48326 - CLEAR)

NDC Code Structure

  • 16714 - Northstar Rxllc

NDC 16714-001-01

Package Description: 1 VIAL, MULTI-DOSE in 1 CARTON > 100 mL in 1 VIAL, MULTI-DOSE

NDC Product Information

Doxorubicin Hydrochloride with NDC 16714-001 is a a human prescription drug product labeled by Northstar Rxllc. The generic name of Doxorubicin Hydrochloride is doxorubicin hydrochloride. The product's dosage form is injection, solution and is administered via intravenous form.

Labeler Name: Northstar Rxllc

Dosage Form: Injection, Solution - A liquid preparation containing one or more drug substances dissolved in a suitable solvent or mixture of mutually miscible solvents that is suitable for injection.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Doxorubicin Hydrochloride Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • DOXORUBICIN HYDROCHLORIDE 2 mg/mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • SODIUM CHLORIDE (UNII: 451W47IQ8X)
  • WATER (UNII: 059QF0KO0R)
  • HYDROCHLORIC ACID (UNII: QTT17582CB)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravenous - Administration within or into a vein or veins.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Anthracycline Topoisomerase Inhibitor - [EPC] (Established Pharmacologic Class)
  • Anthracyclines - [CS]
  • Topoisomerase Inhibitors - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Northstar Rxllc
Labeler Code: 16714
FDA Application Number: ANDA203622 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 03-22-2021 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

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Information for Patients

Doxorubicin

Doxorubicin is pronounced as (dox oh roo' bi sin)

Why is doxorubicin medication prescribed?
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 dise...
[Read More]


is

...
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* Please review the disclaimer below.

Doxorubicin Hydrochloride Product Label Images

Doxorubicin Hydrochloride Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

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/m2 to 500 mg/m2 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 [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)].

1.1 Adjuvant Breast Cancer

Doxorubicin Hydrochloride Injection 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.

1.2 Other Cancers

  • Doxorubicin Hydrochloride Injection is indicated for the treatment ofacute lymphoblastic leukemiaacute myeloblastic leukemiaHodgkin lymphomanon-Hodgkin lymphoma (NHL)metastatic breast cancermetastatic Wilms’ tumormetastatic neuroblastomametastatic soft tissue sarcomametastatic bone sarcomametastatic ovarian carcinomametastatic transitional cell bladder carcinomametastatic thyroid carcinomametastatic gastric carcinomametastatic bronchogenic carcinoma

The recommended dosage of Doxorubicin Hydrochloride Injection is 60 mg/m2 administered as an intravenous bolus on day 1 of each 21-day treatment cycle, in combination with cyclophosphamide, for a total of four cycles.

  • The recommended dosage of Doxorubicin Hydrochloride Injection when used as a single agent is 60 mg/m2 to 75 mg/m2 intravenously every 21 days.The recommended dosage of Doxorubicin Hydrochloride Injection when administered in combination with other chemotherapy drugs, is 40 mg/m2 to 75 mg/m2 intravenously every 21 to 28 days.Consider use of the lower Doxorubicin Hydrochloride Injection dose in the recommended dosage range or longer intervals between cycles for heavily pretreated patients, elderly patients, or obese patients.Cumulative doses above 550 mg/m2 are associated with an increased risk of cardiomyopathy [see Warnings and Precautions (5.1)].

2.3 Dosage Modifications For Adverse Reactions

CardiomyopathyDiscontinue Doxorubicin Hydrochloride Injection in patients who develop signs or symptoms of cardiomyopathy [see Warnings and Precautions (5.1)].

2.4 Dosage Modifications For Hepatic Impairment

Doxorubicin Hydrochloride Injection is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C or serum bilirubin greater than 5 mg/dL) [see Contraindications (4)]. Dosage modifications for Doxorubicin Hydrochloride Injection in patients with elevated serum total bilirubin concentrations [see Warnings and Precautions (5.5), Use in Specific Populations (8.6)] are provided in Table 1.Table 1. Recommended Dosage Modification for Elevated Serum Total BilirubinSerum total bilirubin concentrationDosage Modification1.2 to 3 mg/dL50%3.1 to 5 mg/dL75%greater than 5 mg/dLDo not initiate Doxorubicin Hydrochloride Injection;discontinue Doxorubicin Hydrochloride Injection

2.5 Preparation And Administration

  • Doxorubicin Hydrochloride Injection is a cytotoxic drug. Follow applicable special handling and disposal procedures.1PreparationDilution of Doxorubicin Hydrochloride InjectionDilute Doxorubicin Hydrochloride Injection in 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.Protect from light following preparation until completion of infusion.Use within 1 hour. If not used within 1 hour, discard the diluted product.AdministrationVisually inspect for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard if the solution is discolored, cloudy, or contains particulate matter.Administration by Intravenous InjectionAdminister diluted Doxorubicin Hydrochloride Injection 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 intravenously over 3 to 10 minutes. Decrease the rate of infusion if erythematous streaking along the vein proximal to the site of infusion or facial flushing occur.Administration by Continuous Intravenous InfusionAdminister Doxorubicin Hydrochloride Injection solution only through a central intravenous line. Decrease the rate of infusion if erythematous streaking along the vein proximal to the site of infusion or facial flushing occur.Protect from light from preparation for infusion until completion of infusion.Management of Suspected ExtravasationImmediately discontinue Doxorubicin Hydrochloride Injection for burning or stinging sensation or other evidence indicating peri­venous infiltration or extravasation. Manage confirmed or suspected extravasation as follows:Do not remove the needle until attempts are made to aspirate extravasated fluid.Do not flush the line.Avoid applying pressure to the site.Apply ice to the site intermittently for 15 minutes, 4 times a day for 3 days.If the extravasation is in an extremity, elevate the extremity.In adults, consider administration of dexrazoxane [see Warnings and Precautions (5.3)].Management of Contact with Skin or EyesTreat accidental contact with the skin or eyes immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. Do not abrade the skin by using a scrub brush. Seek medical attention.Incompatibility with Other DrugsDo not admix Doxorubicin Hydrochloride Injection with other drugs. If Doxorubicin Hydrochloride Injection is mixed with heparin or fluorouracil, a precipitate may form. Avoid contact with alkaline solutions which can lead to hydrolysis of doxorubicin hydrochloride.

3 Dosage Forms And Strengths

  • Doxorubicin Hydrochloride Injection, USP: 200 mg/100 mL (2 mg/mL) clear red solution in a multiple-dose vial

4 Contraindications

  • Doxorubicin Hydrochloride Injection is contraindicated in patients with:Severe myocardial insufficiency [see Warnings and Precautions (5.1)]Recent (occurring within the past 4 to 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)]

5.1 Cardiomyopathy And Arrhythmias

CardiomyopathyDoxorubicin 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/m2 of doxorubicin hydrochloride, 3 to 5% at a dose of 400 mg/m2, 5 to 8% at a dose of 450 mg/m2, and 6 to 20% at a dose of 500 mg/m2, 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 Injection, 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/m2. Use the same method of assessment of LVEF at all time points [see Use in Specific Populations (8.4)]. Discontinue Doxorubicin Hydrochloride Injection in patients who develop signs or symptoms of cardiomyopathy [see Dosage and Administration (2.3)].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/m2 and who will continue to receive doxorubicin hydrochloride.ArrhythmiasDoxorubicin 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, can 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 a dosage modification of doxorubicin hydrochloride.

5.2 Secondary 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.

5.3 Extravasation And Tissue Necrosis

Extravasation of doxorubicin hydrochloride can cause severe local tissue injury manifesting as blistering, ulceration, and necrosis requiring wide excision of the affected area and skin grafting. Extravasation should be considered if a patient experiences a burning or stinging sensation or shows other evidence indicating peri-venous infiltration or extravasation; however, extravasation may be present in patients who do not experience a stinging or burning sensation or when blood return is present on aspiration of the infusion needle. When given via a peripheral venous line, infuse Doxorubicin Hydrochloride Injection over 10 minutes or less to minimize the risk of thrombosis or perivenous extravasation. If extravasation is suspected, immediately discontinue the intravenous injection or continuous intravenous infusion [see Dosage and Administration (2.5)]. Apply ice to the site intermittently for 15 minutes, 4 times a day for 3 days. In adults, if appropriate, administer dexrazoxane at the site of extravasation as soon as possible and within the first 6 hours after extravasation.

5.4 Severe Myelosuppression

Doxorubicin hydrochloride can cause myelosuppression. In Study 1, the incidence of severe myelosuppression was: grade 4 leukopenia (0.3%), grade 3 leukopenia (3%), and grade 4 thrombocytopenia (0.1%). A dose-dependent, reversible neutropenia is the predominant manifestation of myelosuppression from doxorubicin hydrochloride. When doxorubicin hydrochloride is administered every 21 days, the neutrophil count reaches its nadir 10 to 14 days after administration with recovery usually occurring by day 21. Obtain complete blood counts prior to each treatment and carefully monitor patients during treatment for possible clinical complications due to myelosuppression. Delay next dose of Doxorubicin Hydrochloride Injection if severe myelosuppression has not improved. Consider dose reduction for patients with prolonged myelosuppression based on severity of reaction.

5.5 Use In Patients With Hepatic Impairment

The clearance of doxorubicin hydrochloride is decreased in patients with elevated serum bilirubin with an increased risk of toxicity [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. Doxorubicin Hydrochloride Injection is contraindicated in patients with severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin level greater than 5 mg/dL) [see Contraindications (4)]. Reduce the dose of Doxorubicin Hydrochloride Injection in patients with serum bilirubin levels of 1.2 to 5 mg/dL [see Dosage and Administration (2.4)]. Obtain liver tests including ALT, AST, alkaline phosphatase, and bilirubin prior to and during therapy.

5.6 Tumor Lysis Syndrome

Doxorubicin hydrochloride can induce tumor lysis syndrome in patients with rapidly growing tumors. Evaluate blood uric acid levels, potassium, calcium, phosphate, and creatinine after initial treatment. Hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor lysis syndrome.

5.7 Potentiation Of Radiation Toxicity And Radiation Recall

Doxorubicin hydrochloride can increase radiation-induced toxicity to the myocardium, mucosa, skin, and liver. Radiation recall, including but not limited to cutaneous and pulmonary toxicity, can occur in patients who receive doxorubicin hydrochloride after prior radiation therapy.

5.8 Embryo-Fetal Toxicity

Based on findings in animals and its mechanism of action, Doxorubicin Hydrochloride Injection can cause fetal harm when administered to a pregnant woman; avoid the use of Doxorubicin Hydrochloride Injection during the 1st trimester. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2nd and 3rd trimesters. Doxorubicin hydrochloride was teratogenic and embryotoxic in rats and rabbits at doses lower than the recommended human dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Doxorubicin Hydrochloride Injection and for 6 months after treatment. Advise males with female partners of reproductive potential to use effective contraception during treatment with Doxorubicin Hydrochloride Injection and for 3 months after treatment. Advise males with pregnant partners to use condoms during treatment with Doxorubicin Hydrochloride Injection and for at least 10 days after the final dose [see Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1)].

6 Adverse Reactions

  • The following clinically significant adverse reactions are described elsewhere in 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)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.Breast CancerThe safety data below were collected from 1492 women who received doxorubicin hydrochloride at a dose of 60 mg/m2 and cyclophosphamide at a dose of 600 mg/m2 (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 2. No treatment-related deaths were reported in patients on either arm of the study.Table 2. Selected Adverse Reactions in Patients with Early Breast Cancer Involving Axillary Lymph NodesConventionalAdverse ReactionsAC*CMFN=1492N=739%%Alopecia9271Vomiting Vomiting ≤12 hours3425 Vomiting >12 hours3712 Intractable52Leukopenia Grade 3 (1,000 to 1,999 /mm3) 3.49.4 Grade 4 (<1000 /mm3)0.30.3Shock, sepsis21Systemic infection21Cardiac dysfunction Asymptomatic 0.20.1 Transient 0.10 Symptomatic0.10Thrombocytopenia Grade 3 (25,000 to 49,999 /mm3)00.3 Grade 4 (<25,000 /mm3)0.10AC = doxorubicin hydrochloride, cyclophosphamide; CMF = cyclophosphamide, methotrexate, fluorouracil* Includes pooled data from patients who received either AC for 4 cycles or AC for 4 cycles followed by CMF for 3 cycles

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Doxorubicin Hydrochloride Injection. 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 shockCutaneous - Skin and nail hyperpigmentation, oncolysis, rash, itching, photosensitivity, urticaria, acral erythema, palmar plantar erythrodysesthesiaGastrointestinal - Nausea, mucositis, stomatitis, necrotizing colitis, typhlitis, gastric erosions, gastrointestinal tract bleeding, hematochezia, esophagitis, anorexia, abdominal pain, dehydration, diarrhea, hyperpigmentation of the oral mucosaHypersensitivity - AnaphylaxisLaboratory Abnormalities - Increased ALT, increased ASTNeurological - Peripheral sensory and motor neuropathy, seizures, comaOcular - Conjunctivitis, keratitis, lacrimationVascular - Phlebosclerosis, phlebitis/thrombophlebitis, hot flashes, thromboembolismOther - Malaise/asthenia, fever, chills, weight gain

7.1 Effect Of Other Drugs On Doxorubicin Hydrochloride Injection

Inhibitors of CYP3A4, CYP2D6, and P-gpConcomitant use of doxorubicin hydrochloride with inhibitors of CYP3A4, CYP2D6, or P-glycoprotein (P-gp), increased concentrations of doxorubicin hydrochloride, which may increase the incidence and severity of adverse reactions of doxorubicin hydrochloride. Avoid concomitant use of Doxorubicin Hydrochloride Injection with inhibitors of CYP3A4, CYP2D6, or P-gp.Inducers of CYP3A4, CYP2D6, or P-gpConcomitant use of doxorubicin hydrochloride with inducers of CYP3A4, CYP2D6, or P-gp may decrease the concentration of doxorubicin hydrochloride. Avoid concomitant use of Doxorubicin Hydrochloride Injection with inducers of CYP3A4, CYP2D6, or P-gp.PaclitaxelPaclitaxel, when given prior to doxorubicin hydrochloride, increases the plasma-concentrations of doxorubicin hydrochloride and its metabolites. Administer Doxorubicin Hydrochloride Injection prior to paclitaxel if used concomitantly.

7.2 Concomitant Use Of Trastuzumab

Concomitant use of trastuzumab and doxorubicin hydrochloride results in an increased risk of cardiac dysfunction. Avoid concomitant administration of Doxorubicin Hydrochloride Injection and trastuzumab [see Warnings and Precautions (5.1)].Patients receiving doxorubicin hydrochloride after stopping treatment with trastuzumab may also be at an increased risk of developing cardiotoxicity. Trastuzumab may persist in the circulation for up to 7 months. Therefore, avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab when possible. If anthracyclines are used before this time, carefully monitor cardiac function.

7.3 Concomitant Use Of Dexrazoxane

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 compared to doxorubicin hydrochloride-based chemotherapy alone.

7.4 Concomitant Use Of 6-Mercaptopurine

Doxorubicin hydrochloride may potentiate 6-mercaptopurine-induced hepatotoxicity. In 11 patients with refractory leukemia treated with 6-mercaptopurine (500 mg/m2 intravenously daily for 5 days per cycle every 2 to 3 weeks) and doxorubicin hydrochloride (50 mg/m2 intravenous once per cycle every 2 to 3 weeks) alone or with vincristine and prednisone, all developed hepatic dysfunction manifested by increased total serum bilirubin, alkaline phosphatase and aspartate aminotransferase.

8.1 Pregnancy

Risk SummaryBased on findings in animals and its mechanism of action, Doxorubicin Hydrochloride Injection can cause fetal harm when administered to a pregnant woman; avoid the use of Doxorubicin Hydrochloride Injection during the 1st trimester. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2nd and 3rd trimesters. Doxorubicin hydrochloride was teratogenic and embryotoxic in rats and embryotoxic in rabbits when administered during organogenesis at doses approximately 0.07 times (based on body surface area) the recommended human dose of 60 mg/m2 (see Data). Advise pregnant women of the potential risk to a fetus.In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.DataAnimal 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.

8.2 Lactation

Risk SummaryDoxorubicin hydrochloride was measured in the milk of one lactating patient after therapy with 70 mg/m2 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 hydrochloride was detectable in the milk up to 72 hours. There are no data on the effects of doxorubicin hydrochloride on the breastfed child or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with Doxorubicin Hydrochloride Injection and for 10 days after the final dose.

8.3 Females And Males Of Reproductive Potential

Pregnancy TestingVerify the pregnancy status of females of reproductive potential prior to initiating Doxorubicin Hydrochloride Injection.ContraceptionFemalesDoxorubicin Hydrochloride Injection can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)]. Advise female patients of reproductive potential to use highly effective contraception during treatment with Doxorubicin Hydrochloride Injection and for 6 months after treatment [see Use in Specific Populations (8.1)].MalesDoxorubicin hydrochloride may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities. Due to the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with Doxorubicin Hydrochloride Injection and for 3 months after treatment [see Nonclinical Toxicology (13.1)]. Males with pregnant partners should use condoms during treatment and for at least 10 days after the final dose [see Nonclinical Toxicology (13.1), Use in Specific Populations (8.1)].InfertilityFemalesIn females of reproductive potential, doxorubicin hydrochloride may cause infertility and result in amenorrhea. Premature menopause can occur. Recovery of menses and ovulation is related to age at treatment [see Nonclinical Toxicology (13.1)].MalesDoxorubicin hydrochloride may result in oligospermia, azoospermia, and permanent loss of fertility. Sperm counts have been reported to return to normal levels in some men. This may occur several years after the end of therapy [see Nonclinical Toxicology (13.1)].

8.4 Pediatric 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 hydrochloride clearance was increased in patients aged 2 years to 20 years as compared to adults, while doxorubicin hydrochloride clearance was similar in infants less than 2 years as compared to adults [see Clinical Pharmacology (12.3)].

8.5 Geriatric 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.

8.6 Hepatic Impairment

The clearance of doxorubicin hydrochloride was reduced in patients with elevated serum total bilirubin levels. Doxorubicin Hydrochloride Injection is contraindicated in patients with severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin levels greater than 5 mg/dL) [see Contraindications (4)]. Reduce the dose of Doxorubicin Hydrochloride Injection in patients with serum total bilirubin levels greater than 1.2 mg/dL [see Dosage and Administration (2.4), Warnings and Precautions (5.5)].

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/m2) 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 to 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.

11 Description

Doxorubicin hydrochloride, USP is an anthracycline topoisomerase inhibitor isolated from cultures of Streptomyces peucetius var. caesius. The chemical name of doxorubicin hydrochloride, USP is: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-7,8,9,10­ tetrahydro-6,8,11-trihydroxy-8-(hydroxylacetyl)-1-methoxy-, hydrochloride (8S-cis)-. The molecular weight of doxorubicin hydrochloride, USP is 579.98, and the molecular formula is C27H29NO11•HCl. The chemical structure of doxorubicin hydrochloride, USP is: Doxorubicin Hydrochloride Injection USP, for intravenous use, is a clear red, sterile, isotonic aqueous solution provided in a vial containing 200 mg/100 mL of doxorubicin hydrochloride, USP. The drug product has demonstrated inherent antimicrobial activity suitable for a multiple dose presentation. Each milliliter of solution contains 2 mg of doxorubicin hydrochloride, USP. Inactive ingredients include sodium chloride 0.9%, USP, and water for injection, USP, quantity sufficient. The pH of the solution is adjusted to 3 with hydrochloric acid, USP.

12.1 Mechanism 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 hydrochloride. Intercalation inhibits nucleotide replication and action of DNA and RNA polymerases. The interaction of doxorubicin hydrochloride with topoisomerase II to form DNA-cleavable complexes appears to be an important mechanism of doxorubicin hydrochloride cytocidal activity.

12.3 Pharmacokinetics

Pharmacokinetic studies conducted in patients with various types of tumors have shown that doxorubicin hydrochloride follows multiphasic disposition after intravenous injection. In four patients, doxorubicin hydrochloride demonstrated dose-independent pharmacokinetics across a dose range of 30 mg/m2 to 70 mg/m2.DistributionThe distribution half-life is approximately 5 minutes. Steady-state distribution volume ranges from 809 L/m2 to 1214 L/m2. Binding of doxorubicin hydrochloride and its major metabolite, doxorubicinol, to plasma proteins is 75% and is independent of plasma concentration of doxorubicin hydrochloride up to 1.1 mcg/mL.Doxorubicin hydrochloride does not cross the blood brain barrier.EliminationPlasma clearance is ranges from 324 mL/min/m2 to 809 mL/min/m2. The terminal half-life is 20 hours to 48 hours.MetabolismDoxorubicin hydrochloride is a substrate of CYP3A4, CYP2D6, and P-gp.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 hydrochloride. The relative exposure of doxorubicinol, i.e., the ratio between the AUC of doxorubicinol and the AUC of doxorubicin hydrochloride is approximately 0.5.ExcretionPlasma clearance 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.Specific PopulationsWeightSystemic clearance of doxorubicin hydrochloride 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 PatientsFollowing administration of doses ranging from 10 mg/m2 to 75 mg/m2 of doxorubicin hydrochloride to 60 patients ranging from 2 months to 20 years, doxorubicin hydrochloride clearance averaged 1443 ± 114 mL/min/m2. Further analysis demonstrated that clearance in 52 patients ranging from 2 to 20 years (1540 mL/min/m2) was increased compared with adults. However, clearance in infants younger than 2 years of age (813 mL/min/m2) was decreased compared with older patients (ranging from 2 to 20 years) and approached the range of clearance values determined in adults [see Use in Specific Populations (8.4)].SexA published clinical study involving 6 men and 21 women with no prior anthracycline therapy reported a significantly higher median doxorubicin hydrochloride clearance in men compared to women (1088 mL/min/m2 versus 433 mL/min/m2). However, the terminal half-life of doxorubicin hydrochloride was longer in men compared to women (54 versus 35 hours).Patients with Hepatic ImpairmentThe clearance of doxorubicin hydrochloride and doxorubicinol was reduced in patients with elevated serum total bilirubin concentrations [see Dosage and Administration (2.4), Warnings and Precautions (5.5)].

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Doxorubicin hydrochloride treatment can increase the risk of secondary malignancies based on postmarketing reports [see Warnings and Precautions (5.2)]. Doxorubicin hydrochloride was mutagenic in the in vitro Ames assay, and clastogenic in multiple in vitro assays (CHO cell, V79 hamster cell, human lymphoblast, and SCE assays) and the in vivo mouse micronucleus assay.Doxorubicin hydrochloride decreased fertility in female rats at the doses of 0.05 and 0.2 mg/kg/day (approximately 0.005 and 0.02 times the recommended human dose, based on body surface area).A single intravenous dose of 0.1 mg/kg doxorubicin hydrochloride (approximately 0.01 times the recommended human dose based on body surface area) was toxic to male reproductive organs in animal studies, producing testicular atrophy, diffuse degeneration of the seminiferous tubules, and oligospermia/hypospermia in rats. Doxorubicin hydrochloride induces DNA damage in rabbit spermatozoa and dominant lethal mutations in mice.

14 Clinical Studies

The efficacy of doxorubicin hydrochloride-containing regimens for the post-operative, adjuvant treatment of surgically resected breast cancer was evaluated in a meta-analysis conducted by the Early Breast Cancer Trialists Collaborative Group (EBCTCG). The EBCTCG meta-analyses compared cyclophosphamide, methotrexate, and fluorouracil (CMF) to no chemotherapy (19 trials including 7523 patients) and doxorubicin hydrochloride-containing regimens with CMF as an active control (6 trials including 3510 patients). Data from the meta-analysis of trials comparing CMF to no therapy were used to establish the historical treatment effect size for CMF regimens. The major efficacy outcome measures were disease-free survival (DFS) and overall survival (OS).Of the 3510 women (2157 received doxorubicin hydrochloride-containing regimens and 1353 received CMF treatment) with early breast cancer involving axillary lymph nodes included in the six trials from the meta-analyses, approximately 70% were premenopausal and 30% were postmenopausal.At the time of the meta-analysis, 1745 first recurrences and 1348 deaths had occurred. The analyses demonstrated that doxorubicin hydrochloride-containing regimens retained at least 75% of the historical CMF adjuvant effect on DFS with a hazard ratio (HR) of 0.91 (95% CI: 0.82, 1.01) and on OS with a HR of 0.91 (95% CI: 0.81, 1.03). Efficacy results are provided in Table 3 and Figures 1 and 2.Table 3. Summary of Randomized Trials Comparing Doxorubicin Hydrochloride-Containing Regimens Versus CMF in Meta-AnalysisRegimensNo. of CyclesNo. ofDoxorubicin Hydrochloride-ContainingStudyRegimens vs CMF(starting year)PatientsHR** (95% CI)DFSOSNSABP B-15 (1984)AC41562*0.93 (0.82, 1.06)0.97 (0.83, 1.12)CMF6776SECSG 2 (1976)FAC62600.86 (0.66, 1.13)0.93 (0.69, 1.26)CMF6268ONCOFRANCE (1978)FACV121380.71 (0.49, 1.03)0.65 (0.44, 0.96)CMF12113SE SwedenAC621BCG A (1980)0.59 (0.22, 1.61)0.53 (0.21, 1.37)CMF622NSABC IsraelAVbCMF†455Br0283 (1983)60.91 (0.53, 1.57)0.88 (0.47, 1.63)CMF650Austrian BCSG 3 (1984)CMFVA61211.07 (0.73, 1.55)0.93 (0.64, 1.35)CMF8124Doxorubicin Hydrochloride -2157Combined StudiesContaining Regimen0.91 (0.82, 1.01)0.91 (0.81, 1.03)CMF1353Abbreviations: DFS=disease free survival; OS=overall survival; AC=doxorubicin hydrochloride, cyclophosphamide; AVbCMF=doxorubicin hydrochloride, vinblastine, cyclophosphamide, methotrexate, fluorouracil; CMF=cyclophosphamide, methotrexate, fluorouracil; CMFVA=cyclophosphamide, methotrexate, fluorouracil, vincristine, doxorubicin hydrochloride; FAC=fluorouracil, doxorubicin hydrochloride, cyclophosphamide; FACV=fluorouracil, doxorubicin hydrochloride, cyclophosphamide, vincristine; HR=hazard ratio; CI=confidence interval* 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.** Hazard ratio of less than 1 indicates that the treatment with doxorubicin hydrochloride-containing regimens is associated with lower risk of disease recurrences or death compared to the treatment with CMF.† Patients received alternating cycles of AVb and CMF.Figure 1. Meta-analysis of Disease-Free SurvivalFigure 2. Meta-analysis of Overall Survival

15 References

  • “Hazardous Drugs”. OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

16 How Supplied/Storage And Handling

Doxorubicin Hydrochloride Injection, USP is supplied in flip-top vials, as a clear, red solution containing doxorubicin hydrochloride USP, 2 mg/mL in the following package strength:Multiple-Dose VialNDC 16714-001-01: 200 mg/100 mL (2 mg/mL)For the multiple-dose vial: Store under refrigeration between 2° to 8°C (36° to 46°F). Protect from light. Retain in carton until contents are used.StorageStorage of Doxorubicin Hydrochloride Injection, USP under refrigerated conditions can result in the formation of a gelled product. Place gelled product at room temperature [15º to 30ºC (59º to 86ºF)] for 2 to 4 hours to return the product to a slightly viscous, mobile solution.Handling and DisposalDoxorubicin Hydrochloride Injection, USP is a cytotoxic drug. Follow applicable special handling and disposal procedures.1Sterile, Nonpyrogenic, Preservative-free.The vial stopper is not made with natural rubber latex.

17 Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information). CardiomyopathyAdvise patients that Doxorubicin Hydrochloride Injection can cause irreversible myocardial damage and to contact a healthcare provider for symptoms of heart failure during or after treatment [see Warnings and Precautions (5.1)].Secondary MalignancyAdvise patients of the increased risk of treatment-related leukemia [see Warnings and Precautions (5.2)].MyelosuppressionAdvise patients that Doxorubicin Hydrochloride Injection can reduce the absolute neutrophil count resulting in an increased risk of infection and to contact a healthcare provider for new onset fever or symptoms of infection [see Warnings and Precautions (5.4)].Embryo-Fetal ToxicityAdvise pregnant women and females of reproductive potential of the potential risk to a fetus, and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.8), Use in Specific Populations (8.1)].Advise females of reproductive potential to use effective contraception during treatment with Doxorubicin Hydrochloride Injection and for 6 months after treatment [see Warnings and Precautions (5.8), Use in Specific Populations (8.3)].Advise patients that Doxorubicin Hydrochloride Injection may induce chromosomal damage in sperm, which may lead to loss of fertility and offspring with birth defects. Advise males with female partners of reproductive potential to use effective contraception during treatment with Doxorubicin Hydrochloride Injection and for 3 months after treatment [see Warnings and Precautions (5.8), Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)].Advise males with pregnant partners to use condoms during treatment with Doxorubicin Hydrochloride Injection for at least 10 days after the final dose [see Use in Specific Populations (8.3)].LactationAdvise females not to breastfeed during treatment with Doxorubicin Hydrochloride Injection and for 10 days after the final dose [see Use in Specific Populations (8.2)].InfertilityAdvise females and males of the potential loss of fertility from Doxorubicin Hydrochloride Injection [see Use in Specific Populations (8.3)].Gastrointestinal and Dermatologic Adverse ReactionsAdvise patients that Doxorubicin Hydrochloride Injection can cause nausea, vomiting, diarrhea, mouth/oral pain and sores and to contact a healthcare provider should they develop any severe symptoms that prevent them from eating and drinking [see Adverse Reactions (6)]. Advise patients that Doxorubicin Hydrochloride Injection can cause alopecia [see Adverse Reactions (6.1)].Administration Advise patients that Doxorubicin Hydrochloride Injection can cause their urine to appear red for 1 to 2 days after administration.Manufactured For:Northstar Rx LLCMemphis, TN 38141Manufactured In Romania By:Sindan Pharma SRLBucharest 1, Romania 011171  Rev. A 9/2020

Patient Information

  • Doxorubicin Hydrochloride (dox" oh roo' bi sin hye" droe klor' ide) InjectionWhat is the most important information I should know about Doxorubicin Hydrochloride Injection? Doxorubicin Hydrochloride Injection may cause serious side effects including:Heart muscle problems. Doxorubicin Hydrochloride Injection can cause heart muscle damage that may lead to heart failure. Heart failure means your heart does not pump blood well. Heart failure is irreversible in some cases and can lead to death. Heart failure can happen during your treatment with Doxorubicin Hydrochloride Injection or months to years after stopping treatment. Your risk of heart muscle damage increases with higher total amounts of Doxorubicin Hydrochloride Injection that you receive in your lifetime. Your risk of heart failure is higher if you:have other heart problemshave had or are currently receiving radiation therapy to your chesthave had treatment with certain other anti-cancer medicinestake other medicines that can have severe side effects on your heartTell your healthcare provider if you get any of these symptoms of heart failure during or after treatment with Doxorubicin Hydrochloride Injection:extreme tiredness or weaknessfast heartbeatshortness of breathswelling of your feet and anklesYour healthcare provider will do tests to check the strength of your heart muscle before, during, and after your treatment with Doxorubicin Hydrochloride Injection.Heart rhythm problems. Doxorubicin Hydrochloride Injection can cause serious heart rhythm problems that may lead to death. This can happen during your infusion, within a few hours after your infusion or anytime during treatment with Doxorubicin Hydrochloride Injection. Tell your healthcare provider if you get any symptoms of heart rhythm problems, such as feeling as if your heart is beating fast, irregular or slow, or you feel lightheaded, dizzy, short of breath, chest discomfort or you faint.Risk of new cancers. You may have an increased risk of developing certain blood cancers called acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after treatment with Doxorubicin Hydrochloride Injection. Talk with your healthcare provider about your risk of developing new cancers if you receive Doxorubicin Hydrochloride Injection.Skin damage at or near the vein where doxorubicin hydrochloride is given. Doxorubicin Hydrochloride Injection can damage the skin if it leaks out of the vein and might cause blisters, skin sores or severe tissue damage, which may require skin grafts. Tell your healthcare provider if you get burning or stinging during your infusion.Decreased blood cell counts. Doxorubicin Hydrochloride Injection can cause a decrease in neutrophils (a type of white blood cell important in fighting bacterial infections) and platelets (important for clotting and to control bleeding). This may lead to a serious infection, the need for blood transfusions, treatment in a hospital or death. Your healthcare provider will check your blood cell counts before each infusion and during treatment with Doxorubicin Hydrochloride Injection. Call your healthcare provider right away if you get a fever (temperature of 100.4°F or higher) or chills with shivering.What is Doxorubicin Hydrochloride Injection?Doxorubicin Hydrochloride Injection is a prescription medicine used to treat certain types of cancers. Doxorubicin Hydrochloride Injection may be used alone or along with other anti-cancer medicines.Do not receive Doxorubicin Hydrochloride Injection if:you have had a recent heart attack (within the past 4 to 6 weeks) or have severe heart problems.your blood cell counts (platelets, red blood cells, and white blood cells) are very low because of prior chemotherapy.you have severe liver problems.you have had a severe allergic reaction to Doxorubicin Hydrochloride InjectionBefore you receive Doxorubicin Hydrochloride Injection, tell your healthcare provider about all of your medical conditions, including if you:have heart problems including heart failure.are currently receiving radiation therapy or plan to receive radiation to the chest.have liver problems.have had an allergic reaction to Doxorubicin Hydrochloride Injection.are pregnant or plan to become pregnant. Doxorubicin Hydrochloride can harm your unborn baby. You should not become pregnant during treatment with Doxorubicin Hydrochloride Injection. Tell your healthcare provider right away if you become pregnant or think you may be pregnant.Females who are able to become pregnant:Your healthcare provider will check to see if you are pregnant before you start treatment with Doxorubicin Hydrochloride InjectionYou should use effective birth control (contraception) during treatment with Doxorubicin Hydrochloride Injection and for 6 months after treatment. Males:Doxorubicin hydrochloride can affect your sperm and could cause birth defects.If you have a female partner who can become pregnant, you should use effective birth control during treatment with Doxorubicin Hydrochloride Injection and for 3 months after treatmentIf you have a pregnant partner, you should use condoms during treatment with Doxorubicin Hydrochloride Injection and for at least 10 days after the final doseTalk to your healthcare provider about birth control methods that may be right for youare breastfeeding or plan to breastfeed. Doxorubicin hydrochloride can pass into your breast milk. Do not breastfeed during treatment with doxorubicin hydrochloride and for 10 days after the final dose. Talk to your healthcare provider about the best way to feed your baby during this time. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How will I receive Doxorubicin Hydrochloride Injection?Doxorubicin hydrochloride will be given to you into your vein through an intravenous (IV) line.Your healthcare provider will do blood tests to check for side effects during treatment with Doxorubicin Hydrochloride Injection.Your healthcare provider may stop your treatment, change the timing of your treatment, or change the dose of your treatment if you have certain side effects while receiving Doxorubicin Hydrochloride Injection.What are the possible side effects of Doxorubicin Hydrochloride Injection? Doxorubicin Hydrochloride may cause serious side effects, including:See “What is the most important information I should know about Doxorubicin Hydrochloride Injection?”The most common side effects of Doxorubicin Hydrochloride Injection include:total hair loss (alopecia). Your hair may re-grow after your treatment.nauseavomitingOther side effects:Red colored urine. You may have red colored urine for 1 to 2 days after your infusion of Doxorubicin Hydrochloride Injection. This is normal. Tell your healthcare provider if it does not stop in a few days, or if you see what looks like blood or blood clots in your urine.Call your healthcare provider if you have severe symptoms that prevent you from eating or drinking, such as:nauseavomitingdiarrheamouth pain or soresDoxorubicin Hydrochloride may cause fertility problems in males. This could affect your ability to father a child. Talk to your healthcare provider if this is a concern for you.Doxorubicin Hydrochloride may cause fertility problems in females. Your periods (menstrual cycle) may completely stop when you receive Doxorubicin Hydrochloride Injection. Your periods may or may not return following treatment. Early menopause has also happened. Talk to your healthcare provider if this is a concern for you.These are not all of the possible side effects of Doxorubicin Hydrochloride Injection.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.General information about the safe and effective use of Doxorubicin Hydrochloride Injection.Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.You can ask your pharmacist or healthcare provider for information about Doxorubicin Hydrochloride Injection that is written for health professionals.For more information, call NorthStar at 1-800-206-7821. What are the ingredients in Doxorubicin Hydrochloride Injection? Active ingredient: doxorubicin hydrochlorideInactive ingredients: 0.9% sodium chloride, water for injection, and hydrochloric acid.Manufactured For: Northstar Rx LLC, Memphis, TN 38141Manufactured In Romania By: Sindan Pharma SRL, Bucharest 1, Romania 011171This Patient Information has been approved by the U.S. Food and Drug Administration.                                                    Rev. A 9/2020

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