• 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%–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 cardiot...
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 . Doxorubicin Hydrochloride Injection is indicated for the treatment of • acute lymphoblastic leukemia • acute myeloblastic leukemia • Hodgkin lymphoma • non-Hodgkin lymphoma (NHL) • metastatic breast cancer • m...
The recommended dosage of Doxorubicin Hydrochloride Injection 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 . • The recommended dosage of Doxorubicin Hydrochloride Injection when used as a single agent is 60 mg/m 2 to 75 mg/m 2 intravenously every 21 days. • The recommended dosage of Doxorubicin Hydrochlor...
Doxorubicin Hydrochloride Injection Doxorubicin Hydrochloride Injection is a sterile, isotonic solution, available in single-dose polypropylene (CYTOSAFE) ® vials, and multiple-dose polypropylene (CYTOSAFE) ® vials: Unit of Sale Total Strength/Total Volume (Concentration) NDC 0069-4004-05 Carton of 1 Single-dose Vial 10 mg/5 mL (2 mg/mL) NDC 0069-4015-10 Carton of 1 Single-dose Vial 20 mg/10 mL (2 mg/mL) NDC 0069-...
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www.pfizer.comDoxorubicin 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.
Doxorubicin Hydrochloride Injection is indicated for the treatment of
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.
Cardiomyopathy
Discontinue Doxorubicin Hydrochloride Injection in patients who develop signs or symptoms of cardiomyopathy [see Warnings and Precautions (5.1)].
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.
| Serum Total Bilirubin Concentration | Dosage Modification |
|---|---|
1.2–3 mg/dL | 50% |
3.1–5 mg/dL | 75% |
Greater than 5 mg/dL | Do not initiate Doxorubicin Hydrochloride Injection; |
Doxorubicin Hydrochloride Injection is a hazardous drug. Follow applicable special handling and disposal procedures.1
Preparation
Dilution of Doxorubicin Hydrochloride Injection
Administration
Administration by Intravenous Injection
Administration by Continuous Intravenous Infusion
Management of Suspected Extravasation
Immediately discontinue Doxorubicin Hydrochloride Injection for burning or stinging sensation or other evidence indicating peri-venous infiltration or extravasation. Manage confirmed or suspected extravasation as follows:
Management of Contact with Skin or Eyes
Treat 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 Drugs
Do 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.
Doxorubicin Hydrochloride Injection:
Doxorubicin Hydrochloride Injection are contraindicated in patients with:
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/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.
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, 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.
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.
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.
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.
The clearance of doxorubicin 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.
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.
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.
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)].
The following clinically significant adverse reactions are described elsewhere in the labeling.
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 Cancer
The 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.
| Adverse Reactions | AC* N = 1492 | Conventional CMF N = 739 |
|---|---|---|
| % | % | |
| AC = doxorubicin hydrochloride, cyclophosphamide; CMF = cyclophosphamide, methotrexate, fluorouracil | ||
Alopecia | 92 | 71 |
Vomiting | ||
Vomiting ≤12 hours | 34 | 25 |
Vomiting >12 hours | 37 | 12 |
Intractable | 5 | 2 |
Leukopenia | ||
Grade 3 (1,000–1,999 /mm3) | 3.4 | 9.4 |
Grade 4 (<1000 /mm3) | 0.3 | 0.3 |
Shock, sepsis | 2 | 1 |
Systemic infection | 2 | 1 |
Cardiac dysfunction | ||
Asymptomatic | 0.2 | 0.1 |
Transient | 0.1 | 0 |
Symptomatic | 0.1 | 0 |
Thrombocytopenia | ||
Grade 3 (25,000–49,999 /mm3) | 0 | 0.3 |
Grade 4 (<25,000 /mm3) | 0.1 | 0 |
* Includes pooled data from patients who received either AC for 4 cycles or AC for 4 cycles followed by CMF for 3 cycles
The following adverse reactions have been identified during postapproval 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 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 ALT, increased AST
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
Inhibitors of CYP3A4, CYP2D6, and P-gp
Concomitant use of doxorubicin hydrochloride with inhibitors of CYP3A4, CYP2D6, or P-glycoprotein (P-gp), increased concentrations of doxorubicin, 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-gp
Concomitant use of doxorubicin hydrochloride with inducers of CYP3A4, CYP2D6, or P-gp may decrease the concentration of doxorubicin. Avoid concomitant use of Doxorubicin Hydrochloride Injection with inducers of CYP3A4, CYP2D6, or P-gp.
Paclitaxel
Paclitaxel, when given prior to doxorubicin hydrochloride, increases the plasma-concentrations of doxorubicin and its metabolites. Administer Doxorubicin Hydrochloride Injection prior to paclitaxel if used concomitantly.
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 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.
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.
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 2–3 weeks) and doxorubicin hydrochloride (50 mg/m2 intravenous once per cycle every 2–3 weeks) alone or with vincristine and prednisone, all developed hepatic dysfunction manifested by increased total serum bilirubin, alkaline phosphatase and aspartate aminotransferase.
Risk Summary
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 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.
Data
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 embryo-fetal 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.
Risk Summary
Doxorubicin 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 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.
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating Doxorubicin Hydrochloride Injection.
Contraception
Females
Doxorubicin 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)].
Males
Doxorubicin 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)].
Infertility
Females
In 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)].
Males
Doxorubicin 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)].
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 infants less than 2 years as compared to adults [see Clinical Pharmacology (12.3)].
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.
The clearance of doxorubicin 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)].
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 4–7 after the overdose and chills and pyrexia on day 7. The patient was treated with antibiotics and platelets and recovered 18 days after overdose.
Doxorubicin hydrochloride is an anthracycline topoisomerase inhibitor isolated from cultures of Streptomyces peucetius var. caesius. The chemical name of doxorubicin hydrochloride 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 chemical structure of doxorubicin hydrochloride is:
Doxorubicin Hydrochloride Injection, for intravenous use is a clear red, sterile, isotonic aqueous solution provided in vials containing 10 mg/5 mL doxorubicin hydrochloride (equivalent to 9.37 mg of doxorubicin free base), 20 mg/10 mL doxorubicin hydrochloride (equivalent to 18.74 mg of doxorubicin free base), 50 mg/25 mL doxorubicin hydrochloride (equivalent to 46.86 mg of doxorubicin free base), 150 mg/75 mL doxorubicin hydrochloride (140.58 mg of doxorubicin free base), or 200 mg/100 mL doxorubicin hydrochloride (equivalent to 187.4 mg of doxorubicin free base). The drug product has demonstrated inherent antimicrobial activity suitable for a multiple dose presentation. Each milliliter of solution contains 2 mg of doxorubicin hydrochloride and 9 mg of sodium chloride. The pH of the solution is adjusted to 3.0 with hydrochloric acid, USP.
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.
Pharmacokinetic studies conducted in patients with various types of tumors have shown that doxorubicin follows multiphasic disposition after intravenous injection. In four patients, doxorubicin demonstrated dose-independent pharmacokinetics across a dose range of 30 mg/m2 to 70 mg/m2.
Distribution
The distribution half-life is approximately 5 minutes. Steady-state distribution volume ranges from 809 L/m2 to 1214 L/m2. Binding of doxorubicin and its major metabolite, doxorubicinol, to plasma proteins is 75% and is independent of plasma concentration of doxorubicin up to 1.1 µg/mL.
Doxorubicin does not cross the blood brain barrier.
Elimination
Plasma clearance is ranges from 324 mL/min/m2 to 809 mL/min/m2. The terminal half-life is 20 hours to 48 hours.
Metabolism
Doxorubicin 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. 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 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 Populations
Weight
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 mg/m2 to 75 mg/m2 of doxorubicin hydrochloride to 60 patients ranging from 2 months to 20 years, doxorubicin 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)].
Sex
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/m2 versus 433 mL/min/m2). 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 elevated serum total bilirubin concentrations [see Dosage and Administration (2.4), Warnings and Precautions (5.5)].
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.
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.
| Study (starting year) | Regimens | No. of Cycles | No. of Patients | Doxorubicin Hydrochloride‑Containing Regimens vs. CMF HR* (95% CI) | |
|---|---|---|---|---|---|
| DFS | OS | ||||
| Abbreviations: 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 | |||||
| |||||
NSABP B-15 | AC | 4 | 1562† | 0.93 (0.82, 1.06) | 0.97 (0.83, 1.12) |
| |||||
CMF | 6 | 776 | |||
| |||||
SECSG 2 | FAC | 6 | 260 | 0.86 (0.66, 1.13) | 0.93 (0.69, 1.26) |
| |||||
CMF | 6 | 268 | |||
| |||||
ONCOFRANCE | FACV | 12 | 138 | 0.71 (0.49, 1.03) | 0.65 (0.44, 0.96) |
| |||||
CMF | 12 | 113 | |||
| |||||
SE Sweden BCG A | AC | 6 | 21 | 0.59 (0.22, 1.61) | 0.53 (0.21, 1.37) |
| |||||
CMF | 6 | 22 | |||
| |||||
NSABC Israel Br0283 | AVbCMF‡ | 4 | 55 | 0.91 (0.53, 1.57) | 0.88 (0.47, 1.63) |
| |||||
CMF | 6 | 50 | |||
| |||||
Austrian BCSG 3 | CMFVA | 6 | 121 | ||
1.07 (0.73, 1.55) | 0.93 (0.64, 1.35) | ||||
CMF | 8 | 124 | |||
Combined Studies | Doxorubicin Hydrochloride-Containing Regimen | 2157 | |||
0.91 (0.82, 1.01) | 0.91 (0.81, 1.03) | ||||
CMF | 1353 | ||||
* 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.
† 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.
‡ Patients received alternating cycles of AVb and CMF.
Figure 1. Meta-analysis of Disease-Free Survival |
 |
Figure 2. Meta-analysis of Overall Survival |
 |
www.osha.gov/SLTC/hazardousdrugs/index.htmlDoxorubicin Hydrochloride Injection
Doxorubicin Hydrochloride Injection is a sterile, isotonic solution, available in single-dose polypropylene (CYTOSAFE)® vials, and multiple-dose polypropylene (CYTOSAFE)® vials:
Unit of Sale | Total Strength/Total Volume (Concentration) |
NDC 0069-4004-05 Carton of 1 Single-dose Vial | 10 mg/5 mL (2 mg/mL) |
NDC 0069-4015-10 Carton of 1 Single-dose Vial | 20 mg/10 mL (2 mg/mL) |
NDC 0069-4026-25 Carton of 1 Single-dose Vial | 50 mg/25 mL (2 mg/mL) |
NDC 0069-4037-01 Carton of 1 Multiple-dose Vial | 200 mg/100 mL (2 mg/mL) |
Retain in carton until contents are used. For single-dose vials, discard unused portion.
Doxorubicin Hydrochloride Injection is a sterile, isotonic solution, available in single-dose ONCO-TAIN® glass vials, and multiple-dose ONCO-TAIN® glass vials:
Unit of Sale | Total Strength/Total Volume (Concentration) |
NDC 0069-4205-05 Carton of 1 Single-dose Vial | 10 mg/5 mL (2 mg/mL) |
NDC 0069-0255-10 Carton of 1 Single-dose Vial | 20 mg/10 mL (2 mg/mL) |
NDC 0069-3358-25 Carton of 1 Single-dose Vial | 50 mg/25 mL (2 mg/mL) |
NDC 0069-1442-04 Carton of 1 Multiple-dose Vial | 200 mg/100 mL (2 mg/mL) |
ONCO-TAIN® is the vial external protection system.
Retain in carton until contents are used. For single-dose ONCO-TAIN® glass vials, discard unused portion.
Storage
Store all vials at 2°C to 8°C (36°F to 46°F). Protect from light.
Storage of Doxorubicin Hydrochloride Injection under refrigerated conditions can result in the formation of a gelled product. Place gelled product at room temperature [15°C to 30°C (59°F to 86°F)] for 2 to 4 hours to return the product to a slightly viscous, mobile solution.
Handling and Disposal
Doxorubicin Hydrochloride Injection is a hazardous drug. Follow applicable special handling and disposal procedures.1
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Cardiomyopathy
Advise 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 Malignancy
Advise patients of the increased risk of treatment-related leukemia [see Warnings and Precautions (5.2)].
Myelosuppression
Advise 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 Toxicity
Advise 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 and for at least 10 days after the final dose [see Use in Specific Populations (8.3)].
Lactation
Advise 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)].
Infertility
Advise females and males of the potential loss of fertility from Doxorubicin Hydrochloride Injection [see Use in Specific Populations (8.3)].
Gastrointestinal and Dermatologic Adverse Reactions
Advise 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.
This product's labeling may have been updated. For the most current prescribing information, please visit www.pfizer.com.
Distributed by
Pfizer Labs
Division of Pfizer Inc.
New York, NY 10001
PREMIERProRx® is a registered trademark of Premier Healthcare Alliance, L.P., used under license.
LAB-0702-8.0
| This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 7/2024 | ||
Patient Information | ||
What is the most important information I should know about Doxorubicin?
| ||
|
| |
Your healthcare provider will do tests to check the strength of your heart muscle before, during, and after your treatment with Doxorubicin. | ||
| ||
What is Doxorubicin? | ||
Do not receive Doxorubicin if:
| ||
Before you receive Doxorubicin, tell your healthcare provider about all of your medical conditions, including if you:
| ||
How will I receive Doxorubicin?
| ||
What are the possible side effects of Doxorubicin? The most common side effects of Doxorubicin include:
Other side effects:
Doxorubicin 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 may cause fertility problems in females. Your periods (menstrual cycle) may completely stop when you receive Doxorubicin. 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. | ||
General information about the safe and effective use of Doxorubicin. | ||
What are the ingredients in Doxorubicin? Pfizer Labs Division of Pfizer Inc. New York, NY 10001 
LAB-0703-5.0 For more information, call 1-800-438-1985 or visit | ||
NDC 0069-4004-05
Single-dose
Discard unused portion
Rx only
DOXOrubicin
Hydrochloride Injection
10 mg/5 mL
(2 mg/mL)
For Intravenous Use Only
Caution: Cytotoxic Agent
NDC 0069-4004-05
Rx only
Single-dose: Discard unused portion
DOXOrubicin
Hydrochloride
Injection
10 mg/5 mL
(2 mg/mL)
For Intravenous Use Only
Cytosafe® Vial
Caution: Cytotoxic Agent
PREMIERProRx®
NDC 0069-4015-10
Single-dose
Discard unused portion
Rx only
DOXOrubicin
Hydrochloride Injection
20 mg/10 mL
(2 mg/mL)
For Intravenous Use Only
Caution: Cytotoxic Agent
NDC 0069-4015-10
Rx only
Single-dose: Discard unused portion
DOXOrubicin
Hydrochloride
Injection
20 mg/10 mL
(2 mg/mL)
For Intravenous Use Only
Cytosafe® Vial
Caution: Cytotoxic Agent
PREMIERProRx®
NDC 0069-4026-25
Single-dose
Discard unused portion
Rx only
DOXOrubicin
Hydrochloride Injection
50 mg/25 mL
(2 mg/mL)
For Intravenous Use Only
Caution: Cytotoxic Agent
NDC 0069-4026-25
Rx only
Single-dose: Discard unused portion
DOXOrubicin
Hydrochloride
Injection
50 mg/25 mL
(2 mg/mL)
For Intravenous Use Only
Cytosafe® Vial
Caution: Cytotoxic Agent
PREMIERProRx®
NDC 0069-4037-01
Multiple-dose Vial
Rx only
DOXOrubicin
Hydrochloride Injection
200 mg/100 mL
(2 mg/mL)
For Intravenous Use Only
Caution: Cytotoxic Agent
PREMIERProRx®
NDC 0069-4037-01
Rx only
Multiple-dose Vial
DOXOrubicin
Hydrochloride
Injection
200 mg/100 mL
(2 mg/mL)
For Intravenous Use Only
Cytosafe® Vial
Caution: Cytotoxic Agent
PREMIERProRx®
NDC 0069-4205-05
Single-dose vial
Discard unused portion
Rx only
DOXOrubicin
Hydrochloride Injection
10 mg/5 mL
(2 mg/mL)
For Intravenous Use Only
NDC 0069-4205-05
Single-dose vial. Discard unused portion
DOXOrubicin
Hydrochloride
Injection
10 mg/5 mL
(2 mg/mL)
For Intravenous Use Only
PREMIERProRx®
Rx only
Warning: Hazardous Drug
NDC 0069-0255-10
Single-dose vial
Discard unused portion
Rx only
DOXOrubicin
Hydrochloride Injection
20 mg/10 mL
(2 mg/mL)
For Intravenous Use Only
Warning: Hazardous Drug
NDC 0069-0255-10
Single-dose vial. Discard unused portion
DOXOrubicin
Hydrochloride
Injection
20 mg/10 mL
(2 mg/mL)
For Intravenous Use Only
PREMIERProRx®
Rx only
Warning: Hazardous Drug
NDC 0069-3358-25
Single-dose vial
Discard unused portion
Rx only
DOXOrubicin
Hydrochloride Injection
50 mg/25 mL
(2 mg/mL)
For Intravenous Use Only
Warning: Hazardous Drug
NDC 0069-3358-25
Single-dose vial. Discard unused portion
DOXOrubicin
Hydrochloride
Injection
50 mg/25 mL
(2 mg/mL)
For Intravenous Use Only
PREMIERProRx®
Rx only
Warning: Hazardous Drug
NDC 0069-1442-04
Multiple-dose Vial
Rx only
DOXOrubicin
Hydrochloride Injection
200 mg/100 mL
(2 mg/mL)
For Intravenous Use Only
Warning: Hazardous Drug
NDC 0069-1442-04
Multiple-dose Vial
DOXOrubicin
Hydrochloride
Injection
200 mg/100 mL
(2 mg/mL)
For Intravenous Use Only
PREMIERProRx®
Rx only
Warning: Hazardous Drug
| RxCUI | RxNorm string | TTY | SPL version |
|---|---|---|---|
| 1790097 | DOXOrubicin HCl 10 MG in 5 mL Injection | PSN | 14 |
| 1191138 | DOXOrubicin HCl 2 MG/ML Injectable Solution | PSN | 14 |
| 1790099 | DOXOrubicin HCl 20 MG in 10 ML Injection | PSN | 14 |
| 1790100 | DOXOrubicin HCl 50 MG in 25 ML Injection | PSN | 14 |
| 1790099 | 10 ML doxorubicin hydrochloride 2 MG/ML Injection | SCD | 14 |
| 1790100 | 25 ML doxorubicin hydrochloride 2 MG/ML Injection | SCD | 14 |
| 1790097 | 5 ML doxorubicin hydrochloride 2 MG/ML Injection | SCD | 14 |
| 1191138 | doxorubicin hydrochloride 2 MG/ML Injectable Solution | SCD | 14 |
| 1790097 | doxorubicin hydrochloride 10 MG per 5 ML Injection | SY | 14 |
| 1790099 | doxorubicin hydrochloride 20 MG per 10 ML Injection | SY | 14 |
| 1790100 | doxorubicin hydrochloride 50 MG per 25 ML Injection | SY | 14 |
| Class | Version | Type | Effective |
|---|---|---|---|
| DOXORUBICIN Pharmacologic Class Indexing | 2 | Indexing - Pharmacologic Class | 20180813 |
| Resource | Code type | Value | Equivalent identifiers | Source image |
|---|---|---|---|---|
| Barcode | DataBar Limited | (01)10300690255108 | GTIN-14: 10300690255108 GTIN storage (14 digits): 10300690255108 | doxorubicin-16.jpg |
| Barcode | DataBar Limited | (01)10300691442040 | GTIN-14: 10300691442040 GTIN storage (14 digits): 10300691442040 | doxorubicin-20.jpg |
| Barcode | DataBar Limited | (01)10300693358257 | GTIN-14: 10300693358257 GTIN storage (14 digits): 10300693358257 | doxorubicin-18.jpg |
| Barcode | DataBar Stacked | (01)10300694205055 | GTIN-14: 10300694205055 GTIN storage (14 digits): 10300694205055 | doxorubicin-14.jpg |
| Barcode | EAN-13 | 0300694004057 | GTIN-13: 0300694004057 EAN-13: 0300694004057 GTIN-12: 300694004057 UPC-A: 300694004057 GTIN storage (14 digits): 00300694004057 | doxorubicin-07.jpg |
| Barcode | EAN-13 | 0300694015107 | GTIN-13: 0300694015107 EAN-13: 0300694015107 GTIN-12: 300694015107 UPC-A: 300694015107 GTIN storage (14 digits): 00300694015107 | doxorubicin-09.jpg |
| Barcode | EAN-13 | 0300694026257 | GTIN-13: 0300694026257 EAN-13: 0300694026257 GTIN-12: 300694026257 UPC-A: 300694026257 GTIN storage (14 digits): 00300694026257 | doxorubicin-11.jpg |
| Barcode | EAN-13 | 0300694037017 | GTIN-13: 0300694037017 EAN-13: 0300694037017 GTIN-12: 300694037017 UPC-A: 300694037017 GTIN storage (14 digits): 00300694037017 | doxorubicin-13.jpg |
| Data code | Code 128 | PAA145618 | doxorubicin-10.jpg |
| Package NDC | Product | Description | Form | Quantity | Strength | SPL version |
|---|---|---|---|---|---|---|
| 0069-0255-10 | Doxorubicin Hydrochloride | 1 in 1 CARTON | INJECTION, SOLUTION | 1 | 14 | |
| 0069-0255-10 | Doxorubicin Hydrochloride | 10 mL in 1 VIAL, SINGLE-DOSE | INJECTION, SOLUTION | 10 | 14 | |
| 0069-1442-04 | Doxorubicin Hydrochloride | 100 mL in 1 VIAL, MULTI-DOSE | INJECTION, SOLUTION | 100 | 14 | |
| 0069-1442-04 | Doxorubicin Hydrochloride | 1 in 1 CARTON | INJECTION, SOLUTION | 1 | 14 | |
| 0069-3358-25 | Doxorubicin Hydrochloride | 25 mL in 1 VIAL, SINGLE-DOSE | INJECTION, SOLUTION | 25 | 14 | |
| 0069-3358-25 | Doxorubicin Hydrochloride | 1 in 1 CARTON | INJECTION, SOLUTION | 1 | 14 | |
| 0069-4004-05 | Doxorubicin Hydrochloride | 5 mL in 1 VIAL, SINGLE-DOSE | INJECTION, SOLUTION | 5 | 14 | |
| 0069-4004-05 | Doxorubicin Hydrochloride | 1 in 1 CARTON | INJECTION, SOLUTION | 1 | 14 | |
| 0069-4015-10 | Doxorubicin Hydrochloride | 10 mL in 1 VIAL, SINGLE-DOSE | INJECTION, SOLUTION | 10 | 14 | |
| 0069-4015-10 | Doxorubicin Hydrochloride | 1 in 1 CARTON | INJECTION, SOLUTION | 1 | 14 | |
| 0069-4026-25 | Doxorubicin Hydrochloride | 1 in 1 CARTON | INJECTION, SOLUTION | 1 | 14 | |
| 0069-4026-25 | Doxorubicin Hydrochloride | 25 mL in 1 VIAL, SINGLE-DOSE | INJECTION, SOLUTION | 25 | 14 | |
| 0069-4037-01 | Doxorubicin Hydrochloride | 100 mL in 1 VIAL, MULTI-DOSE | INJECTION, SOLUTION | 100 | 14 | |
| 0069-4037-01 | Doxorubicin Hydrochloride | 1 in 1 CARTON | INJECTION, SOLUTION | 1 | 14 | |
| 0069-4205-05 | Doxorubicin Hydrochloride | 1 in 1 CARTON | INJECTION, SOLUTION | 1 | 14 | |
| 0069-4205-05 | Doxorubicin Hydrochloride | 5 mL in 1 VIAL, SINGLE-DOSE | INJECTION, SOLUTION | 5 | 14 |
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 0069-4004-05 | ML - Milliliter | 0069-4004 | c1c6742e-2516-424c-999e-efa7553455ac | 1 | 2014-04-03 |
| 0069-4015-10 | ML - Milliliter | 0069-4015 | ea1005f8-ccd2-4259-8815-879f208f6c7e | 1 | 2014-04-03 |
| 0069-4026-25 | ML - Milliliter | 0069-4026 | 43c552a6-1493-4414-af01-d49531768ab1 | 1 | 2014-04-03 |
| 0069-4037-01 | ML - Milliliter | 0069-4037 | 8993f8b6-acad-4234-84d6-feb26d6f8db7 | 1 | 2014-04-03 |
| 0069-4205-05 | ML - Milliliter | 0069-4205 | 6d7a834f-1e95-4468-bad1-eae825c6be2b | 1 | 2024-12-10 |
| 0069-0255-10 | ML - Milliliter | 0069-0255 | 10c56971-b58c-43fc-8562-643774f25abf | 1 | 2024-11-05 |
| 0069-3358-25 | ML - Milliliter | 0069-3358 | 98bd6605-8023-4ed9-8ba4-d4af620d5946 | 1 | 2024-12-10 |
| 0069-1442-04 | ML - Milliliter | 0069-1442 | a5b17f37-05ca-4a82-872d-508c4438a459 | 1 | 2024-11-05 |
| Ingredient | Type | UNII | SPL version | Uploaded |
|---|---|---|---|---|
| DOXORUBICIN HYDROCHLORIDE | ACTIVE INGREDIENT | 82F2G7BL4E | 2 | |
| DOXORUBICIN | ACTIVE MOIETY | 80168379AG | 2 | |
| HYDROCHLORIC ACID | INACTIVE INGREDIENT | QTT17582CB | 2 | |
| SODIUM CHLORIDE | INACTIVE INGREDIENT | 451W47IQ8X | 2 |
Every source-derived product name is available through these pages.
| Product NDC | Package NDC |
|---|---|
| 0069-4004 | 0069-4004-05 |
| 0069-4015 | 0069-4015-10 |
| 0069-4026 | 0069-4026-25 |
| 0069-4037 | 0069-4037-01 |
| 0069-4205 | 0069-4205-05 |
| 0069-0255 | 0069-0255-10 |
| 0069-3358 | 0069-3358-25 |
| 0069-1442 | 0069-1442-04 |
Every source-derived ingredient row is available through these pages.
| Version | Effective date | Source | Hydrated |
|---|---|---|---|
| 11 | 2023-05-04 | full-release | 2026-05-31 20:49:03 |
Inactive Ingredient Database values describe FDA-listed use contexts. The match method and ambiguity count are shown because ingredient names, routes, and dosage forms are not always unique. Browse recovered IID releases and source provenance.
| DailyMed ingredient | IID ingredient | UNII | Dosage form / route | Potency | Maximum daily exposure | Match |
|---|---|---|---|---|---|---|
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| HYDROCHLORIC ACID | HYDROCHLORIC ACID | QTT17582CB | INJECTION, SOLUTION / INTRAVENOUS | 1037 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| HYDROCHLORIC ACID | HYDROCHLORIC ACID | QTT17582CB | INJECTION, SOLUTION / INTRAVENOUS | 1037 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| HYDROCHLORIC ACID | HYDROCHLORIC ACID | QTT17582CB | INJECTION, SOLUTION / INTRAVENOUS | 1037 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| HYDROCHLORIC ACID | HYDROCHLORIC ACID | QTT17582CB | INJECTION, SOLUTION / INTRAVENOUS | 1037 mg | ||
| HYDROCHLORIC ACID | HYDROCHLORIC ACID | QTT17582CB | INJECTION, SOLUTION / INTRAVENOUS | 1037 mg | ||
| HYDROCHLORIC ACID | HYDROCHLORIC ACID | QTT17582CB | INJECTION, SOLUTION / INTRAVENOUS | 1037 mg | ||
| HYDROCHLORIC ACID | HYDROCHLORIC ACID | QTT17582CB | INJECTION, SOLUTION / INTRAVENOUS | 1037 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| HYDROCHLORIC ACID | HYDROCHLORIC ACID | QTT17582CB | INJECTION, SOLUTION / INTRAVENOUS | 1037 mg |
All distinct exact application/product contexts derived from this label’s complete NDC list are paginated below.
| Application-product | Trade name | Ingredient | Strength | Dosage form / route | TE codes | RLD / RS | Approval date |
|---|---|---|---|---|---|---|---|
| N050629-001 | DOXORUBICIN HYDROCHLORIDE | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 |
| N050629-002 | DOXORUBICIN HYDROCHLORIDE | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 |
| N050629-003 | DOXORUBICIN HYDROCHLORIDE | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 |
| Application-product | TE code |
|---|---|
| N050629-001 | AP |
| N050629-002 | AP |
Observed FDA ZIP history: Each table is queried independently by exact application/product key from successfully parsed Orange Book snapshots. Capture times identify archived source observations; absence or a change between snapshots is not inferred. FDA publication files that were not recoverable as structured ZIP data are not represented as states.
| Captured | Edition | Application-product | Trade name | Strength | Dosage form / route | Product TE source text | RLD / RS | Approval date | Source SHA-256 |
|---|---|---|---|---|---|---|---|---|---|
| 2026-09-14 22:38:34 | 2026-08 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | 84e616aacf4f… | |
| 2026-08-18 06:07:40 | 2026-07 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | caaa826d4ba7… | |
| 2026-02-19 14:30 UTC | 2026-02 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | 011fe1cb6892… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | 31067a03dcf5… | |
| 2025-08-23 18:47 UTC | 2025-08 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | 6a471c1ec25d… |
| 2025-08-23 18:47 UTC | 2025-08 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | 6a471c1ec25d… |
| 2025-08-23 18:47 UTC | 2025-08 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | 6a471c1ec25d… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | fd3edfee7708… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | fd3edfee7708… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | fd3edfee7708… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | b8a1b40f171c… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | b8a1b40f171c… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | b8a1b40f171c… | |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | 03ed91905a0d… | |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | 2680178bc6a6… | |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | 5bbf6a4d5a75… | |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | d8e5a09893c0… | |
| 2024-10-29 15:01 UTC | 2024-10 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | d06236e962d9… | |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N050629-002 | DOXORUBICIN HYDROCHLORIDE | 200MG/100ML | INJECTABLE / INJECTION | AP | RLD, RS | 1988-05-03 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N050629-003 | DOXORUBICIN HYDROCHLORIDE | 150MG/75ML | INJECTABLE / INJECTION | RLD | 2011-03-28 | 79d66fd596c7… | |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | N050629-001 | DOXORUBICIN HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD, RS | 1987-12-23 | 301d65b070ca… |
| Captured | Edition | Application-product | TE code | Order | Source SHA-256 |
|---|---|---|---|---|---|
| 2026-09-14 22:38:34 | 2026-08 | N050629-001 | AP | 1 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N050629-002 | AP | 1 | 84e616aacf4f… |
| 2026-08-18 06:07:40 | 2026-07 | N050629-001 | AP | 1 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N050629-002 | AP | 1 | caaa826d4ba7… |
| 2026-02-19 14:30 UTC | 2026-02 | N050629-001 | AP | 1 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N050629-002 | AP | 1 | 011fe1cb6892… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N050629-001 | AP | 1 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N050629-002 | AP | 1 | 31067a03dcf5… |
| 2025-08-23 18:47 UTC | 2025-08 | N050629-001 | AP | 1 | 6a471c1ec25d… |
| 2025-08-23 18:47 UTC | 2025-08 | N050629-002 | AP | 1 | 6a471c1ec25d… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N050629-001 | AP | 1 | fd3edfee7708… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N050629-002 | AP | 1 | fd3edfee7708… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N050629-001 | AP | 1 | b8a1b40f171c… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N050629-002 | AP | 1 | b8a1b40f171c… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N050629-001 | AP | 1 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N050629-002 | AP | 1 | 03ed91905a0d… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N050629-001 | AP | 1 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N050629-002 | AP | 1 | 2680178bc6a6… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N050629-001 | AP | 1 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N050629-002 | AP | 1 | 5bbf6a4d5a75… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N050629-001 | AP | 1 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N050629-002 | AP | 1 | d8e5a09893c0… |
| 2024-10-29 15:01 UTC | 2024-10 | N050629-001 | AP | 1 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N050629-002 | AP | 1 | d06236e962d9… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N050629-001 | AP | 1 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N050629-002 | AP | 1 | 79d66fd596c7… |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | N050629-001 | AP | 1 | 301d65b070ca… |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | N050629-002 | AP | 1 | 301d65b070ca… |
| 2024-06-18 03:08 UTC · 5 captures of this ZIP | 2024-06 | N050629-001 | AP | 1 | 1e350fbaab3a… |
| 2024-06-18 03:08 UTC · 5 captures of this ZIP | 2024-06 | N050629-002 | AP | 1 | 1e350fbaab3a… |
| 2024-05-31 18:47 UTC | 2024-05 | N050629-001 | AP | 1 | 8072bd15b7f6… |
| 2024-05-31 18:47 UTC | 2024-05 | N050629-002 | AP | 1 | 8072bd15b7f6… |
| 2022-06-29 02:47 UTC · 2 captures of this ZIP | 2022-06 | N050629-001 | AP | 1 | 5c6f7cd8ea54… |
| 2022-06-29 02:47 UTC · 2 captures of this ZIP | 2022-06 | N050629-002 | AP | 1 | 5c6f7cd8ea54… |
| 2022-04-08 23:34 UTC | 2022-04 | N050629-001 | AP | 1 | 5d02ea3f76ae… |
| 2022-04-08 23:34 UTC | 2022-04 | N050629-002 | AP | 1 | 5d02ea3f76ae… |
| 2022-04-04 05:41 UTC | 2022-04 | N050629-001 | AP | 1 | 4b0b4de00fa7… |
| 2022-04-04 05:41 UTC | 2022-04 | N050629-002 | AP | 1 | 4b0b4de00fa7… |
| 2019-12-13 00:20 UTC | 2019-12 | N050629-001 | AP | 1 | 74a2ff9319b5… |
| 2019-12-13 00:20 UTC | 2019-12 | N050629-002 | AP | 1 | 74a2ff9319b5… |
OpenFDA label data provides additional search and identifier links. DailyMed’s Structured Product Label is the canonical label on FDA.report. Matching records are deduplicated before they are shown below.
| Brand | Generic | Manufacturer | SPL set ID | Effective date | Available safety fields | Join |
|---|---|---|---|---|---|---|
| Doxorubicin Hydrochloride | DOXORUBICIN HYDROCHLORIDE | Pfizer Laboratories Div Pfizer Inc | 00634b2b-4e48-4178-8877-28582af894ad | 2026-04-30 | Boxed warning, Warnings, Adverse reactions | 0069-3358-25 0069-4037-01 0069-4205-05 0069-0255-10 0069-4026-25 0069-1442-04 0069-4004-05 0069-4015-10 0069-4037 0069-4004 0069-3358 0069-4026 0069-0255 0069-4015 0069-1442 0069-4205 00069402625 00069144204 00069025510 00069403701 00069400405 00069420505 00069401510 00069335825 b4c94e1f-f7c7-4b4b-9fe2-111903c0d312 00634b2b-4e48-4178-8877-28582af894ad |
Adverse event summaries are temporarily unavailable. Other product information remains available.