Doxorubicin Hydrochloride is indicated:

• As part of combination adjuvant chemotherapy for the treatment of women with axillary lymph node involvement after surgical removal of primary breast cancer.
• For the management of acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, metastatic breast cancer, metastatic Wilms' tumor, metastatic neuroblastoma, metastatic soft tissue sarcoma, metastatic bone sarcomas, metastatic ovarian carcinoma, metastatic transitional cell carcinoma of the bladder, metastatic thyroid carcinoma, metastatic gastric carcinoma, and metastatic bronchogenic carcinoma.

Doxorubicin Hydrochloride is a cytotoxic anthracycline antibiotic and a topoisomerase II inhibitor. Its anticancer activity is mainly related to its ability to intercalate between nucleotide base pairs of DNA and bind to cell membrane lipids. This intercalation disrupts DNA replication and interferes with the activity of DNA and RNA polymerases, which are essential for cell growth and division. Another important mechanism is the interaction of Doxorubicin with topoisomerase II, forming DNA-cleavable complexes that prevent the repair of DNA strands. This process leads to DNA damage and ultimately causes the death of cancer cells.

Single agent: 60 to 75 mg/m² given intravenously every 21 days.

In combination therapy: 40 to 75 mg/m² given intravenously every 21 to 28 days. Doxorubicin HCl should be discontinued in patients who develop signs or symptoms of cardiomyopathy, and dose should be reduced in patients with hepatic impairment. As an intravenous injection, Doxorubicin HCl is administered 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 over 3 to 10 minutes. The rate of Doxorubicin HCl administration should be decreased if erythematous streaking along the vein proximal to the site of infusion or facial flushing occur. As intravenous Infusion, Doxorubicin HCl is administered only through a central catheter.

Management of Suspected Extravasation: Doxorubicin HCl should be discontinued in case of burning or stinging sensation or other evidence indicating perivenous infiltration or extravasation. Confirmed or suspected extravasation are managed as follows:

• The needle should not be removed until attempts are made to aspirate extravasated fluid
• The line should not be flushed
• Pressure should not be applied to the site
• Ice should be applied to the site intermittently for 15 min 4 times a day for 3 days
• If the extravasation is in an extremity, extremity should be elevated
• In adults, administration of dexrazoxane should be considered

Incompatibility with Other Drugs: Doxorubicin hydrochloride should not be admixed with other drugs. If Doxorubicin HCl is mixed with heparin or fluorouracil a precipitate may form. Avoid contact with alkaline solutions which can lead to hydrolysis of Doxorubicin hydrochloride.

Doxorubicin is a major substrate of cytochrome P450 CYP3A4 and CYP2D6, and P-glycoprotein (P-gp). Avoid concurrent use of doxorubicin HCl with inhibitors and inducers of CYP3A4, CYP2D6, or P-gp. Concurrent use of trastuzumab and doxorubicin HCl results in an increased risk of cardiac dysfunction. Avoid concurrent administration of doxorubicin and trastuzumab. Paclitaxel, when given prior to doxorubicin HCl, increases the plasma concentrations of doxorubicin and its metabolites. Administer doxorubicin HCl prior to paclitaxel if used concomitantly.

Doxorubicin Hydrochloride should not be used in patients with:

• Severe cardiac insufficiency
• Recent myocardial infarction within the past 4–6 weeks
• Severe and persistent drug-induced bone marrow suppression
• Severe liver impairment (Child-Pugh Class C or serum bilirubin greater than 5 mg/dL)
• Severe allergic reaction to Doxorubicin, including anaphylaxis

The most commonly reported adverse drug reactions (>10%) include alopecia, nausea, and vomiting. Other adverse reactions include cardiomyopathy and arrhythmias, secondary malignancies, extravasation with tissue necrosis, severe myelosuppression, tumor lysis syndrome, radiation sensitization, and radiation recall.

Doxorubicin Hydrochloride is classified as Pregnancy Category D and may cause harm to the unborn baby if used during pregnancy. Women who may become pregnant should use effective contraception during treatment and for at least 6 months after completing therapy. Doxorubicin has been found to be excreted in human breast milk. Because of the risk of serious adverse effects in nursing infants, a decision should be made either to stop breastfeeding or discontinue the medication, depending on the importance of treatment for the mother.

Pediatric use: Pediatric patients receiving doxorubicin HCl are at risk of developing delayed cardiovascular complications. Long-term, periodic cardiovascular monitoring is recommended for all children treated with doxorubicin HCl.

Geriatric use: No significant differences in safety or effectiveness have been observed between elderly and younger patients.

Hepatic impaired patients: Clearance of doxorubicin is reduced in patients with elevated serum bilirubin levels. Dose reduction is recommended in patients with bilirubin levels above 1.2 mg/dL. Doxorubicin HCl is contraindicated in patients with severe hepatic impairment.

Symptoms of Doxorubicin overdose are usually an extension of its pharmacological effects. Extremely high doses (such as 250–500 mg) have been reported to be fatal. Overdose may cause acute heart muscle damage within 24 hours and severe bone marrow suppression, with the most severe effects typically appearing 10–15 days after administration. Delayed heart failure may occur even up to six months later. Patients should be carefully monitored and provided with supportive care.

Cytotoxic Chemotherapy

Store Doxorubicin Hydrochloride in a dry place at 2°C–8°C. Protect from light and do not freeze. Keep out of the reach of children.