Doxorubicin has been successfully used to induce regression in disseminated neoplastic conditions such as acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms' tumor, neuroblastoma, soft tissue and bone sarcomas, breast carcinoma, ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gastric carcinoma, Hodgkin's disease, malignant lymphoma, and bronchogenic carcinoma. The small cell histologic type of bronchogenic carcinoma is the most responsive compared to other cell types.

Doxorubicin is also indicated as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following the resection of primary breast cancer.

Doxorubicin hydrochloride is a cytotoxic, anthracycline topoisomerase II inhibitor. Its cytotoxic effect on malignant cells and toxic effects on various organs are thought to be related to nucleotide base intercalation and cell membrane lipid binding activities. Intercalation inhibits nucleotide replication and the action of DNA and RNA polymerases. The interaction of Doxorubicin with topoisomerase II to form DNA-cleavable complexes appears to be a key mechanism of its cytocidal activity.

Single-agent therapy: 60 to 75 mg/m², administered intravenously every 21 days.

Combination therapy: 40 to 75 mg/m², administered intravenously every 21 to 28 days.

Doxorubicin HCl should be discontinued in patients who develop signs or symptoms of cardiomyopathy, and the dose should be reduced in patients with hepatic impairment.

Intravenous Injection

Administer 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 administration rate should be decreased if erythematous streaking along the vein proximal to the infusion site or facial flushing occurs.

Intravenous Infusion

Administer only through a central catheter.

Management of Suspected Extravasation

Doxorubicin HCl should be immediately discontinued if burning, stinging, or other signs of perivenous infiltration or extravasation occur. Management steps include:

Do not remove the needle until attempts are made to aspirate extravasated fluid.
Do not flush the line.
Do not apply pressure to the site.
Apply ice intermittently for 15 minutes, four times a day, for three days.
Elevate the affected extremity if extravasation occurs in a limb.
In adults, consider administering dexrazoxane.
Incompatibility with Other Drugs

Doxorubicin hydrochloride should not be mixed with other drugs. When mixed with heparin or fluorouracil, a precipitate may form. Avoid contact with alkaline solutions, as they can cause hydrolysis of Doxorubicin hydrochloride.

Adribin is a major substrate of cytochrome P450 CYP3A4, CYP2D6, and P-glycoprotein (P-gp). Avoid concurrent use with inhibitors and inducers of CYP3A4, CYP2D6, or P-gp. The concurrent use of Trastuzumab and Adribin HCl increases the risk of cardiac dysfunction, so co-administration should be avoided. Paclitaxel, when given before Adribin HCl, increases plasma concentrations of Adribin and its metabolites. If used together, administer Adribin HCl before Paclitaxel.

Doxorubicin HCl is contraindicated in patients with:

Severe myocardial insufficiency
Recent myocardial infarction (within the past 4–6 weeks)
Severe persistent drug-induced myelosuppression
Severe hepatic impairment (Child-Pugh Class C or serum bilirubin > 5 mg/dL)
Severe hypersensitivity reaction to Doxorubicin HCl, including anaphylaxis

The most common (>10%) adverse effects include alopecia, nausea, and vomiting. Other reactions include:

Cardiomyopathy and arrhythmias
Secondary malignancies
Extravasation and tissue necrosis
Severe myelosuppression
Tumor lysis syndrome
Radiation sensitization and radiation recall

Pregnancy Category D – Doxorubicin HCl can cause fetal harm when administered to a pregnant woman. If used during pregnancy or if the patient becomes pregnant while taking it, she should be informed of the potential risks to the fetus.

Female patients of reproductive potential should use highly effective contraception during treatment and for six months after treatment.

Doxorubicin is excreted in human milk, so breastfeeding should be discontinued due to the risk of serious adverse reactions in nursing infants.

Pediatric Use: Children treated with Adribin HCl are at risk for late cardiovascular dysfunction. Long-term periodic cardiovascular monitoring is recommended.

Geriatric Use: No significant differences in safety and effectiveness compared to younger patients.

Hepatic Impairment: Clearance is reduced in patients with elevated serum bilirubin levels.

Dose reduction is required if bilirubin >1.2 mg/dL.

Severe hepatic impairment (Child-Pugh Class C) is a contraindication.

Symptoms of overdose are likely to be an extension of Adribin’s pharmacological action.

Single doses of 250 mg and 500 mg have been fatal.
Acute myocardial degeneration may occur within 24 hours.
Severe myelosuppression peaks 10 to 15 days after administration.
Delayed cardiac failure may occur up to six months after overdose.

Preparation for Administration

Reconstitute Adribin injection with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.

Protect from light after preparation until infusion is completed.

Inspect visually for precipitates, visible particles, or discoloration before use.

Precautions During Handling

Handling Adribin HCl requires caution. Proper handling and disposal of anticancer drugs should be followed.

Wear impervious gloves when handling vials and IV sets.

If the drug contacts skin or mucosa, immediately wash the area with soap and water or sodium bicarbonate solution, and flush mucosa with water.

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