Doxorubicin Hydrochloride

DOXORUBICIN HYDROCHLORIDE- doxorubicin hydrochloride injection, solution
Actavis Pharma, Inc.

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 INDICATIONS AND USAGE

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 of

  • acute lymphoblastic leukemia
  • acute myeloblastic leukemia
  • Hodgkin lymphoma
  • non-Hodgkin lymphoma (NHL)
  • metastatic breast cancer
  • metastatic Wilms’ tumor
  • metastatic neuroblastoma
  • metastatic soft tissue sarcoma
  • metastatic bone sarcoma
  • metastatic ovarian carcinoma
  • metastatic transitional cell bladder carcinoma
  • metastatic thyroid carcinoma
  • metastatic gastric carcinoma
  • metastatic bronchogenic carcinoma

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage for Adjuvant Breast Cancer

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.

2.2 Recommended Dosage for Other Cancers

  • 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

Cardiomyopathy

Discontinue 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 Bilirubin

Serum total bilirubin concentration

Dosage Modification

1.2 to 3 mg/dL

50%

3.1 to 5 mg/dL

75%

greater than 5 mg/dL

Do 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.1

Preparation

Dilution of Doxorubicin Hydrochloride Injection

  • Dilute 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.

Administration

  • Visually 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 Injection

  • Administer 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 Infusion

  • Administer 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 Extravasation

    Immediately 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 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.

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