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 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, USP 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 [see Clinical Studies (14)].

1.2 Other Cancers

DOXOrubicin hydrochloride injection, USP 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 Dose

Adjuvant Breast Cancer

The recommended dose 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 [see Clinical Studies (14)].

Metastatic Disease, Leukemia, or Lymphoma

  • The recommended dose of doxorubicin hydrochloride injection when used as a single agent is 60 to 75 mg/m2 intravenously every 21 days.
  • The recommended dose of doxorubicin hydrochloride injection, when administered in combination with other chemotherapy drugs, is 40 to 75 mg/m2 intravenously every 21 to 28 days.
  • Consider use of the lower doxorubicin dose in the recommended dose 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)].

2.2 Dose Modifications

Cardiac Impairment

Discontinue doxorubicin in patients who develop signs or symptoms of cardiomyopathy.

Hepatic Impairment

Doxorubicin hydrochloride injection is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C or serum bilirubin greater than 5.0 mg/dL) [see Contraindications (4)].

Decrease the dose of doxorubicin hydrochloride injection in patients with elevated serum total bilirubin concentrations as follows:

Serum Bilirubin Concentration

Doxorubicin Hydrochloride Injection Dose Reduction

1.2 to 3.0 mg/dL

50 %

3.1 to 5.0 mg/dL

75 %

greater than 5.0 mg/dL

Do not initiate doxorubicin hydrochloride injection
Discontinue doxorubicin hydrochloride injection

[see Warnings and Precautions (5.5) and Use in Specific Population (8.7)]


2.3 Preparation and Administration

Preparation for Continuous Intravenous Infusion

Dilute doxorubicin hydrochloride injection solution in 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Protect from light following preparation until completion of infusion.

Administration

Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard if the solution is discolored, cloudy, or contains particulate matter.

Storage of vials of doxorubicin hydrochloride injection following reconstitution 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.

Administration by Intravenous Injection:

  • Administer 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 doxorubicin hydrochloride injection intravenously over 3 to 10 minutes. Decrease the rate of doxorubicin hydrochloride injection administration if erythematous streaking along the vein proximal to the site of infusion or facial flushing occur.

    Administration by Continuous Intravenous Infusion:

  • Infuse only through a central catheter. Decrease the rate of doxorubicin hydrochloride injection administration 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

    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 min 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)].

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 injection.

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