Doxorubicin PhaRes 2 mg/ml

INDICATIONS

Doxorubicin Hydrochloride is indicated:

As a component of multiagent adjuvant chemotherapy for treatment of women with axillary lymph node involvement following resection of primary breast cancer.
For the treatment 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 bladder carcinoma, metastatic thyroid carcinoma, metastatic gastric carcinoma, metastatic bronchogenic carcinoma.

PHARMACOLOGY

Doxorubicin hydrochloride is a cytotoxic, anthracycline topoisomerase IIinhibitor. The cytotoxic effect of Doxorubicin HCl 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 HCl cytocidal activity.

DOSAGE & ADMINISTRATION

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.

INTERACTION

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.

SIDE EFFECTS

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

PREGNANCY & LACTATION

Pregnancy Category D. Doxorubicin HCl can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus. Female patients of reproductive potential should be advised to use highly effective contraception during treatment with Doxorubicin HCl and for 6 months after treatment. There is evidence of Doxorubicinbe excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from Doxorubicin HCl, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

USE IN SPECIAL POPULATIONS

Pediatric use: Pediatric patients treated with Doxorubicin HCl are at risk for developing late cardiovasculardysfunction. Long-term periodic cardiovascular monitoring is recommended for all pediatric patients who have received Doxorubicin HCl.Geriatric use: No overall differences in safety and effectiveness have been found compared with younger patients.Hepatic impaired patients: The clearance of Doxorubicin is reduced in patients with elevated serum bilirubin levels. The dose of Doxorubicin HCl should be decreased in patients with serum bilirubin levels greater than 1.2 mg/dl. Doxorubicin HCl is contraindicated in patients with severe hepatic impairment.

THERAPEUTIC CLASS

Cytotoxic Chemotherapy

STORAGE CONDITIONS

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