Arodoxin (Doxorubicin Hydrochloride USP)

Description

Doxorubicin hydrochloride (HCl) is a cytotoxic, anthracycline topoisomerase II inhibitor. 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 the 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.

Presentation

Arodoxin 10 Injection: Each vial contains Doxorubicin Hydrochloride USP 10 mg, as a 5 ml concentrated solution for IV Infusion.
Arodoxin 50 Injection: Each vial contains Doxorubicin Hydrochloride USP 50 mg, as a 25 ml concentrated solution for IV Infusion.

Indications

as a component of multi-agent adjuvant chemotherapy for the 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.

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 the 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 occurs. In 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 HCl 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 HCl.

Dose Modifications:
Cardiac Impairment: Doxorubicin should be discontinued in patients who develop signs or symptoms of cardiomyopathy.
Hepatic Impairment: Doxorubicin HCl is contraindicated in patients with severe hepatic impairment. Decrease the dose of Doxorubicin HCl in patients with elevated serum total bilirubin concentrations as follows:

Contrainidications

Severe myocardial insufficiency
Recent (occurring within the past 4-6 weeks) myocardial infarction
Severe persistent drug-induced myelosuppression
Severe hepatic impairment (defined as Child-Pugh Class C or serum bilirubin level greater than 5 mg/dl)
Severe hypersensitivity reaction to Doxorubicin HCl including anaphylaxis

Warning & Precautions

Pregnancy: 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.

Nursing mothers: 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.
Pediatric use: Pediatric patients treated with Doxorubicin HCl are at risk for developing late cardiovascular dysfunction. 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.

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.

Drug 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.

Use in special groups

Pediatric use: Pediatric patients treated with Doxorubicin HCl are at risk for developing late cardiovascular dysfunction. 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.

Packing

Arodoxin 10 Injection: Each box contains a single dose glass vial of Doxorubicin HCl 10 mg.
Arodoxin 50 Injection: Each box contains a single dose glass vial of Doxorubicin HCl 50 mg.