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Doxorubicin Hydrochloride Liposome Injection for Intravenous Infusion

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Doxorubicin Hydrochloride Liposome Injection for Intravenous Infusion -----------------------------------------INDICATIONS AND USAGE-------------------------------------------- 2.6 Patients With Impaired Hepatic Function HFS was generally observed after 2 or 3 cycles of treatment but may occur earlier. In most patients the Doxorubicin hydrochloride is an anthracycline topoisomerase inhibitor indicated for: Limited clinical experience exists in treating patients with hepatic impairment with doxorubicin reaction is mild and resolves in one to two weeks so that prolonged delay of therapy need not occur. - Ovarian cancer (1.1) hydrochloride liposome injection. Based on experience with doxorubicin hydrochloride, it is However, dose modification may be required to manage HFS [see Dosage and Administration (2.5)]. After failure of platinum-based chemotherapy. recommended that the doxorubicin hydrochloride liposome injection dosage be reduced if the bilirubin The reaction can be severe and debilitating in some patients and may require discontinuation of is elevated as follows: serum bilirubin 1.2 to 3 mg/dL -give ½ normal dose; serum bilirubin > 3 mg/dL - treatment. give ¼ normal dose. - AIDS-related Kaposi's Sarcoma (1.2) After failure of prior systemic chemotherapy or intolerance to such therapy. 5.5 Radiation Recall Reaction HIGHLIGHTS OF PRESCRIBING INFORMATION 2.7 Preparation for Intravenous Administration Recall reaction has occurred with doxorubicin hydrochloride liposome injection administration after Each 10 mL vial contains 20 mg doxorubicin hydrochloride at a concentration of 2 mg/mL. ---- ----------------------------------DOSAGE AND ADMINISTRATION --------------------------------------- radiotherapy. These highlights do not include all the information needed to use doxorubicin hydrochloride safely and Each 25 mL vial contains 50 mg doxorubicin hydrochloride at a concentration of 2 mg/mL. Administer doxorubicin hydrochloride liposome injection at an initial rate of 1 mg/min to minimize the effectively. See full prescribing information for doxorubicin hydrochloride liposome injection. 5.6 Fetal Mortality risk of infusion reactions. If no infusion related reactions occur, increase rate of infusion to complete Doxorubicin hydrochloride liposome injection doses up to 90 mg must be diluted in 250 mL of 5% Pregnancy Category D administration over 1 hour. Do not administer as bolus injection or undiluted solution (2.1). Dextrose Injection, USP prior to administration. Doses exceeding 90 mg should be diluted in 500 mL of 2 Doxorubicin hydrochloride liposome injection can cause fetal harm when administered to a pregnant Doxorubicin Hydrochloride Liposome Injection - Ovarian cancer: 50 mg/m IV every 4 weeks for 4 courses minimum (2.2) 5% Dextrose Injection, USP prior to administration. Aseptic technique must be strictly observed since woman. There are no adequate and well-controlled studies in pregnant women. If doxorubicin 2 - AIDS-related Kaposi's Sarcoma: 20 mg/m IV every 3 weeks (2.3) no preservative or bacteriostatic agent is present in doxorubicin hydrochloride liposome injection. hydrochloride liposome injection is to be used during pregnancy, or if the patient becomes pregnant for intravenous infusion Diluted doxorubicin hydrochloride liposome injection should be refrigerated at 2°C to 8°C (36°F to 46°F) during therapy, the patient should be apprised of the potential hazard to the fetus. If pregnancy occurs in ------------------------------------- DOSAGE FORMS AND STRENGTHS ------------------------------------- and administered within 24 hours. the first few months following treatment with doxorubicin hydrochloride liposome injection, the Initial U.S. Approval: 1995 Single use vial: 20 mg/10 mL and 50 mg/25 mL (3) prolonged half-life of the drug must be considered. Women of childbearing potential should be advised Do not use with in-line filters. to avoid pregnancy during treatment with doxorubicin hydrochloride liposome injection. [see Use in Do not mix with other drugs. WARNING: INFUSION REACTIONS, MYELOSUPPRESSION, CARDIOTOXICITY, LIVER -------------------------------------------- CONTRAINDICATIONS -------------------------------------------- Specific Populations (8.1)]. Do not use with any diluent other than 5% Dextrose Injection. IMPAIRMENT, SUBSTITUTION - Hypersensitivity reactions to a conventional formulation of doxorubicin hydrochloride or the components of doxorubicin hydrochloride liposome injection (4, 5.2) Do not use any bacteriostatic agent, such as benzyl alcohol. 5.7 Toxicity Potentiation See full prescribing information for complete boxed warning. The doxorubicin in doxorubicin hydrochloride liposome injection may potentiate the toxicity of other ---------------------------------------WARNINGS AND PRECAUTIONS--------------------------------------- Doxorubicin hydrochloride liposome injection is not a clear solution but a translucent, red liposomal anticancer therapies. Exacerbation of cyclophosphamide-induced hemorrhagic cystitis and dispersion. enhancement of the hepatotoxicity of 6-mercaptopurine have been reported with the conventional - Myocardial damage may lead to congestive heart failure and may occur as the total - Hand-Foot Syndrome may occur. Dose modification or discontinuation may be required (5.4) formulation of doxorubicin hydrochloride. Radiation-induced toxicity to the myocardium, mucosae, cumulative dose of doxorubicin hydrochloride approaches 550 mg/m 2. Cardiac toxicity - Radiation recall reaction may occur (5.5) Parenteral drug products should be inspected visually for particulate matter and discoloration prior to skin, and liver have been reported to be increased by the administration of doxorubicin hydrochloride. may also occur at lower cumulative doses with mediastinal irradiation or concurrent administration, whenever solution and container permit. Do not use if a precipitate or foreign matter is cardiotoxic agents (5.1). -------------------------------------------------ADVERSE REACTIONS---------------------------------------- present. Most common adverse reactions (>20%) are asthenia, fatigue, fever, anorexia, nausea, vomiting, 5.8 Monitoring: Laboratory Tests - Acute infusion-related reactions, sometimes reversible upon terminating or slowing Complete blood counts, including platelet counts, should be obtained frequently and at a minimum prior stomatitis, diarrhea, constipation, hand and foot syndrome, rash, neutropenia, thrombocytopenia and infusion, occurred in up to 10% of patients. Serious and sometimes fatal Rapid flushing of the infusion line should be avoided. to each dose of doxorubicin hydrochloride liposome injection [see Warnings and Precautions (5.3)]. allergic/anaphylactoid-like infusion reactions have been reported. Medications/ anemia (6). emergency equipment to treat such reactions should be available for immediate use 2.8 Procedure for Proper Handling and Disposal (5.2). To report SUSPECTED ADVERSE REACTIONS contact CARACO Pharmaceutical Laboratories Ltd. at Caution should be exercised in the handling and preparation of doxorubicin hydrochloride liposome 6 ADVERSE REACTIONS - Severe myelosuppression may occur (5.3) 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. injection. 6.1 Overall Adverse Reactions Profile - Reduce dosage in patients with impaired hepatic function (2.6). --------------------------------------------- DRUG INTERACTIONS -------------------------------------------- The following adverse reactions are discussed in more detail in other sections of the labeling. - Accidental substitution of doxorubicin hydrochloride liposome injection resulted in - Doxorubicin hydrochloride may interact with drugs known to interact with conventional The use of gloves is required. - Cardiac Toxicity [see Warnings and Precautions (5.1)] severe side effects. Do not substitute on mg per mg basis with doxorubicin formulations of Doxorubicin hydrochloride. (7) - Infusion reactions [see Warnings and Precautions (5.2)] If doxorubicin hydrochloride liposome injection comes into contact with skin or mucosa, immediately hydrochloride (2.1). - Myelosuppression [see Warnings and Precautions (5.3)] --------------------------------------------USE IN SPECIFIC POPULATIONS -------------------------------- wash thoroughly with soap and water. - Hand-Foot syndrome [see Warnings and Precautions (5.4)] - Doxorubicin hydrochloride liposome injection can cause fetal harm when used during pregnancy. (5.6, 8.1) Doxorubicin hydrochloride liposome injection should be considered an irritant and precautions should The most common adverse reactions observed with doxorubicin hydrochloride liposome injection are --------------------------------------------- RECENT MAJOR CHANGES -------------------------------------- be taken to avoid extravasation. With intravenous administration of doxorubicin hydrochloride liposome Contraindications, Nursing Mother (4) Removed 9/2012 - Discontinue nursing during treatment with doxorubicin hydrochloride liposome injection (8.3). asthenia, fatigue, fever, nausea, stomatitis, vomiting, diarrhea, constipation, anorexia, hand-foot injection, extravasation may occur with or without an accompanying stinging or burning sensation, syndrome, rash and neutropenia, thrombocytopenia and anemia. even if blood returns well on aspiration of the infusion needle. If any signs or symptoms of extravasation See 17 for PATIENT COUNSELING INFORMATION. have occurred, the infusion should be immediately terminated and restarted in another vein. Revised: 09/2012 The most common serious adverse reactions observed with doxorubicin hydrochloride
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