Doxorubicin Hydrochloride Liposome injection is indicated for the treatment of:

Ovarian Cancer: Doxorubicin Hydrochloride Liposome injection is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.

AIDS-Related Kaposi's Sarcoma: It is indicated for the treatment of AIDS-related Kaposi's sarcoma in patients with disease that has progressed on prior combination chemotherapy or in patients who are intolerant to such therapy.

Multiple Myeloma: For the treatment of patients with multiple myeloma in combination with Bortezomib, who have not previously received Bortezomib and have received at least one prior therapy.

Also indicated for monotherapy for patients with metastatic breast cancer, where the patient is associated with increased cardiac risk with conventional doxorubicin.

20 mg Injection: Each 10 ml contains Doxorubicin Hydrochloride USP 20 mg (as pegylated liposome).
50 mg Injection: Each 25 ml contains Doxorubicin Hydrochloride USP 50 mg (as pegylated liposome).

Doxorubicin is a cytotoxic anthracycline antibiotic isolated from Streptomyces peucetius var. caesius. Doxorubicin Hydrochloride Liposome injection is doxorubicin hydrochloride encapsulated in stealth liposomes for intravenous administration. Greater than 90% of the drug is encapsulated in the stealth liposomes.

The active ingredient of Doxorubicin Hydrochloride Liposome injection is doxorubicin hydrochloride. The mechanism of action of doxorubicin hydrochloride is thought to be related to its ability to bind DNA and inhibit nucleic acid synthesis. Cell structure studies have demonstrated rapid cell penetration and perinuclear chromatin binding, rapid inhibition of mitotic activity and nucleic acid synthesis, and induction of mutagenesis and chromosomal aberrations.

Doxorubicin Hydrochloride Liposome injection displays linear pharmacokinetics over the range of 10–20 mg/m². Disposition occurs in two phases after administration of Doxorubicin Hydrochloride Liposome injection, with a relatively short first phase (5 hours) and a prolonged second phase (55 hours), which accounts for the majority of the area under the curve (AUC).

Distribution: Direct measurement of Doxorubicin Hydrochloride Liposome injection shows that at least 90% of the drug (the assay used cannot quantify less than 5–10% free doxorubicin) remains liposome-encapsulated during circulation.

Metabolism: Doxorubicinol, the major metabolite of doxorubicin, was detected at concentrations of 0.8 to 26.2 ng/mL in the plasma of patients who received 10 or 20 mg/m² of Doxorubicin Hydrochloride Liposome injection.

Excretion: The plasma clearance of total Doxorubicin Hydrochloride Liposome injection was 0.041 L/h/m² at a dose of 20 mg/m². Following administration of doxorubicin hydrochloride, the plasma clearance of doxorubicin is 24 to 35 L/h/m².

Ovarian Cancer Patients: The recommended dose is 50 mg/m² intravenously over 60 minutes every 28 days until disease progression or unacceptable toxicity.

AIDS-Related Kaposi's Sarcoma: The recommended dose is 20 mg/m² intravenously over 60 minutes every 21 days until disease progression or unacceptable toxicity.

Multiple Myeloma: The recommended dose is 30 mg/m² intravenously over 60 minutes on day 4 of each 21-day cycle for eight cycles or until disease progression or unacceptable toxicity. Administer it after Bortezomib on day 4 of each cycle.

Dose Modification: Guidelines have been proposed since Doxorubicin Hydrochloride Liposome injection exhibits nonlinear pharmacokinetics at 50 mg/m². Dose adjustments may thus result in non-proportional greater change in plasma concentration and exposure to the drug. Patients should be carefully monitored for toxicity. Adverse events such as Palmar-Plantar Erythema (PPE), hematologic toxicities, and stomatitis may be managed by dose delays and adjustments. Subsequent to the first appearance of a Grade 2 or higher adverse event, dosing should be adjusted and/or delayed as described in the following tables and should not be increased at any given time.

Pediatric Use: The safety and effectiveness of Doxorubicin Hydrochloride Liposome injection in pediatric patients have not been established.

Administration

Preparation: Dilute Doxorubicin Hydrochloride Liposome doses up to 90 mg in 250 mL of 5% Dextrose Injection, USP prior to administration. Dilute doses exceeding 90 mg in 500 mL of 5% Dextrose Injection, USP prior to administration. Refrigerate diluted Doxorubicin Hydrochloride Liposome at 2°C to 8°C and administer within 24 hours.

Administration: Administer the first dose at an initial rate of 1 mg/min. If no infusion-related adverse reactions are observed, increase the infusion rate to complete the administration of the drug over one hour. Do not rapidly flush the infusion line. Do not mix it with other drugs.

Exercise caution in the concomitant use of medicinal products known to interact with standard doxorubicin hydrochloride. Pegylated liposomal doxorubicin, like other doxorubicin hydrochloride preparations, may potentiate the toxicity of other anti-cancer therapies.

It is contraindicated in patients who have a history of severe hypersensitivity reactions, including anaphylaxis, to doxorubicin hydrochloride.

• Increased risk of getting an infection
• Breathlessness and looking pale
• Tiredness and weakness
• Feeling or being sick
• Inflammation of the lining of the mouth, throat, food pipe, and stomach
• Soreness, redness, and peeling of your hands and feet
• Loss of appetite
• Hair loss
• Diarrhea or constipation
• Pain in different parts of the body
• Skin changes

Pregnancy: Based on findings in animals and its mechanism of action, Doxorubicin Hydrochloride Liposome injection can cause fetal harm when administered to a pregnant woman. Avoid the use of Doxorubicin Hydrochloride Liposome injection during the first trimester.

Lactation: It is not known whether Doxorubicin Hydrochloride Liposome injection is present in human milk. Because many drugs, including anthracyclines, are excreted in human milk and because of the potential for serious adverse reactions in breastfed infants from Doxorubicin Hydrochloride Liposome injection, discontinue breastfeeding during treatment with it.

Females and Males of Reproductive Potential: Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating Doxorubicin Hydrochloride Liposome injection.

Contraception: Doxorubicin Hydrochloride Liposome injection can cause fetal harm when administered to a pregnant woman. Doxorubicin Hydrochloride Liposome injection may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities.

Infertility: In females of reproductive potential, Doxorubicin Hydrochloride Liposome injection may cause infertility and result in amenorrhea. Doxorubicin Hydrochloride Liposome injection may result in oligospermia, azoospermia, and permanent loss of fertility.

Cardiomyopathy: Doxorubicin Hydrochloride can cause myocardial damage, including acute left ventricular failure.

Infusion-Related Reactions: Flushing, shortness of breath, facial swelling, headache, chills, chest pain, back pain, tightness in the chest and throat, fever, tachycardia, pruritus, rash, cyanosis, syncope, bronchospasm, asthma, apnea, and hypotension.

Hand-Foot Syndrome (HFS): HFS or other skin toxicity required discontinuation of Doxorubicin Hydrochloride Liposome injection in 4.2% of patients.

Secondary Oral Neoplasms: Secondary oral cancers, primarily squamous cell carcinoma, have been reported from post-marketing experience in patients with long-term (more than one year) exposure to Doxorubicin Hydrochloride Liposome injection.

Embryo-Fetal Toxicity: Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during and for 6 months after treatment with Doxorubicin Hydrochloride Liposome injection.

Antineoplastic preparations

Store unopened vials of Doxorubicin Hydrochloride Liposome injection at 2–8°C. Do not freeze. Prolonged freezing may adversely affect liposomal drug products; however, short-term freezing (less than 1 month) does not appear to have a deleterious effect on Doxorubicin Hydrochloride Liposome injection.