Adult Dosing

Paclitaxel and platinum refractory metastatic carcinoma of the ovary

• 50 mg/m² IV at a rate of 1 mg/min or over 1 hr q4 wks, minimum 4 courses

AIDS-related Kaposi's sarcoma

• 20 mg/m² IV at a rate of 1 mg/min or over 1 hr q3 wks

Multiple myeloma

• 30 mg/m² at a rate of 1 mg/min or over 1 hr on day 4 following bortezomib IV bolus for 8 cycles

Note:

• For toxicity related dose adjustments please see the package insert
• Do not administer as a bolus injection or an undiluted solution
• To be used as IV only, not for IM or SC administration

Pediatric Dosing

• The safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Ovarian Cancer (progressed or recurred after platinum-based chemotherapy)
• AIDS-Related Kaposi’s Sarcoma failure or intolerance chemotherapy
• Multiple Myeloma in combination with bortezomib

• Hypersensitivity to any of the ingredients of the product
• IM and SC administration

• Myocardial damage leading to congestive heart failure occurs as total cumulative dose of doxorubicin HCl approaches 550 mg/m2, the risk of cardiac toxicity was seen in 11% patients. Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dosage. Cardiac toxicity can also occur at lower cumulative doses in patients with prior mediastinal irradiation or receiving concurrent cyclophosphamide therapy
• Acute infusion-related reactions sometimes life-threatening or fatal including flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension have been reported in 10% of patients. After discontinuation of therapy or slowing of the infusion rate these reactions resolve over the course of several hours to a day. Emergency medicine and equipment to treat these reactions should be readily available for immediate use. Administer doxorubicin liposomal at an initial rate of 1 mg/min to minimize the risk of infusion reactions
• Severe myleosuppression resulting in superinfection, neutropenic fever, sepsis or hemorrhage may develop with doxorubicin liposomal infusion. Monitor hematological parameters
• In patients with hepatic impairment dose should be reduces [Dose Adjustments]
• Accidental substitution of doxorubicin liposomal for doxorubicin HCL on a mg per mg basis has resulted in severe side effects

Renal Dose Adjustment

• Renal impairment: Dose adjustments not defined

Hepatic Dose Adjustment

• Serum bilirubin 1.2-3 mg/dL (20.5-51 µmol/L): 50% of the usual dose
• Serum bilirubin > 3 mg/dL (> 51 µmol/L): 25% of the usual dose

• Myocardial damage leading to congestive heart failure occurs as total cumulative dose of doxorubicin HCl approaches 550 mg/m2 including prior use of other anthracyclines or anthracenediones [US Black Box Warnings]
• Acute infusion-related reactions sometimes life-threatening or fatal occurs with doxorubicin liposomal infusion, discontinue the therapy and provide emergency treatment [US Black Box Warnings]
• Myelosupression including anemia, leukopenia, thrombocytopenia, neutropenia, have been reported with doxorubicin liposomal infusion. Carefully monitor hematologic parameters including white blood cell, neutrophil, platelet counts, and Hgb/Hct prior to and during the therapy [US Black Box Warnings]
• Hand-Foot Syndrome (palmar-plantar skin eruptions) characterized by swelling, pain, erythema and desquamation of the skin occurs with doxorubicin liposomal. Mild reaction resolves in one to two weeks, severe and debilitating requires discontinuation of treatment
• Doxorubicin liposomal administration causes recall reaction after radiotherapy
• Doxorubicin liposomal causes fetal harm, should not be administered to pregnant women and women of childbearing potential should be advised to avoid pregnancy during treatment
• The doxorubicin potentiate the toxicity of other anticancer therapies
• Post marketing studies reported secondary oral cancers and primarily squamous cell carcinoma in patients with long term exposure to the therapy

Cautions: Use cautiously in

• Hepatic impairment
• History of cardiac disease
• Cardiotoxic agent use
• Depressed bone marrow reserve
• Recent anthracycline use
• Prior mediastinal radiation
• Concurrent cyclophosphamide

Pregnancy Category:D

Breastfeeding: Breastfeeding is contraindicated during maternal antineoplastic therapy. It might be possible to breastfeed safely during intermittent therapy, however defining an appropriate abstinence interval is difficult due to high levels and persistence of doxorubicinol in milk. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 7 Jan 2011). Because of the potential for possible serious adverse reactions in nursing infants manufacturer advises to discontinue nursing prior to taking this drug.

• CV: Cardiac toxicity, vasodilation, tachycardia, deep thrombophlebitis, hypotension, cardiac arrest
• CNS: Headache, dizziness, somnolence, depression
• HEMA: Myelosupression, neutropenia, thrombocytopenia, anemia, ecchymosis
• GI: Nausea, stomatitis, vomiting, diarrhea, constipation, anorexia, oral moniliasis, esophagitis, dysphagia, rectal bleeding, ileus, SGPT increase, peripheral neuropathy, paresthesia/dysesthesia
• RESP: Pharyngitis, dyspnea, cough, rhinitis, pneumonia, sinusitis
• METABOLIC: Dehydration, weight loss, hyperbilirubinemia, hypokalemia, hypercalcemia, hyponatremia
• LOCAL: Infusion reactions
• DERM: Hand-Foot syndrome, rash, alopecia, pruritus, skin discoloration, vesiculobullous rash, maculopapular rash, exfoliative dermatitis, herpes zoster, dry skin, herpes simplex, fungal dermatitis, furunculosis, acne
• EENT: Epistaxis, conjunctivitis, taste perversion, dry eyes
• GU: Urinary tract infection, hematuria, vaginal moniliasis
• MISC: asthenia, fatigue, fever, mucous membrane disorder, infection, allergic reaction, chills

• Liposomal doxorubicin is doxorubicin HCl encapsulated in long-circulating liposomes
• Liposomes are microscopic vesicles composed of a phospholipid bilayer that are capable of encapsulating active drugs
• Active ingredient Doxorubicin HCL is antineoplastic Agent; penetrates cell and binds to perinuclear chromatin thereby inhibiting mitotic activity and nucleic acid synthesis and induce mutagenesis and chromosomal aberrations
• Metabolized by liver to doxorubicinol
• Excretion: Primarily in bile/feces; minimally in urine
• Half Life: 55 hrs

US Trade Name(s)

• Doxil

US Availability

doxorubicin liposomal (generic)

• INJ: 20 mg/10 mL vial
• INJ: 50 mg/25 mL vial

Doxil

• INJ: 20 mg/10 mL vial
• INJ: 50 mg/25 mL vial

Canadian Trade Name(s)

• Caelyx
• Myocet

Canadian Availability

Caelyx

• INJ: 2 mg/mL (10, 25 mL vials)

Myocet

• INJ: 2 mg/mL (25 mL vial)

UK Trade Name(s)

• Caelyx
• Myocet

UK Availability

Caelyx

• INJ: 2 mg/mL (10, 25 mL vials)

Myocet

• INJ: 2 mg/mL (25 mL vial)

Australian Trade Name(s)

• Caelyx

Australian Availability

Caelyx

• INJ: 2 mg/mL (10, 25 mL vials)

[Outline]

Hematology/Oncology

Antineoplastics

Anthracyclines