Doxorubicin Hydrochloride Liposome Prescribing Information
• Doxorubicin hydrochloride liposome injection can cause myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy was 11% when the cumulative anthracycline dose was between 450 mg/m2 to 550 mg/m2. Assess left ventricular cardiac function prior to initiation of doxorubicin hydrochloride liposome injection and during and after treatment[see.]5.1 CardiomyopathyDoxorubicin hydrochloride can cause myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy with doxorubicin hydrochloride is generally proportional to the cumulative exposure. Include prior use of other anthracyclines or anthracenediones in calculations of cumulative dose. The risk of cardiomyopathy may be increased at lower cumulative doses in patients with prior mediastinal irradiation.
In a clinical study in 250 patients with advanced cancer who were treated with doxorubicin hydrochloride liposome injection, the risk of cardiomyopathy was 11% when the cumulative anthracycline dose was between 450 mg/m2to 550 mg/m2. Cardiomyopathy was defined as >20% decrease in resting left ventricular ejection fraction (LVEF) from baseline where LVEF remained in the normal range or a >10% decrease in LVEF from baseline where LVEF was less than the institutional lower limit of normal. Two percent of patients developed signs and symptoms of congestive heart failure without documented evidence of cardiomyopathy.
Assess left ventricular cardiac function (e.g. MUGA or echocardiogram) prior to initiation of doxorubicin hydrochloride liposome injection, during treatment to detect acute changes, and after treatment to detect delayed cardiomyopathy. Administer doxorubicin hydrochloride liposome injection to patients with a history of cardiovascular disease only when the potential benefit of treatment outweighs the risk.
• Serious, life-threatening, and fatal infusion-related reactions can occur with doxorubicin hydrochloride liposome injection. Acute infusion-related reactions occurred in 11% of patients with solid tumors. Withhold doxorubicin hydrochloride liposome injection for infusion-related reactions and resume at a reduced rate. Discontinue doxorubicin hydrochloride liposome injection for serious or life-threatening infusion-related reactions[see.]5.2 Infusion-Related ReactionsSerious, life-threatening, and fatal infusion-related reactions characterized by one or more of the following symptoms can occur with doxorubicin hydrochloride liposome injection: 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. Of 239 patients with ovarian cancer treated with doxorubicin hydrochloride liposome injection in Trial 4, 7% of patients experienced acute infusion-related reactions resulting in dose interruption. All occurred during cycle 1 and none during subsequent cycles. Across multiple studies of doxorubicin hydrochloride liposome injection monotherapy including this and other studies enrolling 760 patients with various solid tumors, 11% of patients had infusion-related reactions. The majority of infusion-related events occurred during the first infusion.
Ensure that medications to treat infusion-related reactions and cardiopulmonary resuscitative equipment are available for immediate use prior to initiation of doxorubicin hydrochloride liposome injection. Initiate doxorubicin hydrochloride liposome injection infusions at a rate of 1 mg/min and increase rate as tolerated
[see Dosage and Administration (2.6)]. Withhold doxorubicin hydrochloride liposome injection for Grade 1, 2, or 3 infusion-related reactions and resume at a reduced infusion rate. Discontinue doxorubicin hydrochloride liposome injection infusion for serious or life-threatening infusion-related reactions.
Doxorubicin hydrochloride liposome injection is an anthracycline topoisomerase inhibitor indicated for:
• Ovarian cancer:After failure of platinum-based chemotherapy()1.1 Ovarian CancerDoxorubicin 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:After failure of prior systemic chemotherapy or intolerance to such therapy()1.2 AIDS-Related Kaposi’s SarcomaDoxorubicin hydrochloride liposome injection is indicated for the treatment of AIDS-related Kaposi’s sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy.
• Multiple Myeloma:In combination with bortezomib in patients who have not previously received bortezomib and have received at least one prior therapy()1.3 Multiple MyelomaDoxorubicin hydrochloride liposome injection, in combination with bortezomib, is indicated for the treatment of patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.
Administer doxorubicin hydrochloride liposome injection at an initial rate of 1 mg/min to minimize the risk of infusion reactions. If no infusion-related reactions occur, increase rate of infusion to complete administration over 1 hour. Do not administer as bolus injection or undiluted solution (
Administer doxorubicin hydrochloride liposome injection at an initial rate of 1 mg/min to minimize the risk of infusion reactions. If no infusion-related reactions occur, increase rate of infusion to complete administration over 1 hour. Do not administer as bolus injection or undiluted solution .
• Ovarian cancer:50 mg/m2intravenously every 4 weeks• AIDS-related Kaposi’s Sarcoma:20 mg/m2intravenously every 3 weeks• Multiple Myeloma:30 mg/m2intravenously on day 4 following bortezomib
The recommended dose of doxorubicin hydrochloride liposome injection is 50 mg/m2intravenously over 60 minutes every 28 days until disease progression or unacceptable toxicity.
The recommended dose of doxorubicin hydrochloride liposome injection is 20 mg/m2intravenously over 60 minutes every 21 days until disease progression or unacceptable toxicity.
The recommended dose of doxorubicin hydrochloride liposome injection is 30 mg/m2intravenously over 60 minutes on day 4 of each 21-day cycle for eight cycles or until disease progression or unacceptable toxicity. Administer doxorubicin hydrochloride liposome injection after bortezomib on day 4 of each cycle
Do not increase doxorubicin hydrochloride liposome injection after a dose reduction for toxicity.
Toxicity | Dose Adjustment |
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Hand-Foot Syndrome (HFS) | |
Grade 1: Mild erythema, swelling, or desquamation not interfering with daily activities |
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Grade 2: Erythema, desquamation, or swelling interfering with, but not precluding normal physical activities; small blisters or ulcerations less than 2 cm in diameter |
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Grade 3: Blistering, ulceration, or swelling interfering with walking or normal daily activities; cannot wear regular clothing |
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Grade 4: Diffuse or local process causing infectious complications, or a bed ridden state or hospitalization |
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Stomatitis | |
Grade 1: Painless ulcers, erythema, or mild soreness |
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Grade 2: Painful erythema, edema, or ulcers, but can eat |
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Grade 3: Painful erythema, edema, or ulcers, and cannot eat |
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Grade 4: Requires parenteral or enteral support |
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Neutropenia or Thrombocytopenia | |
Grade 1 | No dose reduction |
Grade 2 | Delay until ANC ≥ 1,500 and platelets ≥ 75,000; resume treatment at previous dose |
Grade 3 | Delay until ANC ≥ 1,500 and platelets ≥ 75,000; resume treatment at previous dose |
Grade 4 | Delay until ANC ≥ 1,500 and platelets ≥ 75,000; resume at 25% dose reduction or continue previous dose with prophylactic granulocyte growth factor |
Toxicity | Doxorubicin hydrochloride liposome injection |
Fever ≥38°C and |
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On any day of drug administration after Day 1 of each cycle:
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Grade 3 or 4 non-hematologic drug related toxicity | Do not dose until recovered to Grade <2, then reduce dose by 25%. |
For neuropathic pain or peripheral neuropathy, no dosage adjustments are required for doxorubicin hydrochloride liposome injection. Refer to bortezomib manufacturer’s prescribing information.
Preparation
Dilute doxorubicin hydrochloride liposome injection 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 injection at 2°C to 8°C (36°F to 46°F) and administer within 24 hours.
Administration
Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if a precipitate or foreign matter is present.
Do not use with in-line filters.
Administer the first dose of doxorubicin hydrochloride liposome injection 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 mix doxorubicin hydrochloride liposome injection with other drugs.
Management of Suspected Extravasation
Discontinue doxorubicin hydrochloride liposome injection for burning or stinging sensation or other evidence indicating perivenous infiltration or extravasation. Manage confirmed or suspected extravasation as follows:
• Do not remove the needle until attempts are made to aspirate extravasated fluid• Do not flush the line• Avoid applying pressure to the site• Apply ice to the site intermittently for 15 minute 4 times a day for 3 days• If the extravasation is in an extremity, elevate the extremity
Doxorubicin hydrochloride liposome injection is a cytotoxic drug. Follow applicable special handling and disposal procedures.1If doxorubicin hydrochloride liposome injection comes into contact with skin or mucosa, immediately wash thoroughly with soap and water.
• Ovarian cancer:50 mg/m2 intravenously every 4 weeks ()2.2 Ovarian CancerThe recommended dose of doxorubicin hydrochloride liposome injection is 50 mg/m2intravenously over 60 minutes every 28 days until disease progression or unacceptable toxicity.
• AIDS-related Kaposi’s Sarcoma:20 mg/m2 intravenously every 3 weeks()2.3 AIDS-Related Kaposi’s SarcomaThe recommended dose of doxorubicin hydrochloride liposome injection is 20 mg/m2intravenously over 60 minutes every 21 days until disease progression or unacceptable toxicity.
• Multiple Myeloma:30 mg/m2 intravenously on day 4 following bortezomib ()2.4 Multiple MyelomaThe recommended dose of doxorubicin hydrochloride liposome injection is 30 mg/m2intravenously over 60 minutes on day 4 of each 21-day cycle for eight cycles or until disease progression or unacceptable toxicity. Administer doxorubicin hydrochloride liposome injection after bortezomib on day 4 of each cycle
[see Clinical Studies (14.3)].
Doxorubicin hydrochloride liposome injection: 20 mg/10 mL (2 mg/mL) and 50 mg/25 mL (2 mg/mL) in single-dose vials. The drug product appears as a translucent, red liposomal dispersion.
• Lactation: Discontinue breastfeeding ().8.2 LactationRisk Summary
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 doxorubicin hydrochloride liposome injection.
Doxorubicin hydrochloride liposome injection is contraindicated in patients who have a history of severe hypersensitivity reactions, including anaphylaxis, to doxorubicin hydrochloride
Serious, life-threatening, and fatal infusion-related reactions characterized by one or more of the following symptoms can occur with doxorubicin hydrochloride liposome injection: 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. Of 239 patients with ovarian cancer treated with doxorubicin hydrochloride liposome injection in Trial 4, 7% of patients experienced acute infusion-related reactions resulting in dose interruption. All occurred during cycle 1 and none during subsequent cycles. Across multiple studies of doxorubicin hydrochloride liposome injection monotherapy including this and other studies enrolling 760 patients with various solid tumors, 11% of patients had infusion-related reactions. The majority of infusion-related events occurred during the first infusion.
Ensure that medications to treat infusion-related reactions and cardiopulmonary resuscitative equipment are available for immediate use prior to initiation of doxorubicin hydrochloride liposome injection. Initiate doxorubicin hydrochloride liposome injection infusions at a rate of 1 mg/min and increase rate as tolerated