DOXILine.com - Prescribing Information

PRESCRIBING INFORMATION

Introduction

Full Prescribing Information

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Indications:

DOXIL^® (doxorubicin HCl liposome injection) is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after prior platinum-based therapy
DOXIL in combination with VELCADE^® (bortezomib) is indicated for the treatment of patients with multiple myeloma who have not previously received VELCADE and have received at least one prior therapy
DOXIL is indicated for the treatment of AIDS-related Kaposi's sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy

IMPORTANT SAFETY INFORMATION

BOXED WARNINGS:
Cardiotoxicity, infusion reaction, myelosuppression, liver impairment, substitution

The use of DOXIL may lead to cardiac toxicity. Myocardial damage may lead to congestive heart failure and may occur as the total cumulative dose of doxorubicin HCl approaches 550mg/m²

Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dose
Cardiac toxicity may also occur at lower cumulative doses (400 mg/m²) in patients with prior mediastinal irradiation or who are receiving concurrent cyclophosphamide therapy

Acute infusion-related reactions including, but not limited to, flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension have occurred in up to 10% of patients treated with DOXIL. In most patients, these reactions have resolved within several hours to a day once the infusion is terminated. In some patients, reactions resolved with slowing of the infusion rate

Serious and sometimes life-threatening or fatal allergic/anaphylactoid-like infusion reactions have occurred. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use
The initial rate of infusion should be 1mg/min to minimize the risk of infusion reactions

Severe myelosuppression may occur
DOXIL dosage should be reduced in patients with impaired hepatic function
Accidental substitution has resulted in severe side effects. Do not substitute for doxorubicin HCl on a mg per mg basis.

Contraindications

Patients with a history of hypersensitivity reactions to a conventional doxorubicin formulation or the components of DOXIL
Nursing mothers

Additional Safety Information

Congestive heart failure or cardiomyopathy may occur after discontinuation of anthracycline therapy
For patients with a history of cardiovascular disease, or if the results of cardiac monitoring indicate possible cardiac injury, the benefit of therapy must be weighed against the risk of myocardial injury
In the randomized multiple myeloma study, 25 patients (8%) in the VELCADE for Injection arm and 42 patients (13%) in the VELCADE plus DOXIL arm experienced left ventricular ejection fraction decrease (defined as absolute decrease > 15% over baseline or a > 5% decrease below institutional lower limit of normal)

Myelosuppression may occur; frequently monitor complete blood count (including platelet count), at least prior to each dose of DOXIL

In patients with recurrent ovarian cancer or AIDS-related Kaposi's sarcoma, hematologic toxicity (based on platelet count or absolute neutrophil count) may require dose reduction or delay in administration of DOXIL
In patients with multiple myeloma, hematologic toxicity (based on platelet count, absolute neutrophil count, hemoglobin level, or neutropenia with fever) may require dose reduction, delay in administration, or suspension of DOXIL and/or VELCADE
Persistent severe myelosuppression may result in superinfection, neutropenic fever, or hemorrhage
Sepsis occurring during neutropenia has resulted in discontinuation of treatment and in rare cases of death

DOXIL may potentiate the toxicity of other anticancer therapies, especially hematologic toxicities, when used in combination with other therapies that suppress bone marrow
Hand-foot syndrome (HFS) may occur during therapy with DOXIL

Based on HFS toxicity grade, dose reduction, delay in administration, or discontinuation of DOXIL may be required
HFS was generally observed after 2 to 3 cycles of treatment, but may occur earlier

The reaction was mild in most patients, resolving in 1 to 2 weeks
The reaction can be severe and debilitating in some patients, resulting in discontinuation of therapy

DOXIL is an irritant, not a vesicant; use precautions to avoid extravasation
DOXIL can cause fetal harm when used during pregnancy
Recall reaction has occurred with DOXIL administration after radiotherapy
DOXIL may interact with drugs known to interact with the conventional formulation of doxorubicin HCl
In patients with recurrent ovarian cancer, the most common all-grade adverse reactions (ARs) > 20% (DOXIL vs topotecan, respectively) included: asthenia (40% vs 51%), fever (21% vs 31%), nausea (46% vs 63%), stomatitis (41% vs 15%), vomiting (33% vs 44%), diarrhea (21% vs 35%), anorexia (20% vs 22%), dyspnea (15% vs 23%), HFS (51% vs 1%), and rash (29% vs 12%)

In addition, 19% vs 52.3% reported alopecia (all grades).
Grade 3/4 hematologic ARs reported in > 5% (DOXIL vs topotecan, respectively) were neutropenia (12% vs 76%) and anemia (6% vs 29%)

In patients with multiple myeloma, the most common all-grade ARs > 20% (VELCADE plus DOXIL vs VELCADE, respectively) included: neutropenia (36% vs 22%), thrombocytopenia (33% vs 28%), anemia (25% vs 21%), fatigue (36% vs 28%), pyrexia (31% vs 22%), asthenia (22% vs 18%), nausea (48% vs 40%), diarrhea (46% vs 39%), vomiting (32% vs 22%), constipation (31% vs 31%), mucositis/stomatitis (20% vs 5%), peripheral neuropathy (42% vs 45%), neuralgia (17% vs 20%), and rash (22% vs 18%)

In patients with AIDS-related Kaposi's sarcoma, ARs reported in > 5% of DOXIL-treated patients were: neutropenia (ANC < 1000/mm³, 46%; < 500/mm³, 11%), anemia (Hb < 10 g/dL, 58%; < 8 g/dL, 16%), thrombocytopenia (< 150,000 platelets/mm³, 61%), nausea (18%), asthenia (7%), fever (8%), alopecia (9%), vomiting (8%), diarrhea (5%), and stomatitis (5%)

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