DOXIL is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after prior platinum-based 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.
Contraindiction
Patients with a history of hypersensitivity reactions to a conventional doxorubicin formulation or the components of DOXIL
Nursing mothers
Additional Safety Information
Cardiac function should be carefully monitored.
— 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
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, hematologic toxicity (based on platelet count or absolute neutrophil count) may require dose reduction or delay in administration of DOXIL
— 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%)
Please see accompanying full Prescribing Information, including Boxed WARNINGS
