Dose Modifications

Patient support for managing adverse reactions

The DOXIL^® dose may be reduced or delayed to help manage adverse reactions such as hematologic toxicities, hand-foot syndrome, and stomatitis. Once the dose of DOXIL^® has been reduced, it should not be increased at a later time.

For hematologic toxicities
For HFS and stomatitis

Recommended Dose Modification Guidelines for Hematologic Toxicities

Recommended Guidelines for HFS and Stomatitis

Prior to infusion, patients should be monitored for myelosuppression, hand-foot syndrome, and stomatitis

IMPORTANT SAFETY INFORMATION

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 550 mg/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 1 mg/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

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
In the randomized multiple myeloma study, 25 patients (8%) in the VELCADE^® arm and 42 patients (13%) in the DOXIL^® plus VELCADE^® 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, 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 adverse reactions ≥20% (DOXIL^® plus VELCADE^® 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 addition, 19% vs <1% reported HFS

Please click here to see full Prescribing Information, including Boxed WARNINGS, for DOXIL^®.

VELCADE^® is a registered trademark of Millennium Pharmaceuticals, Inc.

INDICATION

DOXIL^® is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy