DOXIL—Common Side Effects

DOXIL (doxorubicin HCl liposome injection)

Range of Possible Side Effects
You have probably been down this road before—you are well aware that chemotherapy drugs can cause a variety of side effects. Many of the side effects associated with DOXIL are mild to moderate and may be minimized.

It is still important to understand your risks. Side effects are a serious matter, but many can be prevented, managed and often reversed by delaying or reducing doses.

Hand-Foot Syndrome
You may experience a skin reaction called hand-foot syndrome (HFS), also called palmar-plantar erythrodysesthesia (PPE). See Managing Side Effects for hints on how to manage and help prevent symptoms.

Hand-foot syndrome usually occurs on the palms of the hands and soles of the feet. However, it can also occur on other parts of the body where your clothes may be tight or where friction, pressure, rubbing, warmth, and/or sweating occur.

You or your caregiver should check regularly for signs of skin irritation and hand-foot syndrome. If you already have peripheral neuropathy (numbness or tingling in the hands and feet) from previous treatment or other conditions, you may not notice the symptoms as easily.

Common signs and symptoms of hand-foot syndrome may include:

Redness
Rash
Pain or tenderness
Swelling
Tingling, burning, or itching
Flaking or peeling of the skin
Small blisters or sores

In most patients, the reaction is mild and improves in one to two weeks without a delay in therapy. However, hand-foot syndrome can become severe in some patients and may require either delaying or stopping therapy.

At the first sign of any of these symptoms, please tell your doctor or nurse immediately. They may have specific suggestions to help you reduce the severity of hand-foot syndrome. Because its frequency and severity are usually associated with the chemotherapy dose and/or schedule, hand-foot syndrome may be treated with a delay and/or reduction in therapy until the symptoms are resolved. A delay or reduction in dose typically does not reduce the effectiveness of treatment.

Stomatitis
Another skin-related reaction is stomatitis, a mouth irritation characterized by inflammation or sores. Stomatitis may be prevented by avoiding certain foods and beverages. Your doctor or nurse can provide you with specific guidelines to help prevent stomatitis. For example, you might be told to suck on ice chips or sip cool beverages as often as possible.

Some common symptoms of stomatitis include:

Mouth sores
Dry, swollen tongue
Pain or burning in the mouth
Difficulty swallowing

Hair Loss
Hair loss, or alopecia, is typically mild with DOXIL therapy. When it does occur, the hair usually grows back after completion of therapy. In a clinical study, some hair loss occurred in 19.2% of patients.

Nausea and Vomiting
Nausea and vomiting are usually mild and may be prevented with medication.

RELATED RESOURCES

FREQUENTLY ASKED QUESTIONS

GLOSSARY

Indications:

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