DOXIL® safety profile1,2

Cardia safety data1,2

DOXIL® can cause myocardial damage, including congestive heart failure, as the total cumulative dose of doxorubicin HCl approaches 550 mg/m2.

  • The incidence of symptomatic cardiac adverse events was 10% in the DOXIL® + bortezomib group and 7% in the bortezomib-only group across all grades of severity2
    • Two-thirds of patients in both arms had prior anthracycline treatment2
    • No difference in congestive heart failure* incidence between groups (3% in each study arm)2
  • In the Phase 3 study, left ventricular ejection fraction (LVEF) decrease was defined as an absolute decrease ≥15% from the subject's baseline or decrease to less than the institutional lower limit of normal and at least an absolute decrease ≥5% from the subject's baseline2
    • 9% of subjects in the DOXIL® + bortezomib arm and 7% in the bortezomib arm experienced a LVEF-defined decrease2
    • Among all subjects with protocol-defined LVEF decrease in the combination group, there were 3% of subjects with LVEF <45%2
    • The risk of cardiomyopathy may be increased at lower cumulative doses in patients with prior mediastinal irradiation1

*Includes ventricular dysfunction, cardiac failure, right ventricular failure, congestive cardiac failure, chronic cardiac failure, acute pulmonary edema, and pulmonary edema.

Please see Important Safety Information, including BOXED WARNINGS, for additional information.


Infusion-related reactions warning1

Serious and sometimes life-threatening infusion-related reactions characterized by 1 or more of the following symptoms can occur with DOXIL®: 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. The majority of infusion-related events occurred during the first infusion. Across multiple studies of DOXIL® monotherapy enrolling 760 patients with various solid tumors, 11% of patients had infusion-related reactions.1



Hematologic adverse reactions (ARs)1



Nonhematologic adverse reactions (ARs)1

Peripheral neuropathy includes the following adverse reactions: peripheral sensory neuropathy, neuropathy peripheral, polyneuropathy, peripheral motor neuropathy, and neuropathy NOS.

Rash includes the following adverse reactions: rash, rash erythematous, rash macular, rash maculo-papular, rash pruritic, exfoliative rash, and rash generalized. Only patients with concomitant medication forms are included in these data (DOXIL® [n=238]; topotecan [n=234]).



DOXIL® with bortezomib has an established tolerability profile in a pretreated patient population (all patients had at least 1 prior therapy; 66% had ≥1 prior therapy). Patients in the DOXIL® + bortezomib combination group were treated for a median number of 4.5 months (range, 21 days-13.5 months)1:

  • No increase in neuropathy in the combination arm
  • Incidence of thromboembolic events was 1% in both treatment arms

References

  1. DOXIL® (doxorubicin HCl liposome injection) Prescribing Information. Janssen Products, LP, Horsham, PA.

  2. Data on file. Janssen Products, LP, Horsham, PA.

  

IMPORTANT SAFETY INFORMATION

WARNING: CARDIOMYOPATHY and INFUSION-RELATED REACTIONS

DOXIL® (doxorubicin HCl liposome injection) can cause myocardial damage, including congestive heart failure, as the total cumulative dose of doxorubicin HCl approaches 550 mg/m2. In a clinical study of 250 patients with advanced cancer who were treated with DOXIL®, the risk of cardiotoxicity was 11% when the cumulative anthracycline dose was between 450-550 mg/m2. Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dosage. The risk of cardiomyopathy may be increased at lower cumulative doses in patients with prior mediastinal irradiation. See additional information on Cardiomyopathy in Warnings and Precautions below.

Acute infusion-related reactions consisting of, but not limited to, flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension occurred in 11% of patients with solid tumors treated with DOXIL®. Serious, life-threatening and fatal infusion reactions have been reported. Medications/emergency equipment to treat such reactions should be available for immediate use. See additional information on Infusion-Related Reactions in Warnings and Precautions below.

Contraindications

DOXIL® is contraindicated in patients who have a history of severe hypersensitivity reactions, including anaphylaxis, to doxorubicin HCl.

Warnings and Precautions

Cardiomyopathy: Doxorubicin HCl can result in myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy with doxorubicin HCl is generally proportional to the cumulative exposure. The relationship between cumulative DOXIL® dose and the risk of cardiac toxicity has not been determined. Assess left ventricular cardiac function (e.g. MUGA or echocardiogram) prior to initiation of DOXIL®, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity. Administer DOXIL® to patients with a history of cardiovascular disease only when the potential benefit of treatment outweighs the risk.

Infusion-Related Reactions: Serious and sometimes life-threatening infusion-related reactions characterized by one or more of the following symptoms can occur with DOXIL®: 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. The majority of infusion-related events occurred during the first infusion. Ensure that medications to treat infusion-related reactions and cardiopulmonary resuscitative equipment is available for immediate use prior to initiation of DOXIL®. Initiate DOXIL® infusions at a rate of 1 mg/min and increase rate as tolerated. In the event of an infusion-related reaction, temporarily stop the drug until resolution then resume at a reduced infusion rate. Discontinue DOXIL® infusion for serious or life-threatening infusion-related reactions.

Hand-foot syndrome (HFS): 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

  • Delay DOXIL® for the first episode of Grade 2 or greater HFS

  • Discontinue DOXIL® if HFS is severe and debilitating

Secondary Oral Neoplasms: Cases of secondary oral cancer have been reported in patients with more than one year's exposure to DOXIL®. Cases were diagnosed both during treatment and up to 6 years after the last dose. Patients should be examined at regular intervals for the presence of oral ulceration or any oral discomfort that may be indicative of secondary oral cancer.

Embryofetal Toxicity: Based on animal data, DOXIL® can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during and for 6 months after treatment with DOXIL®.

Adverse Reactions

Most common adverse reactions observed with DOXIL® (>20%) are asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand-foot syndrome, rash, neutropenia, thrombocytopenia, and anemia.

Use in Specific Populations

Lactation: Because of the potential for serious adverse reactions in nursing infants, discontinue nursing during treatment with DOXIL®.

INDICATIONS

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

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.

DOXIL® 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.

Click here to see the full Prescribing Information, including BOXED WARNINGS.

020669-150414

IMPORTANT SAFETY INFORMATION

WARNING: CARDIOMYOPATHY and INFUSION-RELATED REACTIONS

DOXIL® (doxorubicin HCl liposome injection) can cause myocardial damage, including congestive heart failure, as the total cumulative dose of doxorubicin HCl approaches 550 mg/m2. In a clinical study of 250 patients with advanced cancer who were treated with DOXIL®, the risk of cardiotoxicity was 11% when the cumulative anthracycline dose was between 450-550 mg/m2. Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dosage. The risk of cardiomyopathy may be increased at lower cumulative doses in patients with prior mediastinal irradiation. See additional information on Cardiomyopathy in Warnings and Precautions below.

Acute infusion-related reactions consisting of, but not limited to, flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension occurred in 11% of patients with solid tumors treated with DOXIL®. Serious, life-threatening and fatal infusion reactions have been reported. Medications/emergency equipment to treat such reactions should be available for immediate use. See additional information on Infusion-Related Reactions in Warnings and Precautions below.

Contraindications

DOXIL® is contraindicated in patients who have a history of severe hypersensitivity reactions, including anaphylaxis, to doxorubicin HCl.

Warnings and Precautions

Cardiomyopathy: Doxorubicin HCl can result in myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy with doxorubicin HCl is generally proportional to the cumulative exposure. The relationship between cumulative DOXIL® dose and the risk of cardiac toxicity has not been determined. Assess left ventricular cardiac function (e.g. MUGA or echocardiogram) prior to initiation of DOXIL®, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity. Administer DOXIL® to patients with a history of cardiovascular disease only when the potential benefit of treatment outweighs the risk.

Infusion-Related Reactions: Serious and sometimes life-threatening infusion-related reactions characterized by one or more of the following symptoms can occur with DOXIL®: 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. The majority of infusion-related events occurred during the first infusion. Ensure that medications to treat infusion-related reactions and cardiopulmonary resuscitative equipment is available for immediate use prior to initiation of DOXIL®. Initiate DOXIL® infusions at a rate of 1 mg/min and increase rate as tolerated. In the event of an infusion-related reaction, temporarily stop the drug until resolution then resume at a reduced infusion rate. Discontinue DOXIL® infusion for serious or life-threatening infusion-related reactions.

Hand-foot syndrome (HFS): 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

  • Delay DOXIL® for the first episode of Grade 2 or greater HFS

  • Discontinue DOXIL® if HFS is severe and debilitating

Secondary Oral Neoplasms: Cases of secondary oral cancer have been reported in patients with more than one year's exposure to DOXIL®. Cases were diagnosed both during treatment and up to 6 years after the last dose. Patients should be examined at regular intervals for the presence of oral ulceration or any oral discomfort that may be indicative of secondary oral cancer.

Embryofetal Toxicity: Based on animal data, DOXIL® can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during and for 6 months after treatment with DOXIL®.

Adverse Reactions

Most common adverse reactions observed with DOXIL® (>20%) are asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand-foot syndrome, rash, neutropenia, thrombocytopenia, and anemia.

Use in Specific Populations

Lactation: Because of the potential for serious adverse reactions in nursing infants, discontinue nursing during treatment with DOXIL®.

INDICATIONS

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

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.

DOXIL® 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.

Click here to see the full Prescribing Information, including BOXED WARNINGS.

020669-150414

INDICATIONS

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

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.

DOXIL® 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.

Please see full Prescribing Information, including BOXED WARNINGS, for DOXIL® at www.DOXIL.com.

020669-150414