DOXIL® safety profile1-3
Cardiac safety data1
Based on a Phase 3 study, DOXIL® can cause myocardial damage, including congestive heart failure, as the total cumulative dose of doxorubicin HCl approaches 550 mg/m2.
- The risk of cardiomyopathy may be increased at lower cumulative doses in patients with prior mediastinal irradiation
- Please see Important Safety Information, including BOXED WARNINGS, for additional information
Patients treated with DOXIL® who experienced a drug-related cardiovascular disorder2
In study arm A, 3.8% of patients treated with DOXIL® (n=239) experienced a drug-related cardiovascular disorder.*
*One patient death due to cardiac arrest of unknown relationship. Two DOXIL®-treated subjects died due to cardiac arrest unrelated to drug.
†These patients did not continue with the trial.
- Patients’ left ventricular ejection fraction (LVEF) was assessed by a multiple-gated acquisition (MUGA) scan at baseline and at end of study3
- Study eligibility criteria included ≥50% LVEF. Patients were excluded if they had a history of cardiac disease meeting New York State Heart Association Classification ≥23
- Treatment with either study drug was temporarily suspended or discontinued if either3:
- LVEF value decreased to <45%
- Absolute LVEF decrease of 20% compared with baseline value
DOXIL® 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 irradiation1
LVEF changes from baseline
For those patients treated with DOXIL® who received a baseline and ≥1 postdose LVEF evaluation (n=132), the mean absolute change from baseline to last LVEF measurement was -2.7%.2,3
- 61 patients received cumulative DOXIL® doses ≥300 mg/m2, and 14 of those exceeded 450 mg/m2
- None of these patients had clinical signs or symptoms of congestive heart failure3
- There was no evidence of a direct relationship between a change from baseline LVEF and a cumulative DOXIL® dose of ≥300 mg/m2 2,3
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. Of 239 patients with ovarian cancer treated with DOXIL® in Trial 4, 7% of patients experienced acute infusion-related reactions resulting in dose interruption. All occurred during Cycle 1 and none during subsequent cycles. Across multiple studies of DOXIL® monotherapy including this and other studies enrolling 760 patients with various solid tumors, 11% of patients had infusion-related reactions.1
Hematologic adverse reactions (ARs)1
Data on adverse reactions, dose adjustments, and supportive therapies are based on a randomized, multicenter, open-label trial of patients with progressed or relapsed epithelial ovarian cancer after platinum-based chemotherapy (N=474).1,3 Patients received DOXIL® for median of 3.2 months (range, 1 day-25.8 months).
Supportive therapies used for hematologic adverse reactions (ARs)3
*Only patients with concomitant medication forms are included in these data (DOXIL® [n=238]; topotecan [n=234]).2
†Only patients with transfusion forms are included in these data (DOXIL® [n=227]; topotecan [n=230]).2
G-CSF=granulocyte- or granulocyte-marcophage colony-stimulating factor.
Nonhematologic adverse reactions (ARs)1
Patients requiring a delay, interruption, or reduction in dose due to adverse reactions1
- 57.3% for DOXIL® vs 78.3% for topotecan
The leading cause of dose modification was hand-foot syndrome (HFS) in the DOXIL® group (25.2% of doses) vs hematologic toxicity in the topotecan group (43.3% of doses).3 HFS or other skin toxicity required discontinuation of DOXIL® in 4.2% of patients.1
DOXIL® (doxorubicin HCl liposome injection) Prescribing Information. Janssen Products, LP, Horsham, PA.
Data on file. Janssen Products, LP, Horsham, PA.
Gordon AN, Fleagle JT, Guthrie D, et al. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001;19(14):3312-3322.