Beleodaq Drug Information

• The following clinically significant adverse reactions are described in more detail in other sections of the prescribing information.
• Hematologic Toxicity [see Warnings and Precautions ( 5.1 )]
• Infection [see Warnings and Precautions ( 5.2 )]
• Hepatotoxicity [see Warnings and Precautions ( 5.3 )]
• Tumor Lysis Syndrome [see Warnings and Precautions ( 5.4 )]
• Gastrointestinal Toxicity [see Warnings and Precautions ( 5.5 )] The most common adverse reactions (>25%) are nausea, fatigue, pyrexia, anemia, and vomiting. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Acrotech Biopharma Inc at 1-888-292-9617 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Beleodaq may not reflect the rates observed in practice. Adverse Reactions in Patients with Peripheral T-Cell Lymphoma The safety of Beleodaq was evaluated in 129 patients with relapsed or refractory PTCL in the single arm clinical trial in which patients were administered Beleodaq at a dosage of 1,000 mg/m 2 administered over 30 minutes by IV infusion once daily on Days 1 through 5 of a 21-day cycle [see Clinical Studies ( 14 ) ] . The median duration of treatment was 2 cycles (range 1 – 33 cycles). The most common adverse reactions observed in the trial of patients with relapsed or refractory PTCL treated with Beleodaq were nausea, fatigue, pyrexia, anemia, and vomiting [see Clinical Studies ( 14 ) ] . Table 3 summarizes the adverse reactions regardless of causality from the trial in patients with relapsed or refractory PTCL. Table 3: Adverse Reactions Occurring in ≥ 10% of Patients with Relapsed or Refractory PTCL (NCI CTC Grade 1-4) Adverse Reactions Percentage of Patients (%) (N=129) All Grades Grade 3 or 4 All Adverse Reactions 97 61 Nausea 42 1 Fatigue 37 5 Pyrexia 35 2 Anemia 32 11 Vomiting 29 1 Constipation 23 1 Diarrhea 23 2 Dyspnea 22 6 Rash 20 1 Peripheral Edema 20 0 Cough 19 0 Thrombocytopenia 16 7 Pruritus 16 3 Chills 16 1 Increased Blood Lactate Dehydrogenase 16 2 Decreased Appetite 15 2 Headache 15 0 Infusion Site Pain 14 0 Hypokalemia 12 4 Prolonged QT 11 4 Abdominal pain 11 1 Hypotension 10 3 Phlebitis 10 1 Dizziness 10 0 Note: Adverse reactions are listed by order of incidence in the “All Grades” category first, then by incidence in “the Grade 3 or 4” category; Measured by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0 Serious Adverse Reactions Sixty-one patients (47.3%) experienced serious adverse reactions while taking Beleodaq or within 30 days after their last dose of Beleodaq. The most common serious adverse reactions (> 2%) were pneumonia, pyrexia, infection, anemia, increased creatinine, thrombocytopenia, and multi-organ failure. One treatment-related death associated with hepatic failure was reported in the trial. One patient with baseline hyperuricemia and bulky disease experienced Grade 4 tumor lysis syndrome during the first cycle of treatment and died due to multi-organ failure. A treatment-related death from ventricular fibrillation was reported in another monotherapy clinical trial with Beleodaq. ECG analysis did not identify QTc prolongation. Discontinuations due to Adverse Reactions Twenty-five patients (19.4%) discontinued treatment with Beleodaq due to adverse reactions. The adverse reactions reported most frequently as the reason for discontinuation of treatment included anemia, febrile neutropenia, fatigue, and multi-organ failure. Dosage Modifications due to Adverse Reactions In the trial, dosage adjustments due to adverse reactions occurred in 12% of Beleodaq-treated patients.

UGT1A1 Inhibitors

Avoid concomitant administration of Beleodaq with UGT1A1inhibitors. If concomitant use of a UGT1A1 inhibitor is unavoidable, modify the Beleodaq dose . Belinostat is primarily metabolized by UGT1A1. Concomitant use with a UGT1A1 inhibitor increases belinostat exposure , which may increase the risk of Beleodaq adverse reactions.

Pregnancy Risk Summary Based on its mechanism of action, Beleodaq can cause teratogenicity and/or embryo-fetal lethality because it is genotoxic and targets actively dividing cells . There are no available data on Beleodaq use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. No animal reproduction studies were conducted with Beleodaq. Advise pregnant women of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Pediatric Use The safety and effectiveness of Beleodaq in pediatric patients have not been established.

No specific information is available on the treatment of overdosage of Beleodaq. There is no antidote for Beleodaq and it is not known if Beleodaq is dialyzable. If an overdose occurs, general supportive measures should be instituted as deemed necessary by the treating physician.

The elimination half-life of belinostat is 1.1 hours .