Belinostat

Beleodaq is indicated for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This indication is approved under accelerated approval based on tumor response rate and duration of response. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial. Beleodaq is a histone deacetylase inhibitor indicated for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).

Beleodaq is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from the lysine residues of histones and some non-histone proteins. In vitro, belinostat caused the accumulation of acetylated histones and other proteins, inducing cell cycle arrest and/or apoptosis of some transformed cells. Belinostat shows preferential cytotoxicity towards tumor cells compared to normal cells. Belinostat inhibited the enzymatic activity of histone deacetylases at nanomolar concentrations (<250 nM).

Recommended dosage of Beleodaq is 1,000 mg/m 2 administered over 30 minutes by intravenous infusion once daily on days 1 through 5 of a 21-day cycle. Cycles can be repeated until disease progression or unacceptable toxicity. Treatment discontinuation or interruption with or without dosage reductions by 25% may be needed to manage adverse reactions. Reduce dosage in patients with moderate hepatic or renal impairment. Avoid use in patients with severe hepatic or renal impairment. Modify dosage in patients known to be homozygous for the UGT1A1*28 allele. See the full prescribing information for preparation and administration instructions.

None None.

Hematologic Toxicity: Thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia: Monitor blood counts and modify dosage for hematologic toxicities. Infection: Serious and fatal infections (e.g., pneumonia and sepsis). Hepatotoxicity: Beleodaq may cause hepatic toxicity and liver function test abnormalities. Monitor liver function tests and omit or modify dosage for hepatic toxicities. Tumor lysis syndrome: Monitor patients with advanced stage disease and/or high tumor burden and take appropriate precautions. Gastrointestinal Toxicity: Nausea, vomiting and diarrhea occur with Beleodaq and may require antiemetic and antidiarrheal medications. Embryo-Fetal Toxicity: Can cause fetal harm.

The following clinically significant adverse reactions are described in more detail in other sections of the prescribing information. • Hematologic Toxicity • Infection • Hepatotoxicity • Tumor Lysis Syndrome • Gastrointestinal Toxicity The most common adverse reactions (>25%) are nausea, fatigue, pyrexia, anemia, and vomiting.

UGT1A1 Inhibitors: Avoid use or modify dosage if use is unavoidable. 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.

Store Beleodaq (belinostat) for injection at room temperature 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F and 86°F).