BELEODAQ

The pharmacokinetic characteristics of belinostat were analyzed from pooled data from phase 1/2 clinical studies that used doses of belinostat ranging from 150 to 1200 mg/m 2 (0.15 to 1.2 times the approved recommended dosage).

DistributionThe mean belinostat volume of distribution approaches total body water, indicating that belinostat has limited body tissue distribution. In vitro plasma studies have shown that between 92.9% and 95.8% of belinostat is bound to protein in an equilibrium dialys...

Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL) In an open-label, single-arm, non-randomized international trial conducted at 62 centers, 129 patients with relapsed or refractory PTCL were treated with Beleodaq 1,000 mg/m 2 administered over 30 minutes via IV infusion once daily on Days 1 through 5 of a 21-day cycle. There were 120 patients who had histologically confirmed PTCL by central review evaluable for efficacy. Patients were treated with repeat cycles every three weeks until disease progression or unacceptable toxicity. Efficacy was evaluated using response rate (complete resp...

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, pyrexi...

None None. ( 4 )

Hematologic Toxicity : Thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia: Monitor blood counts and modify dosage for hematologic toxicities. ( 2.2 , 5.1 ) Infection : Serious and fatal infections (e.g., pneumonia and sepsis) ( 5.2 ) Hepatotoxicity : Beleodaq may cause hepatic toxicity and liver function test abnormalities. Monitor liver function tests and omit or modify dosage for hepatic toxicities. ( 2.2 , 5.3 ) Tumor lysis syndrome : Monitor patients with advanced stage d...

7 DRUG INTERACTIONS UGT1A1 Inhibitors: Avoid use or modify dosage if use is unavoidable. ( 2.6 , 7.1 ) 7.1 UGT1A1 Inhibitors Avoid concomitant administration of Beleodaq with UGT1A1inhibitors. If concomitant use of a UGT1A1 inhibitor is unavoidable, modify the Beleodaq dose [see Dosage and Administration ( 2.6 )] . Belinostat is primarily metabolized by UGT1A1. Concomitant use with a UGT1A1 inhibi...