Belinostat Disease Interactions

Tumor lysis syndrome has occurred in patients treated with belinostat. It is recommended to monitor patients with advanced stage disease and/or high tumor burden and take appropriate precautions.

Belinostat can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and/or anemia. It is recommended to monitor blood counts weekly during treatment, and modify dosage as necessary. It is recommended to monitor complete blood counts at baseline and weekly and to perform serum chemistry tests, including renal and hepatic functions prior to the start of the first dose of each cycle. Absolute neutrophil count (ANC) should be greater than or equal to 1.0 x 10 9/L and the platelet count should be greater than or equal to 50 x 10 9/L prior to the start of each cycle and prior to resuming treatment following toxicity. Discontinue belinostat in patients who have recurrent ANC nadirs less than 0.5 x 10 9/L and/or recurrent platelet count nadirs less than 25 x 10 9/L after two dosage reductions. Close monitoring is recommended.

Belinostat is metabolized by the liver, primarily by hepatic UGT1A1. Hepatic impairment is expected to increase exposure to belinostat, which can result in fatal hepatotoxicity and liver function test abnormalities. Reduce the starting dose of belinostat to 750 mg/m2 in patients known to be homozygous for the UGT1A1*28 allele to minimize dose limiting toxicities. There is insufficient data to recommend a dose of belinostat in patients with moderate and severe hepatic impairment. It is recommended to monitor liver function tests before treatment and before the start of each cycle and to interrupt or adjust dosage until recovery, or permanently discontinue belinostat based on the severity of the hepatic toxicity. Care should be taken when using belinostat in these patients.

Serious and sometimes fatal infections, including pneumonia and sepsis, have occurred with the use of belinostat. Do not administer belinostat to patients with an active infection. Close monitoring is recommended.

Belinostat exposure is not altered in patients with creatinine clearance (CrCl) > 39 mL/min. There is insufficient data to recommend a dose of belinostat in patients with CrCl <= 39 mL/min. Care should be taken when using belinostat in these patients.