Hematologic Toxicity Beleodaq can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and/or anemia; monitor blood counts weekly during treatment, and modify dosage as necessary [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS]. Infections Serious and sometimes fatal infections, including pneumonia and sepsis, have occurred with Beleodaq. Do not administer Beleodaq to patients with an active infection. Patients with a history of extensive or intensive chemotherapy may be at higher risk of life threatening infections [see ADVERSE REACTIONS]. Hepatotoxicity Beleodaq can cause fatal hepatotoxicity and liver function test abnormalities [see ADVERSE REACTIONS]. Monitor liver function tests before treatment and before the start of each cycle. Interrupt or adjust dosage until recovery, or permanently discontinue Beleodaq based on the severity of the hepatic toxicity [see DOSAGE AND ADMINISTRATION]. Tumor Lysis Syndrome Tumor lysis syndrome has occurred in Beleodaq-treated patients in the clinical trial of patients with relapsed or refractory PTCL [see Clinical Studies]. Monitor patients with advanced stage disease and/or high tumor burden and take appropriate precautions [see ADVERSE REACTIONS]. Gastrointestinal Toxicity Nausea, vomiting and diarrhea occur with Beleodaq [see ADVERSE REACTIONS] and may require the use of antiemetic and antidiarrheal medications. Embryo-fetal Toxicity Beleodaq can cause fetal harm when administered to a pregnant woman. Beleodaq may cause teratogenicity and/or embryo-fetal lethality because it is genotoxic and targets actively dividing cells [see Nonclinical Toxicology]. Women of childbearing potential should be advised to avoid pregnancy while receiving Beleodaq. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of potential hazard to the fetus [see Use in Specific Populations]. Patient Counseling Informaton Physicians should discuss the FDA approved PATIENT INFORMATION Leaflet with patients prior to treatment with Beleodaq. Instruct patients to read the Patient Information Leaflet carefully. Advise the patient or the caregiver to read the FDA-approved patient labeling (PATIENT INFORMATION). Advise patients or their caregivers:
- To report symptoms of nausea, vomiting and diarrhea so that appropriate antiemetic and antidiarrheal medications can be administered [see WARNINGS AND PRECAUTIONS].
- To report any symptoms of thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia [see WARNINGS AND PRECAUTIONS].
- To immediately report symptoms of infection (e.g., pyrexia) [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].
- Of the potential risk to the fetus and for women to avoid pregnancy while receiving Beleodaq [see WARNINGS AND PRECAUTIONS].
- To understand the importance of monitoring liver function test abnormalities and to immediately report potential symptoms of liver injury [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenicity studies have not been performed with belinostat. Belinostat was genotoxic in a bacterial reverse mutation test (Ames assay), an in vitro mouse lymphoma cell mutagenesis assay, and an in vivo rat micronucleus assay. Beleodaq may impair male fertility. Fertility studies using belinostat were not conducted. However, belinostat effects on male reproductive organs observed during the 24-week repeat-dose dog toxicology study included reduced organ weights of the testes/epididymides that correlated with a delay in testicular maturation. Use In Specific Populations Pregnancy Pregnancy Category D [see WARNINGS AND PRECAUTIONS]. Risk Summary Beleodaq may cause teratogenicity and/or embryo-fetal lethality because it is a genotoxic drug and targets actively dividing cells [see Nonclinical Toxicology]. Women should avoid pregnancy while receiving Beleodaq. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of potential hazard to the fetus. Animal Data No reproductive and developmental animal toxicology studies have been conducted with belinostat. Nursing Mothers It is not known whether belinostat is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Beleodaq, a decision should be made whether to discontinue nursing or discontinue drug, taking into account the importance of the drug to the mother. Pediatric Use Pediatric patients were not included in clinical trials. The safety and effectiveness of Beleodaq in pediatric patients have not been established. Geriatric Use In the single-arm trial, 48% of patients (n = 62) were ≥ 65 years of age and 10% of patients (n=13) were ≥ 75 years of age [see Clinical Studies]. The median age of the trial population was 63 years. Patients ≥ 65 years of age had a higher response rate to Beleodaq treatment than patients < 65 years of age (36% versus 16%) while no meaningful differences in response rate were observed between patients ≥ 75 years of age and those < 75 years of age. No clinically meaningful differences in serious adverse reactions were observed in patients based on age ( < 65 years compared with ≥ 65 years or < 75 years of age compared with ≥ 75 years of age). Use In Patients With Hepatic Impairment Belinostat is metabolized in the liver and hepatic impairment is expected to increase exposure to belinostat. Patients with moderate and severe hepatic impairment (total bilirubin > 1.5 x upper limit of normal (ULN)) were excluded from clinical trials. There is insufficient data to recommend a dose of Beleodaq in patients with moderate and severe hepatic impairment [see CLINICAL PHARMACOLOGY]. Use In Patients With Renal Impairment Approximately 40% of the belinostat dose is excreted renally, primarily as metabolites. Belinostat exposure is not altered in patients with Creatinine Clearance (CLcr) > 39 mL/min. There is insufficient data to recommend a dose of Beleodaq in patients with CLcr ≤ 39 mL/min. [see CLINICAL PHARMACOLOGY]. Last reviewed on RxList: 8/1/2014
This monograph has been modified to include the generic and brand name in many instances.