"The U.S. Food and Drug Administration today approved Beleodaq (belinostat) for the treatment of patients with peripheral T-cell lymphoma (PTCL), a rare and fast-growing type of non-Hodgkin lymphoma (NHL). The action was taken under the agency&rsq"...
Pulmonary embolism occurred in 5% (4/86) of patients receiving ZOLINZA, and deep vein thrombosis has also been reported. Monitor for signs and symptoms of these events, particularly in patients with a prior history of thromboembolic events [see ADVERSE REACTIONS].
Treatment with ZOLINZA can cause dose-related thrombocytopenia and anemia. Monitor blood counts every 2 weeks during the first 2 months of therapy and monthly thereafter. Adjust dosage or discontinue treatment with ZOLINZA as clinically appropriate. [See DOSAGE AND ADMINISTRATION, Severe thrombocytopenia when combined with other Histone Deacetylase (HDAC) Inhibitors, and ADVERSE REACTIONS]
Gastrointestinal disturbances, including nausea, vomiting and diarrhea, have been reported [see ADVERSE REACTIONS] and may require the use of antiemetic and antidiarrheal medications. Fluid and electrolytes should be replaced to prevent dehydration [see ADVERSE REACTIONS]. Pre-existing nausea, vomiting, and diarrhea should be adequately controlled before beginning therapy with ZOLINZA.
Hyperglycemia has been observed in patients receiving ZOLINZA and was severe in 5% (4/86) of patients [see ADVERSE REACTIONS]. Monitor serum glucose every 2 weeks during the first 2 months of therapy and monthly thereafter.
Clinical Chemistry Abnormalities
Obtain chemistry tests, including serum electrolytes, creatinine, magnesium, and calcium, every 2 weeks during the first 2 months of therapy and monthly thereafter. Correct hypokalemia and hypomagnesemia prior to administration of ZOLINZA. Monitor potassium and magnesium more frequently in symptomatic patients (e.g., patients with nausea, vomiting, diarrhea, fluid imbalance or cardiac symptoms).
Severe Thrombocytopenia When Combined With Other Histone Deacetylase (HDAC) Inhibitors
Severe thrombocytopenia leading to gastrointestinal bleeding has been reported with concomitant use of ZOLINZA and other HDAC inhibitors (e.g., valproic acid). Monitor platelet counts more frequently. [See DRUG INTERACTIONS].
Pregnancy Category D
ZOLINZA can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of ZOLINZA in pregnant women. Results of animal studies indicate that vorinostat crosses the placenta and is found in fetal plasma at levels up to 50% of maternal concentrations. Doses up to 50 and 150 mg/kg/day were tested in rats and rabbits, respectively (~0.5 times the human exposure based on AUC0-24 hours). Treatment-related, developmental effects including decreased mean live fetal weights, incomplete ossifications of the skull, thoracic vertebra, sternebra, and skeletal variations (cervical ribs, supernumerary ribs, vertebral count and sacral arch variations) in rats at the highest dose of vorinostat tested. Reductions in mean live fetal weight and an elevated incidence of incomplete ossification of the metacarpals were seen in rabbits dosed at 150 mg/kg/day. The no observed effect levels (NOELs) for these findings were 15 and 50 mg/kg/day ( < 0.1 times the human exposure based on AUC) in rats and rabbits, respectively. A dose-related increase in the incidence of malformations of the gall bladder was noted in all drug treatment groups in rabbits versus the concurrent control. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Patient Counseling Information
See FDA-Approved Patient Labeling (PATIENT INFORMATION)
Patients should be instructed to drink at least 2 L/day of fluid to prevent dehydration and should promptly report excessive vomiting or diarrhea to their physician. Patients should be instructed about the signs of deep vein thrombosis and should consult their physician should any evidence of deep vein thrombosis develop. Patients receiving ZOLINZA should seek immediate medical attention if unusual bleeding occurs. ZOLINZA capsules should not be opened or crushed.
Patients should be instructed to read the patient insert carefully.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenicity studies have not been performed with vorinostat.
Vorinostat was mutagenic in vitro in the bacterial reverse mutation assays (Ames test), caused chromosomal aberrations in vitro in Chinese hamster ovary (CHO) cells and increased the incidence of micro-nucleated erythrocytes when administered to mice (Mouse Micronucleus Assay).
Effects on the female reproductive system were identified in the oral fertility study when females were dosed for 14 days prior to mating through gestational day 7. Doses of 15, 50 and 150 mg/kg/day to rats resulted in approximate exposures of 0.15, 0.36 and 0.70 times the expected clinical exposure based on AUC. Dose dependent increases in corpora lutea were noted at ≥ 15 mg/kg/day, which resulted in increased peri-implantation losses were noted at ≥ 50 mg/kg/day. At 150 mg/kg/day, there were increases in the incidences of dead fetuses and in resorptions.
No effects on reproductive performance were observed in male rats dosed (20, 50, 150 mg/kg/day; approximate exposures of 0.15, 0.36 and 0.70 times the expected clinical exposure based on AUC), for 70 days prior to mating with untreated females. [See WARNINGS AND PRECAUTIONS]
Use In Specific Populations
Pregnancy Category D [See WARNINGS AND PRECAUTIONS]
It is not known whether this drug 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 ZOLINZA, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
The safety and effectiveness of ZOLINZA in pediatric patients have not been established.
Of the total number of patients with CTCL in trials (N=107), 46 % were 65 years of age and over, while 15 % were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals should be considered, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Use In Patients With Hepatic Impairment
ZOLINZA was studied in 42 patients with non-CTCL cancer and varying degrees of hepatic impairment after single and multiple-dose administration. Compared to patients with normal liver function, AUC increases of 50 to 66% were observed in patients with hepatic impairment. The incidence of Grade 3 or 4 thrombocytopenia increased in patients with mild (bilirubin of 1 to 1.5 x ULN and AST < ULN, or bilirubin ≤ ULN and AST > ULN) and moderate (bilirubin 1.5 to ≤ 3 x ULN) hepatic impairment treated daily at doses of 300 and 200 mg respectively.
Patients with severe hepatic impairment (bilirubin > 3 x ULN) have not been treated at doses greater than 200 mg a day. Reduce the initial dose of ZOLINZA in patients with bilirubin 1 to 3 x ULN or AST > ULN. [See DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY]
Use In Patients With Renal Impairment
Vorinostat was not evaluated in patients with renal impairment. However, renal excretion does not play a role in the elimination of vorinostat. Patients with pre-existing renal impairment should be treated with caution. [See CLINICAL PHARMACOLOGY]This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 10/15/2015
Additional Zolinza Information
Zolinza - User Reviews
Zolinza User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.