efore beginning therapy with ZOLINZA.
5.4 Hyperglycemia
Hyperglycemia has been observed in patients receiving ZOLINZA and was severe in 5% (4/86) of patients [see Adverse Reactions (6.1)]. Monitor serum glucose every 2 weeks during the first 2 months of therapy and monthly thereafter.
5.5 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).
5.6 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 (7.2)].
5.7 Prenancy
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.
6 ADVERSE REACTIONS
The following serious adverse reactions have been associated with ZOLINZA in clinical trials and are discussed in greater detail in other sections of the label [see Warnings and Precautions (5)].
Thromboembolism [see Warnings and Precautions (5.1)]
Myelosuppression [see Warnings and Precautions (5.2)]
Gastrointestinal Toxicity [see Warnings and Precautions (5.3)]
Hyperglycemia [see Warnings and Precautions (5.4)]
Clinical Chemistry Abnormalities [see Warnings and Precautions (5.5)]
Severe thrombocytopenia when combined with other Histone Deacetylase (HDAC) Inhibitors [see Warnings and Precautions (5.6)]
The most common drug-related adverse reactions can be classified into 4 symptom complexes: gastrointestinal symptoms (diarrhea, nausea, anorexia, weight decrease, vomiting, constipation), constitutional symptoms (fatigue, chills), hematologic abnormalities (thrombocytopenia, anemia), and taste disorders (d
