zolinza

Important safety information

Thromboembolism: Monitor for pertinent signs and symptoms of pulmonary embolism and deep vein thrombosis. ( 5.1 ) Myelosuppression: Thrombocytopenia and anemia may require dose modification or discontinuation. Monitor blood counts every 2 weeks during the first 2 months of therapy and monthly thereafter. ( 2.2 , 5.2 , 6 ) Gastrointestinal Toxicity: Nausea, vomiting and diarrhea; patients may require antiemetics, antidiarrheals, and fluid and electrolyte replacement to prevent dehydration. ( 5.3 , 6 ) Hyperglycemia: Monitor blood glucose every 2 weeks during the first 2 months of therapy and monthly thereafter. ( 5.4 ) Clinical Chemistry Abnormalities: Measure and correct abnormal electrolytes, creatinine, magnesium and calcium at baseline. Monitor every 2 weeks during the first 2 months of therapy and at least monthly during treatment. ( 5.5 ) Severe Thrombocytopenia with Concomitant Use of other HDAC Inhibitors: Severe thrombocytopenia with gastrointestinal bleeding has been reported with concomitant use of ZOLINZA and other HDAC inhibitors (e.g., valproic acid). Monitor platelet counts more frequently. ( 5.6 , 7.2 ) Embryo-Fetal Toxicity: Fetal harm can occur when administered to a pregnant woman. Women should be apprised of the potential harm to the fetus. ( 5.7 ) 5.1 Thromboembolism 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 (6) ] . 5.2 Myelosuppression 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 (2.2) , Warnings and Precautions (5.6) and Adverse Reactions (6) ]. 5.3 Gastrointestinal Toxicity Gastrointestinal disturbances, including nausea, vomiting and diarrhea, have been reported [see Adverse Reactions (6) ] and may require the use of antiemetic and antidiarrheal medications. Fluid and electrolytes should be replaced to prevent dehydration [see Adverse Reactions (6.1) ] . Pre-existing nausea, vomiting, and diarrhea should be adequately controlled before 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 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, ZOLINZA can cause fetal harm when administered to a pregnant woman. There are insufficient data on ZOLINZA use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, vorinostat crossed the placenta and caused adverse developmental outcomes at exposures approximately 0.5 times the human exposure based on AUC 0-24 hours . Advise females of reproductive potential to use effective contraception during treatment and for at least 6 months after the last dose. Advise males with female sexual partners of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose [see Use in Specific Populations (8.1 , 8.3) and Clinical Pharmacology (12.1) ] .