The results were heterogenous, with clear evidence of increased risk relative to placebo but not relative to other diabetes treatments and higher risk associated with combinations of rosiglitazone with insulin or metformin. Based on the 1.4x increased risk relative to control groups, FDA scientist David Graham presented an analysis suggesting that rosiglitazone had caused 83,000 excess heart attacks between 1999 and 2007.: 4  The advisory panel voted 20 : 3 that the evidence available indicated that rosiglitazone increased the risk of cardiovascular events and 22 : 1 that the overall risk:benefit ratio of rosiglitazone justified its continued marketing in the United States. The FDA placed restrictions on the drug, including adding a boxed warning about heart attacks, but did not withdraw it.In 2000 a study to address the concerns regarding cardiovascular safety was requested by the European Medicines Agency (EMA). GSK agreed to perform post-marketing a long-term cardiovascular morbidity/mortality study in patients on rosiglitazone in combination with a sulfonylurea or metformin: the RECORD study. The results as published in 2009 showed that rosiglitazone was non-inferior to treatment with metformin or a sulfonylurea with respect to the rate of cardiovascular events and cardiovascular death. European regulators concluded that due in part to design limitations, the results neither proved nor eliminated concerns of excess cardiovascular risk.In February 2010, the FDAs associate director of drug safety, recommended rosiglitazone be taken off the market.
Pegaspargase, sold under the brand name Oncaspar, is a medication used in the treatment of acute lymphoblastic leukemia (ALL). Often it is used together with anthracycline, vincristine, and corticosteroids (for example prednisone and dexamethasone). Pegaspargase can be administered either via an intravenous infusion or a intramuscular injection.Known side effects include allergic reactions, coagulopathy, high blood sugar, affected liver function, pancreas inflammation, and blood clots in the brain. There is no data regarding the usage of pegaspargase during pregnancy. Therefor caution should be observed and pegaspargase should only be used during pregnancy when the benefits outweigh the possible risks. Pegaspargase is a modified version of the enzyme asparaginase which has undergone PEGylation. It works by breaking down the amino acid asparagine that are circulating in the bloodstream. The circulating asparagine is essential for the cancer cells to enable growth since they cant produce their own, in contrast to normal cells. The normal cells are therefor less affected by pegaspargase. Pegaspargase was approved for medical use in the United States in 1994. It is on the World Health Organizations List of Essential Medicines. It is made by Sigma-Tau. References
External links
"Pegaspargase". Drug Information Portal. U.S. National Library of Medicine.