Calcium and phosphate compatibility: Revisited again

The subject of the compatibility between calcium and phosphates was revisited in an April 1994 FDA safety alert,1,2 6–16 years after the four seminal research articles appeared in 1978,3 1980,4 1982,5 and 1988.6 In the 1980s there were two case reports of nonfatal adverse events involving calcium phosphate precipitation in total parenteral nutrient (TPN) admixtures.7,8 A review of the main determinants of parenteral drug and admixture compatibility and stability also appeared during that decade.9 Soon after the April 1994 safety alert, several publications on calcium phosphate precipitation in TPN formulations appeared.10,-18 Thus, this article is yet another revisit of calcium and phosphate compatibility with i.v. formulations. This article discusses the chemistry and practical compatibility or solubility factors relevant to the safe administration of combination therapy with calcium gluconate and potassium or sodium phosphate injections. Patient case reports that led to adverse events and pharmaceutical and clinical factors important to calcium phosphate solubility are also presented.