Erroneous determination of hyperphosphatemia (‘pseudohyperphosphatemia’) in sera of patients that have been treated with liposomal amphotericin B (AmBisome)

Case-Control Study and Case Series of Pseudohyperphosphatemia during Exposure to Liposomal Amphotericin B

“…Hyperphosphatemia is a serious condition that can result from a multitude of causes, including rhabdomyolysis, tumor lysis syndrome, acute and chronic kidney disease, hypoparathyroidism, acromegaly, and excessive phosphorus administration (10,16). Standard treatment involves dietary phosphorus restriction and administration of phosphate binders.…”

“…The product information for AmBisome was updated in 2012 to reflect the possible assay interference (1); http://www.accessdata.fda.gov /drugsatfda_docs/appletter/2012/050740s021ltr.pdf. Jensen et al found that LAmB interfered with the PHOSm assay, a timed-rate phosphorus assay, but not the PHS assay, an endpoint-based phosphorus assay (10). The influence on the rate of formation of the phosphomolybdate complex correlated with the presence and amount of LAmB.…”

“…Two in vitro studies demonstrated a dose-dependent, linear rise in phosphorus measurements when serum was spiked with LAmB. A 0.0072-to 0.0090-mmol/liter increase in phosphorus correlated with a 1-mg/liter increase in LAmB concentration (8,10). No effect was observed using a comparable placebo molecule without active drug, leading the authors to conclude that active drug in the liposomal formulation (LAmB) is involved in the assay interference (10).…”

“…A 0.0072-to 0.0090-mmol/liter increase in phosphorus correlated with a 1-mg/liter increase in LAmB concentration (8,10). No effect was observed using a comparable placebo molecule without active drug, leading the authors to conclude that active drug in the liposomal formulation (LAmB) is involved in the assay interference (10). In 2008, pseudohyperphosphatemia caused by LAmB was detailed in a product corrective action statement released by Beckman and Coulter, Inc., to hospital laboratories that use Synchron chemistry systems to measure serum phosphorus by the PHOSm assay.…”

The care and feeding of a commercial liposomal product: liposomal amphotericin B (AmBisome®)

“…If indeed these cases were a pseudohyperphosphatemia, it would be very undesirable to treat it, alter diet, or alter anti-fungal therapy. In collaboration with Beckman scientists (Jensen et al 2010) we carried out studies using the PHOSm kit, an alternate kit PHS, and titrations with both AmBisome and placebo in serum samples (in this case, the placebo followed the AmBisome formulation absent drug). Titrations were also carried out with two methods to attempt to remove liposomes from the sample: the reagent LipoClear Plus (Iris International, Los Angeles, CA) -often used for lipemic samples -and microcentrifugation using a Microcon 30 (Millipore, Billerica, MA).…”