Phosphates in medications: Impact on dialysis patients

Maintaining phosphorus balance in in-center hemodialysis (ICHD) patients is problematic despite recommended dietary restriction, dialysis, and phosphate binder use. Rarely is P content in prescribed medications considered, but this source should raise concern. Data was obtained from the Fresenius Kidney Care (FKC) electronic data warehouse Knowledge Center and MedReview-eRx accessed Surescripts, housing > 80% of US-filled prescriptions. Adult FKC ICHD patients prescribed ≥ 1 medication in the MedReview-eRx database were analyzed (695,759 prescriptions). Information collected included medication dose, dose unit, dose timing, strength, start and stop dates, refills, demographic information, admission history, and modality type. Numbers of patients, prescriptions by individual medication, and drug class were then analyzed. Medications prescribed > 100 times were reported. Median doses/day (number of tablets) were calculated for each medication (open order on randomly selected day). Phosphate content of medications taken in FKC clinics was assessed using routinely used pharmacology references, and potential resulting phosphate and pill burden were also calculated. The top five prescribed drug classes in FKC dialysis patients were calcium-channel blockers (22%), proton pump inhibitors (PPIs; 18%), acetaminophen-opioid (AO; 13%), angiotensin-converting enzyme inhibitors (ACEi; 10%), and α2-agonists (9%). The maximum phosphate added for different medications varied by manufacturer. For instance, at median daily doses, phosphate contributions from the top five medications prescribed were 112 mg for amlodipine, 116.2 mg from lisinopril, 6.7 mg from clonidine, 0 mg from acetaminophen, and 200 mg for omeprazole. Prescribing these together could increase the daily phosphate load by 428 mg, forcing the patient to exceed the recommended daily intake (RDI) with food and drink. Phosphate content in medications prescribed to HD patients can substantially contribute to the daily phosphate load and, in combination, may even exceed the daily recommended dietary phosphate intake. Healthcare providers should monitor all medications containing phosphate prescribed in order to minimize risk of uncontrolled hyperphosphatemia and poor adherence.

[1]  Baihai Su,et al.  The role of phosphate-containing medications and low dietary phosphorus-protein ratio in reducing intestinal phosphorus load in patients with chronic kidney disease , 2019, Nutrition & Diabetes.

[2]  M. Adams,et al.  Phosphate-Containing Prescription Medications Contribute to the Daily Phosphate Intake in a Third of Hemodialysis Patients. , 2017, Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.

[3]  P. Barretti,et al.  Most consumed processed foods by patients on hemodialysis: Alert for phosphate-containing additives and the phosphate-to-protein ratio. , 2016, Clinical nutrition ESPEN.

[4]  Lisa Gutekunst.  An Update on Phosphate Binders: A Dietitian's Perspective. , 2016, Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.

[5]  Ananda Sen,et al.  Phosphate binder pill burden, patient‐reported non‐adherence, and mineral bone disorder markers: Findings from the DOPPS , 2016, Hemodialysis international. International Symposium on Home Hemodialysis.

[6]  G. Trifirò,et al.  Medication is an additional source of phosphate intake in chronic kidney disease patients. , 2015, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[7]  A. Santoro,et al.  Phosphate balance in ESRD: diet, dialysis and binders against the low evident masked pool , 2015, Journal of Nephrology.

[8]  R. Sherman,et al.  The Phosphate Content of Prescription Medication: A New Consideration , 2015, Therapeutic innovation & regulatory science.

[9]  R. Sherman,et al.  A dearth of data: the problem of phosphorus in prescription medications. , 2015, Kidney international.

[10]  F. Funk,et al.  The iron-based phosphate binder PA21 has potent phosphate binding capacity and minimal iron release across a physiological pH range in vitro. , 2014, Clinical nephrology.

[11]  A. Cupisti,et al.  Phosphate control in dialysis , 2013, International journal of nephrology and renovascular disease.

[12]  A. Rastogi,et al.  Hyperphosphatemia in patients with ESRD: assessing the current evidence linking outcomes with treatment adherence , 2013, BMC Nephrology.

[13]  K. Kalantar-Zadeh,et al.  Management of natural and added dietary phosphorus burden in kidney disease. , 2013, Seminars in nephrology.

[14]  X. Calvet,et al.  Clinical usefulness of lanthanum carbonate for serum phosphate control in difficult patients , 2012, International Urology and Nephrology.

[15]  N. Mason.  Polypharmacy and medication-related complications in the chronic kidney disease patient , 2011, Current opinion in nephrology and hypertension.

[16]  D. Fouque,et al.  Dietary phosphate assessment in dialysis patients. , 2010, Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.

[17]  M. Kuhlmann.  Phosphate Elimination in Modalities of Hemodialysis and Peritoneal Dialysis , 2010, Blood Purification.

[18]  Sarfaraz Niazi,et al.  Handbook of Pharmaceutical Manufacturing Formulations, Second Edition , 2009 .

[19]  Sarfaraz K Niazi.  Handbook of Pharmaceutical Manufacturing Formulations: Volume One, Compressed Solid Products , 2009 .

[20]  Yi-Wen Chiu,et al.  Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients. , 2009, Clinical journal of the American Society of Nephrology : CJASN.

[21]  Rob Horne,et al.  A systematic review of the prevalence and determinants of nonadherence to phosphate binding medication in patients with end-stage renal disease , 2008, BMC nephrology.

[22]  R. Bogner,et al.  Determination of calcium salt solubility with changes in pH and PCO2, simulating varying gastrointestinal environments , 2007, The Journal of pharmacy and pharmacology.

[23]  M. Rodehutscord,et al.  Investigations on the availability of inorganic phosphate from different sources with growing White Pekin ducks. , 2004, Poultry science.

[24]  H. Manley,et al.  Medication prescribing patterns in ambulatory haemodialysis patients: comparisons of USRDS to a large not-for-profit dialysis provider. , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[25]  Keith C. Norris,et al.  K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. , 2003, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[26]  A. Torres,et al.  Caloric rather than protein deficiency predominates in stable chronic haemodialysis patients. , 1995, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[27]  J Fangman,et al.  Effect of hematocrit on solute removal during high efficiency hemodialysis. , 1990, Kidney international.

[28]  N. Laird,et al.  Assessment of nutritional status of the National Cooperative Dialysis Study population. , 1983, Kidney international. Supplement.

[29]  I. Greenwald.  THE SOLUBILITY OF CALCIUM PHOSPHATE I. THE EFFECT OF pH AND OF AMOUNT OF SOLID PHASE , 1942 .

[30]  F. Hirayama,et al.  A Comparison of the Phosphorus Content in Prescription Medications for Hemodialysis Patients in Japan. , 2017, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[31]  G. Chertow,et al.  The Phosphate Binder Equivalent Dose , 2011, Seminars in dialysis.

[32]  N. Sawada,et al.  Phosphate restriction in diet therapy. , 2007, Contributions to nephrology.

[33]  National Kidney Foundation K-DOQI: Clinical practice guidelines for bone metabolism and disease in chronic kidney disease , 2007 .

[34]  L. Chow.  Solubility of calcium phosphates. , 2001, Monographs in oral science.