Abstract
Background
Limited data are available on the prevalence of inappropriate prescribing of renally cleared drugs in elderly patients in Australia.
Objectives
To quantify and compare the extent of inappropriate prescribing (defined as at least one drug prescribed in an excessive dose or when contraindicated with respect to renal function) of renally cleared drugs in elderly patients across the community and aged care settings, and to determine factors associated with patients being prescribed one or more potentially inappropriate renally cleared drugs.
Methods
This retrospective study examined de-identified Home Medicines Review (HMR) and Residential Medication Management Review (RMMR) cases pertaining to 30,898 patients aged 65 years and over. Only 25 % (n = 7625) of these patients had documented information on their renal function. Among them, 4035 patients were prescribed at least one of the 31 renally cleared drugs examined in this study. For these patients, details including demographics, medications, medical conditions and pathology test results were extracted. Creatinine clearance was estimated using the Cockcroft–Gault formula, and the prevalence of inappropriate prescribing of the 31 drugs was examined on the basis of conformity with the recommendations in the Australian Medicines Handbook. Multivariate logistic regression was performed to determine the factors associated with patients being prescribed one or more potentially inappropriate renally cleared drugs.
Results
The mean (±standard deviation) ages of the HMR patients (n = 3315; 59 % female) and RMMR patients (n = 720; 68 % female) were 78.3 ± 7.2 and 86 ± 7.3 years, respectively. Over one quarter of the patients (n = 1135 out of 4035; 28.1 %) prescribed the renally cleared drugs examined in this study had evidence of inappropriate prescribing of at least one of the drugs, with respect to their renal function. The drugs/drug classes most commonly prescribed inappropriately were perindopril, fenofibrate, glibenclamide, gliptins, metformin, olmesartan, bisphosphonates and strontium. The factors independently associated with patients being prescribed one or more potentially inappropriate renally cleared drugs were advancing age [odds ratio (OR) 1.06 per year increase, 95 % confidence interval (CI) 1.05–1.07; P < 0.001], the total number of renally cleared drugs prescribed (OR 1.44 per unit increase, 95 % CI 1.29–1.61; P < 0.001), presence of diabetes (OR 1.51, 95 % CI 1.30–1.76; P < 0.001), presence of heart failure (OR 1.38, 95 % CI 1.13–1.69; P < 0.005) and living in aged care facilities (OR 1.28, 95 % CI 1.06–1.5; P < 0.05).
Conclusion
Inappropriate prescribing of renally cleared drugs is common in older Australians. Intervention studies to improve prescribing of renally cleared drugs in the elderly appear to be warranted.
Similar content being viewed by others
References
Boyd CM, McNabney MK, Brandt N, et al. Guiding principles for the care of older adults with multimorbidity: an approach for clinicians: American Geriatrics Society Expert Panel on the Care of Older Adults with Multimorbidity. J Am Geriatr Soc. 2012;60(10):1–25.
Rajska-Neumann A, Wieczorowska-Tobis K. Polypharmacy and potential inappropriateness of pharmaco-logical treatment among community-dwelling elderly patients. Arch Gerontol Geriatr. 2007;44:303–9. doi:10.1016/j.archger.2007.01.040.
Manley HJ, McClaran ML, Overbay DK, et al. Factors associated with medication-related problems in ambulatory hemodialysis patients. Am J Kidney Dis. 2003;41(2):386–93. doi:10.1053/ajkd.2003.50048.
Rowe JW, Andres R, Tobin JD, et al. The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study. J Gerontol. 1976;31(2):155–63.
Jick H. Adverse drug effects in relation to renal function. Am J Med. 1977;62(4):514–7.
Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc. 1985;33(4):278–85.
Culleton BF, Larson MG, Evans JC, et al. Prevalence and correlates of elevated serum creatinine levels: the Framingham Heart Study. Arch Intern Med. 1999;159(15):1785–90.
Stevens LA, Levey AS. Chronic kidney disease in the elderly—how to assess risk. N Engl J Med. 2005;352(20):2122–4. doi:10.1056/NEJMe058035.
Montamat SC, Cusack BJ, Vestal RE. Management of drug therapy in the elderly. N Engl J Med. 1989;321(5):303–9. doi:10.1056/nejm198908033210507.
Bell JS, Blacker N, Leblanc VT, et al. Prescribing for older people with chronic renal impairment. Aust Fam Physician. 2013;42(1–2):24–8.
Faull R. Prescribing in renal disease. Aust Prescr. 2007;30:17–20.
Jones SA, Bhandari S. The prevalence of potentially inappropriate medication prescribing in elderly patients with chronic kidney disease. Postgrad Med J. 2013;89(1051):247–50. doi:10.1136/postgradmedj-2012-130889.
Papaioannou A, Clarke JA, Campbell G, et al. Assessment of adherence to renal dosing guidelines in long-term care facilities. J Am Geriatr Soc. 2000;48(11):1470–3.
Hanlon JT, Wang X, Handler SM, et al. Potentially inappropriate prescribing of primarily renally cleared medications for older veterans affairs nursing home patients. J Am Med Dir Assoc. 2011;12(5):377–83. doi:10.1016/j.jamda.2010.04.008.
Rahimi AR, Kennedy K, Thomason M, et al. Improper renal dosing in long-term care facilities. South Med J. 2008;101(8):802–5. doi:10.1097/SMJ.0b013e31817f1f71.
Cantu TG, Ellerbeck EF, Yun SW, et al. Drug prescribing for patients with changing renal function. Am J Hosp Pharm. 1992;49(12):2944–8.
Hu KT, Matayoshi A, Stevenson FT. Calculation of the estimated creatinine clearance in avoiding drug dosing errors in the older patient. Am J Med Sci. 2001;322(3):133–6.
Wong NA, Jones HW. An analysis of discharge drug prescribing amongst elderly patients with renal impairment. Postgrad Med J. 1998;74(873):420–2.
Roughead EE, Anderson B, Gilbert AL. Potentially inappropriate prescribing among Australian veterans and war widows/widowers. Intern Med J. 2007;37(6):402–5. doi:10.1111/j.1445-5994.2007.01316.x.
Stafford AC, Alswayan MS, Tenni PC. Inappropriate prescribing in older residents of Australian care homes. J Clin Pharm Ther. 2011;36(1):33–44. doi:10.1111/j.1365-2710.2009.01151.x.
Somers M, Rose E, Simmonds D, et al. Quality use of medicines in residential aged care. Aust Fam Physician. 2010;39(6):413–6.
Castelino RL, Hilmer SN, Bajorek BV, et al. Drug Burden Index and potentially inappropriate medications in community-dwelling older people: the impact of Home Medicines Review. Drugs Aging. 2010;27(2):135–48. doi:10.2165/11531560-000000000-00000.
Department of Health and Ageing, Australian Government. Medication management reviews. Available at: http://www.health.gov.au/internet/main/publishing.nsf/Content/medication_management_reviews.htm. Accessed 2 Oct 2013.
Veterans’ MATES. Veterans’ medicines advice and therapeutics education services. Therapeutic brief 30—know your patient’s renal function—an important prescribing consideration. Department of Veterans Affairs. 2012. Available at: https://www.veteransmates.net.au/VeteransMATES/documents/module_materials/M30_TherBrief.pdf. Accessed 13 Sept 2012.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41.
Rossi S. Australian medicines handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2012.
Fick DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Arch Intern Med. 2003;163(22):2716–24. doi:10.1001/archinte.163.22.2716.
Gallagher P, Barry P, O’Mahony D. Inappropriate prescribing in the elderly. J Clin Pharm Ther. 2007;32(2):113–21. doi:10.1111/j.1365-2710.2007.00793.x.
Doody HK, Peterson GM, Watson D, et al. Retrospective evaluation of potentially inappropriate prescribing in hospitalized patients with renal impairment. Curr Med Res Opin. 2015;31(3):525–35. doi:10.1185/03007995.2015.1010036.
Stevens LA, Viswanathan G, Weiner DE. Chronic kidney disease and end-stage renal disease in the elderly population: current prevalence, future projections, and clinical significance. Adv Chronic Kidney Dis. 2010;17(4):293–301. doi:10.1053/j.ackd.2010.03.010.
Rothberg MB, Kehoe ED, Courtemanche AL, et al. Recognition and management of chronic kidney disease in an elderly ambulatory population. J Gen Intern Med. 2008;23(8):1125–30. doi:10.1007/s11606-008-0607-z.
Gheewala PA, Peterson GM, Curtain CM, et al. Impact of the pharmacist medication review services on drug-related problems and potentially inappropriate prescribing of renally cleared medications in residents of aged care facilities. Drugs Aging. 2014;31(11):825–35. doi:10.1007/s40266-014-0208-y.
Sweileh WM, Janem SA, Sawalha AF, et al. Medication dosing errors in hospitalized patients with renal impairment: a study in Palestine. Pharmacoepidemiol Drug Saf. 2007;16(8):908–12. doi:10.1002/pds.1412.
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis. 2002;39:S1–266.
Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296–305. doi:10.1056/NEJMoa041031.
Hou FF, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006;354(2):131–40. doi:10.1056/NEJMoa053107.
Elung-Jensen T, Heisterberg J, Kamper AL, et al. Blood pressure response to conventional and low-dose enalapril in chronic renal failure. Br J Clin Pharmacol. 2003;55(2):139–46.
Neubeck M, Fliser D, Pritsch M, et al. Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure: consequence of dose adjustment. Eur J Clin Pharmacol. 1994;46(6):537–43.
Kunz R, Friedrich C, Wolbers M, et al. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med. 2008;148(1):30–48.
Jacobsen P, Andersen S, Rossing K, et al. Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy. Kidney Int. 2003;63(5):1874–80. doi:10.1046/j.1523-1755.2003.00940.x.
Munar MY, Singh H. Drug dosing adjustments in patients with chronic kidney disease. Am Fam Physician. 2007;75(10):1487–96.
Ahmed A. Use of angiotensin-converting enzyme inhibitors in patients with heart failure and renal insufficiency: how concerned should we be by the rise in serum creatinine? J Am Geriatr Soc. 2002;50(7):1297–300.
Ahmed AK, Kamath NS, El Kossi M, et al. The impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease. Nephrol Dial Transplant. 2010;25(12):3977–82. doi:10.1093/ndt/gfp511.
Bhandari S. Multi-centre randomised controlled trial of angiotensin converting enzyme inhibitor (ACEi) / angiotensin receptor blocker (ARB) withdrawal in advanced renal disease; the STOP-ACEi Trial. 2014. Available at http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0017/105173/PRO-11-30-07.pdf. Accessed 13 March 2015.
Chronic kidney disease (CKD) management in general practice. 2nd ed. Melbourne: Kidney Health Australia; 2012. Available at www.kidney.org.au. Last accessed on 6 Feb 2015.
National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Washington, DC: National Osteoporosis Foundation; 2010. Available at http://nof.org/files/nof/public/content/file/344/upload/159.pdf. Last accessed 7 Oct 2013.
Courtney AE, Maxwell AP. Chronic kidney disease and bisphosphonate treatment: are prescribing guidelines unnecessarily restrictive? Postgrad Med J. 2009;85(1004):327–30. doi:10.1136/pgmj.2008.076356.
Miller PD. Treatment of osteoporosis in chronic kidney disease and end-stage renal disease. Curr Osteoporos Rep. 2005;3(1):5–12.
Wetmore JB, Benet LZ, Kleinstuck D, et al. Effects of short-term alendronate on bone mineral density in haemodialysis patients. Nephrology (Carlton). 2005;10(4):393–9. doi:10.1111/j.1440-1797.2005.00436.x.
Miller PD, Roux C, Boonen S, et al. Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: a pooled analysis of nine clinical trials. J Bone Miner Res. 2005;20(12):2105–15. doi:10.1359/jbmr.050817.
Miller PD, Jamal SA, Evenepoel P, et al. Renal safety in patients treated with bisphosphonates for osteoporosis: a review. J Bone Miner Res. 2013;28(10):2049–59. doi:10.1002/jbmr.2058.
Jamal SA, Bauer DC, Ensrud KE, et al. Alendronate treatment in women with normal to severely impaired renal function: an analysis of the fracture intervention trial. J Bone Miner Res. 2007;22(4):503–8. doi:10.1359/jbmr.070112.
Linnebur SA, Milchak JL. Assessment of oral bisphosphonate use in elderly patients with varying degrees of kidney function. Am J Geriatr Pharmacother. 2004;2(4):213–8.
Yanae M, Nakao M, Fujiwara K, et al. A survey of the dosage of zoledronic acid and investigation of the relationship between renal function and adverse events. Gan To Kagaku Ryoho. 2012;39(7):1093–8.
Sadowski CA, Spencer T, Yuksel N. Use of oral bisphosphonates by older adults with fractures and impaired renal function. Can J Hosp Pharm. 2011;64(1):36–41.
Gangji AS, Cukierman T, Gerstein HC, et al. A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin. Diabetes Care. 2007;30(2):389–94. doi:10.2337/dc06-1789.
Shorr RI, Ray WA, Daugherty JR, et al. Individual sulfonylureas and serious hypoglycemia in older people. J Am Geriatr Soc. 1996;44(7):751–5.
Khanal A, Castelino RL, Peterson GM, et al. Dose adjustment guidelines for medications in patients with renal impairment: how consistent are drug information sources? Intern Med J. 2014;44(1):77–85. doi:10.1111/imj.12291.
Khanal A, Peterson GM, Castelino RL, et al. Renal drug dosing recommendations: evaluation of product information for brands of the same drug. Intern Med J. 2014;44(6):591–6. doi:10.1111/imj.12446.
Lesar TS, Briceland L, Stein DS. Factors related to errors in medication prescribing. JAMA. 1997;277(4):312–7.
Parodi Lopez N, Villan Villan YF, Granados Menendez MI, et al. Potentially inappropriate prescribing in patients over 65-years-old in a primary care health centre. Aten Primaria. 2014;46(6):290–7. doi:10.1016/j.aprim.2013.12.007.
Nissenson AR, Pereira BJ, Collins AJ, et al. Prevalence and characteristics of individuals with chronic kidney disease in a large health maintenance organization. Am J Kidney Dis. 2001;37(6):1177–83. doi:10.1053/ajkd.2001.24520.
Coresh J, Astor BC, Greene T, et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2003;41(1):1–12. doi:10.1053/ajkd.2003.50007.
Silverberg D, Wexler D, Blum M, et al. The association between congestive heart failure and chronic renal disease. Curr Opin Nephrol Hypertens. 2004;13(2):163–70.
Field TS, Rochon P, Lee M, et al. Computerized clinical decision support during medication ordering for long-term care residents with renal insufficiency. J Am Med Inform Assoc. 2009;16(4):480–5. doi:10.1197/jamia.M2981.
National Kidney Disease Education Program (NKDEP). Chronic kidney disease and drug dosing: information for providers. Estimation of kidney function for prescription medication dosage in adults. 2012. Available at: http://nkdep.nih.gov/resources/ckd-drug-dosing-508.pdf. Last accessed 9 Dec 2014.
Mathew TH, Johnson DW, Jones GR. Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: revised recommendations. Med J Aust. 2007;187(8):459–63.
Stevens LA, Coresh J, Greene T, et al. Assessing kidney function—measured and estimated glomerular filtration rate. N Engl J Med. 2006;354(23):2473–83. doi:10.1056/NEJMra054415.
Huang SM, Temple R, Xiao S, et al. When to conduct a renal impairment study during drug development: US Food and Drug Administration perspective. Clin Pharmacol Ther. 2009;86(5):475–9. doi:10.1038/clpt.2009.190.
Chronic kidney disease and drug dosing: information for providers. National Kidney Disease Education Program (US), 2010. Available at: http://nkdep.nih.gov/resources/ckd-drug-dosing-508.pdf. Last accessed 24 March 2015.
Stevens LA, Levey AS. Use of the MDRD study equation to estimate kidney function for drug dosing. Clin Pharmacol Ther. 2009;86(5):465–7. doi:10.1038/clpt.2009.124.
Johnson D. CARI guidelines: diagnosis, classification and staging of chronic kidney disease. 2012. Kidney Health Australia. Available at: http://www.cari.org.au/CKD/CKD%20early/Diag_Classification_Staging_ECKD.pdf. Last accessed 5 Dec 2014.
Johnson DW, Jones GR, Mathew TH, et al. Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: new developments and revised recommendations. Med J Aust. 2012;197(4):224–5.
Acknowledgments
The four authors listed undertook all work related to this study; there were no other contributors. No sources of funding were used in the preparation of this article. The authors have no potential conflicts of interest that are directly relevant to the content of this article.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Khanal, A., Peterson, G.M., Castelino, R.L. et al. Potentially Inappropriate Prescribing of Renally Cleared Drugs in Elderly Patients in Community and Aged Care Settings. Drugs Aging 32, 391–400 (2015). https://doi.org/10.1007/s40266-015-0261-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40266-015-0261-1