A significant proportion of older people are prescribed statins and are also exposed to polypharmacy, placing them at increased risk of statin–drug interactions.
To describe the prevalence rates of potential and clinically relevant statin–drug interactions in older inpatients according to frailty status.
A cross-sectional study of patients aged ≥65 years who were prescribed a statin and were admitted to a teaching hospital between 30 July and 10 October 2014 in Sydney, Australia, was conducted. Data on socio-demographics, comorbidities and medications were collected using a standardized questionnaire. Potential statin–drug interactions were defined if listed in the Australian Medicines Handbook and three international drug information sources: the British National Formulary, Drug Interaction Facts and Drug-Reax®. Clinically relevant statin–drug interactions were defined as interactions with the highest severity rating in at least two of the three international drug information sources. Frailty was assessed using the Reported Edmonton Frail Scale.
A total of 180 participants were recruited (median age 78 years, interquartile range 14), 35.0 % frail and 65.0 % robust. Potential statin–drug interactions were identified in 10 % of participants, 12.7 % of frail participants and 8.5 % of robust participants. Clinically relevant statin–drug interactions were identified in 7.8 % of participants, 9.5 % of frail participants and 6.8 % of robust participants. Depending on the drug information source used, the prevalence rates of potential and clinically relevant statin–drug interactions ranged between 14.4 and 35.6 % and between 14.4 and 20.6 %, respectively.
In our study of frail and robust older inpatients taking statins, the overall prevalence of potential statin–drug interactions was low and varied significantly according to the drug information source used.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Morgan TK, Williamson M, Pirotta M, et al. A national census of medicines use: a 24-hour snapshot of Australians aged 50 years and older. Med J Aust. 2012;196(1):50–3.
Doan J, Zakrzewski-Jakubiak H, Roy J, Turgeon J, Tannenbaum C. Prevalence and risk of potential cytochrome P450-mediated drug–drug interactions in older hospitalized patients with polypharmacy. Ann Pharmacother. 2013;47(3):324–32.
Johnell K, Klarin I. The relationship between number of drugs and potential drug–drug interactions in the elderly: a study of over 600,000 elderly patients from the Swedish Prescribed Drug Register. Drug Saf. 2007;30(10):911–8.
Hines LE, Murphy JE. Potentially harmful drug–drug interactions in the elderly: a review. Am J Geriatr Pharmacother. 2011;9(6):364–77.
Becker ML, Kallewaard M, Caspers PW, et al. Hospitalisations and emergency department visits due to drug–drug interactions: a literature review. Pharmacoepidemiol Drug Saf. 2007;16(6):641–51.
Gnjidic D, Johnell K. Clinical implications from drug–drug and drug–disease interactions in older people. Clin Exp Pharmacol Physiol. 2013;40(5):320–5.
Hilmer SN, McLachlan AJ, Le Couteur DG. Clinical pharmacology in the geriatric patient. Fundam Clin Pharmacol. 2007;21(3):217–30.
Bennett A, Gnjidic D, Gillett M, et al. Prevalence and impact of fall-risk-increasing drugs, polypharmacy, and drug–drug interactions in robust versus frail hospitalised falls patients: a prospective cohort study. Drugs Aging. 2014;31(3):225–32.
Gnjidic D, Hilmer SN, Blyth FM, et al. High-risk prescribing and incidence of frailty among older community-dwelling men. Clin Pharmacol Ther. 2012;91(3):521–8.
Wynne HA, Cope LH, Herd B, et al. The association of age and frailty with paracetamol conjugation in man. Age Ageing. 1990;19(6):419–24.
Johnston C, Hilmer SN, McLachlan AJ, et al. The impact of frailty on pharmacokinetics in older people: using gentamicin population pharmacokinetic modeling to investigate changes in renal drug clearance by glomerular filtration. Eur J Clin Pharmacol. 2014;70(5):549–55.
Abarca J, Malone DC, Armstrong EP, et al. Concordance of severity ratings provided in four drug interaction compendia. J Am Pharm Assoc. 2004;44(2):136–41.
Olvey EL, Clauschee S, Malone DC. Comparison of critical drug–drug interaction listings: the Department of Veterans Affairs medical system and standard reference compendia. Clin Pharmacol Ther. 2010;87(1):48–51.
Sweidan M, Reeve JF, Brien JA, et al. Quality of drug interaction alerts in prescribing and dispensing software. Med J Aust. 2009;190(5):251–4.
Vitry AI. Comparative assessment of four drug interaction compendia. Br J Clin Pharmacol. 2007;63(6):709–14.
Gnjidic D, Le Couteur DG, Blyth FM, et al. Statin use and clinical outcomes in older men: a prospective population-based study. BMJ Open. 2013;3(3):e002333. doi:10.1136/bmjopen-2012-002333.
Afilalo J, Duque G, Steele R, et al. Statins for secondary prevention in elderly patients: a hierarchical Bayesian meta-analysis. J Am Coll Cardiol. 2008;51(1):37–45.
Roberts CG, Guallar E, Rodriguez A. Efficacy and safety of statin monotherapy in older adults: a meta-analysis. J Gerontol A Biol Sci Med Sci. 2007;62(8):879–87.
Paoletti R, Corsini A, Bellosta S. Pharmacological interactions of statins. Atheroscler Suppl. 2002;3:35–40.
Bellosta S, Corsini A. Statin drug interactions and related adverse reactions. Expert Opin Drug Saf. 2012;11(6):933–46.
Bottorff MB. Statin safety and drug interactions: clinical implications. Am J Cardiol. 2006;97(8A):27C–31C.
Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006;80(6):565–81.
Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation. 2004;109(23 Suppl 1):Iii50–7.
Patel AM, Shariff S, Bailey DG, et al. Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Ann Intern Med. 2013;158(12):869–76.
Bakhai A, Rigney U, Hollis S, Emmas C. Co-administration of statins with cytochrome P450 3A4 inhibitors in a UK primary care population. Pharmacoepidemiol Drug Saf. 2012;21(5):485–93.
Karimi S, Hough A, Beckey C, Parra D. Results of a safety initiative for patients on concomitant amiodarone and simvastatin therapy in a Veterans Affairs medical center. J Manag Care Pharm. 2010;16(7):472–81.
Ming EE, Davidson MH, Gandhi SK, et al. Concomitant use of statins and CYP3A4 inhibitors in administrative claims and electronic medical records databases. J Clin Lipidol. 2008;2(6):453–63.
Petropoulos JB, Bello-Quintero CE. Frequency of simvastatin prescriptions with potentially interacting medications in a Veterans Affairs health care system. J Manag Care Pharm. 2004;10(3):239–43.
Piacentini N, Trifiro G, Tari M, Moretti S, Arcoraci V. Statin-macrolide interaction risk: a population-based study throughout a general practice database. Eur J Clin Pharmacol. 2005;61(8):615–20.
Egger SS, Bravo AER, Hess L, Schlienger RG, Krahenbuhl S. Age-related differences in the prevalence of potential drug–drug interactions in ambulatory dyslipidaemic patients treated with statins. Drugs Aging. 2007;24(5):429–40.
Elliott RA. Problems with medication use in the elderly: an Australian perspective. J Pharm Pract Res. 2006;36(1):58–66.
Australian medicines handbook. Adelaide: Australian Medicines Handbook Pty Ltd, 2014.
Joint Formulary Committee. British national formulary. 68th ed. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2014.
Tatro D, editor. Drug interaction facts. Facts and comparisons [database online]. St Louis: Wolters Kluwer Health; 2012.
Klasko R, editor. Drug-Reax® system [database on CD-ROM]. Greenwood Village: Thomson Micromedex; 2003.
Roughead EE, Kalisch LM, Barratt JD, Gilbert AL. Prevalence of potentially hazardous drug interactions amongst Australian veterans. Br J Clin Pharmacol. 2010;70(2):252–7.
Dolton MJ, Pont L, Stevens G, McLachlan AJ. Prevalence of potentially harmful drug interactions in older people in Australian aged-care facilities. J Pharm Pract Res. 2012;42(1):33–6.
Hilmer SN, Perera V, Mitchell S, et al. The assessment of frailty in older people in acute care. Australas J Ageing. 2009;28(4):182–8.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.
Einarson TR, Metge CJ, Iskedjian M, Mukherjee J. An examination of the effect of cytochrome P450 drug interactions of hydroxymethylglutaryl-coenzyme a reductase inhibitors on health care utilization: a Canadian population-based study. Clin Ther. 2002;24:2126–36.
Australian Bureau of Statistics. Population by age and sex. Australian states and territories, June 2013. ABS cat. no. 3235.0. 2013. http://www.abs.gov.au/Ausstats/abs@.nsf/mf/3235.0. Accessed 27 Oct 2014.
Kerr KP, Mate KE, Magin PJ, et al. The prevalence of co-prescription of clinically relevant CYP enzyme inhibitor and substrate drugs in community-dwelling elderly Australians. J Clin Pharm Ther. 2014;39(4):383–9.
Westaway KP, Frank OR, Husband AJ, et al. Safe use of statins in elderly people. J Pharm Pract Res. 2014;44(3):138–42.
Ronaldson KJ, O’Shea JM, Boyd IW. Risk factors for rhabdomyolysis with simvastatin and atorvastatin. Drug Saf. 2006;29(11):1061–7.
Zakrzewski-Jakubiak H, Doan J, Lamoureux P, Singh D, Turgeon J, Tannenbaum C. Detection and prevention of drug–drug interactions in the hospitalized elderly: utility of new cytochrome p450-based software. Am J Geriatr Pharmacother. 2011;9(6):461–70.
Best O, Gnjidic D, Hilmer SN, Naganathan V, McLachlan AJ. Investigating polypharmacy and drug burden index in hospitalised older people. Intern Med J. 2013;43(8):912–8.
The authors would like to acknowledge Jillian Patterson (Data Analyst, Kolling Institute of Medical Research, Northern Clinical School, Sydney, NSW, Australia) for her assistance in the statistical analysis, and Katie Qi (Pharmacy Honours Student, Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia) for her assistance with data collection. Danijela Gnjidic is supported by the Australian National Health and Medical Research Early Career Fellowship. Sallie-Anne Pearson is a Cancer Institute NSW Career Development Fellow.
Funding and Conflicts of Interest
The authors received no funding to write this paper and have no conflicts of interest to declare.
About this article
Cite this article
Thai, M., Hilmer, S., Pearson, S. et al. Prevalence of Potential and Clinically Relevant Statin–Drug Interactions in Frail and Robust Older Inpatients. Drugs Aging 32, 849–856 (2015). https://doi.org/10.1007/s40266-015-0302-9
- Drug Interaction
- British National Formulary