Frequency of Inappropriate Metformin Use in Patients with Diabetes Mellitus

당뇨병환자에게 부적절하게 사용된 Metformin의 처방빈도 분석

  • Sin, Hye-Yeon (Department of Pharmacy, Gangneung Asan Hospital) ;
  • Jung, Ki-Hwa (College of Pharmacy, Duksung Women's University)
  • Received : 2010.02.02
  • Accepted : 2010.10.15
  • Published : 2010.12.31

Abstract

We evaluated the inappropriateness of metformin use in patients with type 2 diabetes and chronic medical conditions to identify the frequency of the prescription metformin in violation of the food and drug administration (FDA) black box warning. We reviewed medical records of 307 outpatients who received metformin at endocrinology department in a hospital setting between January 1, 2005 and August 30, 2009. Of the 307 outpatients, 25 discontinued treatment of metformin due to elevated serum creatinine level (Scr${\geq}$1.5 mg/dl in male, Scr${\geq}$1.4 mg/dl in female), cancers, and/or liver disease. 5 were lost to follow-up. 89 (29.0%) of the patients had cardiovascular disease, 54.1% for hypertension, 9.8% for liver disease, and 60 (20.8%) for chronic kidney disease. 12 patients (3.9%) with chronic kidney disease and/or elevated serum creatinine level, and 1 patient (0.3%) with lactic acidosis were contraindicated to metformin use. Metformin should be avoided in 7 outpatients (2.3%) with active hepatitis and 1 patient (2.6%) with liver cirrhosis. Of the 307 outpatients, 13 (4.2%) patients who received metformin at the first visit and 16 (8.7%) patients who received metformin at the last visit violated to black box warning. 8 (2.6%) of the patients were in precautionary conditions to metformin use. Adjusted mean difference of serum creatinine was -0.16 mg/dl [95% CI: -0.22 to -0.11 (p<0.05)] and adjusted mean difference of alanine aminotransferase was 4.46 IU/l [95% CI: 2.47 to 6.44 (p<0.05)] between the first visit and the last visit. Critical number of elderly patients who are at the high risks of drug-disease and drug-laboratory interaction is exposed to the inappropriate metformin use in violation of black box warning. The periodic evaluation of metformin use and monitoring prescription through drug utility review (DUR) system is needed to improve patients' safety and to reduce adverse drug events.

Keywords

References

  1. KodaKimble, M. A., Young, L. Y., Kradjan, W. A., Guglielmo, B. J., Alldredge, B. K. and Corelli, R. L. : Applied therapeutics. 8th edition. Lippincot Williams and Wilkins. Philadelphia. chap. 50, 51 (2004).
  2. Bristol-myers squibb company, Princeton. Glucophage and GlucophageXR revised 2009. p14. Available: http://packageinserts. bms.com/pi/pi_glucophage.:pdf.
  3. The Korean food and drug administration. Available:http:// ezdrug.kfda.go.kr/kfda 2.
  4. Szarfman, W., DuMouchel, D., Fram, J. M., Tonning, J., Almenoff, R. D. and Fleischer, J. G. : Lactic Acidosis: 2005 FDA Science Forum. A. Unraveling the Individual Toxicities of Drugs Used in HIV and Diabetes Polytherapy by Hierarchical Bayesian Logistic Regression Data Mining (2005).
  5. Lasser, K. E., Seger, D. L., Yu, D. T., Karson, A. S., Fiskio, J. M., Seger, A. C., Shah, N. R., Gandhi,T. K., Rothschild, J. M. and Bates, D. W. : Adherence to black box warnings for prescription medication in outpatients. Arch. Intern. Med. 166, 338 (2006). https://doi.org/10.1001/archinte.166.3.338
  6. Goulding, M. R. : Inappropriate medication prescribing for elderly ambulatory care patients. Arch. Intern. Med. 164, 308 (2004).
  7. Fick, D. M., Cooper, J. W., Wade, W. E., Waller, J. L., Maclean, J. R. and Beers, M. H. : Updating the Beers Criteria for potentially Inappropriate medication use in older adults. Arch. Intern. Med. 163, 2718 (2003).
  8. Curtis, L. H., Ostbye, T., Sendersky, V., Hutchison, S., Dans, P. E., Wright, A., Woosley, R. L. and Schulman, K. A. : Inappropriate prescription for elderly Americans in a large outpatient population. Arch. Intern. Med. 164, 1621 (2004). https://doi.org/10.1001/archinte.164.15.1621
  9. Maudi, F. A., Wang, Y., Inzucchi, S. E., Setaro, J. F., Harvanek, E. P., Foody, J. M. and Krumholz, H. M. : Metformin and thiazolidinedione use in medicare patients with heart failure. JAMA 290, 81 (2003). https://doi.org/10.1001/jama.290.1.81
  10. Culleton, B. F., Larson, M. G., Evans, J. C., Wilson, P. W. F., Brendan, J., Barrett, B. J., Parfrey, P. S. and Levy, D. : Prevalence and correlate of elevated serum creatinine levels. Arch. Intern. Med. 159, 1785 (1999). https://doi.org/10.1001/archinte.159.15.1785
  11. Coresh, J. C., Wei, G. L., McQuillan, G., Brancati, F. L., Levey, A. S., Jones, C. and Klag, M. : Prevalence of high blood pressure and elevated serum creatinine level in the United States. Arch. Intern. Med. 161, 1207 (2001). https://doi.org/10.1001/archinte.161.9.1207
  12. Horlen, C., Malone, R., Byant, B., Dennis, B., Carey, T., Pignone, M. and Rothman, R. : Frequency of inappropriate metformin prescription. JAMA 287, 2504 (2002). https://doi.org/10.1001/jama.287.19.2504
  13. ARUP consult. The physician's guide to laboratory test selection and interpretation of Clinical guide to laboratory test. Available:http://www.arupconsult.com/Topics/Heart Failure. html#.
  14. Muller, C., Scholer, A., Laule-Kilian, K., Martina, B., Schindler, C., Buser, P., Pfisterer, M. and Perruchoud, A. P. : Use of Btype Natriuretic peptide in the evaluation and management of acute dyspnea. NEJM 350, 647 (2004). https://doi.org/10.1056/NEJMoa031681
  15. AACE Hypertension task force American Association of Clinical Endocrinologists. : Medical guidelines for clinical practice for the diagnosis and treatment of hypertension. Endocri. Pract. 12(2), 199 (2006).
  16. Guideline recommendations : Focused update recommendations. Patients with reduced left ventricular ejection fracion. JACC 53(15), 1 (2005).
  17. Ryden, L., Standl, E., Bartnik, M., Van den Berghe, G., Betterridge, J., de Boer, M. J., Cosen, F., Jonsson, B., Laakso, M., Malmberg, K., Priori, S., Ostergren, J., Tuomilehto, J. and Thrainsdottir, I. : National guideline clearing house: Guideline on diabetes, pre-diabetes and cardiovascular disease. Euro. Societ. of Cardiology (ESC). 72p [711 references] (2007).
  18. Hunt, S. A., Abraham, W. T., Chin, M. H., Feldman, A. M., Francis, G. S., Ganiats, T. G., Jessup, M., Konstam, M. A., Mancini, D. M., Michl , K., Oates, J. A., Racho, P. S., Silver, M. A., Stevensen, L. W. and Yancy, C. W. : ACC/AHA 2005 guideline update for the diagnosis and management outpatient of chronic heart failure in the adult. Americ. Colle. of Card. Found. Aug. 82p. [694references] (2005).
  19. Sarabash, H. M., Remington, T. L., Mar, P., Winston, R. and Walker, P. C. : Retrospective review of metformin in inpatients and outpatients at the University of Michigan. Diabetes Care. 29(1), 170 (2006).