Relationship between drug interactions and drug-related negative clinical outcomes in two community pharmacies

  • Javier Cremades
  • Mario Gonzalo
  • Isabel Arrebola
Keywords: Drug Interactions, Community Pharmacy Services, Spain


Drug interactions may represent an iatrogenic risk that should be controlled in community pharmacies at the dispensing level.

Aim: We analyzed the association between potential drug-drug interactions (DDIs) and negative clinical outcomes.

Methods: We used dispensing data from two community pharmacies: instances where drug dispensing was associated with a potential DDI and a comparison group of randomized dispensing operations with no potential DDI. In cases where potential DDIs were detected, we analyzed the underlying negative clinical outcomes. Age and gender data were included in the analysis.

Results: During the study period, we registered 417 potential DDIs. The proportion of women and age were higher in the study group than in the comparison group. The average potential DDIs per patient was 1.31 (SD=0.72). The Consejo General de Colegios Oficiales de Farmacéuticos (CGCOF) database did not produce an alert in 2.4% of the cases. Over-the-counter medication use was observed in 5% of the potential DDI cases. The drugs most frequently involved in potential DDIs were acenocoumarol, calcium salts, hydrochlorothiazide, and alendronic acid, whereas the most predominant potential DDIs were calcium salts and bisphosphonates, oral antidiabetics and thiazide diuretics, antidiabetics and glucose, and oral anticoagulant and paracetamol. The existence of a drug-related negative clinical outcome was observed only in 0.96% of the potential DDI cases (50% safety cases and 50% effectiveness cases).

Conclusions: Only a small proportion of the detected potential DDIs lead to medication negative outcomes. Considering the drug-related negative clinical outcomes encountered, tighter control would be recommended in potential DDIs with NSAIDs or benzodiazepines.


Download data is not yet available.


1. Merlo J, Liedholm H, Lindblad U, Bjorck-Linne A, Falt J, Lindberg G, Melander A. Prescriptions with potential drug interactions dispensed at Swedish pharmacies in January 1999: cross sectional study. BMJ. 2001;323(7310):427-428.

2. Stokley IH. Interacciones farmacológicas. Barcelona: Pharma Editores; 2004.

3. Calvet A, Díez de Ulzurrum, Pérez MT, Esteras J. Interacciones farmacológicas en tratamientos crónicos: medidas correctoras para su prevención en un área básica de salud. Aten Primaria. 2001;27(1):33-37.

4. Peng CC, Glassman PA, Marks IR, Powler C, Castiglione B, Good CB. Retrospective drug utilization review: incidence of clinically relevant potential drug-drug interactions in a large ambulatory population. J Manag Care Pharm. 2003;9(6):513-522.

5. Becker ML, Kallewaard M, Caspers PW, Schalekamp T, Stricker BH. Potential determinants of drug-drug interaction associated dispensing in community pharmacies. Drug Saf. 2005;28(5):371-378.

6. Manchon ND, Bercoff E, Lemarchand P, Chassagne P, Senant J, Bourreille J. Incidence and severity of drug interactions in the elderly: a prospective study of 639 patients. Rev Med Interne. 1989;10(6):521-525.

7. Huic M, Mucolic V, Vrhovac B, Francetic I, Bakran I, Giljanovic S. Adverse drug reactions resulting in hospital admission. Int J Clin Pharmacol Ther. 1994;32(12):675-682.

8. McDonnell PJ, Jacobs MR. Hospital admissions resulting from preventable adverse drug reactions. Ann Pharmacother. 2002;36(9):1331-1336.

9. Juurlink DN, Mamdani M, Kopp A, Laupacis A, Redelmeier DA. Drug-drug interactions among elderly patients hospitalized for drug toxicity. JAMA. 2003;289(13):1652-1654.

10. Sandson N. Drug-drug interactions: The silent epidemic. Psychiat Serv. 2005;56(1):22-24.

11. Becker ML, Kallewaard M, Caspers PW, Visser LE, Leufkens HG, Stricker BH. Hospitalisations and emergency department visits due to drug-drug interactions: a literature review. Pharmacoepidemiol Drug Saf. 2007;16(6):641-651.

12. Resolución ResAP (2001) 2 sobre el papel de los farmacéuticos en el marco de la seguridad sanitaria. Consejo de Europa.

13. Lien LL, Lien EJ. Preventing potential drug interactions in community pharmacie. J Clin Pharm Ther. 1994;19(6):371-379.

14. Acosta J, Alzaga A, Álvarez L, Gudiel M, Fernández-Llimos F. Análisis del proceso de dispensación y detección de interacción potencial en farmacias de Alcorcón (Madrid) y Bilbao. Seguim Farmacoter. 2004;2(1):32-36.

15. Cavuto NJ, Woosley RL, Sale M. Pharmacies and prevention of potentially fatal drug interactions. JAMA. 1996;275(14):1086-1087.

16. Westein MP, Herings RM, LeufkensHG, Determinants of pharmacist´s interventions linked to prescription processing. Pharm World Sci. 2001;23(3):98-101.

17. Glassman PA, Simon B, Belperio P, Lanto A. Improving recognition of drug interactions: benefits and barriers to using automated drug alerts. Med Care. 2002;40(12):1161-1171.

18. Indermitte J, Beutler M, Bruppacher R, Meier CR, Hersberger KE. Management of drug-interaction alerts in community pharmacies. J Clin Pharm Ther. 2007;32(2):133-142.

19. Barris D, Rodríguez C, Sabio B, Garrido B. Interacciones farmacológicas detectadas en una farmacia comunitaria. Pharm Care Esp. 2003;5:261-267.

20. Consensus Committee. Third Consensus of Granada in Drug Related Problems (DRP) and Negative Outcomes associated with Medication (NOM). Ars Pharm. 2007;48(1):5-17.

21. Linnarsson R. Drug interactions in primary health care. A retrospective database study and its implications for the design of a computerized decision support system. Scand J Prim Health Care. 1993;11(3):181-186.

22. Doubova Dubova SV, Reyes-Morales H, Torres-Arreola Ldel P, Suárez-Ortega. Potential drug-drug and drug-disease interactions in prescriptions for ambulatory patients over 50 years of age in family medicine clinics in Mexico City. BMC Health Serv Res. 2007;7:147.

23. Mahmood M, Malone DC, Skrepnek GH, Abarca J, Armstrong EP, Murphy JE, Grizzle AJ, Ko Y, Woosley RL. Potential drug-drug interactions within Veterans Affairs medical centers. Am J Health Syst Pharm. 2007;64(14):1500-1505.

24. Weideman RA, Bernstein IH, McKinney WP. Pharmacist recognition of potential drug interactions. Am J Health Syst Pharm. 1999;56(15):1524-1529.

25. Halkin H, Katzir I, Kurman I, Jan J, Malkin BB. Preventing drug interactions by online prescription screening in communitypharmacies and medical practices. Clin Pharmacol Ther. 2001;69(4):260-265.

26. Abarca J, Colon LR, Wang VS, Malone DC, Murphy JE, Armstrong EP. Evaluation of the performance of drug-drug interaction screening software in community and hospital pharmacies. J Manag Care Pharm. 2006;12(5):383-389.

27. Egger SS, Rätz Bravo AE, Hess L, Schlienger RG, Krähenbühl S. Age-related differences in the prevalence of potential drug-drug interactions in ambulatory dyslipidaemic patients treated with statins. Drugs Aging. 2007;24(5):429-440.

28. Malone DC, Hutchins DS, Haupert H, Hansten P, Duncan B, Van Bergen RC, Solomon SL, Lipton RB. Assessment of potential drug-drug interactions with a prescription claims database. Am J Health Syst Pharm. 2005;62(19):1983-1991.

29. Stephens M, Kukulka G. Frequency of Drug Interactions Among Primary Care Patients at a Family Medicine Residency Clinic. Abstracts 2006 NAPCRG Annual Meeting PS184.

30. López Vázquez P, Rodriguez Moreno C, Duran Parrondo C, Tato Herrero F, Rodríguez López I, Lado Lado FL. Interacciones entre medicamentos prescritos al alta en un servicio de medicina interna. An Med Interna. 2005;22(2):69-75.

31. Kohler GI, Bode-Boger SM, Busse R, Hoopmann M, Welte T, Boger RH. Drug-drug interactions in medical patients: effects of in-hospital treatment and relation to multiple drug use. Int J Clin Pharmacol Ther. 2000;38(11):504-513.

32. De Diego A, Alvarellos ML, Del Barrio H. Análisis de la compleción de la base de datos del Consejo General de Colegios Oficiales de Farmacéuticos sobre interacciones entre medicamentos. Pharm Care Esp. 1999;1:184-193.
How to Cite
Cremades J, Gonzalo M, Arrebola I. Relationship between drug interactions and drug-related negative clinical outcomes in two community pharmacies. Pharm Pract (Granada) [Internet]. 2009Mar.4 [cited 2020Feb.17];7(1):34-9. Available from:
Original Research