• Nadia Farhanah Syafhan Department of Pharmacy, Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, Indonesia.
  • Maulidya Augustine Department of Pharmacy, Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, Indonesia.
  • Uci Ramadhani Department of Pharmacy, Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, Indonesia.
  • Yetti Hersunaryati Pharmacy Installation of Gatot Soebroto Army Hospital, Jakarta, 10410, Indonesia.


Objective: This study aimed to evaluate the use and potential drug interactions of proton-pump inhibitor (PPI) in outpatients.
Methods: This study is a retrospective descriptive analysis of prescriptions and medical records from outpatients in Gatot Soebroto Army Hospital
selected by purposive sampling who received PPI with one or more other drugs from July to December 2015. The analysis was conducted on 400
prescriptions from 192 patients.
Results: Data showed that 100% of the PPI therapy utilized was appropriate for the patients’ condition, 79.00% was appropriate for the indication,
79.00% was appropriate for the dosage, 79.00% had an appropriate administration duration, and 83.75% was given the appropriate drug. The
potential of PPI interactions with other drugs was found in 324 prescriptions (81.00%) from 475 cases. Of all the cases, 42 were considered major
interactions, 138 were moderate interactions, and 295 cases had minor interactions. There were 14 drugs that could potentially interact with PPI, such
as mycophenolate mofetil, clopidogrel, cilostazol, warfarin, iron, levothyroxine, propranolol, cyclosporine, simvastatin, atorvastatin, cyanocobalamin,
sucralfate, theophylline, and antacids.
Conclusion: PPI use in outpatients at the Gatot Soebroto Army Hospital was not entirely appropriate and had a large number of potential drug
interactions with concurrent drugs.

Keywords: Drug interaction, Drug use, Outpatients, Proton-pump inhibitor


1. Atkins AM, Sekar MC. Proton pump inhibitors: Their misuse, overuse,
and abuse. IOSR J Pharm 2013;3:25-9.
2. Ding J, Heller DA, Ahern FM, Brown TV. The relationship between
proton pump inhibitor adherence and fracture risk in the elderly. Calcif
Tissue Int 2014;94:597-607.
3. Sheen E, Triadafilopoulos G. Adverse effects of long-term proton pump
inhibitor therapy. Dig Dis Sci 2011;56:931-50.
4. van der Hoorn MM, Tett SE, de Vries OJ, Dobson AJ, Peeters GM. The
effect of dose and type of proton pump inhibitor use on risk of fractures
and osteoporosis treatment in older Australian women: A prospective
cohort study. Bone 2015;81:675-82.
5. Setiawati A. Drug interaction. In: Gunawan SG, Setiabudy R,
Elysabeth N, editor. Pharmacology and Therapy. 5th ed. Jakarta: Balai
Penerbit FKUI; 2007. p. 862-85.
6. Tatro DS, editor. Drug Interaction Facts. California: Missouri; 2001.
7. Nasution NK. The Relationship of Diet with the Incidence of Dyspepsia
Syndrome to Student at Faculty of Public Health Universitas Sumatera
Utara in 2015. Medan: Faculty of Public Health, Universitas Sumatera
Utara; 2016.
8. Pilotto A, Franceschi M. Helicobacter pylori infection in older people.
World J Gastroenterol 2014;20:6364-73.
9. Ajarallah BD. Management of diabetic gastroparesis. Saudi J
Gastroenterol 2011;17:97-104.
10. Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L, American
College of Gastroenterology, et al. Clinical guideline: Management of
gastroparesis. Am J Gastroenterol 2013;108:18-37.
11. Ministry of Health of the Republic Indonesia. Formularium National,
Number HK.02.02/MENKES/523/2015. Jakarta: Ministry of Health,
Republic Indonesia; 2013.
12. Indonesian Agency of Drug and Food Supervisory. Indonesian National
Drug Information. Jakarta: Sagung Seto; 2014.
13. Patel K, Dunn J. Updated NICE guidance on the management of
dyspepsia. Prescriber 2015;26:5-6.
14. Wolfe MM, Blanton WP. Proton Pump Inhibitor in Pocket Guide to
Gastrointestinal Drugs. London: Wiley Blackwell; 2014.
15. Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug Information
Handbook with International Trade Names Index. Ohio: Lexicomp; 2009.
16. Firmansyah MA. Management of gastrointestinal disorders in
pregnancy. Medicinus 2014;27:46-51.
17. Landes BD, Petite JP, Flouvat B. Clinical pharmacokinetics of
lansoprazole. Clin Pharmacokinet 1995;28:458-70.
18. Sweetman SC, editor. Martindale-the Complete Drug Reference.
London: Pharmaceutical Press; 2009.
19. Ika PD. Influential Factors against Upper Gastrointestinal Changes
to Patients with Coronary Heart Disease with Antiplatelet Therapy.
Semarang: Universitas Diponegoro; 2013.
20. Pipilis A, Makrygiannis S, Chrisanthopoulou E, Sourlas N,
Kaliambakos S, Ntailianas P, et al. Gastrointestinal bleeding in patients
receiving antiplatelet and anticoagulant therapy: Practical guidance
for restarting therapy and avoiding recurrences. Hellenic J Cardiol
21. Vella V. Drug-induced peptic ulcer disease. J Malta Coll Pharm Pract
22. Vanderhoff BT, Tahboub RM. Proton pump inhibitors: An update. Am
Fam Physician 2002;66:273-80.
23. Durand C, Willett KC, Desilets AR. Proton pump inhibitor use in
hospitalized patients: Is overutilization becoming a problem? Clin Med
Insights Gastroenterol 2012;5:65-76.
24. Mohammad A, Brilakis ES, Weideman RA, Little BB, Banerjee S. The
clinical relevance of the clopidogrel-proton pump inhibitor interaction.
J Cardiovasc Trans Res 2012;5:547-52.
25. Funck-Brentano C, Szymezak J, Steichen O, Ducint D, Molimard M,
Remones V, et al. Effects of rabeprazole on the antiplatelet effects and
pharmacokinetics of clopidogrel in healthy volunteers. Arch Cardiovasc
Dis 2013;106:661-71.
26. Ferreiro JL, Ueno M, Tomasello SD, Capodanno D, Desai B,
Dharmashankar K, et al. Pharmacodynamic evaluation of pantoprazole
therapy on clopidogrel effects: Results of a prospective, randomized,
crossover study. Circ Cardiovasc Interv 2011;4:273-9.
27. Kees MG, Steinke T, Moritz S, Rupprecht K, Paulus EM, Kees F, et al.
Omeprazole impairs the absorption of mycophenolate mofetil but not
of enteric-coated mycophenolate sodium in healthy volunteers. J Clin
Pharmacol 2012;52:1265-72.
28. Kofler S, Shvets N, Bigdeli AK, König MA, Kaczmarek P, Deutsch MA,
et al. Proton pump inhibitors reduce mycophenolate exposure in heart
transplant recipients-a prospective case-controlled study. Am J Transplant
29. Suri A, Bramer SL. Effect of omeprazole on the metabolism of
cilostazol. Clin Pharmacokinet 1999;37 Suppl 2:53-9.
30. Indonesian Agency of Drug and Food Supervisory. Buletin Berita
MESO. Jakarta: BPOM; 2009.
31. Angiolillo DJ, Gibson CM, Cheng S, Ollier C, Nicolas O,
Bergougnan L, et al. Differential effects of omeprazole and pantoprazole
on the pharmacodynamics and pharmacokinetics of clopidogrel in
healthy subjects: Randomized, placebo-controlled, crossover comparison
studies. Clin Pharmacol Ther 2011;89:65-74.
32. Sutfin T, Balmer K, Boström H, Eriksson S, Höglund P, Paulsen O, et al.
Stereoselective interaction of omeprazole with warfarin in healthy men.
Ther Drug Monit 1989;11:176-84.
33. Lacobellis G, editor. Drug-drug Interaction in the Metabolic Syndrome.
New York: Nova Publisher; 2006.
34. Sachmechi I, Reich DM, Aninyei M, Wibowo F, Gupta G, Kim PJ, et al.
Effect of proton pump inhibitors on serum thyroid-stimulating hormone
level in euthyroid patients treated with levothyroxine for hypothyroidism.
Endocr Pract 2007;13:345-9.
35. Ajmera AV, Shastri GS, Gajera MJ, Judge TA. Suboptimal response to
ferrous sulfate in iron-deficient patients taking omeprazole. Am J Ther
36. Singh S, Choudhary N, Rai J, Siddiqui I, Sharma S. A validated RPUPLC
method development for simultaneous estimation of lansoprazole
and naproxen in bulk and tablet dosage from. Asian J Pharm Clin Res
37. Bhargav K, Venkata SB, Venkata SK, Himaja G, Samuel GG, Bhaskar RK.
Pharmacokinetic drug interaction between clopidogrel and esomeprazole
in adult healthy male volunteers. Asian J Pharm Clin Res 2017;10:336-41.
38. Salunkhe PS. Formulation and evaluation of gastroretentive tablets of
antiulcer drug. Asian J Pharm Clin Res 2016;9:48-52.
39. Sipe BE, Jones RJ, Bokhart GH. Rhabdomyolysis causing AV blockade
due to possible atorvastatin, esomeprazole, and clarithromycin
interaction. Ann Pharmacother 2003;37:808-11.
The 2nd Physics and Technologies in Medicine and Dentistry Symposium (PTMDS), Universitas Indonesia. Depok, Indonesia 363
40. Schouler L, Dumas F, Couzigou P, Janvier G, Winnock S, Saric J.
Omeprazol-cyclosporin interaction. Am J Gastroenterol 1991;86:1097.
41. Arranz R, Yañez E, Franceschi JL, Fernández-Rañada JM. More about
omeprazole-cyclosporine interaction. Am J Gastroenterol 1993;88:154-5.
42. Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes
malabsorption of cyanocobalamin (vitamin B12). Ann Intern Med
43. Wedemeyer RS, Blume H. Pharmacokinetic drug interaction profiles of
proton pump inhibitors: An update. Drug Saf 2014;37:201-11.
44. Granneman GR, Karol MD, Locke CS, Cavanaugh JH. Pharmacokinetic
interaction between lansoprazole and theophylline. Ther Drug Monit
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How to Cite
Syafhan, N. F., Augustine, M., Ramadhani, U., & Hersunaryati, Y. (2018). PROTON-PUMP INHIBITOR USE AND POTENTIAL DRUG INTERACTIONS IN OUTPATIENTS. International Journal of Applied Pharmaceutics, 10(1), 358-363.
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