Study protocol: evaluation of a pharmaceutical intervention for safe use of medications in patients with liver cirrhosis

e202601004

Authors

  • Andrea Rodríguez Esquíroz Subdirección de Farmacia y Prestaciones. Servicio Navarro de Salud–Osasunbidea. Pamplona. España. / Grupo de Investigación en Atención Primaria. Instituto de Investigación Sanitaria de Navarra (IdiSNA). Pamplona. España. https://orcid.org/0009-0006-8635-6084
  • Amaya Echeverría Gorriti Subdirección de Farmacia y Prestaciones. Servicio Navarro de Salud–Osasunbidea. Pamplona. España. / Grupo de Investigación en Atención Primaria. Instituto de Investigación Sanitaria de Navarra (IdiSNA). Pamplona. España. https://orcid.org/0000-0001-9225-5323
  • Marta Marín Marín Subdirección de Farmacia y Prestaciones. Servicio Navarro de Salud–Osasunbidea. Pamplona. España. / Grupo de Investigación en Atención Primaria. Instituto de Investigación Sanitaria de Navarra (IdiSNA). Pamplona. España. https://orcid.org/0000-0002-0609-6467
  • Lorea Sanz Álvarez Subdirección de Farmacia y Prestaciones. Servicio Navarro de Salud–Osasunbidea. Pamplona. España. / Grupo de Investigación en Atención Primaria. Instituto de Investigación Sanitaria de Navarra (IdiSNA). Pamplona. España. https://orcid.org/0000-0003-0571-5438
  • Patricia García González Subdirección de Farmacia y Prestaciones. Servicio Navarro de Salud–Osasunbidea. Pamplona. España. / Servicio de Farmacia. Hospital García Orcoyen. Estella. España. https://orcid.org/0000-0002-5029-9368
  • Javier Gorricho Mendívil Subdirección de Farmacia y Prestaciones. Servicio Navarro de Salud–Osasunbidea. Pamplona. España. https://orcid.org/0000-0003-3609-9922
  • Juan Isidro Uriz Otano Servicio de Digestivo, Unidad de Hepatología. Hospital Universitario de Navarra. Servicio Navarro de Salud-Osasunbidea. Pamplona. España.
  • Javier Garjón Parra Subdirección de Farmacia y Prestaciones. Servicio Navarro de Salud–Osasunbidea. Pamplona. España. / Grupo de Investigación en Atención Primaria. Instituto de Investigación Sanitaria de Navarra (IdiSNA). Pamplona. España. https://orcid.org/0000-0002-0126-7431
  • Inés Aguinaga Ontoso Departamento de Ciencias de la Salud. Universidad Pública de Navarra. Instituto de Investigación Sanitaria de Navarra (IdiSNA). Pamplona. España. / CIBER Epidemiologia y Salud Pública (CIBERESP). Instituto de Salud Carlos III. Madrid. España. https://orcid.org/0000-0002-2882-930X

Keywords:

Liver, Liver cirrhosis, Safety, Therapeutics, Drug prescriptions, Pharmacy

Abstract

Liver cirrhosis is the final stage of chronic liver disease and can lead to deterioration of liver function. Because the liver is the main metabolizing organ, patients with liver cirrhosis experience changes that can affect drug effectiveness and safety. There are many drugs whose dosage must be adjusted or which are contraindicated. A lack of information in this field has been detected among health professionals who care for these patients, partly due to the lack of specific clinical guidelines on the management of drugs.

The objective is to present the protocol of a study for the evaluation of a strategy to minimize risks related to the use of medications. This consisted of medication reviews of patients with liver cirrhosis carried out by primary care pharmacists and specific training for health professionals.

The pharmacists made proposals (dose adjustment, substitution for safer alternatives, suspension or monitoring of adverse reactions) through the computerized clinical history, taking into account the stage of the disease (Child-Pugh) and other comorbidities, directed to the doctors responsible for the patient’s pharmacotherapy (hepatologist, primary care doctor or other specialists), who will make the changes they deem appropriate.

To evaluate this strategy, an analysis will be conducted to assess the degree of acceptance of these proposals. The results obtained will provide us with information on the impact of the pharmacist’s review on reducing the risks associated with medications in these patients. This study will help us to design prescription support tools integrated into electronic prescribing to aid decision-making for all healthcare professionals involved in the patients’ pharmacotherapy.

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References

1. Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014;383(9930):1749-1761. http://dx.doi.org/10.1016/S0140-6736(14)60121-5

2. Verbeeck RK. Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. Eur J Clin Pharmacol. 2008;64(12):1147-1161. https://doi.org/10.1007/s00228-008-0553-z

3. García-Cortés M, García-García A. Management of Pharmacologic Adverse Effects in Advanced Liver Disease. Clin Drug Investig . 2022;42(s1):33-38. https://doi.org/10.1007/s40261-022-01150-w

4. Calvo-Salazar RA, David M, Zapata-Mesa MI, Rodríguez-Naranjo CM, Valencia-Acosta NY. Drug-related problems causing hospital admissions in the emergency rooms at of high complexity hospital. Farm Hosp. 2018;42(6):228-233. https://doi.org/10.7399/fh.10996

5. Borgsteede et al. Geneesmiddelen bij Levercirrose [Internet]. https://www.geneesmiddelenbijlevercirrose.nl/. Consultado marzo 2025.

6. Rodríguez Esquíroz A. Uso seguro de medicamentos en pacientes con cirrosis. Boletín Inf Farmacoter Navarra. 2023;1-22. https://www.navarra.es/home_es/Temas/Portal+de+la+Salud/Profesionales/Documentacion+y+publicaciones/Publicaciones+tematicas/Medicamento/BIT/Vol+31/Vol+31+N.htm

7. RxCirrhose [Internet]. https://www.rxcirrhose.ca/?hl=fr. Consultado marzo 2025.

8. Weersink RA, Timmermans L, Monster-Simons MH, Mol PGM, Metselaar HJ, Borgsteede SD et al. Evaluation of information in summaries of product characteristics (SMPCs) on the use of a medicine in patients with hepatic impairment. Front Pharmacol. 2019;10(SEP):1-10. https://doi.org/10.3389/fphar.2019.01031

9. Karsten Dafonte K, Weber L, Chmielewski F, Böhmer AM, Lutz P, Hartmann G et al. Dose Recommendations for Common Drugs in Patients with Liver Cirrhosis: A Systematic Literature Review. Clin Drug Investig. 2023;43(7):475-502. https://doi.org/10.1007/s40261-023-01289-0

10. Rodighiero V. Effects of Liver Disease on Pharmacokinetics An Update. Princ Clin Pharmacol. 2012;37(5):73-87. http://dx.doi.org/10.1016/B978-0-12-385471-1.00007-6

11. Delcò F, Tchambaz L, Schlienger R, Drewe J, Krähenbühl S. Dose adjustment in patients with liver disease. Drug Saf. 2005;28(6):529-545. https://doi.org/10.2165/00002018-200528060-00005

12. Weersink RA, Bouma M, Burger DM, Drenth JPH, Hunfeld NGM, Kranenborg M et al. Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion. BMJ Open. 2016;6(10). https://doi.org/10.1136/bmjopen-2016-012991

13. Johnson TN, Boussery K, Rowland-Yeo K, Tucker GT, Rostami-Hodjegan A. A semi-mechanistic model to predict the effects of liver cirrhosis on drug clearance. Clin Pharmacokinet. 2010;49(3):189-206. https://doi.org/10.2165/11318160-000000000-00000

14. Weersink RA, Bouma M, Burger DM, Drenth JPH, Harkes-Idzinga SF, Hunfeld NGM et al. Evidence-Based Recommendations to Improve the Safe Use of Drugs in Patients with Liver Cirrhosis. Drug Saf . 2018;41(6):603-613. https://doi.org/10.1007/s40264-017-0635-x

15. Hayward KL, Patel PJ, Valery PC, Horsfall LU, Li CY, Wright PL et al. Medication-Related Problems in Outpatients With Decompensated Cirrhosis: Opportunities for Harm Prevention. Hepatol Commun. 2019;3(5):620-631. https://doi.org/10.1002/hep4.1612

16. Danjuma MIM, Naseralallah L, Ansari S, Al Shebly R, Elhams M, AlShamari M et al. Prevalence and global trends of polypharmacy in patients with chronic liver disease: A systematic review and meta-analysis. Medicine (Baltimore). 2023 May 12;102(19):e32608. https://doi.org/10.1097/MD.0000000000032608

17. Gorricho J, Leache L, Tamayo I, Sánchez-Sáez F, Almirantearena M, San Román E et al. Data Resource Profile: Results Analysis Base of Navarre (BARDENA). Int J Epidemiol. 2023 Dec 25;52(6):e301-307. https://doi.org/10.1093/ije/dyad144

18. Rodríguez Esquíroz A, Echeverría Gorriti A, García González P, Gorricho Mendivil J, Sanz Álvarez L, Marín Marín M, Garjón Parra J. 5PSQ-072 Drug prescription in hepatic cirrhosis: pitfalls and room for improvement. Eur J Hosp Pharm. 2025; 32:A183-A184. https://doi.org/10.1136/ejhpharm-2025-eahp.369

19. Smith MY, Morrato EH, Mora N, Nguyen V, Pinnock H, Winterstein AG. The Reporting Recommendations Intended for Pharmaceutical Risk Minimization Evaluation Studies: Standards for Reporting of Implementation Studies Extension (RIMES-SE). Drug Saf. 2024;47(7):655-671. https://doi.org/10.1007/s40264-024-01417-5

20. Centro de información online de medicamentos de la Agencia Española de Medicamentos y Productos Sanitarios. https://cima.aemps.es/cima/publico/buscadoravanzado.html. Consultado marzo 2025.

21. UpToDate [Internet]. https://www.uptodate.com/contents/search. Consultado marzo 2025.

22. Ganne-Carrié N. Épidémiologie de la cirrhose. Rev Prat. 2017;67(7):726-730.22.

23. Gonzalez M, Goracci L, Cruciani G, Poggesi I. Some considerations on the predictions of pharmacokinetic alterations in subjects with liver disease. Expert Opin Drug Metab Toxicol. 2014;10(10):1397-1408. https://doi.org/10.1517/17425255.2014.952628

24. Hayward KL, Weersink RA. Improving Medication-Related Outcomes in Chronic Liver Disease. Hepatol Commun. 2020;4(11):1562-1577. https://doi.org/10.1002/hep4.1612

25. Franz CC, Hildbrand C, Born C, Egger S, Rätz Bravo AE, Krähenbühl S. Dose adjustment in patients with liver cirrhosis: Impact on adverse drug reactions and hospitalizations. Eur J Clin Pharmacol. 2013;69(8):1565-1573. https://doi.org/10.1007/s00228-013-1502-z

26. Thomson MJ, Lok ASF, Tapper EB. Appropriate and Potentially Inappropriate Medication Use in Decompensated Cirrhosis. Hepatology. 2021;73(6):2429-2440. https://doi.org/10.1002/hep.31548

Published

2026-01-26

How to Cite

1.
Rodríguez Esquíroz A, Echeverría Gorriti A, Marín Marín M, Sanz Álvarez L, García González P, Gorricho Mendívil J, et al. Study protocol: evaluation of a pharmaceutical intervention for safe use of medications in patients with liver cirrhosis: e202601004. Rev Esp Salud Pública [Internet]. 2026 Jan. 26 [cited 2026 Apr. 5];100(1):13 páginas. Available from: https://ojs.sanidad.gob.es/index.php/resp/article/view/1242

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