Advertisement

Spontaneous reporting of adverse reactions related to proton pump inhibitors

Published:November 18, 2022DOI:https://doi.org/10.1016/j.dld.2022.10.024

      Abstract

      Background

      Proton pump inhibitors (PPIs) are widely prescribed in all age groups, and their use is increasing. However, their safety profile has been frequently questioned.

      Aims

      The aim of this study was to analyze the characteristics of PPI-related adverse drug reactions (ADRs) reported to the Italian spontaneous reporting system (SRS) database and relative to an Italian region (Sicily).

      Methods

      A 20-year observational, retrospective study was conducted, evaluating PPI-related ADR reports from Sicily between January 1st, 2001, and June 30th, 2021. The factors associated with ADR seriousness were investigated.

      Results

      A total of 148 spontaneous reports of ADRs related to PPIs were analyzed. Lansoprazole was the drug with the highest number of associated reports (30.87%). The most frequently reported ADRs were cutaneous (24.56%) and/or gastrointestinal manifestations (18.10%), the latter especially in the case of lansoprazole-related ADRs (p<0.006). The great majority of ADR reports were relative to on-label prescriptions. Serious ADRs were 39 (26.35%). Serious ADRs were more common in reports including omeprazole than in reports containing other PPIs (p<0.008) and in reports presenting PPIs combined with other drugs than in reports with PPI single therapies (p<0.001).

      Conclusion

      Most PPI-related ADRs are non-serious. Omeprazole and combination therapy seem to be associated with ADR seriousness.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Digestive and Liver Disease
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. http://stats.oecd.org/Index.aspx?DataSetCode=HEALTH_PHMC: [Accessed on 23 November 2021].

        • Scarpignato C.
        • Gatta L.
        • Zullo A.
        • Blandizzi C.
        • SIF-AIGO-FIMMG Group
        Italian Society of Pharmacology, the Italian Association of Hospital Gastroenterologists, and the Italian Federation of General Practitioners. Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression.
        BMC Med. 2016; 14: 179
        • Savarino V.
        • Marabotto E.
        • Furnari M.
        • et al.
        Latest insights into the hot question of proton pump inhibitor safety - a narrative review.
        Dig Liver Dis. 2020; 52: 842-852
        • Scarpignato C.
        • Tolone S.
        Addressing long-term PPI safety.
        Dig Liver Dis. 2020; 52: 853-856
        • Corsonello A.
        • Lattanzio F.
        • Bustacchini S.
        • et al.
        Adverse events of proton pump inhibitors: potential mechanisms.
        Curr Drug Metab. 2018; 19: 142-154
        • Abramowitz J.
        • Thakkar P.
        • Isa A.
        • Truong A.
        • Park C.
        • Rosenfeld R.M.
        Adverse event reporting for proton pump inhibitor therapy: an overview of systematic reviews.
        Otolaryngol Head Neck Surg. 2016; 155: 547-554
      2. European Medicines Agency (2022). Database of Summary of Product Characteristics (SmPCs). https://www.ema.europa.eu/en/medicines/human

        • Schumock G.T.
        • Li E.C.
        • Suda K.J.
        • et al.
        National trends in prescription drug expenditures and projections for 2016.
        Am J Health Syst Pharm. 2016; 73: 1058-1075
        • Casciaro M.
        • Navarra M.
        • Inferrera G.
        • et al.
        PPI adverse drugs reactions: a retrospective study.
        Clin Mol Allergy. 2019; 17: 1
        • Salloum A.
        • Nasr D.
        • Maalouf D.
        Dermatologic adverse reactions to proton-pump inhibitors: a synthetized review.
        J Cosmet Dermatol. 2021; 20: 1073-1079
        • Bose S.
        • Guyer A.
        • Long A.
        • Banerji A.
        Evaluation and management of hypersensitivity to proton pump inhibitors.
        Ann Allergy Asthma Immunol. 2013; 111: 452-457
        • Davidson G.
        • Wenzl T.G.
        • Thomson M.
        • et al.
        Efficacy and safety of once-daily esomeprazole for the treatment of gastroesophageal reflux disease in neonatal patients.
        J Pediatr. 2013; 163: 692-698
        • Martin R.M.
        • Dunn N.R.
        • Freemantle S.
        • Shakir S.
        The rates of common adverse events reported during treatment with proton pump inhibitors used in general practice in England: cohort studies.
        Br J Clin Pharmacol. 2000; 50: 366-372
        • Tolia V.
        • Ferry G.
        • Gunasekaran T.
        • Huang B.
        • Keith R.
        • Book L.
        Efficacy of lansoprazole in the treatment of gastroesophageal reflux disease in children.
        J Pediatr Gastroenterol Nutr. 2002; 35: S308-S318
        • Fiedorek S.
        • Tolia T.
        • Gold B.D.
        • et al.
        Efficacy and safety of lansoprazole in adolescents with symptomatic erosive and non-erosive gastroesophageal reflux disease.
        J Pediatr Gastroenterol Nutr. 2005; 40: 319-327
        • Levy E.I.
        • Hoang D.M.
        • Vandenplas Y.
        The effects of proton pump inhibitors on the microbiome in young children.
        Acta Paediatr. 2020; 109: 1531-1538
        • Lundell L.
        • Miettinen P.
        • Myrvold H.E.
        • et al.
        Nordic GERD Study Group. Comparison of outcomes twelve years after antireflux surgery or omeprazole maintenance therapy for reflux esophagitis.
        Clin Gastroenterol Hepatol. 2009; 7: 1292-1298
        • Galmiche J.P.
        • Hatlebakk J.
        • Attwood S.
        • LOTUS Trial Collaborators
        Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial.
        JAMA. 2011; 305: 1969-1977
        • Johnson D.A.
        Oldfield EC 4th Reported side effects and complications of long-term proton pump inhibitor use: dissecting the evidence.
        Clin Gastroenterol Hepatol. 2013; 11: 458-464
        • Marengoni A.
        • Pasina L.
        • Concoreggi C.
        • et al.
        Understanding adverse drug reactions in older adults through drug-drug interactions.
        Eur J Intern Med. 2014; 25: 843-846
        • Anand B.S.
        • Sanduja S.K.
        • Lichtenberger L.M.
        Effect of omeprazole on the bioavailability of aspirin: a randomized controlled study on healthy volunteers.
        Gastroenterology. 1999; 116: A371
        • Bogman K.
        • Peyer A.K.
        • Torok M.
        • et al.
        HMG-CoA reductase inhibitors and P-glycoprotein modulation.
        Br J Pharmacol. 2001; 132: 1183-1192
        • Capogrosso Sansone A.
        • Convertino I.
        • Galiulo M.T.
        • et al.
        Muscular adverse drug reactions associated with proton pump inhibitors: a disproportionality analysis using the Italian national network of pharmacovigilance database.
        Drug Saf. 2017; 40: 895-909
        • Mitre E.
        • Susi A.
        • Kropp L.E.
        • et al.
        Association between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood.
        JAMA Pediatr. 2018; 172e180315
        • Dipasquale V.
        • Cicala G.
        • Laganà F.
        • et al.
        Adverse reactions related to proton pump inhibitors in pediatric population: an analysis of spontaneous reporting data.
        Expert Opin Drug Saf. 2022; 21: 127-132