Proton pump inhibitors are associated with hypersensitivity reactions to drugs in hospitalized patients: a nested case‐control in a retrospective cohort study

Ramírez, Elena; Cabañas, Rosario; Laserna, L. S.; Fiandor, Ana; Tong, Hoi Y.; Prior, Nieves; Calderón, Óscar; Medrano, Nicolás; Bobolea, Irina; Frías, Jesús; Quirce, Santiago

doi:10.1111/cea.12034

Cited by 37 publications

(38 citation statements)

References 51 publications

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“…The PPIs being potent inhibitors of gastric acid secretion have been extensively studied in preventing aspirininduced GI complications. Recently, we are facing the side effects of long-term PPI therapy, such as Clostridium difficile colitis, community-acquired pneumonia, osteoporosis, iron and vitamin deficiencies, as well as the increase of food allergies [45][46][47][48][49]. The interaction caused by PPIs on the cytochrome enzymes hazard appropriate drug actions of clopidogrel, vitamin K antagonists, and benzodiazepines [50,51].…”

Section: Discussionmentioning

confidence: 99%

PPIs Prevent Aspirin-Induced Gastrointestinal Bleeding Better than H2RAs. A Systematic Review and Meta-analysis

Szabó¹,

Mátics

Hegyi

et al. 2017

JGLD

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Background & Aims: Aspirin is one of the most widely used medication for its analgesic and anti-platelet properties and thus a major cause for gastrointestinal (GI) bleeding. This study compared the preventive effect of histamine-2 receptor antagonists (H2RAs) and proton-pump inhibitors (PPIs) against chronic low-dose aspirin (LDA)-related GI bleeding and ulcer formation.Methods: Electronic databases of Pubmed, Embase and Cochrane Central Register of Controlled Trials were searched for human observations (randomised controlled trials and observational studies) comparing the long term effects of PPIs and H2RAs treatment in the prevention of GI bleeding or ulcer formation in patients on chronic LDA treatment listed up till September 30, 2016. Two independent authors searched databases using PICO questions (aspirin, H2RA, PPI, GI bleeding or ulcer), and reviewed abstracts and articles for comprehensive studies keeping adequate study quality. Data of weighted odds ratios were statistically evaluated using Comprehensive Metaanalysis (Biostat, Inc., Engelwood, MJ, USA), potential bias was checked.Results: Nine studies for GI bleeding and eight studies for ulcer formation were found meeting inclusion criteria, altogether 1,879 patients were included into review. The H2RAs prevented less effectively LDA-related GI bleeding (OR= 2.102, 95% CI: 1.008-4.385, p<0.048) and ulcer formation (OR= 2.257, 95% CI: 1.277-3.989, p<0.005) than PPIs.Conclusion: The meta-analysis showed that H2RAs were less effective in the prevention of LDA-related GI bleeding and ulcer formation suggesting the preferable usage of PPIs in case of tolerance.Abbreviations: COX -1: cyclooxygenase-I enzyme; COX-2: cyclooxygenase-II enzyme; GI: gastrointestinal; H2RA(s): histamine-2 receptor antagonist(s); H. pylori: Helicobacter pylori; LDA: low dose aspirin; NSAID(s): non-steroid anti-inflammatory drug(s); OR: Odds ratio; PPI(s): proton-pump inhibitor(s); RCT: randomized controlled trial; RR: relative risk; UGIB: upper gastrointestinal bleeding.

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Section: Discussionmentioning

confidence: 99%

PPIs Prevent Aspirin-Induced Gastrointestinal Bleeding Better than H2RAs. A Systematic Review and Meta-analysis

Szabó¹,

Mátics

Hegyi

et al. 2017

JGLD

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“…In 161 hospitalized patients, after controlling for confounders, the odds ratio of confirmed drug hypersensitivity was 4.35 (95% CI 2.0-9.45) in those receiving a proton pump inhibitor compared with matched controls. A personal history of drug allergy and a long hospitalization time were also significant risk factors [34]. …”

Section: Triggers and Mechanismsmentioning

confidence: 99%

World Allergy Organization Anaphylaxis Guidelines: 2013 Update of the Evidence Base

Simons

Ardusso

Dimov

et al. 2013

Int Arch Allergy Immunol

247

181

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The World Allergy Organization (WAO) Guidelines for the assessment and management of anaphylaxis are a widely disseminated and used resource for information about anaphylaxis. They focus on patients at risk, triggers, clinical diagnosis, treatment in health care settings, self-treatment in the community, and prevention of recurrences. Their unique strengths include a global perspective informed by prior research on the global availability of essentials for anaphylaxis assessment and management and a global agenda for anaphylaxis research. Additionally, detailed colored illustrations are linked to key concepts in the text [Simons et al.: J Allergy Clin Immunol 2011;127:593.e1-e22]. The recommendations in the original WAO Anaphylaxis Guidelines for management of anaphylaxis in health care settings and community settings were based on evidence published in peer-reviewed, indexed medical journals to the end of 2010. These recommendations remain unchanged and clinically relevant. An update of the evidence base was published in 2012 [Simons et al.: Curr Opin Allergy Clin Immunol 2012;12:389-399]. In 2012 and early 2013, major advances were reported in the following areas: further characterization of patient phenotypes; development of in vitro tests (for some allergens) that help distinguish clinical risk of anaphylaxis from asymptomatic sensitization; epinephrine (adrenaline) research, including studies of a new epinephrine auto-injector for use in community settings, and randomized controlled trials of immunotherapy to prevent food-induced anaphylaxis. Despite these advances, the need for additional prospective studies, including randomized controlled trials of interventions in anaphylaxis is increasingly apparent. This 2013 Update highlights publications from 2012 and 2013 that further contribute to the evidence base for the recommendations made in the original WAO Anaphylaxis Guidelines. Ideally, it should be used in conjunction with these Guidelines and with the 2012 Guidelines Update.

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“…Some studies which evaluated the risk factors for severe reactions in drug-induced anaphylaxis reported that comorbidities involving chronic lung diseases or cardiac diseases and drugs used simultaneously such as β-blockers, ACEI/ARBs, or PPIs increased the risk of severe anaphylaxis, but others did not observe such a relationship [39, 55, 56]. We observed that anaphylaxis was more common in hypersensitive patients and the patients who used ACEI/ARBs in the univariate analysis.…”

Section: Discussionmentioning

confidence: 51%

Evaluation of the Potential Risk Factors for Drug-Induced Anaphylaxis in Adult Patients

Demir¹,

Erdenen²,

Gelincik

et al. 2018

Int Arch Allergy Immunol

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Aim: To investigate the potential risk factors in patients who have experienced anaphylaxis from drugs. Method: The study included 281 adult patients (median age 40 years; 76.5% female) who experienced immediate types of hypersensitivity reaction to a drug. The patients were divided into an anaphylaxis group and a nonanaphylaxis group. The anaphylaxis group was diagnosed according to the criteria of the World Allergy Organization. Skin testing with culprit drugs was performed. In the nonanaphylaxis group, drug provocation tests were performed with culprit drugs, including aspirin or diclofenac, to determine nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Atopy was determined by skin prick tests with the common inhalant allergens. Patients’ demographics, clinical features, and baseline tryptase and total IgE levels were compared between the 2 groups. Results: The median interval between the last reaction in the patient’s history and the study evaluation was 7 months (range 1–120 months). In 52.3% of the patients, reactions were defined as anaphylaxis. The most common culprit drugs were NSAIDs (56.9%) and β-lactams (34.7%). The culprit drugs were used parenterally in 13.2% of the patients. 34.9% of the patients had comorbid diseases and 24.6% used additional drugs, the most common being antihypertensives (10%). Atopy was determined in 28.8% and 28.1% of the patients were smokers. The median serum level of baseline tryptase and total IgE was 3.5 µg/L and 77 kU/L, respectively. In 46.3% of the patients, skin tests with culprit drugs were positive and the positivity ratio was higher in the anaphylaxis group (p = 0.002). Anapyhlaxis was more common in patients who were: hypertensive, atopic, using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and received the culprit drug parenterally (p = 0.034, p = 0.04, p = 0.03, p = 0.035, p = 0.013, and p < 0.001). In the multivariate analysis, it was observed that the parenteral usage of the drug and the presence of atopy were significantly higher in the anaphylaxis group (p < 0.001, odds ratio [OR] = 20.05, confidence interval [CI] 4.75–88.64; p = 0.012, OR = 2.1, CI 1.17–3.74). Age, smoking, family history, and serum levels of baseline tryptase and total IgE did not differ between groups. Conclusion: The parenteral route and atopy increase the risk of drug-induced anaphylaxis. IgE-mediated sensitivity to the culprit drug seems to facilitate anaphylaxis.

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Proton pump inhibitors are associated with hypersensitivity reactions to drugs in hospitalized patients: a nested case‐control in a retrospective cohort study

Abstract: In hospitalized patients, the use of proton pump inhibitors was associated with a significant increase risk of drug hypersensitivity reactions along with a personal history of drug allergies and long hospitalization time.

Cited by 37 publications

References 51 publications

PPIs Prevent Aspirin-Induced Gastrointestinal Bleeding Better than H2RAs. A Systematic Review and Meta-analysis

PPIs Prevent Aspirin-Induced Gastrointestinal Bleeding Better than H2RAs. A Systematic Review and Meta-analysis

World Allergy Organization Anaphylaxis Guidelines: 2013 Update of the Evidence Base

Evaluation of the Potential Risk Factors for Drug-Induced Anaphylaxis in Adult Patients

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