title: Proton pump inhibitors in rheumatic diseases: clinical practice, drug interactions, bone fractures and risk of infections.
abstract: Platelet activation and aggregation are key elements of the pathogenesis of acute coronary syndromes, of endothelial damage in chronic inflammatory and connective tissue disease (i.e. systemic sclerosis-SSc). Patients affected by chronic inflammatory diseases as well as by connective tissue diseases such as systemic sclerosis, often have the need to take anti-platelet therapy (e.g. ASA or clopidogrel). Current consensus recommendations state that patients prescribed clopidogrel plus aspirin should receive a proton pump inhibitor (PPI) to reduce gastrointestinal bleeding. Although each single PPI has similar efficacy in many cases, differences between them should be considered when choosing a treatment regimen. Many studies show PPI and clopidogrel drug interaction, with clopidogrel non-responsiveness in about 25% of the population. Only pantoprazole, which does not inhibit CYP P450 2C19, doesn't seem to have interaction with clopidogrel or other drugs. Patients affected by systemic sclerosis have high frequency of oesophageal mucosal abnormalities and should take long-term PPI therapy. When addressing long-term therapy safety data are clearly needed. Two recent studies have reported increased hip fracture rates with long-term PPI use, raising concerns about adverse effects of this class of drugs on mineral metabolism. The use of PPIs is also associated with an increase in the risk of development of Clostridium difficile infection (CDI) and the use of PPIs during CDI treatment is associated with an increased risk of recurrence. In order to achieve the desired results and, as with all medications, PPIs should always be used appropriately taking care never to exceed correct dosage and duration. When necessary use of pantoprazole arises as one of the best possible choices.
authors.affiliation: Division of Rheumatology, School of Medicine, Catholic University of the Sacred Heart, CIC, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Laria
authors.forename: A
authors.initials: A
authors.lastname: Zoli
authors.forename: E
authors.initials: E
authors.lastname: Gremese
authors.forename: G F
authors.initials: GF
authors.lastname: Ferraccioli
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002136:Calcium, Dietary / Q000493:pharmacokinetics; D000077144:Clopidogrel; D016360:Clostridioides difficile; D015897:Comorbidity; D065731:Cytochrome P-450 CYP2C19; D004198:Disease Susceptibility; D004347:Drug Interactions; D004761:Enterocolitis, Pseudomembranous / Q000453:epidemiology / Q000209:etiology; D005598:Fractures, Spontaneous / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000150:complications; D007239:Infections / Q000453:epidemiology; D010024:Osteoporosis / Q000150:complications; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012216:Rheumatic Diseases / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D012306:Risk; D019851:Thrombophilia / Q000150:complications / Q000188:drug therapy; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics
chemical_list: D000925:Anticoagulants; D002136:Calcium, Dietary; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine; D001241:Aspirin