Adverse drug reactions with oral anticoagulants: data from sicilian spontaneous reporting system database.
Adverse Drug Reaction Reporting Systems
/ statistics & numerical data
Anticoagulants
/ adverse effects
Drug Interactions
Factor Xa Inhibitors
/ adverse effects
Gastrointestinal Diseases
/ chemically induced
Gastrointestinal Hemorrhage
/ chemically induced
Humans
Intracranial Hemorrhages
/ chemically induced
Italy
Vitamin K
/ antagonists & inhibitors
adverse drug reaction
direct oral anticoagulant
pharmacovigilance
spontaneous reporting
vitamin K antagonist
Journal
Journal of clinical pharmacy and therapeutics
ISSN: 1365-2710
Titre abrégé: J Clin Pharm Ther
Pays: England
ID NLM: 8704308
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
revised:
07
01
2021
received:
11
06
2020
accepted:
09
02
2021
pubmed:
2
3
2021
medline:
15
12
2021
entrez:
1
3
2021
Statut:
ppublish
Résumé
Direct oral anticoagulants (DOACs) were developed to avoid the limitations of vitamin K antagonists (VKAs). DOACs are associated with a greater incidence of gastrointestinal bleeding and a smaller number of intracranial haemorrhages than VKAs. Therefore, it is important to deepen our knowledge of their safety profiles. The aim of this study was thus to analyse adverse drug reaction (ADR) reports on DOACs and VKAs using the Sicilian Spontaneous Reporting System (SRS) database. All ADR reports with DOACs and VKAs as suspected drugs that were entered into the Sicilian SRS database during the period 2001-2019 were selected. In detail, all reports with the following single active substances were included: dabigatran etexilate, rivaroxaban, apixaban and edoxaban; acenocoumarol and warfarin were included as a comparator group. Descriptive statistical methodology was used to evaluate characteristics of the reported cases with a case-by-case assessment. Out of 521 reports related to anticoagulants, 444 (85.2%) and 77 (14.8%) involved DOACs and VKAs, respectively. DOAC-related reports were mainly of gastrointestinal disorders. In contrast, VKAs were mostly associated with blood and lymphatic system disorders, injury, investigations and vascular disorders. Many more cases of ADRs in the form of gastrointestinal disorders concerned dabigatran etexilate (n = 179, 73.7%) than the other DOACs, while ADRs in the form of blood disorders were mainly associated with acenocoumarol (n = 27, 57.4%). The most commonly reported Preferred Terms for DOACs were dyspepsia (n = 89, 17.1%), upper abdominal pain (n = 41, 9.2%) and pruritus (n = 26, 5.8%), whereas for VKAs, they were anaemia (n = 21, 27.3%) and hypocoagulable state (n = 18, 3.5%). Potentially interacting concomitant medications particularly included antithrombotic agents (n = 19, 4.3%) for DOACs and proton-pump inhibitors (PPIs) (n = 37, 48.1%) and antithrombotic agents (n = 13, 16.9%) for VKAs. The ADRs most commonly associated with DOACs, especially dabigatran, were gastrointestinal disorders, particularly gastrointestinal bleeding. Our study also highlights the potential role of drug-drug interactions in the ADRs. The cases of gastrointestinal bleeding highlight the need for careful prescribing of DOACs and use of potentially interacting concomitant drugs.
Substances chimiques
Anticoagulants
0
Factor Xa Inhibitors
0
Vitamin K
12001-79-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1027-1040Informations de copyright
© 2021 John Wiley & Sons Ltd.
Références
Monaco L, Biagi C, Conti V, et al. Safety profile of the direct oral anticoagulants: an analysis of the WHO database of adverse drug reactions. Br J Clin Pharmacol. 2017;83(7):1532-1543. https://doi.org/10.1111/bcp.13234
Raj G, Kumar R, Paul MW. Long-term oral anticoagulant therapy: update on indications, therapeutic ranges, and monitoring. Am J Med Sci. 1994;307(2):128-132. https://doi.org/10.1097/00000441-199402000-00011
Mekaj YH, Mekaj AY, Duci SB, Miftari EI. New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events. Ther Clin Risk Manag. 2015;11:967-977. https://doi.org/10.2147/TCRM.S84210
Spina E, Barbieri MA, Cicala G, Bruno A, de Leon J. Clinically relevant drug interactions between newer antidepressants and oral anticoagulants. Expert Opin Drug Metab Toxicol. 2020;16(1):31-44. https://doi.org/10.1080/17425255.2020.1700952
Trailokya A, Hiremath JS, Sawhney JPS, et al. Acenocoumarol: a review of anticoagulant efficacy and safety. J Assoc Physicians India. 2016;64(FEBRUARY):88-93.
Gallagher AM, Rietbrock S, Plumb J, Van Staa TP. Initiation and persistence of warfarin or aspirin in patients with chronic atrial fibrillation in general practice: do the appropriate patients receive stroke prophylaxis? J Thromb Haemost. 2008;6(9):1500-1506. https://doi.org/10.1111/j.1538-7836.2008.03059.x
Morgan CL, McEwan P, Tukiendorf A, Robinson PA, Clemens A, Plumb JM. Warfarin treatment in patients with atrial fibrillation: observing outcomes associated with varying levels of INR control. Thromb Res. 2009;124(1):37-41. https://doi.org/10.1016/j.thromres.2008.09.016
Buller H, Prins M, Lensin A. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287-1297. https://doi.org/10.1056/NEJMoa1113572
Pirlog AM, Pirlog CD, Maghiar MA. DOACS vs vitamin K antagonists: a comparison of phase III clinical trials and a prescriber support tool. Open Access Maced J Med Sci. 2019;7(7):1226-1232. https://doi.org/10.3889/oamjms.2019.289
Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093-2104. https://doi.org/10.1056/NEJMoa1310907
Haas S, ten Cate H, Accetta G, et al. Quality of vitamin K antagonist control and 1-year outcomes in patients with atrial fibrillation: a global perspective from the GARFIELD-AF Registry. PLoS One. 2016;11(10):e0164076. https://doi.org/10.1371/journal.pone.0164076
Xian Y, Xu H, O’Brien EC, et al. Clinical effectiveness of direct oral anticoagulants vs warfarin in older patients with atrial fibrillation and ischemic stroke. JAMA Neurol. 2019;76(10):1192. https://doi.org/10.1001/jamaneurol.2019.2099
Andò G, Capranzano P. Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with chronic kidney disease: a systematic review and network meta-analysis. Int J Cardiol. 2017;231:162-169. https://doi.org/10.1016/j.ijcard.2016.11.303
SPREAD - Stroke Prevention and Educational Awareness Diffusion. Ictus cerebrale: Linee guida italiane di prevenzione e trattamento. 2016. https://www.iso-stroke.it/wp-content/uploads/2017/02/LIBRO-SPREAD-VIII-ED-13-09-16.pdf
Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2019;00:1-61. https://doi.org/10.1093/eurheartj/ehz405
Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-2962. https://doi.org/10.1093/eurheartj/ehw210
Rong F, Jia B, Huang P, Lynn HS, Zhang W. Safety of the direct-acting anticoagulants in patients with atrial fibrillation: a meta-analysis. Thromb Res. 2015;135(6):1117-1123. https://doi.org/10.1016/j.thromres.2015.04.004.
Saraf K, Morris P, Garg P, Sheridan P, Storey R. Non-vitamin K antagonist oral anticoagulants (NOACs): clinical evidence and therapeutic considerations. Postgrad Med J. 2014;90(1067):520-528. https://doi.org/10.1136/postgradmedj-2014-132605.
Southworth MR, Reichman ME, Unger EF. Dabigatran and postmarketing reports of bleeding. N Engl J Med. 2013;368(14):1272-1274. https://doi.org/10.1056/NEJMp1302834
Chatterjee S, Sardar P, Biondi-Zoccai G, Kumbhani DJ. New oral anticoagulants and the risk of intracranial hemorrhage: Traditional and Bayesian meta-analysis and mixed treatment comparison of randomized trials of new oral anticoagulants in atrial fibrillation. JAMA Neurol. 2013;70(12):1486-1490. https://doi.org/10.1001/jamaneurol.2013.4021
Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962. https://doi.org/10.1016/S0140-6736(13)62343-0
Yao X, Abraham NS, Caleb Alexander G, et al. Effect of adherence to oral anticoagulants on risk of stroke and major bleeding among patients with atrial fibrillation. J Am Heart Assoc. 2016;5(2):e003074. https://doi.org/10.1161/JAHA.115.003074
Desai J, Granger CB, Weitz JI, Aisenberg J. Novel oral anticoagulants in gastroenterology practice. Gastrointest Endosc. 2013;78(2):227-239. https://doi.org/10.1016/j.gie.2013.04.179
Ho MH, Ho CW, Cheung E, et al. Continuation of Dabigatran therapy in “Real-World” practice in Hong Kong. PLoS One. 2014;9(8):e101245. https://doi.org/10.1371/journal.pone.0101245
Staerk L, Gislason GH, Lip GYH, et al. Risk of gastrointestinal adverse effects of dabigatran compared with warfarin among patients with atrial fibrillation: a nationwide cohort study. Europace. 2015;17(8):1215-1222. https://doi.org/10.1093/europace/euv119
Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-1151. https://doi.org/10.1056/NEJMoa0905561
Raschi E, Poluzzi E, Koci A, et al. Liver injury with novel oral anticoagulants: assessing post-marketing reports in the US Food and Drug Administration adverse event reporting system. Br J Clin Pharmacol. 2015;80(2):285-293. https://doi.org/10.1111/bcp.12611
Liakoni E, Rätz Bravo AE, Krähenbühl S. Hepatotoxicity of New Oral Anticoagulants (NOACs). Drug Saf. 2015;38(8):711-720. https://doi.org/10.1007/s40264-015-0317-5
Strom BL, Kimmel SE, Hennessy S. Pharmacoepidemiology. Postmarketing Spontaneous Pharmacovigilance Reporting Systems, Fifth Edition. 2012:135-157. https://doi.org/10.1002/9781119959946
Noguchi Y, Tachi T, Teramachi H. Review of statistical methodologies for detecting drug-drug interactions using spontaneous reporting systems. Front Pharmacol. 2019;10(1319):1-13. https://doi.org/10.3389/fphar.2019.01319
Osservatorio Nazionale sull’impiego dei Medicinali. L’uso dei farmaci in Italia. Rapporto Nazionale Anno 2018. Roma: Agenzia Italiana del Farmaco. 2019.
Sessa M, Mascolo A, Callréus T, Capuano A, Rossi F, Andersen M. Direct-acting oral anticoagulants (DOACs) in pregnancy: new insight from VigiBase®. Sci Rep. 2019;9(1):7236. https://doi.org/10.1038/s41598-019-43715-4
Mascolo A, Ruggiero R, Sessa M, et al. Preventable cases of oral anticoagulant-induced bleeding: data from the spontaneous reporting system. Front Pharmacol. 2019;10:425. https://doi.org/10.3389/fphar.2019.00425
Mcdonald CJ, Kalisch Ellett LM, Barratt JD, Caughey GE. An international comparison of spontaneous adverse event reports and potentially inappropriate medicine use associated with dabigatran. Pharmacoepidemiol Drug Saf. 2015;24(4):399-405. https://doi.org/10.1002/pds.3648
Caughey GE, Kalisch Ellett LM, Barratt JD, Shakib S. Apixaban, concomitant medicines and spontaneous reports of haemorrhagic events. Ther Adv Drug Saf. 2017;8(5):157-164. https://doi.org/10.1177/2042098616689771
World Health Organization. VigiBase. https://www.who-umc.org/vigibase/vigibase/
Eudravigilance. European database of suspected adverse drug reaction reports. http://www.adrreports.eu/it/eudravigilance.html
European Medicines Agency. EudraVigilance System Overview. https://www.ema.europa.eu/en/human-regulatory/researchdevelopment/pharmacovigilance/eudravigilance/eudravigilance-system-overview. Published. 2020.
European Medicines Agency. Guideline on good pharmacovigilance practices (GVP) Annex I-Definitions (Rev 4). Heads of Medicine Agencies. EMA/876333/2011 Rev 4*. 2017. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-good-pharmacovigilance-practices-annex-i-definitions-rev-4_en.pdf
Brown EG, Wood L, Wood S. The Medical Dictionary for Regulatory Activities (MedDRA). Drug Saf. 1999;20(2):109-117. https://doi.org/10.2165/00002018-199920020-00002
WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment 2021. Oslo, Norway, 20. https://www.whocc.no/filearchive/publications/2021_guidelines_web.pdf
Oteri A, Minore C, La Cavera C, Cananzi P. Trend d’uso dei Nuovi Anti Coagulanti Orali in Sicilia negli anni 2013 - 2018. Analisi di farmacoutilizzazione e farmacovigilanza.
Agenzia Italiana del Farmaco. Banca Dati Farmaci dell'AIFA. https://farmaci.agenziafarmaco.gov.it/bancadatifarmaci/home
European Medicines Agency. Human medicines. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/landing/epar_search.jsp&mid=WC0b01ac058001d124
IBM Micromedex Web Applications Access. https://www.micromedexsolutions.com/home/dispatch
Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239-245. https://doi.org/10.1038/clpt.1981.154
Horn JR, Hansten PD, Chan LN. Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother. 2007;41(4):674-680. https://doi.org/10.1345/aph.1H423
Osservatorio Nazionale sull’impiego dei Medicinali. L’uso dei farmaci in Italia. Report regionali sul consumo dei farmaci in Italia - anno 2017. Regione Sicilia. Roma: Agenzia Italiana del Farmaco. 2018.
Giardina C, Cutroneo PM, Mocciaro E, et al. Adverse drug reactions in hospitalized patients: Results of the FORWARD (facilitation of reporting in hospital ward) study. Front Pharmacol. 2018;9(350):1-12. https://doi.org/10.3389/fphar.2018.00350
Routledge PA, O’Mahony MS, Woodhouse KW. Adverse drug reactions in elderly patients. Br J Clin Pharmacol. 2003;57(2):121-126. https://doi.org/10.1046/j.1365-2125.2003.01875.x
Charlton B, Adeboyeje G, Barron JJ, Grady D, Shin J, Redberg RF. Length of hospitalization and mortality for bleeding during treatment with warfarin, dabigatran, or rivaroxaban. PLoS One. 2018;13(3):e0193912. https://doi.org/10.1371/journal.pone.0193912
The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Realworld evidence from GARFIELD-AF shows superior reduction in mortality with Non-vitamin K Antagonists Oral Anticoagulants (NOACs) vs. Vitamin K Antagonists (VKAs) in newly diagnosed atrial fibrillation. ESC Congress 2018, Munich, Germany, 28 August 2018.
Larsen TB, Skjøth F, Nielsen PB, Kjaeldgaard JN, Lip GYH. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ. 2016:i3189. https://doi.org/10.1136/bmj.i3189
Vinogradova Y, Coupland C, Hill T, Hippisley-Cox J. Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care. BMJ. 2018:k2505. https://doi.org/10.1136/bmj.k2505
Hernandez I, Zhang Y, Saba S. Comparison of the effectiveness and safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in newly diagnosed Atrial Fibrillation. Am J Cardiol. 2017;120(10):1813-1819. https://doi.org/10.1016/j.amjcard.2017.07.092
Lavalle C, Lullo LD, Bellasi A, et al. Adverse drug reactions during real-life use of direct oral anticoagulants in italy: an update based on data from the italian national pharmacovigilance network. Cardiorenal Med. 2020;10(4):1-11. https://doi.org/10.1159/000507046
Ferri N, Corsini A. Nuovi anticoagulanti orali: considerazioni di farmacologia clinica. G Ital Cardiol. 2015;16(11 Suppl. 1):3S-16S.
Kim I-S, Kim H-J, Kim T-H, et al. Non-vitamin K antagonist oral anticoagulants have better efficacy and equivalent safety compared to warfarin in elderly patients with atrial fibrillation: A systematic review and meta-analysis. J Cardiol. 2018;72(2):105-112. https://doi.org/10.1016/j.jjcc.2018.01.015
Uguccioni M, Terranova A, Di Lullo L. Valutazione delle reazioni avverse agli anticoagulanti orali dirette registrate nella Rete Nazionale di Farmacovigilanza mediante uno specifico indice di rischio. G Ital Cardiol. 2018;19(10 suppl 1):3s-11s. https://doi.org/10.1714/2984.29850
Ntaios G, Papavasileiou V, Makaritsis K, Vemmos K, Michel P, Lip GYH. Real-World setting comparison of nonvitamin-K antagonist oral anticoagulants versus Vitamin-K antagonists for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke. 2017;48(9):2494-2503. https://doi.org/10.1161/STROKEAHA.117.017549
Hosohata K, Oyama S, Niinomi I, Wakabayashi T, Inada A, Iwanaga K. Comparison of safety profiles of new oral anticoagulants with warfarin using the japanese spontaneous reporting database. Clin Drug Investig. 2019;39(7):665-670. https://doi.org/10.1007/s40261-019-00788-3
Caldeira D, Barra M, Ferreira A, et al. Systematic review with meta-analysis: the risk of major gastrointestinal bleeding with non-vitamin K antagonist oral anticoagulants. Aliment Pharmacol Ther. 2015;42(11-12):1239-1249. https://doi.org/10.1111/apt.13412
Caldeira D, Rodrigues R, Abreu D, Anes AM, Rosa MM, Ferreira JJ. Suspected adverse drug reaction reports with oral anticoagulants in Portugal: a pharmacovigilance study. Expert Opin Drug Saf. 2018;17(4):339-345. https://doi.org/10.1080/14740338.2018.1439474
Kolb JM, Flack KF, Chatterjee-Murphy P, et al. Locations and mucosal lesions responsible for major gastrointestinal bleeding in patients on warfarin or dabigatran. Dig Dis Sci. 2018;63(7):1878-1889. https://doi.org/10.1007/s10620-018-5007-6
Schulman S, Shortt B, Robinson M, Eikelboom JW. Adherence to anticoagulant treatment with dabigatran in a real-world setting. J Thromb Haemost. 2013;11(7):1295-1299. https://doi.org/10.1111/jth.12241
Arepally GM, Ortel TL. Changing Practice of Anticoagulation: Will Target-Specific Anticoagulants Replace Warfarin? Annu Rev Med. 2015;66(1):241-253. https://doi.org/10.1146/annurev-med-051113-024633
Lip GYH. Stroke prevention in AF. Nat Rev Cardiol. 2012;9(2):71-73. https://doi.org/10.1038/nrcardio.2011.203
Bernát SI, Rókusz L. The efficacy and safety of acenocoumarol and warfarin therapy in patients with lower limb deep vein thrombosis. Orv Hetil. 2012;153(20):786-790. https://doi.org/10.1556/OH.2012.29350
Anthony CJ, Karim S, Ackroyd-Stolarz S, et al. Intensity of anticoagulation with warfarin and risk of adverse events in patients presenting to the emergency department. Ann Pharmacother. 2011;45(7-8):881-887. https://doi.org/10.1345/aph.1P670
Budnitz DS, Shehab N, Kegler SR, Richards CL. Medication use leading to emergency department visits for adverse drug events in older adults. Ann Intern Med. 2007;147(11):755. https://doi.org/10.7326/0003-4819-147-11-200712040-00006
To K, Reynolds C, Spinler SA. Rash associated with dabigatran etexilate. Pharmacother J Hum Pharmacol Drug Ther. 2013;33(3):e23-e27. https://doi.org/10.1002/phar.1203
Whitehead H, Boyd JM, Blais DM, Hummel J. Drug-induced exanthem following dabigatran. Ann Pharmacother. 2011;45(10):1306. https://doi.org/10.1345/aph.1Q317
Eid TJ, Shah SA. Dabigatran-induced rash. Am J Heal Pharm. 2011;68(16):1489-1490. https://doi.org/10.2146/ajhp110088
Vranckx P, Valgimigli M, Heidbuchel H. The significance of drug-drug and drug-food interactions of oral anticoagulation. Arrhythmia Electrophysiol Rev. 2018;7(1):55-61. https://doi.org/10.15420/aer.2017.50.1
Harskamp RE, Teichert M, Lucassen WAM, van Weert HCPM, Lopes RD. Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-modulating drugs on safety and efficacy of oral anticoagulation therapy in patients with atrial fibrillation. Cardiovasc Drugs Ther. 2019;33:615-623. https://doi.org/10.1007/s10557-019-06907-8
Lee JY, Oh I-Y, Lee J-H, et al. The increased risk of bleeding due to drug-drug interactions in patients administered direct oral anticoagulants. Thromb Res. 2020;195(April):243-249. https://doi.org/10.1016/j.thromres.2020.07.054
Kumar S, Danik SB, Altman RK, et al. Non-Vitamin K antagonist oral anticoagulants and antiplatelet therapy for stroke prevention in patients with atrial fibrillation: a meta-analysis of randomized controlled trials. Cardiol Rev. 2016;24(5):218-223. https://doi.org/10.1097/CRD.0000000000000088
Zhang Y, Souverein PC, Gardarsdottir H, van den Ham HA, Maitland-van der Zee AH, de Boer A. Risk of major bleeding among users of direct oral anticoagulants combined with interacting drugs: A population-based nested case-control study. Br J Clin Pharmacol. 2020;86(6):1150-1164. https://doi.org/10.1111/bcp.14227
Fernandez S, Lenoir C, Samer C, Rollason V. Drug interactions with apixaban: A systematic review of the literature and an analysis of VigiBase, the World Health Organization database of spontaneous safety reports. Pharmacol Res Perspect. 2020;8(5):1-11. https://doi.org/10.1002/prp2.647
Valeriani E, Porreca E, Weitz JI, Schulman S, Candeloro M, Di Nisio M. Impact of concomitant antiplatelet therapy on the efficacy and safety of direct oral anticoagulants for acute venous thromboembolism: Systematic review and meta-analysis. J Thromb Haemost. 2020;18(7):1661-1671. https://doi.org/10.1111/jth.14807
Bertram V, Yeo K, Anoopkumar-Dukie S, Bernaitis N. Proton pump inhibitors co-prescribed with warfarin reduce warfarin control as measured by time in therapeutic range. Int J Clin Pract. 2019;73(11):e13382. https://doi.org/10.1111/ijcp.13382
Teichert M, van Noord C, Uitterlinden AG, et al. Proton pump inhibitors and the risk of overanticoagulation during acenocoumarol maintenance treatment. Br J Haematol. 2011;153(3):379-385. https://doi.org/10.1111/j.1365-2141.2011.08633.x
AIFA. Pradaxa®, Riassunto delle Caratteristiche del Prodotto. 2020. https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_000092_038451_RCP.pdf&retry=0&sys=m0b1l3. Published 2020.
Stangier J, Stähle H, Rathgen K, Fuhr R. Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin Pharmacokinet. 2008;47:47-59. https://doi.org/10.2165/00003088-200847010-00005
Ollier E, Hodin S, Basset T, et al. In vitro and in vivo evaluation of drug-drug interaction between dabigatran and proton pump inhibitors. Fundam Clin Pharmacol. 2015;29:604-614. https://doi.org/10.1111/fcp.12154
Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2020;00:1-125. https://doi.org/10.1093/eurheartj/ehaa612
Dalton SO, Sørensen HT, Johansen C. SSRIs and upper gastrointestinal bleeding: What is known and how should it influence prescribing? CNS Drugs. 2006;20:143-151. https://doi.org/10.2165/00023210-200620020-00005
De Abajo FJ, Montero D, García Rodríguez LA, Madurga M. Antidepressants and risk of upper gastrointestinal bleeding. Basic Clin Pharmacol Toxicol. 2006;98:304-310. https://doi.org/10.1111/j.1742-7843.2006.pto_303.x
Agenzia Italiana del Farmaco. Riassunto delle caratteristiche del prodotto Eliquis. https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_003646_041225_RCP.pdf&retry=0&sys=m0b1l3
Sheikh Rezaei S, Mittlböck M, Reichardt B, Wolzt M. SSRI co-medication with NOAC or VKA does not increase hospitalisation for bleeding: a retrospective nationwide cohort study in Austria 2010-2015. Int J Geriatr Psychiatry. 2019;34(8):1194-1199. https://doi.org/10.1002/gps.5117
Tielleman T, Bujanda D, Cryer B. Epidemiology and risk factors for upper gastrointestinal bleeding. Gastrointest Endosc Clin N Am. 2015;25(3):415-428. https://doi.org/10.1016/j.giec.2015.02.010
Schjerning Olsen A-M, McGettigan P, Gerds TA, et al. Risk of gastrointestinal bleeding associated with oral anticoagulation and non-steroidal anti-inflammatory drugs in patients with atrial fibrillation: a nationwide study. Eur Hear J - Cardiovasc Pharmacother. 2020;6(5):292-300. https://doi.org/10.1093/ehjcvp/pvz069
Agenzia Italiana del Farmaco. ESKIM®, Riassunto delle Caratteristiche del Prodotto. Published 2020. https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_004375_027618_RCP.pdf&retry=0&sys=m0b1l3
Forbes HL, Polasek TM. Potential drug-drug interactions with direct oral anticoagulants in elderly hospitalized patients. Ther Adv Drug Saf. 2017;8(10):319-328. https://doi.org/10.1177/2042098617719815
Gumbrevičius G, Damulevičienė G, Gumbrevičiūtė M, Galaunė V. Possible interaction between dabigatran and ranolazine in patients with renal failure. Med. 2020;56(1):13. https://doi.org/10.3390/medicina56010013
Antoniou T, Macdonald EM, Yao Z, et al. Association between statin use and ischemic stroke or major hemorrhage in patients taking dabigatran for atrial fibrillation. CMAJ. 2017;189(1):E4-E10. https://doi.org/10.1503/cmaj.160303
Lupercio F, Romero J, Peltzer B, et al. Efficacy and safety outcomes of direct oral anticoagulants and amiodarone in patients with atrial fibrillation. Am J Med. 2018;131(5):573.e1-573.e8. https://doi.org/10.1016/j.amjmed.2017.11.047
Steffel J, Giugliano RP, Braunwald E, et al. Edoxaban vs. warfarin in patients with atrial fibrillation on amiodarone: A subgroup analysis of the ENGAGE AF-TIMI 48 trial. Eur Heart J. 2015;36:2239-2245. https://doi.org/10.1093/eurheartj/ehv201
Agenzia Italiana del Farmaco. Xarelto®, Riassunto delle Caratteristiche del Prodotto. Published 2020. https://ec.europa.eu/health/documents/community-register/2018/20180702141274/anx_141274_it.pdf
Bellesini M, Bianchin M, Corradi C, Donadini MP, Raschi E, Squizzato A. Drug-drug interactions between direct oral anticoagulants and hepatitis c direct-acting antiviral agents: looking for evidence through a systematic review. Clin Drug Investig. 2020;40(11):1001-1008. https://doi.org/10.1007/s40261-020-00962-y
Barbieri MA, Cicala G, Cutroneo PM, et al. Ototoxic Adverse Drug Reactions: A Disproportionality Analysis Using the Italian Spontaneous Reporting Database. Front Pharmacol. 2019;10:1161. https://doi.org/10.3389/fphar.2019.01161
Motola D, Vargiu A, Leone R, et al. Influence of regulatory measures on the rate of spontaneous adverse drug reaction reporting in Italy. Drug Saf. 2008;31(7):609-616. https://doi.org/10.2165/00002018-200831070-00006
Russo E, Palleria C, Leporini C, et al. Limitations and obstacles of the spontaneous adverse drugs reactions reporting: two “challenging” case reports. J Pharmacol Pharmacother. 2013;4(5):66-72. https://doi.org/10.4103/0976-500X.120955
Pillans PI. Clinical perspectives in drug safety and adverse drug reactions. Expert Rev Clin Pharmacol. 2008;1(5):695-705. https://doi.org/10.1586/17512433.1.5.695
Bäckström M, Mjörndal T, Dahlqvist R, Nordkvist-Olsson T. Attitudes to reporting adverse drug reactions in northern Sweden. Eur J Clin Pharmacol. 2000;56(9-10):729-732. https://doi.org/10.1007/s002280000202
Mascolo A, Scavone C, Sessa M, et al. Can causality assessment fulfill the new European definition of adverse drug reaction? A review of methods used in spontaneous reporting. Pharmacol Res. 2017;123:122-129. https://doi.org/10.1016/j.phrs.2017.07.005
Thaker SJ, Sinha RS, Gogtay NJ, Thatte UM. Evaluation of inter-rater agreement between three causality assessment methods used in pharmacovigilance. J Pharmacol Pharmacother. 2016;7(1):31-33. https://doi.org/10.4103/0976-500X.179361
Marante KB. The Challenges of Adverse Drug Reaction Evaluation. J Pharmacovigil. 2018;06(03): https://doi.org/10.4172/2329-6887.1000260
Khan LM, Al-Harthi SE, Osman AMM, Sattar MAAA, Ali AS. Dilemmas of the causality assessment tools in the diagnosis of adverse drug reactions. Saudi Pharm J. 2016;24(4):485-493. https://doi.org/10.1016/j.jsps.2015.01.010