Warfarin-drug interactions: An emphasis on influence of polypharmacy and high doses of amoxicillin/clavulanate

Abdel‐Aziz, Mahmoud I.; Ali, Mostafa A. Sayed; Abolghasemi, Hassan; El-Faham, T. H.

doi:10.1002/jcph.583

Cited by 15 publications

(7 citation statements)

References 28 publications

(67 reference statements)

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“…In a prospective study of 120 patients who received a combination of amoxicillin/clavulanate, patients who received the higher maintenance dose (10–12 g/day) versus the usual dose (3.6 g/day) developed a higher proportion of INR values ≥4. 31…”

Section: Vitamin K Antagonist: Warfarinmentioning

confidence: 99%

Drug Interactions Affecting Oral Anticoagulant Use

Mar

Gopinathannair

Gengler

et al. 2022

Circ: Arrhythmia and Electrophysiology

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Oral anticoagulants (OACs) are medications commonly used in patients with atrial fibrillation and other cardiovascular conditions. Both warfarin and direct oral anticoagulants are susceptible to drug-drug interactions (DDIs). DDIs are an important cause of adverse drug reactions and exact a large toll on the health care system. DDI for warfarin mainly involve moderate to strong inhibitors/inducers of cytochrome P450 (CYP) 2C9, which is responsible for the elimination of the more potent S-isomer of warfarin. However, inhibitor/inducers of CYP3A4 and CYP1A2 may also cause DDI with warfarin. Recognition of these precipitating agents along with increased frequency of monitoring when these agents are initiated or discontinued will minimize the impact of warfarin DDI. Direct oral anticoagulants are mainly affected by medications strongly affecting the permeability glycoprotein (P-gp), and to a lesser extent, strong CYP3A4 inhibitors/inducers. Dabigatran and edoxaban are affected by P-gp modulation. Strong inducers of CYP3A4 or P-gp should be avoided in all patients taking direct oral anticoagulant unless previously proven to be otherwise safe. Simultaneous strong CYP3A4 and P-gp inhibitors should be avoided in patients taking apixaban and rivaroxaban. Concomitant antiplatelet/anticoagulant use confers additive risk for bleeding, but their combination is unavoidable in many cases. Minimizing duration of concomitant anticoagulant/antiplatelet therapy as indicated by evidence-based clinical guidelines is the best way to reduce the risk of bleeding.

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Section: Vitamin K Antagonist: Warfarinmentioning

confidence: 99%

Drug Interactions Affecting Oral Anticoagulant Use

Mar

Gopinathannair

Gengler

et al. 2022

Circ: Arrhythmia and Electrophysiology

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“…Pasien keempat menggunakan antibiotik ampisilinsulbaktam, yang secara khusus belum pernah dilaporkan sebagai antibiotik yang meningkatkan risiko kejadian perdarahan. Meski demikian, studi sebelumnya melaporkan bahwa penggunaan penisilin, termasuk amoksisilin dan amoksisilin-klavulanat, dapat memperbesar risiko kejadian perdarahan dan peningkatan nilai INR [13,14,35]. Ampisilin dan amoksisilin merupakan antibiotik aminopenisilin yang memiliki kemiripan struktur, sifat fisika-kimia, dan farmakologi [36] sehingga tidak menutup kemungkinan memiliki efek yang mirip terhadap aktivitas antikoagulasi warfarin.…”

Section: Hasil Dan Diskusiunclassified

“…Mekanisme pasti yang terlibat dalam interaksi warfarin dan antibiotik masih menjadi perdebatan. Meskipun demikian, terdapat dugaan bahwa penghambatan sintesis vitamin K oleh bakteri normal usus menjadi salah satu mekanisme yang dapat mempengaruhi aktivitas antikoagulasi warfarin [11,17,35]. Seftriakson dieliminasi via empedu dan ditemukan dalam konsentrasi yang lebih tinggi pada usus sehingga diasumsikan akan lebih mungkin mengganggu produksi vitamin K oleh flora normal usus tersebut [17].…”

Section: Hasil Dan Diskusiunclassified

Risiko Kejadian Perdarahan Pasca Rawat Inap pada Penggunaan Bersamaan Warfarin dan Antibiotik

2021

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Penggunaan warfarin dan antibiotik bersamaan diketahui dapat meningkatkan risiko perdarahan. Kejadian perdarahan mayor terkait warfarin dapat berupa perdarahan fatal hingga menyebabkan kematian. Penelitian ini bertujuan untuk menganalisis interaksi warfarin dan antibiotik dan efeknya terhadap kejadian perdarahan pada pemeriksaan pertama pasca rawat inap di RSUD Wates. Desain studi berupa kohort retrospektif pada 67 kasus penggunaan warfarin dengan/tanpa antibiotik oleh pasien rawat inap. Data berupa diagnosis, terapi, pemeriksaan pendukung, dan kejadian perdarahan saat rawat inap hingga pemeriksaan pertama diambil dari rekam medik pasien tertanggal Januari 2018 hingga September 2020. Analisis data dilakukan secara statistika menggunakan uji Chi-square atau uji Fisher exact test dan uji independent t-test atau uji Mann Whitney U test. Terdapat perbedaan bermakna pada kejadian perdarahan dalam waktu 7 hari pasca rawat inap antara kelompok antibiotik dan kontrol (16%; 0%; p = 0.017). Antibiotik yang digunakan oleh pasien dengan kejadian perdarahan yaitu golongan sefalosporin, kuinolon, azitromisin, dan ampisilin-sulbaktam. Kejadian perdarahan yang terjadi meliputi hematemesis melena (25%), hematuria (50%), tidak diketahui (25%). Studi ini menyimpulkan bahwa penggunaan bersamaan warfarin dan antibiotik saat rawat inap dapat berpengaruh terhadap kejadian perdarahan dalam waktu 7 hari setelah pasien dipulangkan.Penggunaan warfarin dan antibiotik bersamaan diketahui dapat meningkatkan risiko perdarahan. Kejadian perdarahan mayor terkait warfarin dapat berupa perdarahan fatal hingga menyebabkan kematian. Penelitian ini bertujuan untuk menganalisis interaksi warfarin dan antibiotik dan efeknya terhadap kejadian perdarahan pada pemeriksaan pertama pasca rawat inap di RSUD Wates. Desain studi berupa kohort retrospektif [A1] [A2] pada 67 kasus penggunaan warfarin dengan/tanpa antibiotik oleh pasien rawat inap. Data berupa diagnosis, terapi, pemeriksaan pendukung, dan kejadian perdarahan saat rawat inap hingga pemeriksaan pertama diambil dari rekam medik pasien tertanggal Januari 2018 hingga September 2020. Analisis data dilakukan secara statistika menggunakan uji Chi-square atau uji Fisher exact test dan uji independent t-test atau uji Mann Whitney U test. Terdapat perbedaan bermakna pada kejadian perdarahan dalam waktu tujuh hari pasca rawat inap antara kelompok antibiotik dan kontrol (16%; 0%; p = 0.017). [A3] [A4] Antibiotik yang digunakan oleh pasien dengan kejadian perdarahan yaitu azitromisin, ampisilin-sulbaktam, golongan sefalosporin, dan golongan kuinolon.[A5] [A6] Kejadian perdarahan yang terjadi meliputi hematemesis melena (25%), hematuria (50%), tidak diketahui (25%). Studi ini menyimpulkan bahwa penggunaan bersamaan warfarin dan antibiotik saat rawat inap dapat berpengaruh terhadap kejadian perdarahan dalam waktu tujuh hari setelah pasien dipulangkan [A1]Penulis disarankan mempelajari artikel https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398292/ untuk lebih memahami penulisan artikel dengan desain kohort. [A2]Baik, terimakasih [A3]Tampilan hasil uji dalam studi kohort (adjusted hazard ratio [AHR] = ?; 95% CI, ?; p-value = ) [A4]Tidak dilakukan analisis survival, sementara kejadian perdarahan pada control group adalah 0 sehingga RR adalah tidak terbatas [A5]Ini bukan golongan obat; untuk menghindari multitafsir..kedua obat ini ditulis di awal, sementara yang golongan obat di bagian setelahnya [A6]Sudah kami ubah redaksionalnya

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“…Several studies have reported and investigated pDDIs with paracetamol and the anticoagulant warfarin [16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

“…is interaction is assumed to be a pharmacokinetic interaction [19], resulting in a reduction of warfarin clearance [22] and hence increasing international normalized ratio (INR). is may lead to life-threatening bleeding.…”

Section: Introductionmentioning

confidence: 99%

The risk of drug-drug interactions with paracetamol in a population of hospitalized geriatric patients

Dalhoff

Olsen

Castillo

et al. 2018

Proceedings for Annual Meeting of the Japanese Pharmacological Society

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Aims. is study investigates the consumption of paracetamol and the risk of potential drug-drug interactions and assesses the clinical impact hereof in patients admitted to a department of geriatric medicine. Methods. A retrospective and longitudinal study was conducted in patients who had been receiving paracetamol upon or during hospitalization. e hospital files of the included patients were reviewed, including documentation of concomitant medications, diagnoses, biochemical values, and adverse incidents during admission. ese parameters were used as a clinical follow-up when assessing a clinical probability impact of the identified drug-drug interactions. Results. In total, 104 patients were admitted during the study period. 91 (87.5%) of these (mean age 86 years) received a prescription or were treated with paracetamol. Of these, 10% were evaluated as being at risk of potential drug-drug interactions with paracetamol. Seven of the potential drug-drug interactions were related to treatments with warfarin, one with valsartan and one with phenytoin. Of the nine patients at risk, six did experience either abnormal biochemical values or potential related clinical incidents. Four patients experienced increased INR (range 3.2-4.6), of which one patient suffered from anaemia and one with hematemesis. Two patients experienced increased ALAT/ASAT (55/42 U/I and 87/51 U/I, both females). One experienced hypertension. Conclusion. A large majority of the patients in this study received treatment with paracetamol. Six patients were evaluated as having abnormal biochemical values or were experiencing clinical incidents during their hospitalization potentially related to the identified potential drug-drug interactions.

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Warfarin-drug interactions: An emphasis on influence of polypharmacy and high doses of amoxicillin/clavulanate

Cited by 15 publications

References 28 publications

Drug Interactions Affecting Oral Anticoagulant Use

Drug Interactions Affecting Oral Anticoagulant Use

Risiko Kejadian Perdarahan Pasca Rawat Inap pada Penggunaan Bersamaan Warfarin dan Antibiotik

The risk of drug-drug interactions with paracetamol in a population of hospitalized geriatric patients

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