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1

Prom, Rathasen y Sarah A. Spinler. "The Role of Apixaban for Venous and Arterial Thromboembolic Disease". Annals of Pharmacotherapy 45, n.º 10 (27 de septiembre de 2011): 1262–83. http://dx.doi.org/10.1345/aph.1q119.

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Objective: To provide a comprehensive review of the pharmacology, pharmacokinetics, pharmacodynamics, clinical trial data, adverse effects, and drug interactions of apixaban. Data Sources: An English-language literature search was performed with MEDLINE/PubMed from January 2007 to August 2011 using the search terms apixaban, factor Xa inhibitors. FXa inhibitors, BMS-562247-01, venous thromboembolism. deep vein thrombosis, pulmonary embolism, myocardial infarction, acute coronary syndrome, ACS, atrial fibrillation, atrial arrhythmias, total hip replacement or arthroplasty, total knee replacement or arthroplasty, and orthopedic surgery to identify relevant articles. The references of the retrieved articles, professional society meeting abstracts, and the Web site www.clinicaltrials.gov were reviewed to identify other pertinent articles. Study Selection And Data Abstraction: Pertinent original studies involving apixaban's pharmacology, pharmacokinetics, drug interactions, and clinical efficacy and safety data were included. Data Synthesis: Results of 2 large Phase 3 trials suggest that apixaban is superior for stroke and systemic embolism prevention compared to both aspirin and warfarin in patients with atrial fibrillation (AF); rates of major bleeding and intracranial hemorrhage were similar to those of aspirin but significantly reduced compared to warfarin. Completed trials in orthopedic surgery found apixaban to be superior to enoxaparin in total hip replacement (THR) surgery but inferior in total knee replacement (TKR) surgery, with similar rates of major Weeding. A Phase 3 trial of apixaban in acute coronary syndrome was stopped early because of excess bleeding. Future Phase 3 trials will help to determine apixaban's role for treatment of deep vein thrombosis and pulmonary embolism. Currently, apixaban is approved only in Europe for prophylaxis of venous thromboembolism in adults who have undergone elective THR or TKR. Conclusions: A Phase 3 trial in patients with AF revealed apixaban to be superior to warfarin for stroke and systemic embolism prophylaxis, with lower rates of major bleeding. Further studies will help to confirm the role of apixaban for other indications.
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2

Roşian, Adela-Nicoleta, Ştefan Horia Roşian, Bela Kiss, Maria Georgia Ştefan, Adrian Pavel Trifa, Camelia Diana Ober, Ovidiu Anchidin y Anca Dana Buzoianu. "Interindividual Variability of Apixaban Plasma Concentrations: Influence of Clinical and Genetic Factors in a Real-Life Cohort of Atrial Fibrillation Patients". Genes 11, n.º 4 (17 de abril de 2020): 438. http://dx.doi.org/10.3390/genes11040438.

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(1) Background: Prescribing apixaban for stroke prevention has significantly increased in patients with non-valvular atrial fibrillation (NVAF). The ABCB1 genotype can influence apixaban absorption and bioavailability. The aim of the present study was to assess the factors that influence apixaban’s plasma level and to establish if a certain relationship has clinical relevance. (2) Methods: Fifty-three NVAF patients were treated with 5 mg apixaban twice/day (70.0 years, range: 65–77, 60.4% men). Trough and peak plasma concentrations of apixaban were determined by liquid chromatography-tandem mass-spectrometry (LC-MS/MS), and ABCB1 genotyping was performed. (3) Results: Apixaban plasma concentrations varied considerably. They were higher in women than in men (311.2 ng/dL vs. 252.2 ng/dL; p = 0.05) and were lower in patients with heart failure (149.4 ng/dL vs. 304.5 ng/dL; p < 0.01). Creatinine clearance was inversely correlated with the apixaban plasma level (Spearman correlation: r = −0.365; p = 0.007 for trough concentrations). No statistically significant differences between the genotypic groups of ABCB1 rs1045642 and ABCB1 rs4148738 were found in the trough or peak apixaban plasma concentrations. (4) Conclusions: Pharmacokinetic parameters are influenced by several clinical factors of which renal function is the major determinant. Plasma concentrations measured in women had higher values than those measured in men, and heart failure was associated with decreased plasma levels of apixaban.
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3

Alexander, John, L. Kristin Newby, Hongqiu Yang, Yuchen Barrett, Puneet Mohan, Jessie Wang, Robert Harrington, Lars Wallentin y Richard Becker. "Effect of apixaban, an oral and direct factor Xa inhibitor, on coagulation activity biomarkers following acute coronary syndrome". Thrombosis and Haemostasis 104, n.º 11 (2010): 976–83. http://dx.doi.org/10.1160/th10-04-0247.

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SummaryApixaban is an oral, direct factor Xa inhibitor under development for secondary prevention in acute coronary syndrome (ACS). Apixaban‘s effect on D-dimer and prothrombin fragment 1.2 (F1.2) (coagulation activity biomarkers ) was determined in a randomised, double-blinded, placebo-controlled, phase 2 study. Patients (n=1,715) with either ST-segment elevation or non-ST-segment elevation ACS received either placebo or apixaban 2.5 mg twice daily, 10 mg once daily, 10 mg twice daily or 20 mg once daily for six months. Samples were obtained at baseline (before study drug administration), week 3 and week 26. Apixaban plasma concentrations were measured directly by liquid chromatography/mass spectometry, and anti-Xa activity was determined using apixaban as a reference standard. D-dimer and F 1.2 were measured using ELISA-based methods. Most patients had elevated D-dimer and F1.2 levels at baseline. Both coagulation activity biomarkers decreased by week 3 in all treatment groups, but to a greater degree with apixaban than placebo (p<0.001). In a multivariable analysis, apixaban was independently associated with a change in biomarkers over time (p<0.0001). While the overall decrease did not differ significantly among the three highest apixaban doses, F1.2 was suppressed more rapidly by the 10 mg once daily than the 2.5 mg twice daily dose (p<0.05). There was a strong and direct relationship between apixaban plasma concentrations and anti-Xa-apixaban levels, and an inverse relationship for both measures with coagulation activity biomarkers. In conclusion, the oral direct factor Xa inhibitor apixaban significantly reduced coagulation activity biomarkers among patients with ACS. The 10 mg once daily dose reduced thrombin generation (F 1.2) and fibrin formation (D-dimer) more rapidly and robustly than the 2.5 mg twice daily dose. The effect on both D-dimer and F 1.2 was apixaban concentration-and factor Xa inhibition dependent, durable and provided general guidance for dose selection in phase 3 investigation.
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4

Tellor, Katie B., Michelle Wang, Melissa S. Green y Anastasia L. Armbruster. "Evaluation of Apixaban for the Treatment of Nonvalvular Atrial Fibrillation With Regard to Dosing and Safety in a Community Hospital". Journal of Pharmacy Technology 33, n.º 4 (28 de abril de 2017): 140–45. http://dx.doi.org/10.1177/8755122517706423.

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Background: Apixaban, a direct factor Xa inhibitor, is approved by the US Food and Drug Administration (FDA) for prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Apixaban’s compelling safety and efficacy data, combined with minimal laboratory monitoring, make it an attractive anticoagulant. Objectives: To characterize and evaluate the dosing and safety of apixaban for the treatment of nonvalvular atrial fibrillation at a community hospital. Design/Patients: A retrospective chart review evaluated patients ≥18 years of age who received at least 2 consecutive doses of apixaban from January 1, 2013 to June 30, 2016. Patients with multiple admissions were evaluated for each hospitalization. Patients were excluded if height, weight, or serum creatinine was not documented during hospital admission. Patients who received apixaban for the treatment or prophylaxis of venous thromboembolism were excluded. Prescribing patterns were characterized based on FDA-approved dosing regimens and patient demographics. Safety outcomes included incidences of major, clinically relevant nonmajor, and minor bleeding. Results: Of the 707 patients evaluated, 82% received an FDA-approved apixaban regimen. Of the 127 patients (18%) who received an unapproved regimen, 5.5% (7 patients) received an unapproved frequency and 94.5% (120 patients) received an unapproved dose. The majority (98 patients, 81.7%) were underdosed. Composite bleeding rates were 2.7%, with 1.8% major bleeds, 0.7% clinically relevant nonmajor bleeds, and 0.1% minor bleeds. Conclusions: The use of apixaban must be monitored in order to ensure FDA-approved dosing regimens are being prescribed and patients are not being underdosed.
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5

Münzel, T. y S. Konstantinides. "Apixaban". Hämostaseologie 32, n.º 03 (2012): 203–11. http://dx.doi.org/10.5482/hamo-12-05-0010.

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SummaryApixaban is a potent reversible inhibitor of the activated human coagulation factor X. This new oral anticoagulant has favourable pharmacokinetic and pharmocodynamic properties which include a concentration-dependent anticoagulant effect, good oral bioavailability, balanced elimination and excretion, infrequent drug or food interactions, and the lack of liver toxicity. Apixaban has already completed a large part of its phase 3 clinical trial programme. In the ARISTOTLE study, which focused on stroke prevention in atrial fibrillation, apixaban showed a balanced efficacy and safety profile, being superior to warfarin both in the prevention of strokes and in the risk of causing major bleeding. A further trial related to this indication, AVERROES, demonstrated the clear superiority of apixaban compared to aspirin treatment. In the primary prophylaxis of venous thromboembolism after orthopaedic surgery, apixaban successfully completed the ADVANCE study programme and was approved in Europe for patients undergoing elective hip or knee replacement. The results of the AMPLIFY and AMPLIFY- EXT studies will soon show whether the inhibitor is also effective in the treatment and secondary prophylaxis after acute deep vein thrombosis and pulmonary embolism. On the other hand, the use of apixaban in the primary prophylaxis of venous thrombosis in hospitalised medical patients, and its administration on top of antiplatelet therapy to patients who have suffered an acute coronary syndrome, have not received support by the results of ADOPT and APPRAISE-II, respectively. In conclusion, on the basis of the available evidence, apixaban appears to be a valuable therapeutic option for the prevention of venous thrombosis and embolic stroke.
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6

Watson, Julia, Glen Whiteside y Caroline Perry. "Apixaban". Drugs 71, n.º 15 (octubre de 2011): 2079–89. http://dx.doi.org/10.2165/11596820-000000000-00000.

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7

Deeks, Emma D. "Apixaban". Drugs 72, n.º 9 (junio de 2012): 1271–91. http://dx.doi.org/10.2165/11209020-000000000-00000.

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8

Lam, Sum. "Apixaban". Cardiology in Review 21, n.º 4 (2013): 207–12. http://dx.doi.org/10.1097/crd.0b013e318293d6e6.

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9

Cada, Dennis J., Terri L. Levien y Danial E. Baker. "Apixaban". Hospital Pharmacy 48, n.º 6 (junio de 2013): 494–511. http://dx.doi.org/10.1310/hpj4806-494.

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10

Mendes, Vitor, Sébastien Colombier, François Verdy, Xavier Bechtold, Pierre Schlaepfer, Emmanuelle Scala, Antoine Schneider y Matthias Kirsch. "Cytosorb® hemoadsorption of apixaban during emergent cardio-pulmonary bypass: a case report". Perfusion, 26 de octubre de 2020, 026765912096782. http://dx.doi.org/10.1177/0267659120967827.

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Background: Peri-operative coagulation management of patients receiving apixaban, a new oral anticoagulant, is difficult. The CytoSorb® hemoadsorption device might represent a therapeutic option to reduce apixaban’s pharmacological and inflammatory effects during high-risk surgery. Case presentation: An 83-year-old woman treated with Apixaban underwent emergent redo mitral valve replacement for prosthetic valve endocarditis. A CytoSorb® cartridge was added to the cardio-pulmonary bypass (CPB) circuit. Apixaban-specific anti-factor Xa activity (AFXaA) were measured peri-operatively. After 100 minutes of CPB, a 50% AFXaA rate decrease was observed as compared to pre-CPB values. Furthermore, we noticed 39% and 44% reductions of AFXaA levels in comparison to the expected levels in patients with normal or altered renal function, respectively. Conclusion: Insertion of a CytoSorb® cartridge in the CPB was safe and associated with rapid correction of Apixaban-associated anticoagulation.
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11

Harrington, Josephine, Anna Giczewska, Daniel Wojdyla, Jeffrey B. WASHAM, Marat Fudim, Ziad Hijazi, Renato D. Lopes et al. "Abstract 9290: Relationship Between Body Weight and Pharmacokinetics of Apixaban in Patients With Atrial Fibrillation: Insights from the ARISTOTLE Trial". Circulation 144, Suppl_1 (16 de noviembre de 2021). http://dx.doi.org/10.1161/circ.144.suppl_1.9290.

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Introduction: Apixaban dosing in atrial fibrillation (AF) is 5 mg BID or 2.5 mg BID in patients with ≥2 dose-reduction criteria: age >80 years, weight <60 kg, or creatinine >1.5 mg/dl. There is a question of whether drug monitoring might be useful to guide dosing, particularly in patients with extremely high or low body weight (BW). Previous work has demonstrated that the effects of apixaban versus warfarin are similar across BWs. We aimed to investigate the relationship between BW and exposure to apixaban in patients with AF. Methods: Exposure to apixaban was assessed as area under the curve steady state (AUC SS ) using population pharmacokinetics (PK) data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. The relationship between BW and AUC SS was assessed continuously and by BW categories of ≤60kg, >60-120kg, or >120kg overall and by apixaban dose. Results: Of patients with PK data (n=2924), 8.9% were ≤60kg, and 5.8% >120kg. Compared to the overall group, patients ≤60kg were more likely to be older (74 vs 70 years), female (67 vs 33%), had lower creatinine (0.92 vs 1.02 mg/dL) and higher CHA 2 DS 2 -VASc scores (3.9 vs 3.4). There was a weak but significant correlation between BW and AUC SS assessed continuously (correlation -0.38, p<0.001) and by BW group: ≤60kg [median AUCSS 4089 (25 th 3073, 75 th 5148 ng•hr/ml)], >60-120kg [3566 (2926, 4286 ng•hr/ml)], and >120kg [2699 (2284, 3226 ng•hr/ml)] (p<0.001) (Figure). This relationship persisted with stratification by apixaban dose (data not shown). Conclusions: There is a significant relationship between body weight and predicted exposure to apixaban, including at the extremes of BW, but with wide variation in exposure at every weight. This variation, and the absence of an association between body weight and apixaban’s observed safety and efficacy compared with warfarin, make it unlikely that routine therapeutic monitoring of apixaban will be clinically useful.
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12

Manis, Melanie M., Kat Petersen, Megan Z. Roberts y Jeffrey A. Kyle. "Managing the Drug-Drug Interaction With Apixaban and Primidone: A Case Report". Hospital Pharmacy, 27 de enero de 2023, 001857872211509. http://dx.doi.org/10.1177/00185787221150928.

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The management of the drug-drug interaction (DDI) between primidone, a moderate to strong cytochrome P-450 (CYP) 3A4 inducer, and apixaban, a direct oral anticoagulant (DOAC) and CYP3A4 substrate is complex and limited evidence exists to guide management. This case report describes a 65-year-old male, receiving primidone for essential tremor who developed an acute venous thromboembolism (VTE) requiring oral anticoagulation. DOACs are preferred over vitamin K antagonists for acute VTE treatment. Based on patient-specific variables, provider preference, and the avoidance of other DDIs, apixaban was selected. Apixaban’s package insert recommends avoiding use with concomitant strong P-gp and CYP3A4 inducers due to the decreased exposure to apixaban; however, no recommendations are available for drugs that are moderate to strong CYP3A4 inducers and lack P-gp effects. Given that phenobarbital is an active metabolite of primidone, extrapolation of evidence from such literature is theoretical but provides insight into the management of this multi-faceted DDI. In the absence of the ability to monitor plasma apixaban levels, a management strategy of avoidance with a washout period of primidone based on pharmacokinetic parameters was used in this case. Additional evidence is needed to clearly understand the degree of impact and clinical significance of the DDI between apixaban and primidone.
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13

"Apixaban". Reactions Weekly 1853, n.º 1 (mayo de 2021): 67. http://dx.doi.org/10.1007/s40278-021-94933-5.

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"Apixaban". Reactions Weekly 1853, n.º 1 (mayo de 2021): 66. http://dx.doi.org/10.1007/s40278-021-94932-5.

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"Apixaban". Reactions Weekly 1838, n.º 1 (enero de 2021): 75. http://dx.doi.org/10.1007/s40278-021-89394-0.

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"Apixaban". Reactions Weekly 1839, n.º 1 (enero de 2021): 50. http://dx.doi.org/10.1007/s40278-021-89888-4.

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"Apixaban". Reactions Weekly 1840, n.º 1 (enero de 2021): 59. http://dx.doi.org/10.1007/s40278-021-90202-8.

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"Apixaban". Reactions Weekly 1851, n.º 1 (abril de 2021): 54. http://dx.doi.org/10.1007/s40278-021-94144-7.

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"Apixaban". Reactions Weekly 1856, n.º 1 (mayo de 2021): 86. http://dx.doi.org/10.1007/s40278-021-96079-0.

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"Apixaban". Reactions Weekly 1856, n.º 1 (mayo de 2021): 88. http://dx.doi.org/10.1007/s40278-021-96081-z.

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"Apixaban". Reactions Weekly 1856, n.º 1 (mayo de 2021): 89. http://dx.doi.org/10.1007/s40278-021-96082-z.

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"Apixaban". Reactions Weekly 1856, n.º 1 (mayo de 2021): 85. http://dx.doi.org/10.1007/s40278-021-96078-0.

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"Apixaban". Reactions Weekly 1856, n.º 1 (mayo de 2021): 87. http://dx.doi.org/10.1007/s40278-021-96080-z.

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"Apixaban". Reactions Weekly 1842, n.º 1 (febrero de 2021): 60. http://dx.doi.org/10.1007/s40278-021-90796-2.

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"Apixaban". Reactions Weekly 1843, n.º 1 (febrero de 2021): 56. http://dx.doi.org/10.1007/s40278-021-91158-2.

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"Apixaban". Reactions Weekly 1841, n.º 1 (febrero de 2021): 42. http://dx.doi.org/10.1007/s40278-021-90544-y.

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"Apixaban". Reactions Weekly 1844, n.º 1 (febrero de 2021): 57. http://dx.doi.org/10.1007/s40278-021-91504-z.

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"Apixaban". Reactions Weekly 1852, n.º 1 (abril de 2021): 71. http://dx.doi.org/10.1007/s40278-021-94524-1.

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"Apixaban". Reactions Weekly 1913, n.º 1 (julio de 2022): 81. http://dx.doi.org/10.1007/s40278-022-18231-8.

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"Apixaban". Reactions Weekly 1919, n.º 1 (13 de agosto de 2022): 98. http://dx.doi.org/10.1007/s40278-022-21040-2.

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"Apixaban". Reactions Weekly 1919, n.º 1 (13 de agosto de 2022): 97. http://dx.doi.org/10.1007/s40278-022-21039-3.

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"Apixaban". Reactions Weekly 1912, n.º 1 (junio de 2022): 88. http://dx.doi.org/10.1007/s40278-022-17791-8.

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"Apixaban". Reactions Weekly 1916, n.º 1 (julio de 2022): 62. http://dx.doi.org/10.1007/s40278-022-19521-0.

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"Apixaban". Reactions Weekly 1916, n.º 1 (julio de 2022): 61. http://dx.doi.org/10.1007/s40278-022-19520-0.

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"Apixaban". Reactions Weekly 1917, n.º 1 (julio de 2022): 92. http://dx.doi.org/10.1007/s40278-022-19963-1.

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"Apixaban". Reactions Weekly 1920, n.º 1 (20 de agosto de 2022): 79. http://dx.doi.org/10.1007/s40278-022-21616-6.

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"Apixaban". Reactions Weekly 1907, n.º 1 (mayo de 2022): 78. http://dx.doi.org/10.1007/s40278-022-15337-2.

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"Apixaban". Reactions Weekly 1907, n.º 1 (mayo de 2022): 77. http://dx.doi.org/10.1007/s40278-022-15336-2.

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"Apixaban". Reactions Weekly 1927, n.º 1 (8 de octubre de 2022): 95. http://dx.doi.org/10.1007/s40278-022-24831-4.

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"Apixaban". Reactions Weekly 1923, n.º 1 (10 de septiembre de 2022): 68. http://dx.doi.org/10.1007/s40278-022-22931-8.

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"Apixaban". Reactions Weekly 1922, n.º 1 (3 de septiembre de 2022): 94. http://dx.doi.org/10.1007/s40278-022-22379-3.

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"Apixaban". Reactions Weekly 1910, n.º 1 (junio de 2022): 76. http://dx.doi.org/10.1007/s40278-022-16911-2.

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"Apixaban". Reactions Weekly 1895, n.º 1 (febrero de 2022): 66. http://dx.doi.org/10.1007/s40278-022-10491-9.

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"Apixaban". Reactions Weekly 1905, n.º 1 (mayo de 2022): 86. http://dx.doi.org/10.1007/s40278-022-14476-z.

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"Apixaban". Reactions Weekly 1905, n.º 1 (mayo de 2022): 85. http://dx.doi.org/10.1007/s40278-022-14475-z.

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"Apixaban". Reactions Weekly 1898, n.º 1 (marzo de 2022): 70. http://dx.doi.org/10.1007/s40278-022-11663-5.

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"Apixaban". Reactions Weekly 1883, n.º 1 (noviembre de 2021): 57. http://dx.doi.org/10.1007/s40278-021-06012-3.

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48

Airoldi, Gianluca y Mauro Campanini. "Apixaban". Italian Journal of Medicine, 7 de marzo de 2013, 128–34. http://dx.doi.org/10.4081/itjm.2011.128.

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Introduction: Thromboembolic events represent the final common mechanism in the pathogenesis of the most lethal vascular diseases in the developed countries (including acute coronary syndromes, ischemic stroke, deep vein thrombosis, and pulmonary embolism). Anticoagulant drugs, such as vitamin K antagonists (VKAs), heparin, low-molecular-weight heparin (LMWH), and, more recently, fondaparinux, form the cornerstone of prevention and treatment of thromboembolic diseases, and they are among the most widely used drugs in the Western world. However, these agents have important limitations. VKAs have a narrow therapeutic range and unpredictable pharmacokinetics (PK) and pharmacodynamics (PD), which are heavily influenced by genetic factors, drug-drug interactions, and dietary intake of vitamin K. Frequent laboratory monitoring and careful dose adjustment of VKAs are needed to ensure effective anti-thrombotic protection at a reasonably low risk of bleeding. Heparin, LMWH, and fondaparinux require subcutaneous injection, which makes them unsuitable for long-term treatments. Therefore, there is a real need for new, orally active anticoagulants with predictable PK/PD profiles that can be used without laboratory monitoring. Materials and methods: In this ‘‘state of the art’’ review, the authors examine literature retrieved from a PubMed Medline search with the keyword apixaban and no limits regarding date or language of publication, type of article, or field. Results: Apixaban is an oral anticoagulant developed for the prevention and treatment of venous thromboembolism, for stroke prevention in atrial fibrillation, and for secondary prevention in ischemic heart disease. It is a potent, reversible, highly selective, direct inhibitor of free and prothrombinase-bound factor Xa. It is characterized by > 50% oral bioavailability, peak plasma concentrations 1-3 h after administration, and a 12-h terminal half-life. It also has low potential for drug-drug interactions and is eliminated through mixed renal and metabolic pathways (both CYP-mediated and CYP-independent). Apixaban has exhibited promising efficacy and safety profiles in different clinical conditions.Discussion: Apixaban is a promising new oral anticoagulant. However, additional studies on effectiveness and safety are needed to determine whether it can compete with the coumarins in the prevention and treatment of thromboembolic diseases.
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49

"Apixaban". Reactions Weekly 1857, n.º 1 (mayo de 2021): 62. http://dx.doi.org/10.1007/s40278-021-96447-8.

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"Apixaban". Reactions Weekly 1857, n.º 1 (mayo de 2021): 61. http://dx.doi.org/10.1007/s40278-021-96446-8.

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