Axibel Adverse Reactions

Clinical experience: Prevention of VTE: elective hip or knee replacement surgery: The safety of apixaban has been evaluated in one phase II and three phase III studies including 5,924 patients exposed to apixaban 2.5 mg twice daily undergoing major orthopedic surgery of the lower limbs (elective hip replacement or elective knee replacement) treated for up to 38 days. In total, 11% of the patients treated with Apixaban 2.5 mg twice daily experienced adverse reactions. As with other anticoagulants, bleeding may occur during apixaban therapy in the presence of associated risk factors such as organic lesions liable to bleed. Common adverse reactions were anemia, hemorrhage, contusion, and nausea. The overall incidences of adverse reactions of bleeding, anemia and abnormalities of transaminases (e.g,, alanine aminotransferase levels) were numerically lower in patients on apixaban, compared to enoxaparin in the phase II and phase III studies in elective hip and knee replacement surgery. The adverse reactions should be interpreted within the surgical setting.
As with any anticoagulant, the use of Apixaban may be associated with an increased risk of occult or overt bleeding from any tissue or organ, which may result in post-hemorrhagic anemia.
The signs, symptoms, and severity will vary according to the location and degree or extent of the bleeding (see Precautions and Pharmacology: Pharmacodynamics under Actions).
Adverse reactions in the one phase II study and the three phase III studies are listed in Table 19 by system organ classification (MedDRA) and by frequency. (See Table 19.)

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Prevention of stroke and systemic embolism: NVAF: The safety of apixaban has been evaluated in the ARISTOTLE arid AVERROES studies, including 11,284 patients exposed to apixaban 5 mg twice daily and 602 patients to 2.5 mg twice daily. The apixaban exposures were ≥12 months for 9,375 patients and ≥24 months for 3,369 patients in the two studies. In ARISTOTLE, the mean duration of exposure was 89.2 weeks on apixaban and 87.5 weeks on warfarin; total patient years for exposure was 15,534 on apixaban and 15,184 on warfarin. In AVERROES, the mean duration of exposure was approximately 59 weeks in both treatment groups; total patient years for exposure was 3,193 on apixaban and 3,150 on ASA.
The overall discontinuation rate due to adverse reactions was 1.8% for apixaban and 2.6% for warfarin in the ARISTOTLE study, and was 1.5% for apixaban and 1.3% for ASA in the AVERROES study. The overall incidence of adverse reactions related to bleeding was numerically lower in patients on apixaban compared to warfarin in the ARISTOTLE study (24.3% vs 31.0%). and was similar in patients on apixaban compared to ASA in the AVERROES study (9.6% VS 8.5%).
Adverse reactions in the ARISTOTLE and AVERROES studies are listed in Table 20 by system organ classification (MedDRA) and by frequency. The frequency assignments in Table 20 are primarily based on the frequencies observed in the ARISTOTLE study. The adverse reactions observed in the AVERROES study were consistent with those observed in the ARISTOTLE study. (See Table 20.)

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Treatment of VTE: The safety of apixaban has been evaluated in the AMPLIFY and AMPLIFY-EXT studies, including 2,676 patients exposed to apixaban 10 mg twice daily, 3,359 patients exposed to apixaban 5 mg twice daily, and 840 patients exposed to apixaban 2.5 mg twice daily. The mean duration of exposure to apixaban was 154 days and to enoxaparin/warfarin was 152 days in the AMPLIFY study. The mean duration of exposure to apixaban was approximately 330 days and to placebo was 312 days in the AMPLIFY-EXT study.
In the AMPLIFY study, adverse reactions related to bleeding occurred in 417 (15.6%) of apixaban treated patients compared to 661 (24.6%) of enoxaparin/warfarin-treated patients. The discontinuation rate due to bleeding events was 0.7% in the apixaban-treated patients compared to 1.7% in enoxaparin/warfarin-treated patients in the AMPLIFY study.
In the AMPLIFY-EXT study, adverse reactions related to bleeding occurred in 219 (13.3%) of apixaban-treated patients compared to 72 (8.7%) of placebo-treated patients. The discontinuation rate due to bleeding events was approximately 1% in the apixaban-treated patients compared to 0.4% in those patients in the placebo group in the AMPLIFY-EXT study.
Common adverse reactions (≥1%) were gingival bleeding, epistaxis, contusion, haematuria, hematoma, and menorrhagia.
Adverse reactions in the AMPLIFY and AMPLIFY-EXT studies are listed in Table 21 by system organ classification (MedDRA) and by frequency. (See Table 21.)

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