ELIQUIS (Page 3 of 11)
Other Adverse Reactions
Hypersensitivity reactions (including drug hypersensitivity, such as skin rash, and anaphylactic reactions, such as allergic edema) and syncope were reported in <1% of patients receiving ELIQUIS.
Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery
The safety of ELIQUIS has been evaluated in 1 Phase II and 3 Phase III studies including 5924 patients exposed to ELIQUIS 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 ELIQUIS 2.5 mg twice daily experienced adverse reactions.
Bleeding results during the treatment period in the Phase III studies are shown in Table 3. Bleeding was assessed in each study beginning with the first dose of double-blind study drug.
| Bleeding Endpoint* | ADVANCE-3Hip Replacement Surgery | ADVANCE-2Knee Replacement Surgery | ADVANCE-1Knee Replacement Surgery | |||
|---|---|---|---|---|---|---|
| * All bleeding criteria included surgical site bleeding.† Includes 13 subjects with major bleeding events that occurred before the first dose of ELIQUIS (administered 12 to 24 hours post-surgery).‡ Includes 5 subjects with major bleeding events that occurred before the first dose of ELIQUIS (administered 12 to 24 hours post-surgery).§ Intracranial, intraspinal, intraocular, pericardial, an operated joint requiring re-operation or intervention, intramuscular with compartment syndrome, or retroperitoneal. Bleeding into an operated joint requiring re-operation or intervention was present in all patients with this category of bleeding. Events and event rates include one enoxaparin-treated patient in ADVANCE-1 who also had intracranial hemorrhage.¶ CRNM = clinically relevant nonmajor. | ||||||
| ELIQUIS2.5 mg po bid35±3 days | Enoxaparin 40 mg sc qd 35±3 days | ELIQUIS 2.5 mg po bid 12±2 days | Enoxaparin 40 mg sc qd 12±2 days | ELIQUIS 2.5 mg po bid 12±2 days | Enoxaparin 30 mg sc q12h 12±2 days | |
| First dose 12 to 24 hours post surgery | First dose 9 to 15 hours prior to surgery | First dose 12 to 24 hours post surgery | First dose 9 to 15 hours prior to surgery | First dose 12 to 24 hours post surgery | First dose 12 to 24 hours post surgery | |
| All treated | N=2673 | N=2659 | N=1501 | N=1508 | N=1596 | N=1588 |
| Major (including surgical site) | 22 (0.82%)† | 18 (0.68%) | 9 (0.60%)‡ | 14 (0.93%) | 11 (0.69%) | 22 (1.39%) |
| Fatal | 0 | 0 | 0 | 0 | 0 | 1 (0.06%) |
| Hgb decrease ≥2 g/dL | 13 (0.49%) | 10 (0.38%) | 8 (0.53%) | 9 (0.60%) | 10 (0.63%) | 16 (1.01%) |
| Transfusion of ≥2 units RBC | 16 (0.60%) | 14 (0.53%) | 5 (0.33%) | 9 (0.60%) | 9 (0.56%) | 18 (1.13%) |
| Bleed at critical site§ | 1 (0.04%) | 1 (0.04%) | 1 (0.07%) | 2 (0.13%) | 1 (0.06%) | 4 (0.25%) |
| Major+ CRNM¶ | 129 (4.83%) | 134 (5.04%) | 53 (3.53%) | 72 (4.77%) | 46 (2.88%) | 68 (4.28%) |
| All | 313 (11.71%) | 334 (12.56%) | 104 (6.93%) | 126 (8.36%) | 85 (5.33%) | 108 (6.80%) |
Adverse reactions occurring in ≥1% of patients undergoing hip or knee replacement surgery in the 1 Phase II study and the 3 Phase III studies are listed in Table 4.
| ELIQUIS, n (%) 2.5 mg po bid N=5924 | Enoxaparin, n (%) 40 mg sc qd or 30 mg sc q12h N=5904 | |
|---|---|---|
| Nausea | 153 (2.6) | 159 (2.7) |
| Anemia (including postoperative and hemorrhagic anemia, and respective laboratory parameters) | 153 (2.6) | 178 (3.0) |
| Contusion | 83 (1.4) | 115 (1.9) |
| Hemorrhage (including hematoma, and vaginal and urethral hemorrhage) | 67 (1.1) | 81 (1.4) |
| Postprocedural hemorrhage (including postprocedural hematoma, wound hemorrhage, vessel puncture-site hematoma, and catheter-site hemorrhage) | 54 (0.9) | 60 (1.0) |
| Transaminases increased (including alanine aminotransferase increased and alanine aminotransferase abnormal) | 50 (0.8) | 71 (1.2) |
| Aspartate aminotransferase increased | 47 (0.8) | 69 (1.2) |
| Gamma-glutamyltransferase increased | 38 (0.6) | 65 (1.1) |
Less common adverse reactions in ELIQUIS-treated patients undergoing hip or knee replacement surgery occurring at a frequency of ≥0.1% to <1%:
Blood and lymphatic system disorders: thrombocytopenia (including platelet count decreases)
Vascular disorders: hypotension (including procedural hypotension)
Respiratory, thoracic, and mediastinal disorders: epistaxis
Gastrointestinal disorders: gastrointestinal hemorrhage (including hematemesis and melena), hematochezia
Hepatobiliary disorders: liver function test abnormal, blood alkaline phosphatase increased, blood bilirubin increased
Renal and urinary disorders: hematuria (including respective laboratory parameters)
Injury, poisoning, and procedural complications: wound secretion, incision-site hemorrhage (including incision-site hematoma), operative hemorrhage
Less common adverse reactions in ELIQUIS-treated patients undergoing hip or knee replacement surgery occurring at a frequency of <0.1%:
Gingival bleeding, hemoptysis, hypersensitivity, muscle hemorrhage, ocular hemorrhage (including conjunctival hemorrhage), rectal hemorrhage
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