{ "faithfulness": { "score": 0.9318, "hallucination_rate": 0.0682, "n_hallucinated": 3, "n_claims": 45, "n_supported": 41, "n_clean_supported": 41, "n_contradicted": 3, "n_not_found": 0, "n_uncertain": 1, "n_superseded": 0, "coverage": 1.0, "claims": [ { "claim": "ELIQUIS is approved for reduction of stroke and systemic embolism risk in patients with nonvalvular atrial fibrillation.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "812a8e70-2ce3-436b-84ca-3bb8af10d729", "content": "ELIQUIS (apixaban) \u2014 FDA PRESCRIBING INFORMATION INDICATIONS AND USAGE 1 INDICATIONS AND USAGE ELIQUIS is a factor Xa inhibitor indicated: to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. (1.1) for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. (1.2) for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy. (1.3 , 1.4 , 1.5) 1.1 Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. 1.2 Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. 1.3 Treatment of Deep Vein Thrombosis ELIQUIS is indicated for the treatment of DVT. 1.4 Treatment of Pulmonary Embolism ELIQUIS is indicated for the treatment of PE. 1.5 Reduction in the Risk of Recurrence of DVT and PE ELIQUIS is indicated to reduce the risk of recurrent DVT and PE following initial therapy. DOSAGE AND ADMINISTRATION 2 DOSAGE AND ADMINISTRATION Reduction of", "relevance_score": 0.5, "authority_status": null, "superseded": false }, { "memory_id": "d17f7c6a-ecb2-4c9e-9866-3ca82d820aa4", "content": "Reactions (6.1) ] . Table 9: Key Efficacy Outcomes in Patients with Nonvalvular Atrial Fibrillation in ARISTOTLE (Intent-to-Treat Analysis) ELIQUIS N=9120 n (%/year) Warfarin N=9081 n (%/year) Hazard Ratio (95% CI) P-value The primary endpoint was based on the time to first event (one per subject). Component counts are for subjects with any event, not necessarily the first. Stroke or systemic embolism 212 (1.27) 265 (1.60) 0.79 (0.66, 0.95) 0.01 Stroke 199 (1.19) 250 (1.51) 0.79 (0.65, 0.95) Ischemic without hemorrhage 140 (0.83) 136 (0.82) 1.02 (0.81, 1.29) Ischemic with hemorrhagic conversion 12 (0.07) 20 (0.12) 0.60 (0.29, 1.23) Hemorrhagic 40 (0.24) 78 (0.47) 0.51 (0.35, 0.75) Unknown 14 (0.08) 21 (0.13) 0.65 (0.33, 1.29) Systemic embolism 15 (0.09) 17 (0.10) 0.87 (0.44, 1.75) Figure 4: Kaplan-Meier Estimate of Time to First Stroke or Systemic Embolism in ARISTOTLE (Intent-to-Treat Population) All-cause death was assessed using a sequential testing strategy that allowed testing for superiority if effects on earlier endpoints (stroke plus systemic embolus and major bleeding) were demonstrated. ELIQUIS treatment resulted in a significantly lower rate of all-cause death (p = 0.046) than did treatment with warfarin, primarily because of a reduction in cardiovascular death, particularly stroke deaths. Non vascular death rates were similar in the treatment arms. In ARISTOTLE, the", "relevance_score": 0.25, "authority_status": null, "superseded": false }, { "memory_id": "b913b8d5-35e1-47e0-82ea-246ca3747690", "content": "bleeding, and death from any cause. A total of 18,201 patients were randomized and followed on study treatment for a median of 89 weeks. Forty-three percent of patients were vitamin K antagonist (VKA) \u201cnaive,\u201d defined as having received \u226430 consecutive days of treatment with warfarin or another VKA before entering the study. The mean age was 69 years and the mean CHADS 2 score (a scale from 0 to 6 used to estimate risk of stroke, with higher scores predicting greater risk) was 2.1. The population was 65% male, 83% Caucasian, 14% Asian, and 1% Black. There was a history of stroke, TIA, or non-CNS systemic embolism in 19% of patients. Concomitant diseases of patients in this study included hypertension 88%, diabetes 25%, congestive heart failure (or left ventricular ejection fraction \u226440%) 35%, and prior myocardial infarction 14%. Patients treated with warfarin in ARISTOTLE had a mean percentage of time in therapeutic range (INR 2.0-3.0) of 62%. ELIQUIS was superior to warfarin for the primary endpoint of reducing the risk of stroke and systemic embolism (Table 9 and Figure 4). Superiority to warfarin was primarily attributable to a reduction in hemorrhagic stroke and ischemic strokes with hemorrhagic conversion compared to warfarin. Purely ischemic strokes occurred with similar rates on both drugs. ELIQUIS also showed significantly fewer major bleeds than warfarin [see Adverse", "relevance_score": 0.2, "authority_status": null, "superseded": false } ] }, { "claim": "ELIQUIS is approved for prophylaxis of deep vein thrombosis (DVT) following hip or knee replacement surgery.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "812a8e70-2ce3-436b-84ca-3bb8af10d729", "content": "ELIQUIS (apixaban) \u2014 FDA PRESCRIBING INFORMATION INDICATIONS AND USAGE 1 INDICATIONS AND USAGE ELIQUIS is a factor Xa inhibitor indicated: to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. (1.1) for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. (1.2) for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy. (1.3 , 1.4 , 1.5) 1.1 Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. 1.2 Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. 1.3 Treatment of Deep Vein Thrombosis ELIQUIS is indicated for the treatment of DVT. 1.4 Treatment of Pulmonary Embolism ELIQUIS is indicated for the treatment of PE. 1.5 Reduction in the Risk of Recurrence of DVT and PE ELIQUIS is indicated to reduce the risk of recurrent DVT and PE following initial therapy. DOSAGE AND ADMINISTRATION 2 DOSAGE AND ADMINISTRATION Reduction of", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "2a29ea46-0150-4196-a11f-f94ff98f3476", "content": "death 111 (3.51) 140 (4.42) 0.79 (0.62, 1.02) 0.068 Vascular death 84 (2.65) 96 (3.03) 0.87 (0.65, 1.17) - 14.2 Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery The clinical evidence for the effectiveness of ELIQUIS is derived from the ADVANCE-1, ADVANCE-2, and ADVANCE-3 clinical trials in adult patients undergoing elective hip (ADVANCE-3) or knee (ADVANCE-2 and ADVANCE-1) replacement surgery. A total of 11,659 patients were randomized in 3 double-blind, multi-national studies. Included in this total were 1866 patients age 75 or older, 1161 patients with low body weight (\u226460 kg), 2528 patients with Body Mass Index \u226533 kg/m 2 , and 625 patients with severe or moderate renal impairment. In the ADVANCE-3 study, 5407 patients undergoing elective hip replacement surgery were randomized to receive either ELIQUIS 2.5 mg orally twice daily or enoxaparin 40 mg subcutaneously once daily. The first dose of ELIQUIS was given 12 to 24 hours post surgery, whereas enoxaparin was started 9 to 15 hours prior to surgery. Treatment duration was 32 to 38 days. In patients undergoing elective knee replacement surgery, ELIQUIS 2.5 mg orally twice daily was compared to enoxaparin 40 mg subcutaneously once daily (ADVANCE-2, N=3057) or enoxaparin 30 mg subcutaneously every 12 hours (ADVANCE-1, N=3195). In the ADVANCE-2 study, the first dose of ELIQUIS was given 12 to 24", "relevance_score": 0.5, "authority_status": null, "superseded": false }, { "memory_id": "be008568-bf59-49bd-9351-befecc47e02f", "content": "risk of stroke and systemic embolism in nonvalvular atrial fibrillation: The recommended dose is 5 mg orally twice daily. (2.1) In patients with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily. (2.1) Prophylaxis of DVT following hip or knee replacement surgery: The recommended dose is 2.5 mg orally twice daily. (2.1) Treatment of DVT and PE: The recommended dose is 10 mg taken orally twice daily for 7 days, followed by 5 mg taken orally twice daily. (2.1) Reduction in the risk of recurrent DVT and PE following initial therapy: The recommended dose is 2.5 mg taken orally twice daily. (2.1) 2.1 Recommended Dose Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation The recommended dose of ELIQUIS for most patients is 5 mg taken orally twice daily. The recommended dose of ELIQUIS is 2.5 mg twice daily in patients with at least two of the following characteristics: age greater than or equal to 80 years body weight less than or equal to 60 kg serum creatinine greater than or equal to 1.5 mg/dL Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily. The initial dose should", "relevance_score": 0.2, "authority_status": null, "superseded": false } ] }, { "claim": "ELIQUIS is approved for treatment of DVT.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "812a8e70-2ce3-436b-84ca-3bb8af10d729", "content": "ELIQUIS (apixaban) \u2014 FDA PRESCRIBING INFORMATION INDICATIONS AND USAGE 1 INDICATIONS AND USAGE ELIQUIS is a factor Xa inhibitor indicated: to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. (1.1) for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. (1.2) for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy. (1.3 , 1.4 , 1.5) 1.1 Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. 1.2 Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. 1.3 Treatment of Deep Vein Thrombosis ELIQUIS is indicated for the treatment of DVT. 1.4 Treatment of Pulmonary Embolism ELIQUIS is indicated for the treatment of PE. 1.5 Reduction in the Risk of Recurrence of DVT and PE ELIQUIS is indicated to reduce the risk of recurrent DVT and PE following initial therapy. DOSAGE AND ADMINISTRATION 2 DOSAGE AND ADMINISTRATION Reduction of", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "0173d387-1322-4350-9a0e-f00deabb9880", "content": "be taken 12 to 24 hours after surgery. In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days. Treatment of DVT and PE The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily. Reduction in the Risk of Recurrence of DVT and PE The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3) ] . 2.2 Missed Dose If a dose of ELIQUIS is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose. 2.3 Temporary Interruption for Surgery and Other Interventions ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5.2) ] . ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. Bridging anticoagulation during the 24", "relevance_score": 0.25, "authority_status": null, "superseded": false } ] }, { "claim": "ELIQUIS is approved for treatment of pulmonary embolism (PE).", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "812a8e70-2ce3-436b-84ca-3bb8af10d729", "content": "ELIQUIS (apixaban) \u2014 FDA PRESCRIBING INFORMATION INDICATIONS AND USAGE 1 INDICATIONS AND USAGE ELIQUIS is a factor Xa inhibitor indicated: to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. (1.1) for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. (1.2) for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy. (1.3 , 1.4 , 1.5) 1.1 Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. 1.2 Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. 1.3 Treatment of Deep Vein Thrombosis ELIQUIS is indicated for the treatment of DVT. 1.4 Treatment of Pulmonary Embolism ELIQUIS is indicated for the treatment of PE. 1.5 Reduction in the Risk of Recurrence of DVT and PE ELIQUIS is indicated to reduce the risk of recurrent DVT and PE following initial therapy. DOSAGE AND ADMINISTRATION 2 DOSAGE AND ADMINISTRATION Reduction of", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "ELIQUIS is approved for reduction of recurrent DVT and PE risk following initial therapy.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "812a8e70-2ce3-436b-84ca-3bb8af10d729", "content": "ELIQUIS (apixaban) \u2014 FDA PRESCRIBING INFORMATION INDICATIONS AND USAGE 1 INDICATIONS AND USAGE ELIQUIS is a factor Xa inhibitor indicated: to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. (1.1) for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. (1.2) for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy. (1.3 , 1.4 , 1.5) 1.1 Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. 1.2 Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. 1.3 Treatment of Deep Vein Thrombosis ELIQUIS is indicated for the treatment of DVT. 1.4 Treatment of Pulmonary Embolism ELIQUIS is indicated for the treatment of PE. 1.5 Reduction in the Risk of Recurrence of DVT and PE ELIQUIS is indicated to reduce the risk of recurrent DVT and PE following initial therapy. DOSAGE AND ADMINISTRATION 2 DOSAGE AND ADMINISTRATION Reduction of", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "be008568-bf59-49bd-9351-befecc47e02f", "content": "risk of stroke and systemic embolism in nonvalvular atrial fibrillation: The recommended dose is 5 mg orally twice daily. (2.1) In patients with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily. (2.1) Prophylaxis of DVT following hip or knee replacement surgery: The recommended dose is 2.5 mg orally twice daily. (2.1) Treatment of DVT and PE: The recommended dose is 10 mg taken orally twice daily for 7 days, followed by 5 mg taken orally twice daily. (2.1) Reduction in the risk of recurrent DVT and PE following initial therapy: The recommended dose is 2.5 mg taken orally twice daily. (2.1) 2.1 Recommended Dose Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation The recommended dose of ELIQUIS for most patients is 5 mg taken orally twice daily. The recommended dose of ELIQUIS is 2.5 mg twice daily in patients with at least two of the following characteristics: age greater than or equal to 80 years body weight less than or equal to 60 kg serum creatinine greater than or equal to 1.5 mg/dL Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily. The initial dose should", "relevance_score": 0.25, "authority_status": null, "superseded": false }, { "memory_id": "0173d387-1322-4350-9a0e-f00deabb9880", "content": "be taken 12 to 24 hours after surgery. In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days. Treatment of DVT and PE The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily. Reduction in the Risk of Recurrence of DVT and PE The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3) ] . 2.2 Missed Dose If a dose of ELIQUIS is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose. 2.3 Temporary Interruption for Surgery and Other Interventions ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5.2) ] . ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. Bridging anticoagulation during the 24", "relevance_score": 0.2, "authority_status": null, "superseded": false } ] }, { "claim": "For nonvalvular atrial fibrillation, the recommended dose of ELIQUIS is 5 mg orally twice daily for most patients.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "be008568-bf59-49bd-9351-befecc47e02f", "content": "risk of stroke and systemic embolism in nonvalvular atrial fibrillation: The recommended dose is 5 mg orally twice daily. (2.1) In patients with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily. (2.1) Prophylaxis of DVT following hip or knee replacement surgery: The recommended dose is 2.5 mg orally twice daily. (2.1) Treatment of DVT and PE: The recommended dose is 10 mg taken orally twice daily for 7 days, followed by 5 mg taken orally twice daily. (2.1) Reduction in the risk of recurrent DVT and PE following initial therapy: The recommended dose is 2.5 mg taken orally twice daily. (2.1) 2.1 Recommended Dose Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation The recommended dose of ELIQUIS for most patients is 5 mg taken orally twice daily. The recommended dose of ELIQUIS is 2.5 mg twice daily in patients with at least two of the following characteristics: age greater than or equal to 80 years body weight less than or equal to 60 kg serum creatinine greater than or equal to 1.5 mg/dL Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily. The initial dose should", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "98ce0105-a733-4c18-a318-553423f38bd9", "content": "of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation ARISTOTLE Evidence for the efficacy and safety of ELIQUIS was derived from ARISTOTLE, a multinational, double-blind study in patients with nonvalvular AF comparing the effects of ELIQUIS and warfarin on the risk of stroke and non-central nervous system (CNS) systemic embolism. In ARISTOTLE, patients were randomized to ELIQUIS 5 mg orally twice daily (or 2.5 mg twice daily in subjects with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL) or to warfarin (targeted to an INR range of 2.0-3.0). Patients had to have one or more of the following additional risk factors for stroke: prior stroke or transient ischemic attack (TIA) prior systemic embolism age greater than or equal to 75 years arterial hypertension requiring treatment diabetes mellitus heart failure \u2265New York Heart Association Class 2 left ventricular ejection fraction \u226440% The primary objective of ARISTOTLE was to determine whether ELIQUIS 5 mg twice daily (or 2.5 mg twice daily) was effective (noninferior to warfarin) in reducing the risk of stroke (ischemic or hemorrhagic) and systemic embolism. Superiority of ELIQUIS to warfarin was also examined for the primary endpoint (rate of stroke and systemic embolism), major", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "For nonvalvular atrial fibrillation, a reduced dose of 2.5 mg twice daily applies to patients with at least two of the following characteristics: age \u226580 years, body weight \u226460 kg, or serum creatinine \u22651.5 mg/dL.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "be008568-bf59-49bd-9351-befecc47e02f", "content": "risk of stroke and systemic embolism in nonvalvular atrial fibrillation: The recommended dose is 5 mg orally twice daily. (2.1) In patients with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily. (2.1) Prophylaxis of DVT following hip or knee replacement surgery: The recommended dose is 2.5 mg orally twice daily. (2.1) Treatment of DVT and PE: The recommended dose is 10 mg taken orally twice daily for 7 days, followed by 5 mg taken orally twice daily. (2.1) Reduction in the risk of recurrent DVT and PE following initial therapy: The recommended dose is 2.5 mg taken orally twice daily. (2.1) 2.1 Recommended Dose Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation The recommended dose of ELIQUIS for most patients is 5 mg taken orally twice daily. The recommended dose of ELIQUIS is 2.5 mg twice daily in patients with at least two of the following characteristics: age greater than or equal to 80 years body weight less than or equal to 60 kg serum creatinine greater than or equal to 1.5 mg/dL Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily. The initial dose should", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "164be857-3b6f-430f-8d05-2482c098fd14", "content": "65 years of age and older, while 16% were 75 years of age and older. In the AMPLIFY and AMPLIFY-EXT clinical studies, >32% of subjects were 65 years of age and older and >13% were 75 years of age and older. No clinically significant differences in safety or effectiveness were observed when comparing subjects in different age groups. 8.6 Renal Impairment Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation The recommended dose is 2.5 mg twice daily in patients with at least two of the following characteristics [see Dosage and Administration (2.1) ] : age greater than or equal to 80 years body weight less than or equal to 60 kg serum creatinine greater than or equal to 1.5 mg/dL Patients with End-Stage Renal Disease on Dialysis Clinical efficacy and safety studies with ELIQUIS did not enroll patients with end-stage renal disease (ESRD) on dialysis. In patients with ESRD maintained on intermittent hemodialysis, administration of ELIQUIS at the usually recommended dose [see Dosage and Administration (2.1) ] will result in concentrations of apixaban and pharmacodynamic activity similar to those observed in the ARISTOTLE study [see Clinical Pharmacology (12.3) ] . It is not known whether these concentrations will lead to similar stroke reduction and bleeding risk in patients with ESRD on dialysis as was seen in ARISTOTLE. Prophylaxis of", "relevance_score": 0.5, "authority_status": null, "superseded": false }, { "memory_id": "98ce0105-a733-4c18-a318-553423f38bd9", "content": "of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation ARISTOTLE Evidence for the efficacy and safety of ELIQUIS was derived from ARISTOTLE, a multinational, double-blind study in patients with nonvalvular AF comparing the effects of ELIQUIS and warfarin on the risk of stroke and non-central nervous system (CNS) systemic embolism. In ARISTOTLE, patients were randomized to ELIQUIS 5 mg orally twice daily (or 2.5 mg twice daily in subjects with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL) or to warfarin (targeted to an INR range of 2.0-3.0). Patients had to have one or more of the following additional risk factors for stroke: prior stroke or transient ischemic attack (TIA) prior systemic embolism age greater than or equal to 75 years arterial hypertension requiring treatment diabetes mellitus heart failure \u2265New York Heart Association Class 2 left ventricular ejection fraction \u226440% The primary objective of ARISTOTLE was to determine whether ELIQUIS 5 mg twice daily (or 2.5 mg twice daily) was effective (noninferior to warfarin) in reducing the risk of stroke (ischemic or hemorrhagic) and systemic embolism. Superiority of ELIQUIS to warfarin was also examined for the primary endpoint (rate of stroke and systemic embolism), major", "relevance_score": 0.3333, "authority_status": null, "superseded": false }, { "memory_id": "63a15efd-e2ed-4ff0-b4fd-f6732b879c6a", "content": "pharmacokinetics of apixaban are summarized in Figure 2 [see also Warnings and Precautions (5.2) and Drug Interactions (7) ] . Figure 2: Effect of Coadministered Drugs on the Pharmacokinetics of Apixaban In dedicated studies conducted in healthy subjects, famotidine, atenolol, prasugrel, and enoxaparin did not meaningfully alter the pharmacokinetics of apixaban. In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid. Effect of Coadministered Drugs on Pharmacokinetics of Apixaban Specific Populations The effects of level of renal impairment, age, body weight, and level of hepatic impairment on the pharmacokinetics of apixaban are summarized in Figure 3. Figure 3: Effect of Specific Populations on the Pharmacokinetics of Apixaban * ESRD subjects treated with intermittent hemodialysis; reported PK findings are following single dose of apixaban post hemodialysis. \u2020 Results reflect CrCl of 15 mL/min based on regression analysis. \u2021 Dashed vertical lines illustrate pharmacokinetic changes that were used to inform dosing recommendations. \u00a7 No dose adjustment is recommended for nonvalvular atrial fibrillation patients unless at least 2 of the following patient characteristics (age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine", "relevance_score": 0.25, "authority_status": null, "superseded": false } ] }, { "claim": "For DVT prophylaxis following hip replacement surgery, the recommended dose is 2.5 mg twice daily for 42 days.", "verdict": "contradicted", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "contradicts_current_source", "evidence": [ { "memory_id": "be008568-bf59-49bd-9351-befecc47e02f", "content": "risk of stroke and systemic embolism in nonvalvular atrial fibrillation: The recommended dose is 5 mg orally twice daily. (2.1) In patients with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily. (2.1) Prophylaxis of DVT following hip or knee replacement surgery: The recommended dose is 2.5 mg orally twice daily. (2.1) Treatment of DVT and PE: The recommended dose is 10 mg taken orally twice daily for 7 days, followed by 5 mg taken orally twice daily. (2.1) Reduction in the risk of recurrent DVT and PE following initial therapy: The recommended dose is 2.5 mg taken orally twice daily. (2.1) 2.1 Recommended Dose Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation The recommended dose of ELIQUIS for most patients is 5 mg taken orally twice daily. The recommended dose of ELIQUIS is 2.5 mg twice daily in patients with at least two of the following characteristics: age greater than or equal to 80 years body weight less than or equal to 60 kg serum creatinine greater than or equal to 1.5 mg/dL Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily. The initial dose should", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "0173d387-1322-4350-9a0e-f00deabb9880", "content": "be taken 12 to 24 hours after surgery. In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days. Treatment of DVT and PE The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily. Reduction in the Risk of Recurrence of DVT and PE The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3) ] . 2.2 Missed Dose If a dose of ELIQUIS is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose. 2.3 Temporary Interruption for Surgery and Other Interventions ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5.2) ] . ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. Bridging anticoagulation during the 24", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "For DVT prophylaxis following hip replacement surgery, the initial dose is taken 12 to 24 hours after surgery.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "0173d387-1322-4350-9a0e-f00deabb9880", "content": "be taken 12 to 24 hours after surgery. In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days. Treatment of DVT and PE The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily. Reduction in the Risk of Recurrence of DVT and PE The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3) ] . 2.2 Missed Dose If a dose of ELIQUIS is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose. 2.3 Temporary Interruption for Surgery and Other Interventions ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5.2) ] . ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. Bridging anticoagulation during the 24", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "be008568-bf59-49bd-9351-befecc47e02f", "content": "risk of stroke and systemic embolism in nonvalvular atrial fibrillation: The recommended dose is 5 mg orally twice daily. (2.1) In patients with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily. (2.1) Prophylaxis of DVT following hip or knee replacement surgery: The recommended dose is 2.5 mg orally twice daily. (2.1) Treatment of DVT and PE: The recommended dose is 10 mg taken orally twice daily for 7 days, followed by 5 mg taken orally twice daily. (2.1) Reduction in the risk of recurrent DVT and PE following initial therapy: The recommended dose is 2.5 mg taken orally twice daily. (2.1) 2.1 Recommended Dose Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation The recommended dose of ELIQUIS for most patients is 5 mg taken orally twice daily. The recommended dose of ELIQUIS is 2.5 mg twice daily in patients with at least two of the following characteristics: age greater than or equal to 80 years body weight less than or equal to 60 kg serum creatinine greater than or equal to 1.5 mg/dL Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily. The initial dose should", "relevance_score": 0.5, "authority_status": null, "superseded": false }, { "memory_id": "2a29ea46-0150-4196-a11f-f94ff98f3476", "content": "death 111 (3.51) 140 (4.42) 0.79 (0.62, 1.02) 0.068 Vascular death 84 (2.65) 96 (3.03) 0.87 (0.65, 1.17) - 14.2 Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery The clinical evidence for the effectiveness of ELIQUIS is derived from the ADVANCE-1, ADVANCE-2, and ADVANCE-3 clinical trials in adult patients undergoing elective hip (ADVANCE-3) or knee (ADVANCE-2 and ADVANCE-1) replacement surgery. A total of 11,659 patients were randomized in 3 double-blind, multi-national studies. Included in this total were 1866 patients age 75 or older, 1161 patients with low body weight (\u226460 kg), 2528 patients with Body Mass Index \u226533 kg/m 2 , and 625 patients with severe or moderate renal impairment. In the ADVANCE-3 study, 5407 patients undergoing elective hip replacement surgery were randomized to receive either ELIQUIS 2.5 mg orally twice daily or enoxaparin 40 mg subcutaneously once daily. The first dose of ELIQUIS was given 12 to 24 hours post surgery, whereas enoxaparin was started 9 to 15 hours prior to surgery. Treatment duration was 32 to 38 days. In patients undergoing elective knee replacement surgery, ELIQUIS 2.5 mg orally twice daily was compared to enoxaparin 40 mg subcutaneously once daily (ADVANCE-2, N=3057) or enoxaparin 30 mg subcutaneously every 12 hours (ADVANCE-1, N=3195). In the ADVANCE-2 study, the first dose of ELIQUIS was given 12 to 24", "relevance_score": 0.3333, "authority_status": null, "superseded": false }, { "memory_id": "c24b7b47-06f2-4573-b77c-28d4ee542bef", "content": "hours post surgery, whereas enoxaparin was started 9 to 15 hours prior to surgery. In the ADVANCE-1 study, both ELIQUIS and enoxaparin were initiated 12 to 24 hours post surgery. Treatment duration in both ADVANCE-2 and ADVANCE-1 was 10 to 14 days. In all 3 studies, the primary endpoint was a composite of adjudicated asymptomatic and symptomatic DVT, nonfatal PE, and all-cause death at the end of the double-blind intended treatment period. In ADVANCE-3 and ADVANCE-2, the primary endpoint was tested for noninferiority, then superiority, of ELIQUIS to enoxaparin. In ADVANCE-1, the primary endpoint was tested for noninferiority of ELIQUIS to enoxaparin. The efficacy data are provided in Tables 11 and 12. Table 11: Summary of Key Efficacy Analysis Results During the Intended Treatment Period for Patients Undergoing Elective Hip Replacement Surgery* * Events associated with each endpoint were counted once per subject but subjects may have contributed events to multiple endpoints. \u2020 Total VTE includes symptomatic and asymptomatic DVT and PE. \u2021 Includes symptomatic and asymptomatic DVT. ADVANCE-3 Events During 35-Day Treatment Period ELIQUIS 2.5 mg po bid Enoxaparin 40 mg sc qd Relative Risk (95% CI) P-value Number of Patients N=1949 N=1917 Total VTE \u2020 /All-cause death 27 (1.39%) (0.95, 2.02) 74 (3.86%) (3.08, 4.83) 0.36 (0.22, 0.54) p<0.0001 Number of Patients N=2708 N=2699 All-cause", "relevance_score": 0.25, "authority_status": null, "superseded": false } ] }, { "claim": "For DVT prophylaxis following knee replacement surgery, the recommended dose is 2.5 mg twice daily for 12 days.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "be008568-bf59-49bd-9351-befecc47e02f", "content": "risk of stroke and systemic embolism in nonvalvular atrial fibrillation: The recommended dose is 5 mg orally twice daily. (2.1) In patients with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily. (2.1) Prophylaxis of DVT following hip or knee replacement surgery: The recommended dose is 2.5 mg orally twice daily. (2.1) Treatment of DVT and PE: The recommended dose is 10 mg taken orally twice daily for 7 days, followed by 5 mg taken orally twice daily. (2.1) Reduction in the risk of recurrent DVT and PE following initial therapy: The recommended dose is 2.5 mg taken orally twice daily. (2.1) 2.1 Recommended Dose Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation The recommended dose of ELIQUIS for most patients is 5 mg taken orally twice daily. The recommended dose of ELIQUIS is 2.5 mg twice daily in patients with at least two of the following characteristics: age greater than or equal to 80 years body weight less than or equal to 60 kg serum creatinine greater than or equal to 1.5 mg/dL Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily. The initial dose should", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "0173d387-1322-4350-9a0e-f00deabb9880", "content": "be taken 12 to 24 hours after surgery. In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days. Treatment of DVT and PE The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily. Reduction in the Risk of Recurrence of DVT and PE The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3) ] . 2.2 Missed Dose If a dose of ELIQUIS is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose. 2.3 Temporary Interruption for Surgery and Other Interventions ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5.2) ] . ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. Bridging anticoagulation during the 24", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "For acute DVT and PE treatment, the regimen is 10 mg twice daily for the first 7 days, followed by 5 mg twice daily.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "be008568-bf59-49bd-9351-befecc47e02f", "content": "risk of stroke and systemic embolism in nonvalvular atrial fibrillation: The recommended dose is 5 mg orally twice daily. (2.1) In patients with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily. (2.1) Prophylaxis of DVT following hip or knee replacement surgery: The recommended dose is 2.5 mg orally twice daily. (2.1) Treatment of DVT and PE: The recommended dose is 10 mg taken orally twice daily for 7 days, followed by 5 mg taken orally twice daily. (2.1) Reduction in the risk of recurrent DVT and PE following initial therapy: The recommended dose is 2.5 mg taken orally twice daily. (2.1) 2.1 Recommended Dose Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation The recommended dose of ELIQUIS for most patients is 5 mg taken orally twice daily. The recommended dose of ELIQUIS is 2.5 mg twice daily in patients with at least two of the following characteristics: age greater than or equal to 80 years body weight less than or equal to 60 kg serum creatinine greater than or equal to 1.5 mg/dL Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily. The initial dose should", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "0173d387-1322-4350-9a0e-f00deabb9880", "content": "be taken 12 to 24 hours after surgery. In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days. Treatment of DVT and PE The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily. Reduction in the Risk of Recurrence of DVT and PE The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3) ] . 2.2 Missed Dose If a dose of ELIQUIS is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose. 2.3 Temporary Interruption for Surgery and Other Interventions ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5.2) ] . ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. Bridging anticoagulation during the 24", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "For reduction of recurrent DVT and PE risk, the dose is 2.5 mg twice daily after at least 6 months of prior anticoagulant treatment.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "0173d387-1322-4350-9a0e-f00deabb9880", "content": "be taken 12 to 24 hours after surgery. In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days. Treatment of DVT and PE The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily. Reduction in the Risk of Recurrence of DVT and PE The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3) ] . 2.2 Missed Dose If a dose of ELIQUIS is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose. 2.3 Temporary Interruption for Surgery and Other Interventions ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5.2) ] . ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. Bridging anticoagulation during the 24", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "be008568-bf59-49bd-9351-befecc47e02f", "content": "risk of stroke and systemic embolism in nonvalvular atrial fibrillation: The recommended dose is 5 mg orally twice daily. (2.1) In patients with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily. (2.1) Prophylaxis of DVT following hip or knee replacement surgery: The recommended dose is 2.5 mg orally twice daily. (2.1) Treatment of DVT and PE: The recommended dose is 10 mg taken orally twice daily for 7 days, followed by 5 mg taken orally twice daily. (2.1) Reduction in the risk of recurrent DVT and PE following initial therapy: The recommended dose is 2.5 mg taken orally twice daily. (2.1) 2.1 Recommended Dose Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation The recommended dose of ELIQUIS for most patients is 5 mg taken orally twice daily. The recommended dose of ELIQUIS is 2.5 mg twice daily in patients with at least two of the following characteristics: age greater than or equal to 80 years body weight less than or equal to 60 kg serum creatinine greater than or equal to 1.5 mg/dL Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily. The initial dose should", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "Patients receiving ELIQUIS 5 mg or 10 mg twice daily should have their dose reduced by 50% when coadministered with combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors such as ketoconazole, itraconazole, or ritonavir.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "707a0639-b10c-4b2b-a58a-81513c5a7a65", "content": "Inducers of CYP3A4 and P-gp decrease exposure to apixaban and increase the risk of stroke and other thromboembolic events. Combined P-gp and strong CYP3A4 inhibitors increase blood levels of apixaban. Reduce ELIQUIS dose or avoid coadministration. (2.5 , 7.1 , 12.3) Simultaneous use of combined P-gp and strong CYP3A4 inducers reduces blood levels of apixaban: Avoid concomitant use. (7.2 , 12.3) 7.1 Combined P-gp and Strong CYP3A4 Inhibitors For patients receiving ELIQUIS 5 mg or 10 mg twice daily, the dose of ELIQUIS should be decreased by 50% when coadministered with drugs that are combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . For patients receiving ELIQUIS at a dose of 2.5 mg twice daily, avoid coadministration with combined P-gp and strong CYP3A4 inhibitors [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . Clarithromycin Although clarithromycin is a combined P-gp and strong CYP3A4 inhibitor, pharmacokinetic data suggest that no dose adjustment is necessary with concomitant administration with ELIQUIS [see Clinical Pharmacology (12.3) ] . 7.2 Combined P-gp and Strong CYP3A4 Inducers Avoid concomitant use of ELIQUIS with combined P-gp and strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John\u2019s wort) because such drugs", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "8105342b-bc32-471a-9af5-413747df63b2", "content": "50% when ELIQUIS is coadministered with drugs that are combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Clinical Pharmacology (12.3) ] . In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors [see Drug Interactions (7.1) ] . 2.6 Administration Options For patients who are unable to swallow whole tablets, 5 mg and 2.5 mg ELIQUIS tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice, or mixed with applesauce and promptly administered orally [see Clinical Pharmacology (12.3) ] . Alternatively, ELIQUIS tablets may be crushed and suspended in 60 mL of water or D5W and promptly delivered through a nasogastric tube [see Clinical Pharmacology (12.3) ] . Crushed ELIQUIS tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours. DOSAGE FORMS AND STRENGTHS 3 DOSAGE FORMS AND STRENGTHS 2.5 mg, yellow, round, biconvex, film-coated tablets with \u201c893\u201d debossed on one side and \u201c2\u00bd\u201d on the other side. 5 mg, pink, oval-shaped, biconvex, film-coated tablets with \u201c894\u201d debossed on one side and \u201c5\u201d on the other side. Tablets: 2.5 mg and 5 mg (3) CONTRAINDICATIONS 4 CONTRAINDICATIONS ELIQUIS is contraindicated in patients with the following conditions: Active pathological bleeding [see", "relevance_score": 0.5, "authority_status": null, "superseded": false }, { "memory_id": "f1551753-707d-46a0-8344-278b245079ae", "content": "to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established. 2.4 Converting from or to ELIQUIS Switching from warfarin to ELIQUIS: Warfarin should be discontinued and ELIQUIS started when the international normalized ratio (INR) is below 2.0. Switching from ELIQUIS to warfarin: ELIQUIS affects INR, so that initial INR measurements during the transition to warfarin may not be useful for determining the appropriate dose of warfarin. One approach is to discontinue ELIQUIS and begin both a parenteral anticoagulant and warfarin at the time the next dose of ELIQUIS would have been taken, discontinuing the parenteral anticoagulant when INR reaches an acceptable range. Switching from ELIQUIS to anticoagulants other than warfarin (oral or parenteral): Discontinue ELIQUIS and begin taking the new anticoagulant other than warfarin at the usual time of the next dose of ELIQUIS. Switching from anticoagulants other than warfarin (oral or parenteral) to ELIQUIS: Discontinue the anticoagulant other than warfarin and begin taking ELIQUIS at the usual time of the next dose of the anticoagulant other than warfarin. 2.5 Combined P-gp and Strong CYP3A4 Inhibitors For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose by", "relevance_score": 0.3333, "authority_status": null, "superseded": false } ] }, { "claim": "Patients already taking ELIQUIS 2.5 mg twice daily should avoid coadministration with combined P-gp and strong CYP3A4 inhibitors entirely.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "8105342b-bc32-471a-9af5-413747df63b2", "content": "50% when ELIQUIS is coadministered with drugs that are combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Clinical Pharmacology (12.3) ] . In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors [see Drug Interactions (7.1) ] . 2.6 Administration Options For patients who are unable to swallow whole tablets, 5 mg and 2.5 mg ELIQUIS tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice, or mixed with applesauce and promptly administered orally [see Clinical Pharmacology (12.3) ] . Alternatively, ELIQUIS tablets may be crushed and suspended in 60 mL of water or D5W and promptly delivered through a nasogastric tube [see Clinical Pharmacology (12.3) ] . Crushed ELIQUIS tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours. DOSAGE FORMS AND STRENGTHS 3 DOSAGE FORMS AND STRENGTHS 2.5 mg, yellow, round, biconvex, film-coated tablets with \u201c893\u201d debossed on one side and \u201c2\u00bd\u201d on the other side. 5 mg, pink, oval-shaped, biconvex, film-coated tablets with \u201c894\u201d debossed on one side and \u201c5\u201d on the other side. Tablets: 2.5 mg and 5 mg (3) CONTRAINDICATIONS 4 CONTRAINDICATIONS ELIQUIS is contraindicated in patients with the following conditions: Active pathological bleeding [see", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "707a0639-b10c-4b2b-a58a-81513c5a7a65", "content": "Inducers of CYP3A4 and P-gp decrease exposure to apixaban and increase the risk of stroke and other thromboembolic events. Combined P-gp and strong CYP3A4 inhibitors increase blood levels of apixaban. Reduce ELIQUIS dose or avoid coadministration. (2.5 , 7.1 , 12.3) Simultaneous use of combined P-gp and strong CYP3A4 inducers reduces blood levels of apixaban: Avoid concomitant use. (7.2 , 12.3) 7.1 Combined P-gp and Strong CYP3A4 Inhibitors For patients receiving ELIQUIS 5 mg or 10 mg twice daily, the dose of ELIQUIS should be decreased by 50% when coadministered with drugs that are combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . For patients receiving ELIQUIS at a dose of 2.5 mg twice daily, avoid coadministration with combined P-gp and strong CYP3A4 inhibitors [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . Clarithromycin Although clarithromycin is a combined P-gp and strong CYP3A4 inhibitor, pharmacokinetic data suggest that no dose adjustment is necessary with concomitant administration with ELIQUIS [see Clinical Pharmacology (12.3) ] . 7.2 Combined P-gp and Strong CYP3A4 Inducers Avoid concomitant use of ELIQUIS with combined P-gp and strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John\u2019s wort) because such drugs", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "Combined P-gp and strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) should be avoided as they decrease apixaban exposure.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "707a0639-b10c-4b2b-a58a-81513c5a7a65", "content": "Inducers of CYP3A4 and P-gp decrease exposure to apixaban and increase the risk of stroke and other thromboembolic events. Combined P-gp and strong CYP3A4 inhibitors increase blood levels of apixaban. Reduce ELIQUIS dose or avoid coadministration. (2.5 , 7.1 , 12.3) Simultaneous use of combined P-gp and strong CYP3A4 inducers reduces blood levels of apixaban: Avoid concomitant use. (7.2 , 12.3) 7.1 Combined P-gp and Strong CYP3A4 Inhibitors For patients receiving ELIQUIS 5 mg or 10 mg twice daily, the dose of ELIQUIS should be decreased by 50% when coadministered with drugs that are combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . For patients receiving ELIQUIS at a dose of 2.5 mg twice daily, avoid coadministration with combined P-gp and strong CYP3A4 inhibitors [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . Clarithromycin Although clarithromycin is a combined P-gp and strong CYP3A4 inhibitor, pharmacokinetic data suggest that no dose adjustment is necessary with concomitant administration with ELIQUIS [see Clinical Pharmacology (12.3) ] . 7.2 Combined P-gp and Strong CYP3A4 Inducers Avoid concomitant use of ELIQUIS with combined P-gp and strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John\u2019s wort) because such drugs", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "Clarithromycin, despite being a combined P-gp and strong CYP3A4 inhibitor, requires no dose adjustment based on pharmacokinetic data.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "707a0639-b10c-4b2b-a58a-81513c5a7a65", "content": "Inducers of CYP3A4 and P-gp decrease exposure to apixaban and increase the risk of stroke and other thromboembolic events. Combined P-gp and strong CYP3A4 inhibitors increase blood levels of apixaban. Reduce ELIQUIS dose or avoid coadministration. (2.5 , 7.1 , 12.3) Simultaneous use of combined P-gp and strong CYP3A4 inducers reduces blood levels of apixaban: Avoid concomitant use. (7.2 , 12.3) 7.1 Combined P-gp and Strong CYP3A4 Inhibitors For patients receiving ELIQUIS 5 mg or 10 mg twice daily, the dose of ELIQUIS should be decreased by 50% when coadministered with drugs that are combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . For patients receiving ELIQUIS at a dose of 2.5 mg twice daily, avoid coadministration with combined P-gp and strong CYP3A4 inhibitors [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . Clarithromycin Although clarithromycin is a combined P-gp and strong CYP3A4 inhibitor, pharmacokinetic data suggest that no dose adjustment is necessary with concomitant administration with ELIQUIS [see Clinical Pharmacology (12.3) ] . 7.2 Combined P-gp and Strong CYP3A4 Inducers Avoid concomitant use of ELIQUIS with combined P-gp and strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John\u2019s wort) because such drugs", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "ELIQUIS is contraindicated in patients with active pathological bleeding.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "8105342b-bc32-471a-9af5-413747df63b2", "content": "50% when ELIQUIS is coadministered with drugs that are combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Clinical Pharmacology (12.3) ] . In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors [see Drug Interactions (7.1) ] . 2.6 Administration Options For patients who are unable to swallow whole tablets, 5 mg and 2.5 mg ELIQUIS tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice, or mixed with applesauce and promptly administered orally [see Clinical Pharmacology (12.3) ] . Alternatively, ELIQUIS tablets may be crushed and suspended in 60 mL of water or D5W and promptly delivered through a nasogastric tube [see Clinical Pharmacology (12.3) ] . Crushed ELIQUIS tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours. DOSAGE FORMS AND STRENGTHS 3 DOSAGE FORMS AND STRENGTHS 2.5 mg, yellow, round, biconvex, film-coated tablets with \u201c893\u201d debossed on one side and \u201c2\u00bd\u201d on the other side. 5 mg, pink, oval-shaped, biconvex, film-coated tablets with \u201c894\u201d debossed on one side and \u201c5\u201d on the other side. Tablets: 2.5 mg and 5 mg (3) CONTRAINDICATIONS 4 CONTRAINDICATIONS ELIQUIS is contraindicated in patients with the following conditions: Active pathological bleeding [see", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "dd0a9ca4-2414-420b-b579-d479dee4a860", "content": "Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) [see Adverse Reactions (6.1) ] Active pathological bleeding (4) Severe hypersensitivity to ELIQUIS (4) BOXED WARNING WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) , and Clinical Studies (14.1) ] . (B) SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "ELIQUIS is contraindicated in patients with severe hypersensitivity reactions to the drug, including anaphylactic reactions.", "verdict": "supported", "confidence": 0.95, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "dd0a9ca4-2414-420b-b579-d479dee4a860", "content": "Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) [see Adverse Reactions (6.1) ] Active pathological bleeding (4) Severe hypersensitivity to ELIQUIS (4) BOXED WARNING WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) , and Clinical Studies (14.1) ] . (B) SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "58a85d38-f31b-4f86-ada6-6a947836b6f8", "content": "with higher scores predicting greater risk), prior warfarin use, geographic region, and aspirin use at randomization (Figure 1). Subjects treated with ELIQUIS with diabetes bled more (3% per year) than did subjects without diabetes (1.9% per year). Figure 1: Major Bleeding Hazard Ratios by Baseline Characteristics \u2013 ARISTOTLE Study Note: The figure above presents effects in various subgroups, all of which are baseline characteristics and all of which were prespecified, if not the groupings. The 95% confidence limits that are shown do not take into account how many comparisons were made, nor do they reflect the effect of a particular factor after adjustment for all other factors. Apparent homogeneity or heterogeneity among groups should not be over-interpreted. Table 2: Bleeding Events in Patients with Nonvalvular Atrial Fibrillation in AVERROES ELIQUIS N=2798 n (%/year) Aspirin N=2780 n (%/year) Hazard Ratio (95% CI) P-value Events associated with each endpoint were counted once per subject, but subjects may have contributed events to multiple endpoints. Major 45 (1.41) 29 (0.92) 1.54 (0.96, 2.45) 0.07 Fatal 5 (0.16) 5 (0.16) 0.99 (0.23, 4.29) - Intracranial 11 (0.34) 11 (0.35) 0.99 (0.39, 2.51) - ARISTOTLE Major Bleeding Forest Plot Other Adverse Reactions Hypersensitivity reactions (including drug hypersensitivity, such as skin rash, and anaphylactic reactions, such as", "relevance_score": 0.3333, "authority_status": null, "superseded": false }, { "memory_id": "e4d96b9a-f19b-48a3-ac5f-3515b2a95e57", "content": "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. Table 3: Bleeding During the Treatment Period in Patients Undergoing Elective Hip or Knee Replacement Surgery Bleeding Endpoint* ADVANCE-3 Hip Replacement Surgery ADVANCE-2 Knee Replacement Surgery ADVANCE-1 Knee Replacement Surgery * All bleeding criteria included surgical site bleeding. \u2020 Includes 13 subjects with major bleeding events that occurred before the first dose of ELIQUIS (administered 12 to 24 hours post-surgery). \u2021 Includes 5 subjects with major bleeding events that occurred before the first dose of ELIQUIS (administered 12 to 24 hours post-surgery). \u00a7 Intracranial, intraspinal, intraocular, pericardial, an operated joint requiring re-operation or", "relevance_score": 0.25, "authority_status": null, "superseded": false } ] }, { "claim": "Premature discontinuation of ELIQUIS increases the risk of thrombotic events.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "dd0a9ca4-2414-420b-b579-d479dee4a860", "content": "Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) [see Adverse Reactions (6.1) ] Active pathological bleeding (4) Severe hypersensitivity to ELIQUIS (4) BOXED WARNING WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) , and Clinical Studies (14.1) ] . (B) SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "9e4f7751-027e-497b-b601-69f7bde25861", "content": "(NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity or spinal surgery optimal timing between the administration of ELIQUIS and neuraxial procedures is not known [see Warnings and Precautions (5.3) ] Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary [see Warnings and Precautions (5.3) ] . Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated [see Warnings and Precautions (5.3) ] . WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA See full prescribing information for complete boxed warning. (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS: Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. To reduce this risk, consider coverage with another anticoagulant if ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy. (2.4 , 5.1 , 14.1) (B) SPINAL/EPIDURAL HEMATOMA: Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may", "relevance_score": 0.5, "authority_status": null, "superseded": false }, { "memory_id": "23045ede-f129-440a-950a-0cb911772683", "content": "result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. (5.3) ADVERSE REACTIONS 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the prescribing information. Increased Risk of Thrombotic Events After Premature Discontinuation [see Warnings and Precautions (5.1) ] Bleeding [see Warnings and Precautions (5.2) ] Spinal/Epidural Anesthesia or Puncture [see Warnings and Precautions (5.3) ] Most common adverse reactions (>1%) are related to bleeding. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation The safety of ELIQUIS was evaluated in the ARISTOTLE and AVERROES studies [see Clinical Studies (14) ] , including 11,284 patients exposed to ELIQUIS 5 mg twice daily and 602 patients exposed to ELIQUIS 2.5 mg twice daily. The duration of ELIQUIS exposure was \u226512 months for", "relevance_score": 0.3333, "authority_status": null, "superseded": false } ] }, { "claim": "If ELIQUIS discontinuation occurs for reasons other than pathological bleeding or completion of therapy, coverage with another anticoagulant should be considered.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "9e4f7751-027e-497b-b601-69f7bde25861", "content": "(NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity or spinal surgery optimal timing between the administration of ELIQUIS and neuraxial procedures is not known [see Warnings and Precautions (5.3) ] Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary [see Warnings and Precautions (5.3) ] . Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated [see Warnings and Precautions (5.3) ] . WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA See full prescribing information for complete boxed warning. (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS: Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. To reduce this risk, consider coverage with another anticoagulant if ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy. (2.4 , 5.1 , 14.1) (B) SPINAL/EPIDURAL HEMATOMA: Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "dd0a9ca4-2414-420b-b579-d479dee4a860", "content": "Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) [see Adverse Reactions (6.1) ] Active pathological bleeding (4) Severe hypersensitivity to ELIQUIS (4) BOXED WARNING WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) , and Clinical Studies (14.1) ] . (B) SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "Epidural or spinal hematomas may occur in patients receiving ELIQUIS and undergoing neuraxial anesthesia or spinal puncture, potentially resulting in long-term or permanent paralysis.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "dd0a9ca4-2414-420b-b579-d479dee4a860", "content": "Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) [see Adverse Reactions (6.1) ] Active pathological bleeding (4) Severe hypersensitivity to ELIQUIS (4) BOXED WARNING WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) , and Clinical Studies (14.1) ] . (B) SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "9e4f7751-027e-497b-b601-69f7bde25861", "content": "(NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity or spinal surgery optimal timing between the administration of ELIQUIS and neuraxial procedures is not known [see Warnings and Precautions (5.3) ] Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary [see Warnings and Precautions (5.3) ] . Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated [see Warnings and Precautions (5.3) ] . WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA See full prescribing information for complete boxed warning. (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS: Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. To reduce this risk, consider coverage with another anticoagulant if ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy. (2.4 , 5.1 , 14.1) (B) SPINAL/EPIDURAL HEMATOMA: Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may", "relevance_score": 0.5, "authority_status": null, "superseded": false }, { "memory_id": "23045ede-f129-440a-950a-0cb911772683", "content": "result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. (5.3) ADVERSE REACTIONS 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the prescribing information. Increased Risk of Thrombotic Events After Premature Discontinuation [see Warnings and Precautions (5.1) ] Bleeding [see Warnings and Precautions (5.2) ] Spinal/Epidural Anesthesia or Puncture [see Warnings and Precautions (5.3) ] Most common adverse reactions (>1%) are related to bleeding. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation The safety of ELIQUIS was evaluated in the ARISTOTLE and AVERROES studies [see Clinical Studies (14) ] , including 11,284 patients exposed to ELIQUIS 5 mg twice daily and 602 patients exposed to ELIQUIS 2.5 mg twice daily. The duration of ELIQUIS exposure was \u226512 months for", "relevance_score": 0.3333, "authority_status": null, "superseded": false } ] }, { "claim": "Risk factors for epidural or spinal hematomas in ELIQUIS patients include indwelling epidural catheters.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "dd0a9ca4-2414-420b-b579-d479dee4a860", "content": "Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) [see Adverse Reactions (6.1) ] Active pathological bleeding (4) Severe hypersensitivity to ELIQUIS (4) BOXED WARNING WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) , and Clinical Studies (14.1) ] . (B) SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "9e4f7751-027e-497b-b601-69f7bde25861", "content": "(NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity or spinal surgery optimal timing between the administration of ELIQUIS and neuraxial procedures is not known [see Warnings and Precautions (5.3) ] Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary [see Warnings and Precautions (5.3) ] . Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated [see Warnings and Precautions (5.3) ] . WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA See full prescribing information for complete boxed warning. (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS: Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. To reduce this risk, consider coverage with another anticoagulant if ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy. (2.4 , 5.1 , 14.1) (B) SPINAL/EPIDURAL HEMATOMA: Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "Risk factors for epidural or spinal hematomas in ELIQUIS patients include concomitant use of drugs affecting hemostasis (NSAIDs, platelet inhibitors, other anticoagulants).", "verdict": "supported", "confidence": 0.95, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "dd0a9ca4-2414-420b-b579-d479dee4a860", "content": "Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) [see Adverse Reactions (6.1) ] Active pathological bleeding (4) Severe hypersensitivity to ELIQUIS (4) BOXED WARNING WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) , and Clinical Studies (14.1) ] . (B) SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "Risk factors for epidural or spinal hematomas in ELIQUIS patients include history of traumatic or repeated epidural or spinal punctures.", "verdict": "supported", "confidence": 0.95, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "9e4f7751-027e-497b-b601-69f7bde25861", "content": "(NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity or spinal surgery optimal timing between the administration of ELIQUIS and neuraxial procedures is not known [see Warnings and Precautions (5.3) ] Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary [see Warnings and Precautions (5.3) ] . Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated [see Warnings and Precautions (5.3) ] . WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA See full prescribing information for complete boxed warning. (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS: Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. To reduce this risk, consider coverage with another anticoagulant if ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy. (2.4 , 5.1 , 14.1) (B) SPINAL/EPIDURAL HEMATOMA: Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "dd0a9ca4-2414-420b-b579-d479dee4a860", "content": "Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) [see Adverse Reactions (6.1) ] Active pathological bleeding (4) Severe hypersensitivity to ELIQUIS (4) BOXED WARNING WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) , and Clinical Studies (14.1) ] . (B) SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "Risk factors for epidural or spinal hematomas in ELIQUIS patients include history of spinal deformity or spinal surgery.", "verdict": "supported", "confidence": 0.95, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "dd0a9ca4-2414-420b-b579-d479dee4a860", "content": "Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) [see Adverse Reactions (6.1) ] Active pathological bleeding (4) Severe hypersensitivity to ELIQUIS (4) BOXED WARNING WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) , and Clinical Studies (14.1) ] . (B) SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "9e4f7751-027e-497b-b601-69f7bde25861", "content": "(NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity or spinal surgery optimal timing between the administration of ELIQUIS and neuraxial procedures is not known [see Warnings and Precautions (5.3) ] Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary [see Warnings and Precautions (5.3) ] . Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated [see Warnings and Precautions (5.3) ] . WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA See full prescribing information for complete boxed warning. (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS: Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. To reduce this risk, consider coverage with another anticoagulant if ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy. (2.4 , 5.1 , 14.1) (B) SPINAL/EPIDURAL HEMATOMA: Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "ELIQUIS should be discontinued at least 36 hours prior to elective surgery or invasive procedures with moderate or high bleeding risk.", "verdict": "contradicted", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "contradicts_current_source", "evidence": [ { "memory_id": "0173d387-1322-4350-9a0e-f00deabb9880", "content": "be taken 12 to 24 hours after surgery. In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days. Treatment of DVT and PE The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily. Reduction in the Risk of Recurrence of DVT and PE The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3) ] . 2.2 Missed Dose If a dose of ELIQUIS is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose. 2.3 Temporary Interruption for Surgery and Other Interventions ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5.2) ] . ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. Bridging anticoagulation during the 24", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "For procedures with low bleeding risk or where bleeding would be non-critical and easily controlled, ELIQUIS should be discontinued at least 24 hours prior.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "0173d387-1322-4350-9a0e-f00deabb9880", "content": "be taken 12 to 24 hours after surgery. In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days. Treatment of DVT and PE The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily. Reduction in the Risk of Recurrence of DVT and PE The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3) ] . 2.2 Missed Dose If a dose of ELIQUIS is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose. 2.3 Temporary Interruption for Surgery and Other Interventions ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5.2) ] . ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. Bridging anticoagulation during the 24", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "Bridging anticoagulation during the 24 to 48 hours after stopping ELIQUIS is generally not required.", "verdict": "supported", "confidence": 0.95, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "0173d387-1322-4350-9a0e-f00deabb9880", "content": "be taken 12 to 24 hours after surgery. In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days. Treatment of DVT and PE The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily. Reduction in the Risk of Recurrence of DVT and PE The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3) ] . 2.2 Missed Dose If a dose of ELIQUIS is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose. 2.3 Temporary Interruption for Surgery and Other Interventions ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5.2) ] . ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. Bridging anticoagulation during the 24", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "ELIQUIS should be restarted after adequate hemostasis is established.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "f1551753-707d-46a0-8344-278b245079ae", "content": "to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established. 2.4 Converting from or to ELIQUIS Switching from warfarin to ELIQUIS: Warfarin should be discontinued and ELIQUIS started when the international normalized ratio (INR) is below 2.0. Switching from ELIQUIS to warfarin: ELIQUIS affects INR, so that initial INR measurements during the transition to warfarin may not be useful for determining the appropriate dose of warfarin. One approach is to discontinue ELIQUIS and begin both a parenteral anticoagulant and warfarin at the time the next dose of ELIQUIS would have been taken, discontinuing the parenteral anticoagulant when INR reaches an acceptable range. Switching from ELIQUIS to anticoagulants other than warfarin (oral or parenteral): Discontinue ELIQUIS and begin taking the new anticoagulant other than warfarin at the usual time of the next dose of ELIQUIS. Switching from anticoagulants other than warfarin (oral or parenteral) to ELIQUIS: Discontinue the anticoagulant other than warfarin and begin taking ELIQUIS at the usual time of the next dose of the anticoagulant other than warfarin. 2.5 Combined P-gp and Strong CYP3A4 Inhibitors For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose by", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "When switching from warfarin to ELIQUIS, warfarin should be discontinued and ELIQUIS started when the international normalized ratio (INR) is below 3.0.", "verdict": "contradicted", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "contradicts_current_source", "evidence": [ { "memory_id": "f1551753-707d-46a0-8344-278b245079ae", "content": "to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established. 2.4 Converting from or to ELIQUIS Switching from warfarin to ELIQUIS: Warfarin should be discontinued and ELIQUIS started when the international normalized ratio (INR) is below 2.0. Switching from ELIQUIS to warfarin: ELIQUIS affects INR, so that initial INR measurements during the transition to warfarin may not be useful for determining the appropriate dose of warfarin. One approach is to discontinue ELIQUIS and begin both a parenteral anticoagulant and warfarin at the time the next dose of ELIQUIS would have been taken, discontinuing the parenteral anticoagulant when INR reaches an acceptable range. Switching from ELIQUIS to anticoagulants other than warfarin (oral or parenteral): Discontinue ELIQUIS and begin taking the new anticoagulant other than warfarin at the usual time of the next dose of ELIQUIS. Switching from anticoagulants other than warfarin (oral or parenteral) to ELIQUIS: Discontinue the anticoagulant other than warfarin and begin taking ELIQUIS at the usual time of the next dose of the anticoagulant other than warfarin. 2.5 Combined P-gp and Strong CYP3A4 Inhibitors For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose by", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "When switching from ELIQUIS to warfarin, ELIQUIS should be discontinued and both a parenteral anticoagulant and warfarin started at the time the next ELIQUIS dose would have been taken.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "f1551753-707d-46a0-8344-278b245079ae", "content": "to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established. 2.4 Converting from or to ELIQUIS Switching from warfarin to ELIQUIS: Warfarin should be discontinued and ELIQUIS started when the international normalized ratio (INR) is below 2.0. Switching from ELIQUIS to warfarin: ELIQUIS affects INR, so that initial INR measurements during the transition to warfarin may not be useful for determining the appropriate dose of warfarin. One approach is to discontinue ELIQUIS and begin both a parenteral anticoagulant and warfarin at the time the next dose of ELIQUIS would have been taken, discontinuing the parenteral anticoagulant when INR reaches an acceptable range. Switching from ELIQUIS to anticoagulants other than warfarin (oral or parenteral): Discontinue ELIQUIS and begin taking the new anticoagulant other than warfarin at the usual time of the next dose of ELIQUIS. Switching from anticoagulants other than warfarin (oral or parenteral) to ELIQUIS: Discontinue the anticoagulant other than warfarin and begin taking ELIQUIS at the usual time of the next dose of the anticoagulant other than warfarin. 2.5 Combined P-gp and Strong CYP3A4 Inhibitors For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose by", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "When switching from ELIQUIS to warfarin, the parenteral anticoagulant should be discontinued when INR reaches an acceptable range.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "f1551753-707d-46a0-8344-278b245079ae", "content": "to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established. 2.4 Converting from or to ELIQUIS Switching from warfarin to ELIQUIS: Warfarin should be discontinued and ELIQUIS started when the international normalized ratio (INR) is below 2.0. Switching from ELIQUIS to warfarin: ELIQUIS affects INR, so that initial INR measurements during the transition to warfarin may not be useful for determining the appropriate dose of warfarin. One approach is to discontinue ELIQUIS and begin both a parenteral anticoagulant and warfarin at the time the next dose of ELIQUIS would have been taken, discontinuing the parenteral anticoagulant when INR reaches an acceptable range. Switching from ELIQUIS to anticoagulants other than warfarin (oral or parenteral): Discontinue ELIQUIS and begin taking the new anticoagulant other than warfarin at the usual time of the next dose of ELIQUIS. Switching from anticoagulants other than warfarin (oral or parenteral) to ELIQUIS: Discontinue the anticoagulant other than warfarin and begin taking ELIQUIS at the usual time of the next dose of the anticoagulant other than warfarin. 2.5 Combined P-gp and Strong CYP3A4 Inhibitors For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose by", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "When switching to or from other anticoagulants (non-warfarin), ELIQUIS should be discontinued and the new anticoagulant begun at the usual time of the next dose.", "verdict": "supported", "confidence": 0.95, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "f1551753-707d-46a0-8344-278b245079ae", "content": "to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established. 2.4 Converting from or to ELIQUIS Switching from warfarin to ELIQUIS: Warfarin should be discontinued and ELIQUIS started when the international normalized ratio (INR) is below 2.0. Switching from ELIQUIS to warfarin: ELIQUIS affects INR, so that initial INR measurements during the transition to warfarin may not be useful for determining the appropriate dose of warfarin. One approach is to discontinue ELIQUIS and begin both a parenteral anticoagulant and warfarin at the time the next dose of ELIQUIS would have been taken, discontinuing the parenteral anticoagulant when INR reaches an acceptable range. Switching from ELIQUIS to anticoagulants other than warfarin (oral or parenteral): Discontinue ELIQUIS and begin taking the new anticoagulant other than warfarin at the usual time of the next dose of ELIQUIS. Switching from anticoagulants other than warfarin (oral or parenteral) to ELIQUIS: Discontinue the anticoagulant other than warfarin and begin taking ELIQUIS at the usual time of the next dose of the anticoagulant other than warfarin. 2.5 Combined P-gp and Strong CYP3A4 Inhibitors For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose by", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "5 mg and 2.5 mg ELIQUIS tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice for patients unable to swallow whole tablets.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "8105342b-bc32-471a-9af5-413747df63b2", "content": "50% when ELIQUIS is coadministered with drugs that are combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Clinical Pharmacology (12.3) ] . In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors [see Drug Interactions (7.1) ] . 2.6 Administration Options For patients who are unable to swallow whole tablets, 5 mg and 2.5 mg ELIQUIS tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice, or mixed with applesauce and promptly administered orally [see Clinical Pharmacology (12.3) ] . Alternatively, ELIQUIS tablets may be crushed and suspended in 60 mL of water or D5W and promptly delivered through a nasogastric tube [see Clinical Pharmacology (12.3) ] . Crushed ELIQUIS tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours. DOSAGE FORMS AND STRENGTHS 3 DOSAGE FORMS AND STRENGTHS 2.5 mg, yellow, round, biconvex, film-coated tablets with \u201c893\u201d debossed on one side and \u201c2\u00bd\u201d on the other side. 5 mg, pink, oval-shaped, biconvex, film-coated tablets with \u201c894\u201d debossed on one side and \u201c5\u201d on the other side. Tablets: 2.5 mg and 5 mg (3) CONTRAINDICATIONS 4 CONTRAINDICATIONS ELIQUIS is contraindicated in patients with the following conditions: Active pathological bleeding [see", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "5 mg and 2.5 mg ELIQUIS tablets may be mixed with applesauce and promptly administered orally for patients unable to swallow whole tablets.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "8105342b-bc32-471a-9af5-413747df63b2", "content": "50% when ELIQUIS is coadministered with drugs that are combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Clinical Pharmacology (12.3) ] . In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors [see Drug Interactions (7.1) ] . 2.6 Administration Options For patients who are unable to swallow whole tablets, 5 mg and 2.5 mg ELIQUIS tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice, or mixed with applesauce and promptly administered orally [see Clinical Pharmacology (12.3) ] . Alternatively, ELIQUIS tablets may be crushed and suspended in 60 mL of water or D5W and promptly delivered through a nasogastric tube [see Clinical Pharmacology (12.3) ] . Crushed ELIQUIS tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours. DOSAGE FORMS AND STRENGTHS 3 DOSAGE FORMS AND STRENGTHS 2.5 mg, yellow, round, biconvex, film-coated tablets with \u201c893\u201d debossed on one side and \u201c2\u00bd\u201d on the other side. 5 mg, pink, oval-shaped, biconvex, film-coated tablets with \u201c894\u201d debossed on one side and \u201c5\u201d on the other side. Tablets: 2.5 mg and 5 mg (3) CONTRAINDICATIONS 4 CONTRAINDICATIONS ELIQUIS is contraindicated in patients with the following conditions: Active pathological bleeding [see", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "Crushed ELIQUIS tablets may be suspended in 60 mL of water or D5W and delivered through a nasogastric tube.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "8105342b-bc32-471a-9af5-413747df63b2", "content": "50% when ELIQUIS is coadministered with drugs that are combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Clinical Pharmacology (12.3) ] . In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors [see Drug Interactions (7.1) ] . 2.6 Administration Options For patients who are unable to swallow whole tablets, 5 mg and 2.5 mg ELIQUIS tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice, or mixed with applesauce and promptly administered orally [see Clinical Pharmacology (12.3) ] . Alternatively, ELIQUIS tablets may be crushed and suspended in 60 mL of water or D5W and promptly delivered through a nasogastric tube [see Clinical Pharmacology (12.3) ] . Crushed ELIQUIS tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours. DOSAGE FORMS AND STRENGTHS 3 DOSAGE FORMS AND STRENGTHS 2.5 mg, yellow, round, biconvex, film-coated tablets with \u201c893\u201d debossed on one side and \u201c2\u00bd\u201d on the other side. 5 mg, pink, oval-shaped, biconvex, film-coated tablets with \u201c894\u201d debossed on one side and \u201c5\u201d on the other side. Tablets: 2.5 mg and 5 mg (3) CONTRAINDICATIONS 4 CONTRAINDICATIONS ELIQUIS is contraindicated in patients with the following conditions: Active pathological bleeding [see", "relevance_score": 1.0, "authority_status": null, "superseded": false }, { "memory_id": "8b847d0c-07c9-4ab9-8a34-dec05b014ec3", "content": "effect on the QTc interval in humans at doses up to 50 mg. 12.3 Pharmacokinetics Apixaban demonstrates linear pharmacokinetics with dose-proportional increases in exposure for oral doses up to 10 mg. Absorption The absolute bioavailability of apixaban is approximately 50% for doses up to 10 mg of ELIQUIS. Food does not affect the bioavailability of apixaban. Maximum concentrations (C max ) of apixaban appear 3 to 4 hours after oral administration of ELIQUIS. At doses \u226525 mg, apixaban displays dissolution-limited absorption with decreased bioavailability. Following oral administration of 10 mg of apixaban as 2 crushed 5 mg tablets suspended in 30 mL of water, exposure was similar to that after oral administration of 2 intact 5 mg tablets. Following oral administration of 10 mg of apixaban as 2 crushed 5 mg tablets mixed with 30 g of applesauce, the C max and AUC were 20% and 16% lower, respectively, when compared to administration of 2 intact 5 mg tablets. Following administration of a crushed 5 mg ELIQUIS tablet that was suspended in 60 mL D5W and delivered through a nasogastric tube, exposure was similar to that seen in other clinical trials involving healthy volunteers receiving a single oral 5 mg tablet dose. Distribution Plasma protein binding in humans is approximately 87%. The volume of distribution (Vss) is approximately 21 liters. Metabolism Approximately 25% of an", "relevance_score": 0.5, "authority_status": null, "superseded": false } ] }, { "claim": "Crushed ELIQUIS tablets remain stable in water, D5W, apple juice, and applesauce for up to 2 hours.", "verdict": "uncertain", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "conflicting_sources", "evidence": [ { "memory_id": "8105342b-bc32-471a-9af5-413747df63b2", "content": "50% when ELIQUIS is coadministered with drugs that are combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Clinical Pharmacology (12.3) ] . In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors [see Drug Interactions (7.1) ] . 2.6 Administration Options For patients who are unable to swallow whole tablets, 5 mg and 2.5 mg ELIQUIS tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice, or mixed with applesauce and promptly administered orally [see Clinical Pharmacology (12.3) ] . Alternatively, ELIQUIS tablets may be crushed and suspended in 60 mL of water or D5W and promptly delivered through a nasogastric tube [see Clinical Pharmacology (12.3) ] . Crushed ELIQUIS tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours. DOSAGE FORMS AND STRENGTHS 3 DOSAGE FORMS AND STRENGTHS 2.5 mg, yellow, round, biconvex, film-coated tablets with \u201c893\u201d debossed on one side and \u201c2\u00bd\u201d on the other side. 5 mg, pink, oval-shaped, biconvex, film-coated tablets with \u201c894\u201d debossed on one side and \u201c5\u201d on the other side. Tablets: 2.5 mg and 5 mg (3) CONTRAINDICATIONS 4 CONTRAINDICATIONS ELIQUIS is contraindicated in patients with the following conditions: Active pathological bleeding [see", "relevance_score": 1.0, "authority_status": null, "superseded": false } ], "note": "the corpus contains conflicting sources/versions for this claim (some support it, some refute it); reported as a conflict, not a confident contradiction \u2014 scope the review to the controlling version to resolve" }, { "claim": "ELIQUIS 2.5 mg tablets are yellow round biconvex film-coated tablets debossed with '893' on one side and '2\u00bd' on the other.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "8105342b-bc32-471a-9af5-413747df63b2", "content": "50% when ELIQUIS is coadministered with drugs that are combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Clinical Pharmacology (12.3) ] . In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors [see Drug Interactions (7.1) ] . 2.6 Administration Options For patients who are unable to swallow whole tablets, 5 mg and 2.5 mg ELIQUIS tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice, or mixed with applesauce and promptly administered orally [see Clinical Pharmacology (12.3) ] . Alternatively, ELIQUIS tablets may be crushed and suspended in 60 mL of water or D5W and promptly delivered through a nasogastric tube [see Clinical Pharmacology (12.3) ] . Crushed ELIQUIS tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours. DOSAGE FORMS AND STRENGTHS 3 DOSAGE FORMS AND STRENGTHS 2.5 mg, yellow, round, biconvex, film-coated tablets with \u201c893\u201d debossed on one side and \u201c2\u00bd\u201d on the other side. 5 mg, pink, oval-shaped, biconvex, film-coated tablets with \u201c894\u201d debossed on one side and \u201c5\u201d on the other side. Tablets: 2.5 mg and 5 mg (3) CONTRAINDICATIONS 4 CONTRAINDICATIONS ELIQUIS is contraindicated in patients with the following conditions: Active pathological bleeding [see", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "ELIQUIS 5 mg tablets are pink oval-shaped biconvex film-coated tablets debossed with '894' on one side and '5' on the other.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "8105342b-bc32-471a-9af5-413747df63b2", "content": "50% when ELIQUIS is coadministered with drugs that are combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Clinical Pharmacology (12.3) ] . In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors [see Drug Interactions (7.1) ] . 2.6 Administration Options For patients who are unable to swallow whole tablets, 5 mg and 2.5 mg ELIQUIS tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice, or mixed with applesauce and promptly administered orally [see Clinical Pharmacology (12.3) ] . Alternatively, ELIQUIS tablets may be crushed and suspended in 60 mL of water or D5W and promptly delivered through a nasogastric tube [see Clinical Pharmacology (12.3) ] . Crushed ELIQUIS tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours. DOSAGE FORMS AND STRENGTHS 3 DOSAGE FORMS AND STRENGTHS 2.5 mg, yellow, round, biconvex, film-coated tablets with \u201c893\u201d debossed on one side and \u201c2\u00bd\u201d on the other side. 5 mg, pink, oval-shaped, biconvex, film-coated tablets with \u201c894\u201d debossed on one side and \u201c5\u201d on the other side. Tablets: 2.5 mg and 5 mg (3) CONTRAINDICATIONS 4 CONTRAINDICATIONS ELIQUIS is contraindicated in patients with the following conditions: Active pathological bleeding [see", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "If a dose of ELIQUIS is missed, it should be taken as soon as possible on the same day and twice-daily administration resumed.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "0173d387-1322-4350-9a0e-f00deabb9880", "content": "be taken 12 to 24 hours after surgery. In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days. Treatment of DVT and PE The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily. Reduction in the Risk of Recurrence of DVT and PE The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3) ] . 2.2 Missed Dose If a dose of ELIQUIS is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose. 2.3 Temporary Interruption for Surgery and Other Interventions ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5.2) ] . ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. Bridging anticoagulation during the 24", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "A missed dose of ELIQUIS should not be doubled to make up for the missed dose.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "0173d387-1322-4350-9a0e-f00deabb9880", "content": "be taken 12 to 24 hours after surgery. In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days. Treatment of DVT and PE The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily. Reduction in the Risk of Recurrence of DVT and PE The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3) ] . 2.2 Missed Dose If a dose of ELIQUIS is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose. 2.3 Temporary Interruption for Surgery and Other Interventions ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5.2) ] . ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. Bridging anticoagulation during the 24", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "ELIQUIS is not recommended in pregnancy.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "509581b2-104c-4aa2-ac2e-060dc19b7327", "content": "will decrease exposure to apixaban [see Clinical Pharmacology (12.3) ] . 7.3 Anticoagulants and Antiplatelet Agents Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. APPRAISE-2, a placebo-controlled clinical trial of ELIQUIS in high-risk, post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel, was terminated early due to a higher rate of bleeding with ELIQUIS compared to placebo. The rate of ISTH major bleeding was 2.8% per year with ELIQUIS versus 0.6% per year with placebo in patients receiving single antiplatelet therapy and was 5.9% per year with ELIQUIS versus 2.5% per year with placebo in those receiving dual antiplatelet therapy. In ARISTOTLE, concomitant use of aspirin increased the bleeding risk on ELIQUIS from 1.8% per year to 3.4% per year and concomitant use of aspirin and warfarin increased the bleeding risk from 2.7% per year to 4.6% per year. In this clinical trial, there was limited (2.3%) use of dual antiplatelet therapy with ELIQUIS. USE IN SPECIFIC POPULATIONS 8 USE IN SPECIFIC POPULATIONS Pregnancy: Not recommended. (8.1) Lactation: Discontinue drug or discontinue nursing. (8.2) Severe Hepatic Impairment: Not recommended. (8.7 , 12.2) 8.1 Pregnancy Risk Summary The limited available data on ELIQUIS use in pregnant women are", "relevance_score": 0.5, "authority_status": null, "superseded": false }, { "memory_id": "52388ca8-3709-4200-9236-72d1446d4b20", "content": "insufficient to inform drug-associated risks of major birth defects, miscarriage, or adverse developmental outcomes. Treatment may increase the risk of bleeding during pregnancy and delivery. In animal reproduction studies, no adverse developmental effects were seen when apixaban was administered to rats (orally), rabbits (intravenously) and mice (orally) during organogenesis at unbound apixaban exposure levels up to 4, 1 and 19 times, respectively, the human exposure based on area under plasma-concentration time curve (AUC) at the Maximum Recommended Human Dose (MRHD) of 5 mg twice daily. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Pregnancy confers an increased risk of thromboembolism that is higher for women with underlying thromboembolic disease and certain high-risk pregnancy conditions. Published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy. Fetal/Neonatal adverse reactions Use of", "relevance_score": 0.1667, "authority_status": null, "superseded": false } ] }, { "claim": "Breastfeeding is not recommended during ELIQUIS treatment.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "175c3dec-a160-4d73-8492-b0c95fbc3cc4", "content": "milk production. Apixaban and/or its metabolites were present in the milk of rats (see Data). Because human exposure through milk is unknown, breastfeeding is not recommended during treatment with ELIQUIS. Data Animal Data Maximal plasma concentrations were observed after 30 minutes following a single oral administration of a 5 mg dose to lactating rats. Maximal milk concentrations were observed 6 hours after dosing. The milk to plasma AUC (0-24) ratio is 30:1 indicating that apixaban can accumulate in milk. The concentrations of apixaban in animal milk does not necessarily predict the concentration of drug in human milk. 8.3 Females and Males of Reproductive Potential Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician. The risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including ELIQUIS should be assessed in females of reproductive potential and those with abnormal uterine bleeding. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Of the total subjects in the ARISTOTLE and AVERROES clinical studies, >69% were 65 years of age and older, and >31% were 75 years of age and older. In the ADVANCE-1, ADVANCE-2, and ADVANCE-3 clinical studies, 50% of subjects were", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh class A).", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "ada56e47-790a-4a69-849e-f4aec050123f", "content": "Deep Vein Thrombosis Following Hip or Knee Replacement Surgery, and Treatment of DVT and PE and Reduction in the Risk of Recurrence of DVT and PE No dose adjustment is recommended for patients with renal impairment, including those with ESRD on dialysis [see Dosage and Administration (2.1) ] . Clinical efficacy and safety studies with ELIQUIS did not enroll patients with ESRD on dialysis or patients with a CrCl <15 mL/min; therefore, dosing recommendations are based on pharmacokinetic and pharmacodynamic (anti-FXa activity) data in subjects with ESRD maintained on dialysis [see Clinical Pharmacology (12.3) ] . 8.7 Hepatic Impairment No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh class A). Because patients with moderate hepatic impairment (Child-Pugh class B) may have intrinsic coagulation abnormalities and there is limited clinical experience with ELIQUIS in these patients, dosing recommendations cannot be provided [see Clinical Pharmacology (12.2) ] . ELIQUIS is not recommended in patients with severe hepatic impairment (Child-Pugh class C) [see Clinical Pharmacology (12.2) ] . CLINICAL PHARMACOLOGY 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Apixaban is a selective inhibitor of FXa. It does not require antithrombin III for antithrombotic activity. Apixaban inhibits free and clot-bound FXa, and prothrombinase activity. Apixaban has no", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] }, { "claim": "Dosing recommendations cannot be provided for patients with moderate hepatic impairment (Child-Pugh class B) due to potential intrinsic coagulation abnormalities and limited clinical experience.", "verdict": "supported", "confidence": 0.99, "superseded": false, "recovered": false, "reason_code": "supported_by_current_source", "evidence": [ { "memory_id": "ada56e47-790a-4a69-849e-f4aec050123f", "content": "Deep Vein Thrombosis Following Hip or Knee Replacement Surgery, and Treatment of DVT and PE and Reduction in the Risk of Recurrence of DVT and PE No dose adjustment is recommended for patients with renal impairment, including those with ESRD on dialysis [see Dosage and Administration (2.1) ] . Clinical efficacy and safety studies with ELIQUIS did not enroll patients with ESRD on dialysis or patients with a CrCl <15 mL/min; therefore, dosing recommendations are based on pharmacokinetic and pharmacodynamic (anti-FXa activity) data in subjects with ESRD maintained on dialysis [see Clinical Pharmacology (12.3) ] . 8.7 Hepatic Impairment No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh class A). Because patients with moderate hepatic impairment (Child-Pugh class B) may have intrinsic coagulation abnormalities and there is limited clinical experience with ELIQUIS in these patients, dosing recommendations cannot be provided [see Clinical Pharmacology (12.2) ] . ELIQUIS is not recommended in patients with severe hepatic impairment (Child-Pugh class C) [see Clinical Pharmacology (12.2) ] . CLINICAL PHARMACOLOGY 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Apixaban is a selective inhibitor of FXa. It does not require antithrombin III for antithrombotic activity. Apixaban inhibits free and clot-bound FXa, and prothrombinase activity. Apixaban has no", "relevance_score": 1.0, "authority_status": null, "superseded": false } ] } ], "extraction_capped": true, "as_of": "2026-07-20T02:59:09.763837", "request_id": null, "n_recovered": 0, "llm_calls": 50 }, "completeness": null, "seeded_scoring": [ { "original": "approved for five distinct clinical indications", "corrupted": "approved for four distinct clinical indications", "matched_claims": 0, "verdicts": [], "matched_texts": [], "caught": false, "false_supported": false, "unmatched": true }, { "original": "for 35 days, with the initial dose taken 12 to 24 hours after surgery", "corrupted": "for 42 days, with the initial dose taken 12 to 24 hours after surgery", "matched_claims": 1, "verdicts": [ "contradicted" ], "matched_texts": [ "For DVT prophylaxis following hip replacement surgery, the recommended dose is 2.5 mg twice daily for 42 days." ], "caught": true, "false_supported": false, "unmatched": false }, { "original": "discontinued at least 48 hours prior to elective surgery", "corrupted": "discontinued at least 36 hours prior to elective surgery", "matched_claims": 1, "verdicts": [ "contradicted" ], "matched_texts": [ "ELIQUIS should be discontinued at least 36 hours prior to elective surgery or invasive procedures with moderate or high " ], "caught": true, "false_supported": false, "unmatched": false }, { "original": "warfarin should be discontinued and ELIQUIS started when the international normalized ratio (INR) is below 2.0", "corrupted": "warfarin should be discontinued and ELIQUIS started when the international normalized ratio (INR) is below 3.0", "matched_claims": 1, "verdicts": [ "contradicted" ], "matched_texts": [ "When switching from warfarin to ELIQUIS, warfarin should be discontinued and ELIQUIS started when the international norm" ], "caught": true, "false_supported": false, "unmatched": false }, { "original": "remain stable in water, D5W, apple juice, and applesauce for up to 4 hours", "corrupted": "remain stable in water, D5W, apple juice, and applesauce for up to 2 hours", "matched_claims": 3, "verdicts": [ "supported", "uncertain" ], "matched_texts": [ "5 mg and 2.5 mg ELIQUIS tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice for pa", "5 mg and 2.5 mg ELIQUIS tablets may be mixed with applesauce and promptly administered orally for patients unable to swa", "Crushed ELIQUIS tablets remain stable in water, D5W, apple juice, and applesauce for up to 2 hours." ], "caught": true, "false_supported": false, "unmatched": false }, { "original": "11% of patients treated with ELIQUIS 2.5 mg twice daily experienced adverse reactions", "corrupted": "14% of patients treated with ELIQUIS 2.5 mg twice daily experienced adverse reactions", "matched_claims": 0, "verdicts": [], "matched_texts": [], "caught": false, "false_supported": false, "unmatched": true }, { "original": "milk-to-plasma area under the curve ratio of 30:1 in lactating rats", "corrupted": "milk-to-plasma area under the curve ratio of 25:1 in lactating rats", "matched_claims": 0, "verdicts": [], "matched_texts": [], "caught": false, "false_supported": false, "unmatched": true } ], "seeded_scoring_note": "re-scored 2026-08-08 with the diff-token matcher (eval audit); see dogfood_domain.score_seeded" }