EINSTEIN DVT/PE IMPORTANT SAFETY INFORMATION

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1 EINSTEIN DVT/PE % INDICATIONS is indicated for the treatment of deep vein thrombosis (DVT). is indicated for the treatment of pulmonary embolism (PE). is indicated for the reduction in the risk of recurrence of DVT and of PE following initial 6 months treatment for DVT and/or PE. IMPORTANT SAFETY INFORMATION WARNING: (A) PREMATURE DISCONTINUATION OF INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/ EPIDURAL HEMATOMA A. PREMATURE DISCONTINUATION OF INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant, including, increases the risk of thrombotic events. If anticoagulation with is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant. B. SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas have occurred in patients treated with 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 non-steroidal antiinflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants, see Drug Interactions A history of traumatic or repeated epidural or spinal punctures A history of spinal deformity or spinal surgery Optimal timing between the administration of and neuraxial procedures is not known Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.

2 EINSTEIN DVT AND EINSTEIN PE TRIALS: PATIENTS AT A GLANCE EINSTEIN DVT AND EINSTEIN PE TRIALS: CLINICAL OUTCOMES DVT and PE Treatment Trial Design Single-Agent Treatment Approach EINSTEIN DVT* and EINSTEIN PE Study Designs 1,2 DVT trial population: objectively confirmed symptomatic proximal DVT without symptomatic PE (N=3449) PE trial population: objectively confirmed symptomatic PE with or without symptomatic DVT (N=4832) Randomization 15 mg twice daily Day 21 1 mg/kg twice daily for 5 days INR 2.5 (range ) 20 mg once daily Follow-up (rivaroxaban) At Least as Effective as Standard of Care ( ) Proven Noninferior for Treatment of DVT and/or PE 3 Time to first occurrence of the composite of recurrent DVT or nonfatal or fatal PE # DVT/PE Pooled Data Enoxaparin/warfarin The purpose of the DVT and PE treatment trials (EINSTEIN DVT and EINSTEIN PE) was to compare the efficacy and safety of (rivaroxaban) with standard therapy (, followed by warfarin) for the treatment of acute DVT and acute PE, respectively. 1,2 Primary efficacy outcome: symptomatic recurrent VTE Principal safety outcome: composite of major bleeding or clinically relevant nonmajor bleeding Cumulative Event Rate (%) Days (N=4150) Enoxaparin/warfarin (N=4131) Number of Patients at Risk EINSTEIN DVT Treatment Characteristics Pretreatment with LMWH, heparin, or fondaparinux before randomization 1 0 days: 27% 1 day: 69% 2 days: 4.1% EINSTEIN PE Treatment Characteristics Pretreatment with LMWH, heparin, or fondaparinux before randomization 2 0 days: 7.5% 1 day: 57.4% 2 days: 35% LMWH = low-molecular-weight heparin; VTE = venous thromboembolism. *The EINSTEIN DVT study was a randomized, open-label study to compare the effi cacy and safety of with standard therapy (, followed by warfarin).patients were eligible if they had acute, symptomatic, objectively confi rmed proximal DVT, without symptomatic PE. Patients were randomized from March 2007 to September The EINSTEIN PE study was a randomized, open-label study to compare the effi cacy and safety of with standard therapy ( + warfarin, followed by warfarin). Patients were eligible if they had an acute, symptomatic pulmonary embolism with objective confi rmation, with or without symptomatic DVT. Patients were randomized from March 2007 to March Baseline characteristics were similar in both treatment arms. 0 days pretreatment calculation: 100%-73%=27%. II 2% days pretreatment calculation: 3.9%+0.2%=4.1%. 2% days pretreatment calculation: 33.1%+1.9%=35%. # Intent-to-treat population. CONTRAINDICATIONS Active pathological bleeding Severe hypersensitivity reaction to (eg, anaphylactic reactions) WARNINGS AND PRECAUTIONS Increased Risk of Thrombotic Events After Premature Discontinuation: Premature discontinuation of any oral anticoagulant, including, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from to warfarin in clinical trials in atrial fibrillation patients. If is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant. 2 3

3 EINSTEIN DVT AND EINSTEIN PE TRIALS: CLINICAL OUTCOMES EINSTEIN DVT AND EINSTEIN PE TRIALS: CLINICAL OUTCOMES Single-Agent Treatment Approach 46% Relative Risk Reduction in Major Bleeding Versus Standard of Care ( ) 3 Single-Agent Treatment Approach Rates in Key Bleeding Categories in the Pooled Analysis of the DVT and PE Treatment Trials* 3 j y j g Major Bleeding in the Pooled Analysis of the DVT and PE Treatment Trials* 3 Nonmajor Clinically Relevant # + Major Bleeding 3 Patient category Hazard Ratio (95% CI) vs Patient category Hazard Ratio (95% CI) vs All patients (n=8281) 0.54 ( ) 1.0 (40/4130) PERCENT 1.7 (72/4116) All patients (n=8281) 0.93 ( ) 9.4 (388/4130) PERCENT 10.0 (412/4116) Patients with cancer (n=597) 0.53 ( ) 2.8 (9/316) 5.0 (14/278) Patients with cancer (n=597) 0.93 ( ) 15.2 (48/316) 15.8 (44/278) Patients with previous DVT/PE (n=1610) Fragile patients (n=1573) 0.51 ( ) 0.27 ( ) 0.9 (7/788) 1.3 (10/788) 1.7 (14/813) 4.5 (35/779) Patients with previous DVT/PE (n=1610) Fragile patients (n=1573) 0.77 ( ) 0.85 ( ) 8.9 (70/788) 12.3 (97/788) 11.2 (91/813) 14.0 (109/779) HR (95% CI) HR (95% CI) 10 Principal Safety Outcome: Comparable rates of the composite of major bleeding and clinically relevant nonmajor bleeding across treatment groups 3 9.4% (388/4130) for versus 10.0% (412/4116) for (HR [95% CI]: 0.93 [ ]) 3 WARNINGS AND PRECAUTIONS (cont'd) Risk of Bleeding: increases the risk of bleeding and can cause serious or fatal bleeding. Promptly evaluate any signs or symptoms of blood loss and consider the need for blood replacement. Discontinue in patients with active pathological hemorrhage. A specific antidote for rivaroxaban is not available. Because of high plasma protein binding, rivaroxaban is not expected to be dialyzable. Concomitant use of other drugs affecting hemostasis increases the risk of bleeding. These include aspirin, P2Y 12 platelet inhibitors, other antithrombotic agents, fibrinolytic therapy, and NSAIDs. INR = international normalized ratio. * Bleeding event occurred after randomization and up to 2 days after the last dose of study drug. Although a patient may have had 2 or more events, the patient is counted only once in a category. Treatment schedule in EINSTEIN DVT and EINSTEIN PE studies: 15 mg twice daily for 3 weeks followed by 20 mg once daily; / warfarin (: 1 mg/kg twice daily, warfarin: individually titrated doses to achieve a target INR of 2.5 [range: ]). Major bleeding was defi ned as overt bleeding associated with a fall in hemoglobin of 2 g/dl or more, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, or that occurred in a critical site (intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal), or contributing to death. 4 P= Not adjusted for multiplicity. II Fragility was defined as one or more of the following: age >75 years, CrCl <50 ml/min, or body weight 50 kg. For major bleeding, the P value for the treatment group fragility interaction was 0.011, suggesting heterogeneity. # Clinically relevant nonmajor bleeding was defi ned as overt bleeding not meeting the criteria for a major bleeding event but associated with medical intervention, unscheduled contact (visit or telephone call) with a physician, (temporary) cessation of study treatment, discomfort for the subject such as pain, or impairment of activities of daily life. 4 Arrows indicate statistical difference between and standard of care. 4 5

4 EINSTEIN DVT AND EINSTEIN PE TRIALS: CLINICAL OUTCOMES THERAPY MANAGEMENT Pooled Subgroup Analysis: Outcomes in Patients With Cancer 5 Single-Agent Anticoagulation Strategy From the Moment of Diagnosis Through the End of Treatment Clinical endpoint Recurrent VTE Major bleeding Clinically relevant bleeding Mortality Hazard Ratio (95% CI) 0.67 ( ) 0.42 ( ) 0.80 ( ) 0.93 ( ) N=651 patients vs 4.5 (16/354) 2.3 (8/353) 13.6 (48/353) 4.5 (16/353) PERCENT 6.6 (20/301) 5.0 (15/298) 16.4 (49/298) 5.4 (16/298) Treatment of DVT and PE Reduce risk of recurrent DVT and PE Tablets shown not actual size. 15 mg TWICE DAILY with food for first 21 days ON DAY 22 TRANSITION TO 20 mg ONCE DAILY 20 mg ONCE DAILY with food, at approximately the same time each day for remaining treatment with food, at approximately the same time each day Renal dosing considerations DVT and PE and reduction in risk of recurrence: Avoid using in patients with CrCl <30 ml/min HR (95% CI) 10 Patients with active cancer at baseline: 462 Patients with active cancer diagnosed during study: 193 Patients with recurrent or metastic cancer: 19% (49/258), 25% (52/204) with active cancer at baseline; 19% (18/96), 26% (25/97) with active cancer diagnosed during the study 5 Patients on chemotherapy: XARELTO 25% (88/354), 27% (81/301) with active cancer at baseline or active cancer diagnosed during the study 5 WARNINGS AND PRECAUTIONS (cont d) Spinal/Epidural Anesthesia or Puncture: When neuraxial anesthesia (spinal/epidural anesthesia) or spinal puncture is employed, patients treated with anticoagulant agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis. To reduce the potential risk of bleeding associated with the concurrent use of rivaroxaban and epidural or spinal anesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of rivaroxaban. Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of rivaroxaban is low; however, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known. An epidural catheter should not be removed earlier than 18 hours after the last administration of. The next dose is not to be administered earlier than 6 hours after the removal of the catheter. If traumatic puncture occurs, the administration of is to be delayed for 24 hours. Should the physician decide to administer anticoagulation in the context of epidural or spinal anesthesia/analgesia or lumbar puncture, monitor frequently to detect any signs or symptoms of neurological impairment, such as midline back pain, sensory and motor deficits (numbness, tingling, or weakness in lower limbs), or bowel and/ or bladder dysfunction. Instruct patients to immediately report if they experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though such treatment may not prevent or reverse neurological sequelae. 6 7

5 LIFT HERE TO OPEN THERAPY MANAGEMENT THERAPY MANAGEMENT Switching Patients to and From SWITCHING TO XARELTO Starter Pack for initiation of DVT and/or PE Treatment XARELTO Starter Pack first 30 days for DVT and/or PE treatment From warfarin Stop warfarin and start when INR is <3.0 From unfractionated heparin From other anticoagulants Stop the infusion and start at the same time Start 0 to 2 hours prior to the next scheduled evening administration of the other anticoagulant (rivaroxaban) Tablets NDC Rx only Please see full Prescribing Information, including BOXED WARNINGS, and Medication Guide inside. Starter Pack for treatment of deep vein thrombosis and treatment of pulmonary embolism SWITCHING FROM Days 1-21 Days mg per tablet, twice daily 20 mg per tablet, once daily To warfarin * One approach is to stop and start parenteral anticoagulant and warfarin at time of next scheduled dose 42 tablets 9 tablets First 30-day supply To other anticoagulants BLEED MANAGEMENT Stop and start other anticoagulant when the next dose of would have been given * No clinical trial data are available to guide converting patients from to warfarin. affects INR, so INR measurements made during coadministration with warfarin may not be useful for determining the appropriate dose of warfarin. Oral or parenteral rapid-onset anticoagulants. Bleed Management When Using Promptly evaluate any signs and symptoms of blood loss and consider the need for blood replacement Discontinue in patients with active pathological hemorrhage Partial reversal of prothrombin time prolongation has been seen after administration of prothrombin complex concentrates (PCCs) in healthy volunteers The use of other procoagulant reversal agents like activated prothrombin complex concentrates (APCCs) or recombinant factor VIIa (rfviia) has not been evaluated This is not intended to replace clinical judgment or determine individual patient care. Provides therapy for the first 30 days when patients are most vulnerable to a recurrent event 6 Helps provide a seamless transition of care from diagnosis to follow- up The only pack available for initiation of DVT/PE treatment WARNINGS AND PRECAUTIONS (cont d) Use in Patients With Renal Impairment: Nonvalvular Atrial Fibrillation: Avoid the use of in patients with creatinine clearance (CrCl) <15 ml/min, since drug exposure is increased. Discontinue in patients who develop acute renal failure while on. Treatment of Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), and Reduction in the Risk of Recurrence of DVT and of PE: Avoid the use of in patients with CrCl <30 ml/min due to an expected increase in rivaroxaban exposure and pharmacodynamic effects in this patient population. Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery: Avoid the use of in patients with CrCl <30 ml/min due to an expected increase in rivaroxaban exposure and pharmacodynamic effects in this patient population. Observe closely and promptly evaluate any signs or symptoms of blood loss in patients with CrCl 30 to 50 ml/min. Patients who develop acute renal failure while on should discontinue the treatment. Use in Patients With Hepatic Impairment: No clinical data are available for patients with severe hepatic impairment. Avoid use of in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment or with any hepatic disease associated with coagulopathy, since drug exposure and bleeding risk may be increased. Use With P-gp and Strong CYP3A4 Inhibitors or Inducers: Avoid concomitant use of with combined P-gp and strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, and conivaptan). Avoid concomitant use of with drugs that are P-gp and strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St. John s wort). 8 9

6 THERAPY MANAGEMENT THERAPY MANAGEMENT CarePath Offers Services and Support for Your Patients at Every Step The CarePath Trial Offer Up to a free 30-day supply Eligible patients with an approved chronic indication for (15 mg or 20 mg) Subject to 1 use or 12 months from program start date, whichever comes first The CarePath Savings Card No cost for 12 months Eligible patients with an approved chronic indication for (15 mg or 20 mg)* Patients with commercial insurance receive 12 months at no cost* Continuing support may also be available for eligible patients who have exhausted their 12 months in the program * Per calendar year, subject to a $3,400 maximum annual program benefit. No monthly cap. Not valid for patients enrolled in Medicare Part D or Medicaid. For eligibility requirements and restrictions, visit XareltoCarePath.com or call XARELTO ( ). TRIAL OFFER BIN: GROUP: MEMBER: Please see the enclosed full Prescribing Information, including Boxed Warnings and Medication Guide, for (rivaroxaban) and discuss any questions you have with your doctor. SAVINGS CARD BIN: GROUP: XARELTO01 MEMBER: Please see the accompanying full Prescribing Information, including Boxed Warnings and Medication Guide, for and discuss any questions you have with your doctor. SEE REVERSE ACTIVATE CARD BEFORE USE RESTRICTIONS APPLY SEE REVERSE ACTIVATE CARD BEFORE USE RESTRICTIONS APPLY WARNINGS AND PRECAUTIONS (cont d) Risk of Pregnancy-Related Hemorrhage: In pregnant women, should be used only if the potential benefit justifies the potential risk to the mother and fetus. dosing in pregnancy has not been studied. The anticoagulant effect of cannot be monitored with standard laboratory testing and is not readily reversed. Promptly evaluate any signs or symptoms suggesting blood loss (eg, a drop in hemoglobin and/or hematocrit, hypotension, or fetal distress). Supported by A comprehensive support program offering access, education, and adherence tools to help your patients start and stay on therapy. For more information about, CarePath, and all of its associated programs, visit: WARNINGS AND PRECAUTIONS (cont d) Patients With Prosthetic Heart Valves: The safety and efficacy of have not been studied in patients with prosthetic heart valves. Therefore, use of is not recommended in these patients. Acute PE in Hemodynamically Unstable Patients/Patients Who Require Thrombolysis or Pulmonary Embolectomy: Initiation of is not recommended acutely as an alternative to unfractionated heparin in patients with pulmonary embolism who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy. DRUG INTERACTIONS Avoid concomitant use of with other anticoagulants due to increased bleeding risk, unless benefit outweighs risk. Promptly evaluate any signs or symptoms of blood loss if patients are treated concomitantly with aspirin, other platelet aggregation inhibitors, or NSAIDs. should not be used in patients with CrCl 15 to 80 ml/min who are receiving concomitant combined P-gp and moderate CYP3A4 inhibitors unless the potential benefit justifies the potential risk. USE IN SPECIFIC POPULATIONS Pregnancy Category C: should be used during pregnancy only if the potential benefit justifies the potential risk to mother and fetus. There are no adequate or well-controlled studies of in pregnant women, and dosing for pregnant women has not been established. Use with caution in pregnant patients because of the potential for pregnancy-related hemorrhage and/or emergent delivery with an anticoagulant that is not readily reversible. The anticoagulant effect of cannot be reliably monitored with standard laboratory testing. Labor and Delivery: Safety and effectiveness of during labor and delivery have not been studied in clinical trials. Nursing Mothers: It is not known if rivaroxaban is excreted in human milk. Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Females of Reproductive Potential: Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician

7 In Initial Treatment Trials, EINSTEIN Enrolled a Large and Diverse Patient Population These trials were conducted with different designs and evaluated different populations, so direct comparisons of their results cannot be made Total patients studied PE only Previous VTE Provoked VTE Unprovoked VTE Recent trauma or surgery EINSTEIN DVT and PE pooled *1-3, % Elderly % % DVT only % 65.5% Both DVT and PE % 8.8% Cancer at baseline % 2.7% Average 6-month pill count % % 16.2% % 10.1% % % apixaban AMPLIFY 8, % Excluded by protocol edoxaban Hokusai-VTE % % % % % % Did not specify % Did not specify dabigatran RE-COVER I and II pooled % % % % % % Did not specify % Did not specify Up to + Percentage of patients calculated by pooling total patients with noted characteristic in each trial. * In EINSTEIN PE, 46 patients with suspected PE were either not confirmed or not evaluable, but 6 of these patients had confirmed proximal DVT; in EINSTEIN DVT, 22 patients had both DVT and PE, 1 patient had PE only, and 43 patients were missing, not evaluable, or had no symptomatic DVT and no PE. In the case of 6 patients in the RE-COVER I and RE-COVER II studies, the diagnosis of VTE was made locally and was subsequently not confirmed by the central adjudication committee. Elderly patients were aged >75 years for the EINSTEIN and RE-COVER trial programs, and aged 75 years for the AMPLIFY and Hokusai-VTE trials. Patients defined with having head trauma, other major trauma or major surgery 1 month prior to randomization were excluded from the trial. OVERDOSAGE Discontinue and initiate appropriate therapy if bleeding complications associated with overdosage occur. A specific antidote for rivaroxaban is not available. The use of activated charcoal to reduce absorption in case of overdose may be considered. Due to the high plasma protein binding, rivaroxaban is not expected to be dialyzable. ADVERSE REACTIONS IN CLINICAL STUDIES The most common adverse reactions with were bleeding complications. References: 1. The EINSTEIN Investigators. Oral rivaroxaban for systemic venous thromboembolism. N Engl J Med. 2010;363(26): The EINSTEIN PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14): Prins MH, Lensing AWA, Bauersachs R, et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN DVT and PE randomized studies. Thromb J. 2013;11(10):21. doi: / Protocol for: The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26): Prins MH, Lensing AWA, Brighton TA, et al. Oral rivaroxaban versus with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomized controlled trials. Lancet Haematol Oct;1(1):e37-e46. doi: /s (14) Published online September 28, Limone BL, Hernandez AV, Michalak D, Bookhart BK, Coleman CI. Timing of recurrent venous thromboembolism early after the index event: a meta-analysis of randomized controlled trials. Thromb Res. 2013;132(4): Data on file. Janssen Pharmaceuticals, Inc. Based on Clinical Study Report. 8. Agnelli G, Buller HR, Cohen A, et al, for the AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9): Supplementary Appendix to: Agnelli G, Buller HR, Cohen A, et al; for the AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9): Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369: Schulman S, Kearon C, Kakkar AK, et al; for the RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24): Schulman S, Kakkar AK, Goldhaber SZ, et al; for the RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014;129(7): Online supplement to: Schulman S, Kakkar AK, Goldhaber SZ, et al; for the RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014;129(7): CIRCULATIONAHA DC1/004450_supplemental_material.pdf. Accessed February 23, Eliquis [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; Pradaxa [prescribing information]. Ridgefield, CT: Boehringer lngelheim Pharmaceuticals, Inc.; Savaysa [prescribing information]. Parsippany, NJ: Daiichi Sankyo, Inc.; Data on file. Janssen Pharmaceuticals, Inc. Based on IMS Health, NPA Weekly, January Data on file. Janssen Pharmaceuticals, Inc. Based on IMS Health Longitudinal Prescription Database (LRx), through September Patel MR, Mahaffey KW, Garg J, et al; and the ROCKET AF Steering Committee, for the ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10): Granger CB, Alexander JH, McMurray JJV, et al; for the ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11): Connolly SJ, Ezekowitz MD, Yusuf S, et al; and the RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12): Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107(23) (suppl 1):I9-I Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism [supplemental appendix]. N Engl J Med. 2013;369(15): pdf. Accessed February 24, Giugliano RP, Ruff CT, Braunwald E, et al; for the ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22): Source: IMS Health, Formulary Impact Analyzer, January 2015, all pay types, <30-day supply. Average calculated using approved patient paid amounts. 26. Data on file. Janssen Pharmaceuticals, Inc. Based on IMS Health, NPA Weekly, October

8 THE #1 PRESCRIBED NOVEL ORAL ANTICOAGULANT IN THE US* 17 AMONG NOVEL ORAL ANTICOAGULANTS: Most real-world experience: more than 2 million patients prescribed in the US. 18 Most safety data generated in clinical trials in patients 1-3,8, 10-13,16,19-24 studied with high risk of thrombotic events. Most affordable: the lowest average out-of-pocket cost. 25 Not intended to be a comparison of safety or efficacy outcomes. Cardiologists and Primary Care Physicians prescribe more than any other novel oral anticoagulant 26 * Among Factor Xa inhibitors and direct thrombin inhibitors. Based on the following: CHADS 2 scores 3-6 in ROCKET AF (N=12,402), ARISTOTLE (N=5502), ENGAGE-AF (N=~11,200), and RE-LY (N=5882); risk factors of DVT, PE, DVT/PE, cancer, elderly, previous VTE, provoked VTE, unprovoked VTE, and recent trauma or surgery in EINSTEIN pooled analysis (N=8281), AMPLIFY (N=5395), Hokusai-VTE (N=8240), and RE-COVER I and II (N=5107). CHADS 2 = congestive heart failure, hypertension, age 75 years, diabetes mellitus, prior stroke or transient ischemic attack; DVT = deep vein thrombosis; PE = pulmonary embolism; VTE = venous thromboembolism. is licensed from Bayer HealthCare AG, Leverkusen, Germany. Janssen Pharmaceuticals, Inc March Janssen Pharmaceuticals, Inc.