INDICATIONS AND USAGE Pradaxa ® ( dabigatran etexilate mesylate ) capsules is indicated ::
• to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fi fi brillation
IMPORTANT SAFETY INFORMATION WARNING : ( A ) PREMATURE DISCONTINUATION OF PRADAXA INCREASES THE RISK OF THROMBOTIC EVENTS , ( B ) SPINAL / EPIDURAL HEMATOMA
( A ) PREMATURE DISCONTINUATION OF PRADAXA INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant , including PRADAXA , increases the risk of thrombotic events . If If anticoagulation with PRADAXA 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 may occur in patients treated with PRADAXA 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 anti-inflammatory drugs ( 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 PRADAXA and neuraxial procedures is not known
Monitor patients frequently for signs and symptoms of neurological impairment . If If neurological compromise is noted , urgent treatment is necessary . Consider the benefits and risks before neuraxial intervention in patients who are or will be anticoagulated .
CONTRAINDICATIONS PRADAXA is contraindicated in patients with :: -- active pathological bleeding ;; -- known serious hypersensitivity reaction ( e . g . ., ., anaphylactic reaction or anaphylactic shock ) to PRADAXA ;; -- mechanical prosthetic heart valve
WARNINGS & PRECAUTIONS Increased Risk of Thrombotic Events after Premature Discontinuation Premature discontinuation of any oral anticoagulant ,, including PRADAXA ,, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events .. If If PRADAXA is discontinued for a reason other than pathological bleeding or completion of a course of therapy ,, consider coverage with another anticoagulant and restart PRADAXA as soon as medically appropriate ..
Risk of Bleeding
• PRADAXA increases the risk of bleeding and can cause signifi cant and ,, sometimes ,, fatal bleeding .. Promptly evaluate any signs or symptoms of blood loss ( e . g . ., ., a drop in hemoglobin and / or hematocrit or hypotension ). ). Discontinue PRADAXA in patients with active pathological bleeding ..
• Risk factors for bleeding include concomitant use of medications that increase the risk of bleeding ( e . g . ., ., anti-platelet agents ,, heparin ,, fi fi brinolytic therapy ,, and chronic use of NSAIDs ). ). PRADAXA ’ s ’ anticoagulant activity and half-life are increased in patients with renal impairment ..
• Reversal of Anticoagulant Effect :: A specifi c reversal agent ( idarucizumab ) for dabigatran is available when reversal of the anticoagulant effect of dabigatran is needed ::
• For emergency surgery / urgent procedures
• In life-threatening or uncontrolled bleeding
WARNINGS & PRECAUTIONS
Risk of Bleeding ( cont ’ d ’ ) Hemodialysis can remove dabigatran ;; however clinical experience for hemodialysis as a treatment for bleeding is limited .. Prothrombin complex concentrates or recombinant Factor VIIa may be considered but their use has not been evaluated .. Protamine sulfate and vitamin K are not expected to affect dabigatran anticoagulant activity .. Consider administration of platelet concentrates where thrombocytopenia is present or long-acting antiplatelet drugs have been used ..
Thromboembolic and Bleeding Events in Patients with Prosthetic Heart Valves The use of PRADAXA is contraindicated in patients with mechanical prosthetic valves due to a higher risk for thromboembolic events ,, especially in the post-operative period ,, and an excess of major bleeding for PRADAXA vs .. warfarin .. Use of PRADAXA for the prophylaxis of thromboembolic events in patients with AFib in the setting of other forms of valvular heart disease ,, including bioprosthetic heart valve ,, has not been studied and is not recommended ..
Effect of P-gp Inducers & Inhibitors on Dabigatran Exposure Concomitant use of PRADAXA with P-gp inducers ( e . g . ., ., rifampin ) reduces exposure to dabigatran and should generally be avoided .. P-gp inhibition and impaired renal function are major independent factors in increased exposure to dabigatran .. Concomitant use of P-gp inhibitors in patients with renal impairment is expected to increase exposure of dabigatran compared to either factor alone .. Reduction of Risk of Stroke / Systemic Embolism in NVAF
• For patients with moderate renal impairment ( CrCl 30-50 mL / min ), ), reduce the dose of PRADAXA to 75 mg twice daily when dronedarone or systemic ketoconazole is coadministered with PRADAXA ..
• For patients with severe renal impairment ( CrCl 15-30 mL / min ), ), avoid concomitant use of PRADAXA and P-gp inhibitors ..
ADVERSE REACTIONS The most serious adverse reactions reported with PRADAXA were related to bleeding ..
• Most frequent adverse reactions leading to discontinuation of PRADAXA were bleeding & gastrointestinal ( GI ) events ..
• PRADAXA 150 mg resulted in higher rates of major and any GI bleeds compared to warfarin ..
• In patients ≥75 years of age ,, the risk of major bleeding may be greater with PRADAXA vs warfarin ..
• Patients on PRADAXA 150 mg had an increased incidence of GI adverse reactions .. These were commonly dyspepsia ( including abdominal pain upper ,, abdominal pain ,, abdominal discomfort ,, and epigastric discomfort ) and gastritis-like symptoms ( including GERD ,, esophagitis ,, erosive gastritis ,, gastric hemorrhage ,, hemorrhagic gastritis ,, hemorrhagic erosive gastritis ,, and GI ulcer ). ).
Other Measures Evaluated In NVAF patients ,, a higher rate of clinical MI was reported in patients who received PRADAXA ( 0.7 / 100 patient-years for 150 mg dose ) than in those who received warfarin ( 0.6 ). ).
NOAC = novel oral anticoagulant ;; NVAF = non-valvular atrial fi fi brillation ;; SE = systemic embolism ;; RE-LY = Randomized Evaluation of Long-term anticoagulant therapY ;; HR = hazard ratio ;; CI = confi dence interval ..
Please see accompanying brief summary of full Prescribing Information .
References : 1 . Data on fi fi le .. Boehringer Ingelheim Pharmaceuticals ,, Inc .. 2 . Connolly SJ ,, Wallentin L ,, Yusuf S .. Additional events in the RE-LY Trial [ Letter to the Editor ]. N Engl J Med .. 2014 ;; 371 ( 15 ): 1464-1465 ..
COPYRIGHT © 2016 BOEHRINGER INGELHEIM PHARMACEUTICALS ,, INC .. ALL RIGHTS RESERVED .. PRINTED IN U . S . . A . .. [[ 8 // 16 ]] PC-PX-0342-PROF