Boehringer Ingelheim to Present New Pradaxa® (dabigatran etexilate mesylate) Data at ESC Congress 2013

RIDGEFIELD, Conn., Aug. 23, 2013 /PRNewswire/ -- Boehringer Ingelheim will present five abstracts at the ESC Congress 2013, organized by the European Society of Cardiology, taking place from August 31 to September 4, in Amsterdam, Netherlands, providing additional data about Pradaxa® (dabigatran etexilate mesylate) capsules.

"The broad range of data being presented at this year's ESC further provides important new insights about PRADAXA," said Sabine Luik, MD, senior vice president, medicine & regulatory affairs, U.S. regional medical director, Boehringer Ingelheim Pharmaceuticals, Inc. "Boehringer Ingelheim remains committed to advancing the body of information related to stroke, and to constantly searching for new and innovative ways to improve the lives of patients with cardiovascular disorders."

Boehringer Ingelheim continues to support the ongoing evaluation of PRADAXA, with two analyses of information gathered during the pivotal RE-LY study and the long term safety extension RELY-ABLE study.

• Management of Dyspepsia Symptoms on Dabigatran During RELY-ABLE: Long Term Follow Up Study After RE-LY (R. Nieuwlaat, Poster) [Abstract No. 549, Aug. 31, 2 – 6 p.m. CEST]
• Guidance Adherent Dabigatran Etexilate Treatment Versus Warfarin in the RE-LY Population: An Analysis on the Basis of the European Label Recommendations for Dabigatran Etexilate (G. Lip, Poster) [Abstract No. 4278, Sept. 2, 2 – 6 p.m. CEST]

Additionally, Boehringer Ingelheim will present new preclinical research on its investigational reversal agent:

• Reversal of Dabigatran Clotting Activity in the Rat Ex Vivo by a Specific and Selective Antibody Fragment Antidote: Are There Non-Specific Effects on Warfarin, Rivaroxaban and Apixaban? (J. van Ryn, poster) [Abstract No. 4848, Sept. 3, 8:30 a.m. – 12:30 p.m. CEST]

Other dabigatran research to be presented includes:

• Dabigatran in Patients with a Mechanical Heart Valve: The RE-ALIGN Study (F. Van de Werf, Late-Breaker) [Abstract No. 937, Sept. 1, 11 a.m. – 12:30 p.m. CEST]
  • Boehringer Ingelheim announced last year that this study had been discontinued based on interim results
• Effects of the Direct Thrombin Inhibitor Dabigatran Etexilate Versus Warfarin on Platelet Function (G. Renda, poster) [Abstract No. 1430, Sept. 1, 8:30 a.m. – 12:30 p.m. CEST]

PRADAXA is currently approved by the FDA to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF), and was the first oral anticoagulant approved by the FDA in more than 50 years for this indication. PRADAXA 150mg twice daily is the only medication among the new generation of OACs to demonstrate superior reduction of ischemic stroke compared to warfarin in patients with NVAF. Nearly nine out of 10 strokes caused by atrial fibrillation (AFib) are ischemic strokes. PRADAXA also demonstrated a similar rate of major bleeding events, defined as serious and sometimes fatal bleeding, in patients with NVAF.

Prescribing experience with PRADAXA continues to grow with more than 6 million prescriptions for PRADAXA 150mg and 75mg filled for more than 800,000 NVAF patients in the U.S. since its approval in October of 2010. PRADAXA is included on formularies that insure about 95 percent of covered lives in the U.S., through commercial and Medicare Part D plans. PRADAXA is also included in recommendations from three leading U.S. cardiology guidelines for stroke prevention in AFib.

About Pradaxa® (dabigatran etexilate mesylate) Capsules

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 fibrillation.

IMPORTANT SAFETY INFORMATION ABOUT PRADAXA

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 Stroke with Discontinuation of PRADAXA

Discontinuing PRADAXA in absence of adequate alternative anticoagulation increases the risk of thrombotic events. If PRADAXA must be discontinued for a reason other than pathological bleeding, consider coverage with another anticoagulant.

Risk of Bleeding

• PRADAXA increases the risk of bleeding and can cause significant 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, fibrinolytic therapy, and chronic use of NSAIDs). PRADAXA's anticoagulant activity and half-life are increased in patients with renal impairment.
• A specific reversal agent for dabigatran is not available. Hemodialysis can remove dabigatran; however clinical experience for hemodialysis as a treatment for bleeding is limited. Activated prothrombin complex concentrates, recombinant Factor VIIa, or concentrates of factors II, IX or X 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 safety and efficacy of PRADAXA in patients with bileaflet mechanical prosthetic heart valves (recently implanted or implanted more than 3 months prior to enrollment) was evaluated in the phase 2 RE-ALIGN trial. RE-ALIGN was terminated early because of significantly more thromboembolic events (valve thrombosis, stroke, transient ischemic attack, and myocardial infarction) and an excess of major bleeding (predominantly post-operative pericardial effusions requiring intervention for hemodynamic compromise) for PRADAXA vs warfarin. Therefore, the use of PRADAXA is contraindicated in patients with mechanical prosthetic valves.

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

The 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.

• For patients with moderate renal impairment (CrCl 30-50 mL/min), consider reducing 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

In the pivotal trial comparing PRADAXA to warfarin, the most frequent adverse reactions leading to discontinuation of PRADAXA were bleeding and gastrointestinal (GI) events. PRADAXA 150 mg resulted in higher rates of major GI bleeds and any GI bleeds compared to warfarin. In patients ≥75 years of age, the risk of major bleeding may be greater with PRADAXA than with 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). Drug hypersensitivity reactions were reported in <0.1% of patients receiving PRADAXA.

Other Measures Evaluated

In the pivotal trial, a higher rate of clinical myocardial infarction was reported in patients who received PRADAXA (0.7 per 100 patient-years for 150 mg dose) than in those who received warfarin (0.6).

Click here for full Prescribing Information, including Boxed WARNING, and Medication Guide.

About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.

In 2012, Boehringer Ingelheim achieved net sales of about $19.1 billion (14.7 billion euro). R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.

For more information please visit www.us.boehringer-ingelheim.com

SOURCE Boehringer Ingelheim