Xarelto, INN-Rivaroxaban

The application submitted is a complete dossier composed of administrative information, complete quality data, non-clinical and clinical data based on applicants' own tests and studies and/or bibliographic literature substituting/supporting certain test(s) or study(ies) Licensing status: The product was not licensed in any country at the time of submission of the application. • The CHMP opinions were forwarded in all official languages of the European Union, to the European Commission, which adopted the corresponding Decision on 30 September 2008. Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is a common cause of cardiovascular mortality and morbidity. Subjects undergoing major orthopaedic surgery, which includes hip and knee arthroplasty and hip-fracture repair, represent a group that is at particularly high risk for VTE, especially patients with risk factors (age >60 years, cancer, prior VTE). Some uncertainty exists for what the spontaneous VTE rates would be without prophylaxis when up-to date surgical technique, early mobilisation and other non-pharmacological prophylactic measures are undertaken. It may be that some estimations, based on historical data, overestimate the current risks but it is generally accepted that VTE risks in these patients remain high. Placebo-controlled trials in such populations would hardly be regarded as acceptable. Estimations fetched from the literature and cited by the Applicant are that calf vein thrombi, proximal DVT, clinical PE and fatal PE would be seen in 40-80%, 10-20%, 4-10% and 0.2-5% in such a population, respectively. Thus, routine thromboprophylaxis has been the standard of care for more than 20 years in subjects at moderate and high risk for thromboembolism. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy (2004), an internationally recognised guidance document based on all available data and compiled by leading experts made the following major recommendations for the population targeted for Xarelto (strength of recommendations included within brackets): Elective hip arthroplasty, elective knee arthroplasty, and hip-fracture surgery: (1) low-molecular weight heparin (LMWH, (2) fondaparinux, or (3) dose-adjusted vitamin K antagonist (VKA) (Grade 1A) for at least 10 days (Grade 1A). Hip-fracture surgery: (1) fondaparinux (Grade 1A), (2) LMWH (Grade 1C+), (3) dose-adjusted VKA (Grade 2B), or (4) LDUH (Grade 1B) for at least 10 days (Grade 1A). For subjects undergoing elective hip arthroplasty and hip-fracture surgery, an extended prophylaxis for up to 28 to 35 days after surgery is recommended (Grade 1A). Low-dose unfractionated heparin (LDUH) is not recommended as the only method of thromboprophylaxis in subjects …