Torapix 2.5/Torapix 5 Special Precautions

Haemorrhage risk: As with other anticoagulants, patients taking Apixaban are to be carefully observed for signs of bleeding. It is recommended to be used with caution in conditions with increased risk of haemorrhage such as: congenital or acquired bleeding disorders; active ulcerative gastrointestinal disease; bacterial endocarditis; thrombocytopenia; platelet disorders; history of haemorrhagic stroke; severe uncontrolled hypertension; and recent brain, spinal or ophthalmological surgery. Apixaban is not recommended in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk. Apixaban administration should be discontinued if severe haemorrhage occurs.
In the event of haemorrhagic complications, treatment must be discontinued and the source of bleeding investigated. The initiation of appropriate treatment, e.g. Surgical haemostasis or the transfusion of fresh frozen plasma, should be considered. If life-threatening bleeding cannot be controlled by the previously mentioned measure, administration of prothrombin complex concentrates (PCCs) or recombinant factor VIIa may be considered.
Temporary discontinuation of Apixaban: Discontinuing anticoagulants, including Apixaban, for active bleeding, elective surgery, or invasive procedures places patients at an increased risk of thrombosis. Avoid lapses in therapy, and if anticoagulation with Apixaban must be temporarily discontinued for any reason, restart therapy as soon as possible.
Although treatment with apixaban does not require routine monitoring of exposure, a calibrated quantitative anti-Factor Xa assay may be useful in exceptional situations where knowledge of apixaban exposure may help to inform clinical decisions, e.g., overdose and emergency surgery. Due to an increased bleeding risk, concomitant treatment with any other anticoagulants is contraindicated.
Renal Impairment: *Prevention of stroke and systemic embolism in patients with NVAF: There are no data in patients undergoing dialysis, therefore, Apixaban is not recommended in these patients.
*Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE): Because there is limited clinical experience in patients with creatinine clearance <15 mL/min and no data in patients undergoing dialysis, Apixaban is not recommended in these patients.
Hepatic Impairment: Apixaban is not recommended in patients with severe hepatic impairment. Apixaban may be used with caution in patients with mild or moderate hepatic impairment (Child Pugh A or B).
Interactions with inhibitors of both Cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp): Apixaban can be administered with caution in patients receiving concomitant systemic treatment with strong inhibitors of both Cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp), such as azole-antimycotics (eg. ketoconazole, itraconazole, voriconazole and posaconazole), HIV protease inhibitors (eg, ritonavir). These medicinal products may increase apixaban exposure by 2-fold.
Interactions with inducers of both CYP3A4 and P-gp: The concomitant use of Apixaban with strong CYP3A4 and P-gp inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital or St. John's Wort) may lead to a -50% reduction in Apixaban exposure. Use caution when co-administering Apixaban with strong inducers of both CYP3A4 and P-gp.
For the treatment of DVT or PE, Apixaban is not recommended in patients receiving concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp. For prevention of recurrent DVT and PE, use caution when co-administering Apixaban with strong inducers of both CYP3A4 and P-gp.
Interaction with other medicinal products affecting the hemostasis: The concomitant use of Apixaban with antiplatelet agents increases the risk of bleeding. Care is to be taken if patients are treated concomitantly with non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (ASA). Other platelet aggregation inhibitors or other antithrombotic agents are not recommended concomitantly with Apixaban following surgery.
In patients with atrial fibrillation and a condition that warrants mono or dual antiplatelet therapy, a careful assessment of the potential benefits against the potential risks should be made before combining this therapy with Apixaban.
Patients with prosthetic heart valves: Safety and efficacy of Apixaban have not been studied in patients with prosthetic heart valves, with or without atrial fibrillation. Therefore, the use of Apixaban is not recommended in this setting.
Effects on ability to drive and use machines: Apixaban has no or negligible influence on the ability to drive and use machineries.
Use in Children: The efficacy and safety of Apixaban in children below age 18 have not yet been established. No data are available.
Use in the Elderly: Increasing age may increase haemorrhagic risk.