Apo-Apixaban

Apixaban

Prevention of stroke & systemic embolism in adults w/ non-valvular atrial fibrillation (NVAF), w/ ≥1 risk factors eg, prior stroke or transient ischaemic attack, age ≥75 yr, HTN, DM, symptomatic heart failure (NYHA Class ≥II). Treatment of DVT & pulmonary embolism (PE), & prevention of recurrent DVT & PE in adults. 2.5 mg: Prevention of venous thromboembolic events (VTE) in adults who have undergone elective hip or knee replacement surgery.

Prevention of VTE in elective hip or knee replacement surgery 2.5 mg bd. Take initial dose 12-24 hr after surgery. Duration of treatment: 32-38 days (hip replacement surgery); 10-14 days (knee replacement surgery). Prevention of stroke & systemic embolism in NVAF patient 5 mg bd. Reduce dose to 2.5 mg bd in the presence of at least 2 of the following characteristics: age ≥80 yr, body wt ≤60 kg, or serum creatinine ≥1.5 mg/dL (133 micromol/L). Treatment of DVT & PE 10 mg bd for the 1st 7 days followed by 5 mg bd. Prevention of recurrent DVT & PE Initiate 2.5 mg bd following completion of 6 mth of treatment w/ apixaban 5 mg bd or w/ another anticoagulant. NVAF patient w/ severe renal impairment (CrCl 15-29 mL/min) 2.5 mg bd. NVAF patient undergoing cardioversion For patients initiating treatment w/ apixaban: 5 mg bd for at least 2.5 days (5 single doses) before cardioversion to ensure adequate anticoagulation. Reduce to 2.5 mg bd for at least 2.5 days (5 single doses) if criteria for dose reduction is met. If cardioversion is required before 5 doses of apixaban can be administered: 10 mg loading dose, followed by 5 mg bd. Reduce to 5 mg loading dose followed by 2.5 mg bd if criteria for dose reduction is met. Administer loading dose at least 2 hr before cardioversion.

May be taken with or without food: Swallow w/ water.

Hypersensitivity. Active clinically significant bleeding. Hepatic disease associated w/ coagulopathy & clinically relevant bleeding risk. Lesion or condition if considered a significant risk factor for major bleeding. Concomitant treatment w/ any other anticoagulant agent eg, unfractionated heparin (UFH), LMWH (eg, enoxaparin, dalteparin), heparin derivatives (eg, fondaparinux), oral anticoagulants (eg, warfarin, rivaroxaban, dabigatran) except under specific circumstances of switching anticoagulant therapy, when UFH is given at doses necessary to maintain an open central venous or arterial catheter or when UFH is given during catheter ablation for atrial fibrillation.

Carefully observe for signs of bleeding. Caution in conditions w/ increased risk of haemorrhage. Discontinue if severe haemorrhage occurs. Discontinue at least 48 hr prior to elective surgery or invasive procedures w/ moderate or high risk of bleeding. Discontinue at least 24 hr prior to elective surgery or invasive procedures w/ low risk of bleeding. Restart apixaban after invasive procedure or surgical intervention as soon as possible provided the clinical situation allows & adequate haemostasis has been established. Increased risk of thrombosis when discontinuing anticoagulants, including apixaban, for active bleeding, elective surgery, or invasive procedures. Not recommended as alternative to UFH in patients w/ PE who are haemodynamically unstable or may receive thrombolysis or pulmonary embolectomy. Carefully assess benefits against risks when apixaban is considered for DVT or PE treatment in cancer patients. Perform liver function testing prior to initiating treatment. Interaction w/ other medicinal products affecting haemostasis. Very limited experience w/ use of thrombolytic agents for the treatment of acute ischemic stroke in patients administered apixaban. Not recommended in patients receiving concomitant systemic treatment w/ strong CYP3A4 & P-gp inhibitors eg, azole antimycotics (eg, ketoconazole, itraconazole, voriconazole, posaconazole) & HIV PIs (eg, ritonavir). Caution in patients receiving concomitant systemic treatment w/ strong CYP3A4 & P-gp inducers for the prevention of VTE in elective hip or knee replacement surgery, prevention of stroke & systemic embolism in NVAF patients, & prevention of recurrent DVT & PE. Do not use in patients receiving concomitant systemic treatment w/ strong CYP3A4 & P-gp inducers for the treatment of DVT & PE. Clotting tests (eg, prothrombin time, INR, & aPTT) are affected as expected by the mechanism of action of apixaban. Should not be taken by patients w/ rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Limited experience of apixaban treatment at the recommended dose for NVAF patients when used in combination w/ antiplatelet agents in patients w/ acute coronary syndrome &/or undergoing percutaneous coronary intervention after haemostasis is achieved. Caution in patients w/ severe renal impairment (CrCl 15-29 mL/min) for the prevention of VTE in elective hip or knee replacement surgery, treatment of DVT & PE, & prevention of recurrent DVT & PE; mild or moderate hepatic impairment (Child Pugh A or B); elevated liver enzymes (ALT/AST >2 x ULN or total bilirubin ≥1.5 x ULN). Not recommended in patients w/ CrCl <15 mL/min or those undergoing dialysis; severe hepatic impairment; prosthetic heart valves, w/ or w/o atrial fibrillation; history of thrombosis who are diagnosed w/ antiphospholipid syndrome. Avoid use during pregnancy. Discontinue breast-feeding or discontinue/abstain from apixaban therapy. Safety & efficacy in childn & adolescents <18 yr have not been established. Increasing age may increase haemorrhagic risk. Low body wt (<60 kg) may increase haemorrhagic risk. 2.5 mg: Patients treated w/ antithrombotic agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal haematoma when spinal/epidural anaesth or puncture is employed. Remove indwelling epidural or intrathecal catheters at least 5 hr prior to the 1st dose of apixaban. Extreme caution is recommended when using apixaban in the presence of neuraxial blockade. Not recommended in patients undergoing hip fracture surgery.

Haemorrhage, contusion, epistaxis, haematoma.

Increased AUC & C_max w/ ketoconazole (strong CYP3A4 & P-gp inhibitor); diltiazem (moderate CYP3A4 & weak P-gp inhibitor); naproxen (P-gp inhibitor); clarithromycin (P-gp inhibitor & strong CYP3A4 inhibitor). Reduced plasma conc w/ strong CYP3A4 & P-gp inducers (eg, rifampicin, phenytoin, carbamazepine, phenobarb, St. John's wort). Increased bleeding risk w/ other anticoagulants; SSRIs/SNRIs, NSAIDs, ASA &/or P2Y12 inhibitors; other platelet aggregation inhibitors (eg, GPIIb/IIIa receptor antagonists, dipyridamole, dextran, sulfinpyrazone) or thrombolytic agents. Reduced exposure w/ activated charcoal.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

B01AF02 - apixaban ; Belongs to the class of direct factor Xa inhibitors. Used in the treatment of thrombosis.

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