The new factor Xa inhibitor: Apixaban

Abstract

Cardiovascular diseases are still the most important cause of morbidity and mortality worldwide and anti-thrombotic treatment is widely used as a result. The currently used drugs include heparin and its derivatives, vitamin K antagonists, though efficacious, have their own set of limitations like unpredictable pharmacokinetic profile, parenteral route (with heparin and its derivatives only), narrow therapeutic window, and constant laboratory monitoring for their efficacy and safety. This lead to the development of novel factor Xa inhibitors which could be given orally, have predictable dose response relationship and are associated with lesser hemorrhagic complications. They include rivaroxaban, apixaban, and edoxaban among others. Apixaban has currently been approved for use in patients undergoing total knee or hip replacement surgery and to prevent stroke in patients with atrial fibrillation. Many trials are ongoing for apixaban to firmly establish its place in future, among the anti-thrombotic drugs.

Natural Products for Antithrombosis

“…Cilostazol, a potent inhibitor of cyclic adenosine monophosphate- (cAMP-) phosphodiesterase 3 (PDE 3 ), has serious side effects such as headache and palpitation [ 28 ]. Apixaban is an oral selective direct factor Xa (FXa) inhibitor and its most common adverse event is bleeding [ 29 ], and other adverse events reported are hypersensitivity reactions, syncope, nausea, dizziness, and so forth. Therefore, there is a rising urgent need for novel therapeutic approach to reduce current adverse effects of antithrombotic drugs without impairing their efficacy.…”

Novel oral anticoagulants in the management of coronary artery disease

“…Peak plasma concentrations are achieved in ∼ 3.5 h and the clearance half-life is ∼ 12 h. More than 50% of apixaban is excreted unchanged in feces or urine. The rest is cleared primarily by oxidative metabolism that is catalyzed by CYP3A4/5 [9,10].…”

Direct-Acting Oral Anticoagulants as Prophylaxis Against Thromboembolism in the Nephrotic Syndrome

“…Apixaban has slightly less protein binding (∼86%) and was likewise approved by the U.S. Food and Drug Administration and the European Commission for the prevention of thromboembolic complications for hip and knee replacements, treatment of DVT, and the prevention of stroke and embolization in atrial fibrillation. 45 When added to anti-platelet therapy in acute coronary syndrome to prevent recurrence, it appeared to reduce ischemic events, but also increased the bleeding risk 46 and was not superior to enoxaparin for thromboprophylaxis in hospitalized, medically ill patients. 47 Hepatobiliary elimination accounts for 75% with 25% being renally excreted.…”

“…Apixaban and rivaroxaban are metabolized by CYP3A4 and are substrates of P-glycoprotein; hence, medications that affect these pathways may interact with these medications if coadministered. 45 Recent in vitro evidence suggests that indoxyl sulphate, which rises as renal function declines, results in an upregulation of P-glycoprotein expression, leading to increased hepatic clearance of drugs that are substrates for this glycoprotein, such as cyclosporin. 48 Among 109 heart and kidney transplant recipients in this study, those with higher indoxyl sulphate levels required higher cyclosporin doses.…”

“…DOACs are of proven benefit in scenarios such as thromboprophylaxis in nonvalvular atrial fibrillation, DVT prophylaxis in patients undergoing hip and knee replacement. 45 However, whether the pharmacokinetics and pharmacodynamics of these agents are altered in NS is unknown. Some data suggest that thrombin may directly injure podocytes, 51 so perhaps thrombin inhibitors could have an independent beneficial effect, but whether these agents will be lost in the urine is not described.…”