NOACS- Non-Vitamin K oral anticoagulants. This chart covers information on
( Eliquis ) Mechanism of action, indications, and contraindications are discussed to allow GPs access this information quickly. Switching regimen is clearly displayed for practical use. Advice and follow up with a patient alert card are discussed with suggested dosages. Part of NOACS review on A4Medicine- further charts are planned to be published in future.

Potent oral reversible direct and highly selective inhibitor of factor Xa Inhibits free and clot bound factor Xa and Prothrombinase activity Prevents thrombin generation and thrombus development Apixaban prolongs clotting tests as
○ Prothrombin time ( PT )
○ Activated partial thromboplastin time ( aPTT ) Indirectly inhibits platelet aggregation induced by thrombin

Pharmacokinetics-Administered orally and 87 % bound to plasma proteins Rapidly absorbed with max conc appearing 3-4 hrs after tablet intake Can be taken with or without food Multiple routes of elimination Renal excretion accounts for about 27 % of total apixaban clearance Biliary and direct intestinal excretion contribute to fecal elimination Half life about 12 hrs Metabolised mainly via CYP3A4/5 with minor contributions from CY_1A2 ,2C8,2C9,2C19 and 2J2 No impact of impaired renal function on peal concentrations of apixaban

Renal impairment-No impact of impaired renal function on peak concentration of apixaban
 Apixaban plasma conc ( AUC ) is increased in people with renal impairment compared to individuals with normal creatinine clearance
 Apixaban appears to be a reasonable alternative to warfarin in patients with severe renal impairment ( Stanton BE et al Pharmacotherapy 2017 )
 Out of NOACS only Apixaban has been recently approved for the use in patient with end-stage renal dysfunction on hemodialysis ( Int J Cardiol 2016 Dec

Hepatic impairment-Contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk Not recommended in severe hepatic impairment ( no data exists ) No dose adjustment is needed in patients with mild or moderate hepatic impairment Use with caution in patients with elevated liver enzymes ( ALT and AST > 2 x ULN)
or total bilirubin >= 1.5 x ULN

Indications-Prophylaxis of stroke and systemic embolism in non-valvular AF with one or more risk factors
♦ previous stroke or TIA
♦ age 75 or >
♦ hypertension
♦ diabetes
♦ symptomatic heart failure ( NYHA Class 2 or > ) Prevention of VTE in adults following elective hip or knee replacement surgery Treatment of DVT and PE Prevention of recurrent DVT and PE

Non valvular AF refers to AF that occurs in the absence of mechanical prosthetic heart valves and in absence of moderate to severe mitral stenosis

Conraindications-A creatinine clearance of less than 15 mL/min or GR < 15 Active bleeding Sig risk of major bleeding as
○ current or recent GI ulcer
○ oesophageal varices
○ recent brain or spinal injury
○ recent brain , spine or eye surgery
○ recent intracranial haemorrhoage
○ malignant neaoplasm
○ vascular aneurysm Liver disease associated with coagulopathy and clinically relevant bleeding risk Prosthetic heart valve People taking other anticoagulants If taking cytochrome P3A4enzyme and P glycoprotein inhibitors as ketoconazole , or HIV protease inhibitors as ritonavir Pregnant or breast feeding women

Substantial evidence
 for use of Apixaban is derived from the ARISTOTLE trial-
 Apixaban for Reduction in 
Stroke and Other Thomboembolic Events in Atrial Fibrillation 
( 2012-2016 )

Monitoring not needed Annual renal and LFTs and FBC
○ U/E every 6 months if CrCl 30-60
○ U/E every 3 months if CrCl 15-30 Treatment review every 3 months Dose missed
○ missed dose can be taken up-to 6 hrs prior to when the next dose is due
○ if next dose is due in < 6 hrs -» omit the missed dose and take next 
dose as scheduled Double dose taken – omit next dose and resume treatment in 24 hrs as normal Unsure if taken or not–> not to take another dose and cont with the next dose
( ie after 12 hrs )

Switching anticoagulants From Warfarin to Apixaban Stop Warfain and check INR From Apixaban to Warfarin Warfarin has 
slow onset of action may take 5-10 days before INR is in 
target range INR should be
 checked just before taking the next Apixaban dose