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NOACS-Apixaban

Apixaban is an oral anticoagulant and direct inhibitor of factors Xa which is used to decrease the risk of venous thromboses , systemic embolisation and stroke in patients with atrial fibrillation , and lower the risk of deep vein thrombosis and pulmonary embolus after knee or hip replacement surgery ( Pubchem )

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 )
○ INR
○ 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

LINKS AND RESOURCES

PATIENT INFORMATION

PIL’s from the Eliquis website https://www.eliquis.co.uk/hcp/resources/patient-materials/patient-information-booklets-vte-prophylaxis
or https://www.eliquis.co.uk/hcp/resources/patient-materials/patient-information-booklets-nvaf
Eliquis patient portal https://www.eliquis.co.uk/patient

NHS on apixaban https://www.nhs.uk/medicines/apixaban/

NOAC information for patients from DOH Govt of Western Australia – Living with NOACS https://ww2.health.wa.gov.au/~/media/Files/Corporate/general%20documents/Quality/PDF/Living-with-a-NOAC-2013.ashx

Printable 2 page information from Institute of Safe Medicine Prescribing  https://www.ismp.org/sites/default/files/attachments/2018-11/Eliquisfinal.pdf

Apixaban patient alert card http://medicinesauthority.gov.mt/file.aspx?f=3187

INFORMATION FOR CLINICIANS

FDA on Eliquis https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202155s000lbl.pdf

Hurst KV, O’Callaghan JM, Handa A. Quick reference guide to apixaban [published correction appears in Vasc Health Risk Manag. 2017 Oct 26;13:413]. Vasc Health Risk Manag. 2017;13:263–267. Published 2017 Jul 10. doi:10.2147/VHRM.S121944 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513886/

Marco Proietti, MD, Imma Romanazzi, MD, Giulio Francesco Romiti, MD, Alessio Farcomeni, PhD, and Gregory Y.H. Lip, MD AHA/ASA Journal 2018 https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.117.018395
Interested in knowing about reversal agent Ondexxya ( andexanet elf ) ? – read here https://www.ema.europa.eu/en/news/first-antidote-reversal-anticoagulation-factor-xa-inhibitors-apixaban-rivaroxaban
References Scottish Medicines Consortium Apixaban March 2015 Barts Health NHS Trust : Primary Care Prescribing Information Apixaban Product Monograph Eliquis® 2.5 mg and 5 mg Anticoagulant Pfizer Canada Inc June 2016 Economic Analysis of Apixaban Therapy for Patients with Atrial Fibrillation From a US Perspective : Results from the ARISTOTLE Randomized Clinical Trial Cowper et al JAMA Cardiol 2017 May 1;2 (5) 525-534 Medicine compendium Eliquis 2.5mg film-coated tablets SPC Efficacy and safety of novel anticoagulants versus vitamin K antagonists in patients with mild and moderate to severe renal insufficiency: Focus on apixaban Int J Cardiol Dec 2016 15;225 :77-81 ( Abstract ) Comparison of the Safety nd Effectiveness of Apixaban versus Warfarin in Patients with Severe Renal Impairment Pharmacotherapy . 2017 Apr ; 37 (4) :412-419 ( Abstract ) CKS NHS Anticoagulation- oral December 2016 Drug Monograph- Apixaban ( Eliquis ) Drug Information Provided By Gold Standard Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation : Executive summary Eur Heart J ( 2017 ) 38 (27) :2137-2149 accessed via https://www.escardio.org/Guidelines/Recommended-Reading/
Heart-Rhythm/Novel-Oral-Anticoagulants-for-Atrial-Fibrillation Alert card for Eliquis patients from 
https://www.medicines.org.uk/media/3705/19546340_eliquis_patient_alert_card_web_uk_final-1-.pdf

 

 

 

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