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Edoxaban (Savaysa®) is an oral anticoagulant that impairs thrombin generation by inhibiting factor Xa produced as the result of both the intrinsic and extrinsic coagulation pathways.1 This small molecular weight drug inhibits free, prothrombinase-bound and clot-associated factor Xa in a concentration-dependent manner.1 The product labeling from January 2015 approves the use of edoxaban for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and for the treatment of deep vein thrombosis (DVT), which may lead to pulmonary embolism following 5 to10 days of initial anticoagulant therapy.2,3
Liquid chromatography/tandem mass spectrometry (LC/MS-MS)
Edoxaban has been shown to exhibit dose-dependent anti-FXa activity with predictable pharmacokinetic and pharmacodynamic profiles.4-7 The time to maximum plasma concentration has been estimated to be one to two hours following administration, and drug levels have been shown to remain above baseline levels for as long as 24 hours.4,5,8,9 Edoxaban has a half-life of approximately 10 to 14 hours, and its absolute oral bioavailability is 62% in healthy subjects.7,10,11 Edoxaban distributes to extravascular tissues with relatively low protein binding (40% to 59%).9 Food intake, ethnicity, and gender have no influence on edoxaban absorption, elimination, maximum concentration, half-life, or antifactor Xa activity.12,13
Edoxaban is a substrate for the efflux transporter P-glycoprotein, which acts to pump drugs back into the intestinal lumen, thereby limiting systemic absorption.10,13,14 For this reason, a dose reduction is recommended when edoxaban is coadministered with strong P-glycoprotein inhibitors, including quinidine, verapamil, and dronedarone.15 However, coadministration with other P-glycoprotein substrates (ie, atorvastatin or digoxin) has only minor effects on the pharmacokinetics of edoxaban.10 Certain macrolide antibiotics (erythromycin, azithromycin, and clarithromycin), azole antifungals (ketoconazole and itraconazole), high-dose of aspirin (325 mg/day), and strong P-glycoprotein inhibitors (ritonavir and cyclosporine) increase edoxaban steady-state plasma concentrations.10,16
Once absorbed, edoxaban undergoes biotransformation to various metabolites, some of which are active, the most abundant of which (M4) is formed through hydrolysis.9
Elimination occurs via the kidneys at a rate higher than glomerular filtration, suggesting active secretion into the kidney.5 The renal elimination of edoxaban has been estimated to be from 35%5,9 to 50% in healthy volunteers.7 Administration of lower doses of once-daily edoxaban may be necessary in patients with renal impairment.
Routine therapeutic monitoring of edoxaban level is not required because of the drug's relatively wide therapeutic index. Despite the use of fixed doses of edoxaban, determination of the amount of drug present in a given individual may be valuable in several clinical situations. Measurement of levels can inform clinicians with concerns regarding patient compliance and adherence to therapy. Edoxaban is transported across the intestinal wall by P-glycoprotein and drugs that induce or inhibit P-glycoprotein activity, may decrease or increase the levels of edoxaban, respectively. Therapeutic monitoring can help the clinician assess the potential cause of bleeding or thrombosis while on therapy. Determination of levels may also be useful in preparation for surgery or an invasive procedure. Also, drug level measurement can be valuable in determining drug accumulation in situations of renal failure and when administered with other drugs that may alter metabolism or clearance.
Edoxaban can be measured using a validated liquid chromatography/mass spectrometry (HPLC/MS-MS) method. Use of liquid LC/MS-MS provides highly accurate measurement of edoxaban concentrations without the variable interferences associated with traditional clot-based and chromogenic assays.13 In fact, studies performed using the LabCorp LC/MS-MS method indicate that the assayed drug recovery was unaffected by the presence of lupus anticoagulants or heparin administration. Factor VIII deficiency and multiple factor deficiency associated with coumadin treatment had no affect on the recovery of drug.
0.2 mL (Note: This volume does not allow for repeat testing.)
Transfer plasma to a plastic transport tube.
|Order Code||Order Code Name||Order Loinc||Result Code||Result Code Name||UofM||Result LOINC|
|117060||Edoxaban by LCMS||82468-0||117059||Edoxaban by LCMS||ng/mL||82468-0|