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Apixaban

CPT: 80299
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Synonyms

  • Eliquis®

Expected Turnaround Time

5 - 7 days


Related Documents

For more information, please view the literature below.

Procedures for Hemostasis and Thrombosis: A Clinical Test Compendium


Specimen Requirements


Specimen

Plasma


Volume

1 mL


Minimum Volume

0.5 mL (Note: This volume does not allow for repeat testing.)


Container

Blue-top (sodium citrate) tube (preferred), lavender-top (EDTA) tube, or green-top (heparin) tube


Collection

Transfer plasma to a plastic transport tube.


Storage Instructions

Room temperature


Stability Requirements

Temperature

Period

Room temperature

7 days

Refrigerated

14 days

Frozen

14 days

Freeze/thaw cycles

Stable x3


Test Details


Use

Measurement of drug level in order to monitor therapeutic level and/or diagnose under-dosage or potential toxicity.


Limitations

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.


Methodology

Liquid chromatography/tandem mass spectrometry (LC/MS-MS)


Reference Interval

See table.1

In the ARTISTOTLE trial of non-valvular atrial fibrillation patients,2 steady state plasma concentrations of apixaban were as follows:

2.5 mg (twice daily) dose:

Mean

Range (+/- 2SD)

Peak

171

91–321

Trough

103

41–230

5 mg (twice daily) dose:

Mean

Range (+/- 2SD)

Peak

123

69–221

Trough

79

34–162

In the AMPLIFY trial of venous thromboembolism treatment,3 steady state plasma concentrations of apixaban were as follows:

2.5 mg (twice daily) dose:

Mean

Range (+/- 2SD)

Peak

67

30–153

Trough

32

11–90

5 mg (twice daily) dose:

Mean

Range (+/- 2SD)

Peak

132

59–102

Trough

63

22–77

10 mg (twice daily) dose:

Mean

Range (+/- 2SD)

Peak

251

111–572

Trough

120

41–335


Additional Information

Apixaban is an oral anticoagulant that prevents thrombin generation by inhibiting factor Xa produced as the result of both the intrinsic and extrinsic coagulation pathways.4-6 Apixaban inhibits both free and clot-bound factor Xa and has been approved for clinical use in several thromboembolic disorders, including reduction of stroke risk in non- valvular atrial fibrillation, thromboprophylaxis following hip or knee replacement surgery, the treatment of deep thrombosis or pulmonary embolism, and prevention of recurrent deep vein thrombosis and pulmonary embolism.4,7 This drug inhibits free and prothrombinase-associated factor Xa in a concentration-dependent manner.8,9 Apixaban has a rapid onset, reaching a maximal plasma concentration within one to three hours after oral administration.10,11 Steady-state concentrations are reached within three days with a half-life of 9 to 14 hours in healthy adults.10-11 Oral bioavailability of apixaban is not affected by food intake.9,10 Apixaban is almost insoluble in water and exhibits high plasma protein binding (87%) in humans.11 Approximately one-fourth of apixaban is excreted by the kidneys and about one-half by fecal route.10,11 Significant renal impairment results in decreased clearance and increases overall exposure to the drug.11

The P-glycoprotein (P-gp) multidrug transporter protein facilitates the transport of apixaban across cell membranes and influences the absorption and disposition of the drug in vivo. Apixaban is metabolized by the mixed function oxidase, cytochrome P450 3A4/5 (CYP3A4/5).10 Drugs that affect the activity of CYP3A4/5 and P-gp can potentially affect the pharmacokinetic profile of apixaban.

Routine therapeutic monitoring of apixaban level is not required because of the drug's relatively wide therapeutic index.4 Despite the use of fixed doses of apixaban, determination of the amount drug present in a given individual may be valuable in several clinical situations.12-23 Measurement of levels can inform clinicians with concerns regarding patient compliance and adherence to therapy. Apixaban is transported across the intestinal wall by P-glucoprotein, and drugs that induce or inhibit P-glycoprotein activity may decrease or increase the levels of apixaban, 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 levels measurement can be valuable in determining drug accumulation in situations of renal or hepatic failure and when administered with other drugs that may alter metabolism or clearance.

Apixaban is measured using a validated liquid chromatography-mass spectrometry (LC/MS-MS) method. LC/MS-MS serves as the criterion standard for exact quantification of concentrations of direct oral anticoagulant (DOAC) medications and is considered to be the most accurate method for measurement of these drugs.16,19,20,24,25 Use of liquid LC/MS-MS provides highly accurate measurement of apixaban concentrations without the variable interferences associated with traditional clot-based and chromogenic assays.26 In fact, studies performed using the Labcorp LC/MS-MS method indicates 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 effect on the recovery of drug. Plasma peak concentration of apixaban following a single 5-mg dose had a median value of 96 ng/mL with a +/- two standard deviation range of 40-152 ng/mL (n=20).26,27


Footnotes

1. Annex 1: Summary of product characteristics. European Medicines Agency Web Site. https://www.ema.europa.eu/en/documents/product-information/eliquis-epar-product-information_en.pdf. Accessed December 2020.
2. Avezum A, Lopes RD, Schulte PJ, et al. Apixaban in comparison with warfarin in patients with atrial fibrillation and valvular heart disease: Findings from the Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation (ARISTOLE) trial. Circulation. 2015 Aug 25;132(8):624-632.26106009
3. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808.23808982
4. Hurst KV, O'Callaghan JM, Handa A. Quick reference guide to apixaban. Vasc Health Risk Manag. 2017 Jul 10;13:263-267.28744136
5. Prom R, Spinler SA. The role of apixaban for venous and arterial thromboembolic disease. Ann Pharmacother. 2011 Oct;45(10):1262-1283.21954450
6. Jiménez D, Yusen RD, Ramacciotti E. Apixaban: An oral direct factor-Xa inhibitor. Adv Ther. 2012 Mar;29(3):187-201.22354465
7. Byon W, Garonzik S, Boyd RA, Frost CE. Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review. Clin Pharmacokinet. 2019 Oct;58(10):1265-1279.31089975
8. Wong PC, Crain EJ, Xin B, et al. Apixaban, an oral, direct and highly selective factor Xa inhibitor: In vitro, antithrombotic and antihemostatic studies. J Thromb Haemost. 2008 May;6(5):820-829.18315548
9. Wong PC, Jiang X. Apixaban, a direct factor Xa inhibitor, inhibits tissue-factor induced human platelet aggregation in vitro: Comparison with direct inhibitors of factor VIIa, XIa and thrombin. Thromb Haemost. 2010 Aug;104(2):302-310.20589316
10. Raghavan N, Frost CE, Yu Z, et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos. 2009 Jan;37(1):74-81.18832478
11. Eriksson BI, Quinlan DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor Xa inhibitors in development. Clin Pharmacokinet. 2009;48(1):1-22.19071881
12. Diep R, Garcia D. Should we monitor the direct oral anticoagulants? J Thromb Thrombolysis. 2020 Jul;50(1):30-32.32323189
13. Douketis JD, Spyropoulos AC, Duncan J, et al. Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant. JAMA Intern Med. 2019;179(11):1469-1478.31380891
14. Tripodi A, Ageno W, Ciaccio M, et al. Position Paper on laboratory testing for patients on direct oral anticoagulants. A Consensus Document from the SISET, FCSA, SIBioC and SIPMeL. Blood Transfus. 2018 Sep;16(5):462-470.29106357
15. Raval AN, Cigarroa JE, Chung MK, et al. Management of Patients on Non-Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association. Circulation. 2017 Mar 7;135(10):e604-e633.28167634
16. Samuelson BT, Cuker A, Siegal DM, Crowther M, Garcia DA. Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review. Chest. 2017 Jan;151(1):127-138.27637548
17. Takatsuki S, Kimura T, Sugimoto K, et al. Real-world monitoring of direct oral anticoagulants in clinic and hospitalization settings. SAGE Open Med. 2017 Oct 16;5:2050312117734773.29085636
18. Ten Cate H, Henskens YM, Lancé MD. Practical guidance on the use of laboratory testing in the management of bleeding in patients receiving direct oral anticoagulants. Vasc Health Risk Manag. 2017 Dec 13;13:457-467.29263674
19. Wright C, Brown R, Cuker A. Laboratory measurement of the direct oral anticoagulants: Indications and impact on management in clinical practice. Int J Lab Hematol. 2017 May;39 Suppl 1:31-36.28447413
20. Dale BJ, Chan NC, Eikelboom JW. Laboratory measurement of the direct oral anticoagulants. Br J Haematol. 2016 Feb;172(3):315-336.26492202
21. Martin K, Moll S. Direct oral anticoagulant drug level testing in clinical practice: A single institution experience. Thromb Res. 2016 Jul;143:40-44.27179131
22. Cuker A, Siegal DM, Crowther MA, Garcia DA. Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants. J Am Coll Cardiol. 2014 Sep 16;64(11):1128-1139.25212648
23. Baglin T, Hillarp A, Tripodi A, Elalamy I, Buller H, Ageno W. Measuring Oral Direct Inhibitors (ODIs) of thrombin and factor Xa: A recommendation from the Subcommittee on Control of Anticoagulation of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2013 Jan 24.23347120
24. Schmitz EM, Boonen K, van den Heuvel DJ, et al. Determination of dabigatran, rivaroxaban and apixaban by ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) and coagulation assays for therapy monitoring of novel direct oral anticoagulants. J Thromb Haemost. 2014 Oct;12(10):1636-1646.25142183
25. Ebner M, Birschmann I, Peter A, et al. Limitations of Specific Coagulation Tests for Direct Oral Anticoagulants: A Critical Analysis. J Am Heart Assoc. 2018 Oct 2;7(19):e009807.30371316
26. Barrett YC, Wang J, Song Y, et al. A randomised assessment of the pharmacokinetic, pharmacodynamic and safety interaction between apixaban and enoxaparin in healthy subjects. Thromb Haemost. 2012 May;107(5):916-924.22398784
27. Barrett YC, Wang J, Knabb R, Mohan P. Apixaban decreases coagulation activity in patients with acute deep-vein thrombosis. Thromb Haemost. 2011 Jan;105(1):181-189.20941459

References

Adcock DM, Gosselin R. Direct Oral Anticoagulants (DOACs) in the Laboratory: 2015 Review. Thromb Res. 2015 Jul;136(1):7-12.25981138
Chen A, Stecker E, Warden BA. Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges. J Am Heart Assoc. 2020 Jul 7;9(13):e017559.32538234

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
117085 Apixaban 72608-3 117086 Apixaban ng/mL 72608-3

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