Rivaroxaban
Rivaroxaban is an oral, reversible, direct Factor Xa inhibitor used for anticoagulation.
Indications for measuring +
- Guide dose-adjustment towards optimal drug exposure in relation to drug efficacy and toxicity
- Diagnosis
- Disease resistant to drug versus inadequate drug exposure
- Adverse drug reaction versus underlying disease
- Assessing safety for upcoming intervention associated with increased risk of adverse drug reaction
- Consider alternative gauges of drug effect depending on turnaround time of drug assay
How to measure
Assay details
Timing of sample concentration sample collection
- Trough concentration – i.e. just prior to next dose being due
- At steady state (consider practicalities such as testing on weekdays, etc)
- Consider the half-life in that person
- In healthy young subjects the average half-life is 7 hours meaning steady state is reached approximately 36 hours after commencing or changing dose
- In some patients e.g. those with low clearance, the half-life can increase up to 13 hours
How to interpret
Reference Range
- For patients taking 20 mg daily, the median (5th – 95th centiles) trough concentration is 32 (5 – 155) microgram/L. This provides context regarding where the individual patient is in relation to the population of patients on rivaroxaban. Results outside the 5-95th centiles indicate an extreme outlier
Factors affecting interpretation
- Rivaroxaban is highly protein bound (to albumin). Total rivaroxaban concentration is measured, which comprises the bound and unbound concentrations
- With low serum albumin for a given unbound concentration the total rivaroxaban concentration will be lower
- Caution: if the total concentration is ‘normal’, the unbound (active) concentration may be high
Coagulation tests
- INR increases in a concentration dependent manner
- APTT and TT are not affected by rivaroxaban
- Note: Anti-factor Xa assays will increase in a concentration dependent manner; however, the CHL assay is not calibrated to rivaroxaban not currently recommended
Dose individualisation and adjustment
- Rivaroxaban concentrations increase proportional to dose
- Defined dose forms can lead to issues with practical prescribing. Where possible use whole tablet dosing (rounding to the nearest whole tablet)
- Dose adjustment may result in dosing outside of that which is Medsafe-approved
- Select the initial dose based on clinical factors, such as indication for treatment and renal function. See Hospital HealthPathway Dabigatran and Rivaroxaban
Contacts for help with interpretation
- Medicines Information ph: 03 364 0900
Key references
Foerster KI, Hermann S, Mikus G & Haefeli WE. Drug-drug interactions with direct oral anticoagulants. Clinical pharmacokinetics 2020;59: 967-980. https://link.springer.com/content/pdf/10.1007/s40262-020-00879-x.pdf
Chin PKL (2015). Which Patients May Benefit from Dose Adjustments of Non-Vitamin K Antagonist Oral Anticoagulants? Semin Thromb Hemost 2015;41:195–207.
Mueck W, Lensing AWA, Agnelli G, Decousus H, Prandoni P, Misselwitz. Rivaroxaban. Population Pharmacokinetic Analyses in Patients Treated for Acute Deep-Vein Thrombosis and Exposure Simulations in Patients with Atrial Fibrilation Treated for Stroke Prevention. Clin Pharmacokinet 2011; 50 (10): 675-686.
Mueck W, Stampfuss J, Kubitza D, Becka M. Clinical Pharmacokinetic and Pharmacodynamic Profile of Rivaroxaban. Clin Pharmacokinet 2014;53:1-16.
https://www.medsafe.govt.nz/profs/Datasheet/x/Xareltotab.pdf
Date
2021