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- Pradaxa® (Dabigatran Etexilate)
Measurement of drug level in order to monitor therapeutic level and/or diagnose under-dosage or potential toxicity.
This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.
This test was developed
This test was developed.
Liquid chromatography/tandem mass spectrometry (LC/MS-MS)
Dabigatran etexilate mesylate (Pradaxa®) is a selective, reversible, direct thrombin inhibitor that has been approved for thromboprophylaxis to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.1-4 Dabigatran etexilate is a prodrug that is administered orally and has a bioavailability of 6.5%. After absorption into the bloodstream, the prodrug is converted by ubiquitous esterases to the active drug, dabigatran. Approximately one third of circulating dabigatran is bound to plasma proteins.5 Maximum serum concentrations are reached between 1.5 and 3 hours after dosing.6,7 Pharmacokinetic studies reveal an interindividual coefficient of variation of approximately 30%.6 Dabigatran is widely distributed through the bloodstream but does not cross the blood-brain barrier to an appreciable extent.8 Repeated administration in patients with normal renal function is 14 to 17 hours permitting a once daily administration of the drug.6
Approximately 80% of the dabigatran in the blood is eliminated unchanged through renal excretion.9 As a consequence, there is a risk of drug accumulation in patients with renal impairment.4,10 Renal function should be evaluated before prescribing dabigatran.11,12 The FDA-approved 150-mg twice-daily dabigatran for patients with normal renal function and 75-mg twice-daily for patients with impaired renal function (ie, a creatinine clearance 20 to 50 mL/minute). Renal function should be assessed on a regular basis in situations in which decline anticipated and at least yearly for patients older than 75. Because dabigatran is not metabolized by cytochrome P450 isoenzymes, it has few major interactions with other drugs;9 however, drugs that either induce or inhibit P-glycoprotein can affect the absorption of the drug in the gut.9
There is no reversal agent for dabigatran, although hemodialysis can be employed for rapid removal of the drug in life-threatening circumstances.13 A procoagulant, such as recombinant-activated factor VII, can also be employed in the management of severe bleeding associated with dabigatran.13
Routine therapeutic monitoring of dabigatran levels is not required because of the drug's relatively wide therapeutic index. Despite the use of fixed doses of dabigatran, 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.14 Dabigatran 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 dabigatran, respectively.4 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 or hepatic failure and when administered with other drugs that may alter metabolism or clearance. Total dabigatran, ie, the sum of dabigatran and its pharmacologically active glucuronides,15 is measured after complete alkaline cleavage of the glucuronide conjugates present in the samples using a validated liquid chromatography/mass spectrometry (LC/MS-MS) method. Use of liquid LC/MS-MS provides highly accurate measurement of dabigatran concentrations without the variable interferences associated with traditional clot-based and chromogenic assays.16,17 In fact, studies performed using the LabCorp LC/MS-MS method indicate 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.
0.5 mL (Note: This volume does not allow for repeat testing.)
Blue-top (sodium citrate) tube (preferred), lavender-top (EDTA) tube, or green-top (heparin) tube
Transfer plasma to a plastic transport tube.
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