Assessment of Cross-Reactivity in Three Different Fecal Occult Blood Test Systems with Dabigatran and Dabigatran Etexilate: Identification of Useful Test Methods

Abstract 4360

Anticoagulant therapy can elevate the risk of gastrointestinal (GI) bleeding and may affect its management. Fecal occult blood tests (FOBT) are non-invasive, widely-used tests that may be useful in detecting early and thus treatable stages of GI lesions or bleeding in patients on these therapies. The literature suggests that use of anticoagulants does not diminish the positive predictive value of FOBT, however a potential limitation and concern of these tests is the possibility for drug interactions with test components which may lead to false results.

Dabigatran is a new oral, reversible, direct thrombin inhibitor currently approved for stroke prevention in patients with atrial fibrillation. Dabigatran etexilate (DE) is the prodrug of the active ingredient dabigatran, and is converted by non-specific esterases in plasma and liver to dabigatran. Approximately 6.5% of DE in Pradaxa^® is bioavailable and absorbed in the gut with the remaining eliminated in the feces. The purpose of this study was to investigate any potential cross-reactivity of dabigatran, DE or Pradaxa^® with three commonly-used commercial FOBTs with different detection methods.

Common methods of detection in FOBTs used worldwide include guaiac oxidation in hemoccult tests, immunochromatographic methods with a membrane strip precoated with hemoglobin antibody, or the benzamidine method where heme in hemoglobin induces a blue/green color change. Examples of each method were tested. The Hemoccult II® SENSA® (Beckman Coulter Inc.), EZ DETECT (Biomerica Inc.), and BioNexia® Hb/Hp Complex Professionell (FROST Diagnostika GmbH) FOBT were used for this study and all tests were conducted according to manufacturer's protocol. DE, dabigatran or the contents of a single Pradaxa^® capsule were suspended in a 0.5% cellulose solution. Vehicle solution was used as negative control and human blood used as a positive control.

Isolated human blood samples generated positive results as expected in all three FOBTs whereas the negative controls did not. Exposure to DE, dabigatran or Pradaxa^® suspensions did not result in positive readouts with any detection method of the tested FOBTs.

In conclusion, these studies demonstrate that the prodrug DE and its active drug form dabigatran, as well as any further excipients in the Pradaxa^® formulation do not cross-react with a set of commonly-used fecal occult blood tests. This supports the usefulness of these 3 tests in dabigatran etexilate-treated patients.