Pharmacogenetic Dosage Algorithm for Acenocoumarol

Demographic and clinical factors contribute approximately 20% to the total variability of dose requirements. In recent years it has highlighted the close relationship between the dose requirements of coumarin drugs and certain polymorphisms of genes involved in pharmacokinetics and pharmacodynamics of these drugs. The use of dosing algorithms that include pharmacogenetic information may help in the dose selection, improving efficacy and reducing adverse events. Studies have shown the relationship between genotype variants of CYP2C9 and VKORC1, CYP4F2 and apolipoprotein E (ApoE), which together with the demographic and clinical variants can explain between 50-60% of the variability in the response to these drugs.

Inclusion criteria

• Patients with Auricular fibrillation, venous thromboembolic disease and cardiac valve replacement receiving acenocoumarol.
• Patients with stable dose of acenocoumarol (weekly dose variation of <20% in the last 3 months).
• Patients with an international normalised ratio within the range of 2 to 3 (in Auricular Fibrillation and venous thromboembolic disease) or 2.5 to 3.5 (in cardiac valve replacement) for at least the 3 previous consecutive months.

Exclusion criteria

• Patients with renal failure (calculated creatinine clearance ≤30 ml/min), hepatic disease (stage C of Child Plough Stage), thyroid dysfunction and/or cancer.