Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).

Being a carrier of a combination of polymorphisms of VKORC1 and CYP2C9, rather than of one of these polymorphisms, is associated with severe overanticoagulation. The time to achieve stability is mainly associated with the CYP2C9 genotype.

To our knowledge, these are the first genotype-guided loading and maintenance dose algorithms for PHE and ACE using large cohorts. The utility of these algorithms will be tested in randomized controlled trials.

In a prospective follow-up study of the effects of VKORC1 and CYP2C9 genotypes on the anticoagulation status of patients, we assessed the CYP2C9 and the VKORC1 C1173T genotypes of patients during the initial 6 months of phenprocoumon treatment. We used linear regression models and Cox proportional hazard models to determine the effects of the VKORC1 and CYP2C9 genotypes on phenprocoumon dose requirements, overanticoagulation, and time to achieve stability. Allele frequencies of interest within the cohort (N=281) were 40.8% VKORC1 T-1173, 12.8% CYP2C9*2, and 6.9% CYP2C9*3. In patients with the VKORC1 CC genotype, carriers of a CYP2C9 polymorphism needed dosages that were nearly 30% lower than those for CYP2C9*1/*1 patients (P<0.001). In patients with a VKORC1 polymorphism, differences between carriers of a CYP2C9 polymorphism and CYP2C9*1/*1 were far smaller and largely not statistically significant. A larger part of the variability in dose requirement was explained by the VKORC1 genotype than by the CYP2C9 genotype (28.7% and 7.2%, respectively). Carriers of a combination of a CYP2C9 polymorphism and a VKORC1 polymorphism had a strongly increased risk of severe overanticoagulation (hazard ratio (HR) 7.20, P=0.002). Only carriers of a CYP2C9*2 allele had a decreased chance to achieve stability compared to CYP2C9*1/*1 patients (HR 0.61, P=0.004). In conclusion, the VKORC1 genotype modifies the effect of the CYP2C9 genotype on phenprocoumon dose requirements. A combination of polymorphisms of both genotypes is associated with a strongly increased risk of overanticoagulation, whereas delayed stabilization is mainly associated with the CYP2C9 genotype.

In users of coumarins, SSRI usage was associated with increased risk of hospitalization because of nongastrointestinal bleeding but not because of gastrointestinal bleeding.

Implementation of competency-based pharmacy education (CBPE) is a time-consuming, complicated process, which requires agreement on the tasks of a pharmacist, commitment, institutional stability, and a goal-directed developmental perspective of all stakeholders involved. In this article the main steps in the development of a fully-developed competency-based pharmacy curriculum (bachelor, master) are described and tips are given for a successful implementation. After the choice for entering into CBPE is made and a competency framework is adopted (step 1), intended learning outcomes are defined (step 2), followed by analyzing the required developmental trajectory (step 3) and the selection of appropriate assessment methods (step 4). Designing the teaching-learning environment involves the selection of learning activities, student experiences, and instructional methods (step 5). Finally, an iterative process of evaluation and adjustment of individual courses, and the curriculum as a whole, is entered (step 6). Successful implementation of CBPE requires a system of effective quality management and continuous professional development as a teacher. In this article suggestions for the organization of CBPE and references to more detailed literature are given, hoping to facilitate the implementation of CBPE.

In carriers of the CYP2C9*3 allele more difficulties in terms of stabilization and overanticoagulation were found as compared with wild-type subjects or CYP2C9*2 carriers. CYP2C9 genotyping could be useful to identify potential candidates for more frequent INR controls to minimize problems with acenocoumarol anticoagulation status.

The presence of at least 1 CYP2C9*2 or *3 allele in phenprocoumon users is associated with an increased risk of severe overanticoagulation. Similar to warfarin and acenocoumarol, phenprocoumon had a lower dosage requirement in carriers of CYP2C9*2 or *3 compared with that in CYP2C9 wild-type subjects.