TABLE 3.
Clinical implementation guidelines (Abdullah-Koolmees et al., 2020).
| Guideline | Genetic variants a | Algorithms | Evidence classification b |
|---|---|---|---|
| CPIC (Johnson et al., 2017) | Non-Africans: CYP2C9*2, CYP2C9*3, VKORC1 -1639G > A | Gage and IWPC equations (Gage et al., 2008; International Warfarin Pharmacogenetics Consortium et al., 2009) | Strong |
| African: CYP2C9*2, CYP2C9*3, VKORC1 -1639G > A | Moderate | ||
| African carriers of CYP2C9*5, *6, *8 or *11 | Decrease calculated dose by 15–30% (20–40% in variant homozygotes) | Moderate | |
| African carriers of the CYP2C rs12777823 A allele | Decrease calculated dose by 10–25% | Moderate | |
| CPNDS (Shaw et al., 2015) | CYP2C9*2, CYP2C9*3, VKORC1 -1639G > A | www.warfarindosing.org c | ++++, Moderate |
| DPWG (The Dutch Pharmacogenetics Working Group, 2016) | CYP2C9*2, CYP2C9*3, VKORC1 -1639G > A | EU-PACT algorithms (IWPC equation as the key algorithm) | 4A-D |
| RNPGx (Lamoureux et al., 2017) | CYP2C9*2, CYP2C9*3, VKORC1 -1639G > A | As per dosing table | Advisable |
For the CPIC, guidelines, optional variants such as CYP4F2*3 not included.
CPIC, has three recommendation levels for genotype/phenotype-drug pairs (strong, moderate, and optional); CPNDS, has four levels of evidence (+ to ++++), and three levels for genotyping recommendations (strong, moderate, and optional); DPWG, has five (0–4) levels of evidence and eight for clinical relevance (AA, to F); and, RNPGx, has three levels for genotyping recommendations (essential, advisable, and possibly helpful).
The primary algorithm is Gage 2008 (Gage et al., 2008). Nevertheless, many other studies (Millican et al., 2007; Lenzini et al., 2008; International Warfarin Pharmacogenetics Consortium et al., 2009; King et al., 2010) have contributed to the data and algorithms available at this site. For this reason, warfarindosing.org can also incorporate CYP4F2*3, GGCX, rs11676382 and additional CYP2C9 alleles (CYP2C9*5 and CYP2C9*6). The IWPC, algorithm is also available on this site as a secondary algorithm.
CPIC, Clinical Pharmacogenetics Implementation Consortium; CPNDS, Canadian Pharmacogenomics Network for Drug Safety; DPWG, Dutch Pharmacogenetics Working Group; EU-PACT, European Pharmacogenetics of Anticoagulant Therapy; IWPC, International Warfarin Pharmacogenetics Consortium; RNPGx, French National Network (Réseau) of Pharmacogenetics.