Select an alternative drug rather than thioguanine for intermediate and poor TPMT metabolizers.
The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for thioguanine based on TPMT genotype [Article:21412232]. They recommend selecting an alternative drug for patients carrying inactive alleles.
|Phenotype (Genotype)||Therapeutic Dose Recommendation||Level of Evidence||Clinical Relevance|
|IM (one inactive allele: *2, *3, *4-*18)||Select alternative drug. Insufficient data to allow calculation of dose adjustment.||Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.||Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x109/l; leucopenia 1.0-2.0x109/l; thrombocytopenia 25-50x109/l; severe diarrhea.|
|PM (two inactive alleles: *2, *3, *4-*18)||Select alternative drug. Insufficient data to allow calculation of dose adjustment.||Published case reports, well documented, and having relevant pharmacokinetic or clinical endpoints. Well documented case series.||Clinical effect (S): death; arrhythmia; unanticipated myelosuppression.|