Table 2. Classification of potential clinical effects observed in patients with risk phenotypes, based on DPWG guidelines.
| Class | Clinical Effect |
|---|---|
| AA | Clinical effect (NS): no change or a non-significant change of clinical parameters. Kinetic effect (NS): no change or a non-significant change of kinetic parameters. |
| A | Minor clinical effect (S): QTc prolongation (<450 ms ♀, <470 ms ♂); QTc time increase < 60ms; INR increase < 4.5. Kinetic effect (S): significant change of kinetic parameters |
| B | Clinical effect (S): short-lived discomfort (< 48 hr) without permanent injury: e.g. reduced decrease in resting heart rate; reduction in exercise tachycardia; decreased pain relief from oxycodone; ADE resulting from increased bioavailability of atomoxetine (decreased appetite, insomnia, sleep disturbance, depressive mood, etc); neutropenia > 1.5x109/l; leucopenia > 3.0x109/l; thrombocytopenia > 75x109/l; moderate diarrhea not affecting daily activities; reduced glucose increase following oral glucose tolerance test; muscle complaints creatine kinase <3 times normal upper limit |
| C | Clinical effect (S): long-standing discomfort (48–168 hr) without permanent injury e.g. failure of therapy with tricyclic antidepressants, atypical antipsychotic drugs; extrapyramidal side effects; parkinsonism; ADE resulting from increased bioavailability of tricyclic antidepressants, metoprolol, propafenone (central effects e.g. dizziness); increased INR 4.5–6.0; neutropenia 1.0–1.5x109/l; leucopenia 2.0–3.0x109/l; thrombocytopenia 50-75x109/l; muscle complaints creatine kinase 3–10 times normal upper limit |
| D | 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; myopathy (muscle complaints creatine kinase ≥10 times normal upper limit) |
| E | Clinical effect (S): Failure of lifesaving therapy e.g. anticipated myelosuppression; prevention of breast cancer relapse; arrhythmia; neutropenia < 0.5x109/l; leucopenia < 1.0x109/l; thrombocytopenia < 25x109/l; life-threatening complications from diarrhea; rhabdomyolysis |
| F | Clinical effect (S): death; arrhythmia; unanticipated myelosuppression |
ADE: Adverse Drug Event. DPWG: Dutch Pharmacogenetics Working Group. NS: not statistically significant difference. S: statistically significant difference. INR: international normalized ratio. QTc: Corrected QT interval.