Table 6.
Management of Adverse Effects Associated with Thiopurines
| Adverse event | Action | |
|---|---|---|
| Myelosuppression | ||
| WBC 2.5–3.5 × 109/L | Check metabolites, monitor or consider dose reduction | |
| WBC 1.5–2.5 × 109/L | Stop drug for 1 week and restart at a lower dose with weekly CBC monitoring | |
| WBC < 1.5 × 109/L | Withdraw treatment | |
| Neutropenia (ANC 1–1.5 × 109/L) | Observe, correct metabolites | |
| Neutropenia (ANC < 1.0 × 109/L) | Withdraw treatment, consider G-CSF if febrile | |
| Thrombocytopenia < 150 × 109/L | Observe, screen for NRH | |
| Anemia | Check metabolites | |
| Exclude nutritional deficiencies/anemia of chronic disease/red cell aplasia | ||
| Hepatotoxicity | ||
| 6-MMPR >5,700 pmol/8× 108 RBCs (hypermethylation) | Withdraw the drug, consider LDTA when liver functions normalize | |
| Liver enzymes elevated <2 times | Observe, repeat after 1 week | |
| Liver enzyme elevated >2 times | Withdraw thiopurines; consider incremental dose or LDTA | |
| Cholestatic pattern of injury | Withdraw thiopurines; consider incremental dose or LDTA | |
| Endothelial injury (peliosis hepatis, veno-occlusive disease, nodular regenerative hyperplasia) | Withdraw thiopurines, avoid rechallenge | |
| Gastrointestinal disturbances | ||
| Nausea/vomiting | Incremental dose | |
| Switch from AZA to 6-MP | ||
| Flu like symptoms | ||
| Myalgias, arthralgias, fatigue, fever | Incremental dose | |
| Split dose | ||
| Acute pancreatitis | ||
| Acute pancreatitis | Ensure no abuse of alcohol/smoking | |
| Stop AZA/6-MP | ||
| Consider 6-TG (20–40 mg) | ||
WBC, white blood cells; ANC, absolute neutrophil count; CBC, complete blood count; G-CSF, granulocyte-colony stimulating factor; NRH, nodular regenerative hyperplasia; 6-MMPR, 6-methyl mercaptopurine ribonucleotide; RBC, red blood cells; LDTA, low dose thiopurines with allopurinol; AZA, azathioprine; 6-MP, 6-mercaptopurine; 6-TG, 6-thioguanine.