Steroids, calcineurin inhibitors, antimetabolites and biologics
Mnemonic
Group by mechanism, and each has a signature toxicity:
- Calcineurin inhibitors - ciclosporin, tacrolimus. Block IL-2 production. Nephrotoxic; ciclosporin causes gum hypertrophy and hirsutism, tacrolimus causes diabetes and tremor
- Antimetabolites - azathioprine (needs TPMT testing, and interacts dangerously with allopurinol), mycophenolate (teratogenic), methotrexate (weekly, with folic acid)
- mTOR inhibitors - sirolimus. Poor wound healing, pneumonitis
- Corticosteroids - broad, with the full cushingoid burden
- Biologics - anti-TNF (infliximab, adalimumab: reactivate tuberculosis and hepatitis B), rituximab (anti-CD20)
“Check TPMT before azathioprine, and never give it with allopurinol” is the single most important prescribing rule here, since xanthine oxidase inhibition causes profound myelosuppression.
All raise the risk of infection and of malignancy, particularly skin cancer and post-transplant lymphoproliferative disease, which is why sun protection and surveillance are routine.
Expansion
| Drug | Mechanism | Key toxicity |
|---|---|---|
| Corticosteroids | Broad transcriptional suppression | Cushingoid effects, diabetes, osteoporosis, infection |
| Ciclosporin | Calcineurin inhibition | Nephrotoxicity, hypertension, gum hypertrophy, hirsutism, tremor |
| Tacrolimus | Calcineurin inhibition | Nephrotoxicity, diabetes, tremor; no gum or hair effects |
| Azathioprine | Purine synthesis | Myelosuppression; TPMT testing required; fatal interaction with allopurinol |
| Mycophenolate | IMP dehydrogenase, lymphocyte selective | GI upset, marrow suppression, teratogenic |
| Sirolimus | mTOR | Impaired wound healing, hyperlipidaemia; not nephrotoxic |
| Methotrexate | Dihydrofolate reductase | Hepatotoxicity, pneumonitis, marrow suppression; weekly dosing |
| Biologics | Anti-TNF, anti-CD20, anti-IL-6 | Tuberculosis reactivation, hepatitis B reactivation, infection |
Two errors worth naming explicitly: methotrexate is weekly, and daily prescribing has caused deaths; and allopurinol with azathioprine blocks its metabolism by xanthine oxidase, causing profound marrow failure.
All immunosuppressed patients carry an increased risk of infection with opportunistic organisms and of malignancy, especially skin cancer and lymphoproliferative disease, which is why sun protection and surveillance are part of routine care.