Transplant immunosuppressants
also: ciclosporin · tacrolimus · mycophenolate · calcineurin inhibitor
Overview
The transplant/autoimmune immunosuppressants not covered elsewhere — calcineurin inhibitors and mycophenolate. (Azathioprine→GI, methotrexate→MSK, corticosteroids→Endo, biologics→Derm/MSK.)
Mechanism
Ciclosporin and tacrolimus inhibit calcineurin → block NFAT → ↓IL-2 → ↓T-cell activation. Mycophenolate inhibits inosine monophosphate dehydrogenase → blocks purine (guanosine) synthesis in lymphocytes.
Indications
- Solid-organ transplant (rejection prophylaxis)
- Severe autoimmune disease (e.g. lupus nephritis)
The agents
narrow index, levels
Nephrotoxic; diabetogenic; neurotoxicity, tremor; CYP3A4.
levels
Nephrotoxic; GUM HYPERTROPHY, hypertrichosis, hypertension; CYP3A4.
Myelosuppression, GI; teratogenic.
Adverse effects
Dose by levels.
Cautions & contraindications
Levels swing — grapefruit, azoles, macrolides, rifampicin.
Interactions
- CYP3A4 (ciclosporin/tacrolimus); nephrotoxin stacking
Monitoring & kinetics
Drug levels (CNIs), renal function, BP, glucose, FBC
Oral; narrow therapeutic index — therapeutic drug monitoring.
Source: BNF — Immunosuppressants