Other Immunosuppressants
Examples
Indications
Both
Ciclosporin only
- Ulcerative colitis (unlicensed indication)
- Rheumatoid arthritis
- Psoriasis
Contraindications
Contraindications
- Hypersensitivity to macrolides (tacrolimus)
Caution
- Pregnancy and breast feeding
Mechanism
Both ciclosporin and tacrolimus act as calcineurin inhibitors in T-cells. This blocks the production of cytokines including IL-2, which in turn reduces the production of inflammatory cytokines and the production of more T-cells.
Administration
Oral
Adverse Reactions
Both
- Gastrointestinal disturbance
- Renal impairment
- Hepatic dysfunction
- Hypertension
- Hyperuricaemia
- Electrolyte disturbance (including hyperkalaemia)
- Haematological effects (including anaemia, leucopenia, thrombocytopenia)
- Hyperglycaemia
Ciclosporin only
- Gum hypertrophy
- Hypertrichosis
Tacrolimus only
- Cardiomyopathy
- Arrhythmias
Interactions
Ciclosporin and Tacrolimus are metabolised by CYP3A4 leading to a range of potential drug-drug interactions, particularly with P450 enzyme inducers and inhibitors (link to lecture).
Renal impairment is more likely to occur with other nephrotoxic drugs such as NSAIDs and aminoglycosides.
Hyperkalaemia is a risk with other drugs which raise potassium such as ACE inhibitors or potassium sparing diuretics.
Ciclosporin and tacrolimus should not be used together as ciclosporin concentrations are increased.
Education
Regular monitoring of renal and liver function is needed as well as blood pressure (and echocardiography with tacrolimus).
Pharmacokinetics
Different brands of ciclosporin have different bioavailability, so brand name should be specified when prescribing.
