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Ciclosporin
Discuss the indication for ciclosporin?
Acute severe colitis not responding to steroids
Discuss the mechanism of action of ciclosporin?
It is a lipophilic 11-amino acid cyclic peptide of fungal origin with strong immunosuppressive actions thatacts primarily through inhibition of T-helper cells by binding to cyclophilin (cytosolic protein). This ciclosporin-cyclophilin complex binds to and inhibits calcineurin, a calcium dependent protein phosphatase required for the activation of transcription factors used in early cytokine production. In particular interleukin 2 (IL-2), a cytokine required for T cell activation and proliferation is blocked
Discuss the dose of ciclosporin?
2mg/kg/day by continuous IV infusion (continue up to 7 days depending on the response).
Some centres use oral ciclosporin 5-8mg/kg/day in 2 divided doses with small studies suggesting that oral ciclosporin has the same efficacy and toxicity as the intravenous form.
Discuss the contraindications for ciclosporin use?
Discuss the tests needed before using ciclosporin?
Check the renal function, LFTs, magnesium and cholesterol.
Discuss magnesium and cholesterol?
The risk of seizures is increased in patients with a low cholesterol (<3.0 mmol/l) or magnesium (<0.50 mmol/l). Oral therapy is an alternative in these circumstances. Microemulsion ciclosporin does not contain the chromophore present in intravenous ciclosporin that has been associated with neurotoxicity causing seizures in patients with hypocholesterolaemia or hypomagnesaemia.
Discuss conversion to oral ciclosporin?
Once response occurs IV ciclosporin is converted to oral ciclosporin in 2 divided doses. An oral dose of 5mg/kg/day is equivalent to 2mg/kg/day intravenous dose since the oral bioavailability of neural (ciclosporin) is 30-40%. However the blood levels need to be monitored and the dose titrated accordingly. For patients who are not on an immunomodulator (azathioprine or 6-mercaptopurine) oral ciclosporin should be continued for 3 months whilst an immunomodulator is introduced.
Discuss ciclosporin levels?
The levels could be done at anytime during the 24 hr infusion. Trough levels are needed once the patient is on oral ciclosporin. Aim for ciclosporin levels of 150-250 ng/ml.
Discuss PCP prophylaxis?
PCP prophylaxis with Co-trimoxazole (960mg 1 tab administered three times per week) should be considered especially with triple immunosuppression (steroids, azathiopurine and ciclosporin)
Discuss the side effects?
Author: Dr Simon Chan
Editor: Dr Rakesh Shah
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