Ciclosporin

The effectiveness of ciclosporin in psoriasis was first seen as a serendipitous result of treating a patient following a kidney transplant with the drug and seeing the positive effect on the skin. As a relatively modern treatment for psoriasis, there have been randomised controlled trials showing its efficacy at doses between 2.5–5.0 mg/kg/day (Griffiths et al., 2000). Like methotrexate it does have some potent systemic side effects so it is reserved for treating severe psoriasis.

Its therapeutic action is through its effects on the T-cells thus helping to inhibit the stimulation of cytokines which cause cell proliferation seen in psoriasis. Dosing of ciclosporin can be challenging as absorption (through the small intestine) is incomplete (around 30%) and hugely variable (4–89%) (Camisa, 2004d). Thus, the way that the drug is formulated will significantly affect the bioavailability of the drug and patients should not be switched between formulations without careful consideration of this fact.

As with other systemic medications, ciclosporin has a range of side effects, from the relatively mild to the more severe. The side effects of most concern are those related to nephrotoxicity and the resultant kidney function damage and hypertension. The likelihood of a patient experiencing these negative side effects is increased by prolonged time on the drug and higher dosages. Kidney function and blood pressure must be closely monitored. Ciclosporin is also known to interact with a number of drugs; some of which will decrease ciclosporin levels in the blood and others which will increase them (see Table 8.6). More minor side effects are listed in Box 8.4; these usually disappear once the patient has been taken off the ciclosporin.
     
 
Table 8.6 Drugs which alter serum levels of ciclosporin.

  Drugs which increase ciclosporin levels Drugs which decrease ciclosporin levels
  Bromocriptine Phenytoin
  Danazol Phenobarbitol
  Ketoconazole Carbamazepine
  Fluconazole Rifampin
  Itraconazole Intravenous trimethaprim
  Erythromycin Sulfamethoxazole
  Verapamil  
  Nicardipine  
  Diltiazem  
  Methyltestosterone  
  Oral contraceptives  
 
     

     
 
Box 8.4 Minor symptoms associated with ciclosporin
  • Gum hyperplasia
  • Tremor
  • Hypertrichosis
  • Headache
  • Nausea
  • Paresthesia