[Skip to content]

.

Ciclosporin and tacrolimus

Ciclosporin and tacrolimus are the “calcineurin inhibitors” and are the mainstay of modern immunosuppression. The gradual introduction of ciclosporin from 1978 revolutionised organ transplantation, as loss of organs from acute rejection became the exception rather than the rule. Tacrolimus was discovered later and was approved for use in 1994. They prevent T cells producing a chemical called IL-2, which stimulates them to proliferate and attack. This very specific effect prevents the immune system from attacking a new foreign object, like a transplant, but does not affect the immunity to bacteria and viruses which already exists.

calcineurin inhibitors


Although it was a miracle drug which radically improved the results of organ transplantation, the immunosuppressant effect of ciclosporin was discovered by accident! The drug was being tested as a possible new antibiotic to treat difficult infections and was almost abandoned when it was found to be poor at that task. It was only due to the foresight of researchers at the Sandoz laboratories in Switzerland that the drug was tested as an immunosuppressant for the then experimental field of transplantation.

Both drugs are antibiotics, but are too weak to be useful in treating infection. Ciclosporin comes from a Norwegian fungus called Beauveria nivea. Tacrolimus is produced by bacteria called Streptomyces tsukubaensis, discovered by scientists at Tsukuba University in Japan, and the drug is named after them ('Tsukuba macrolide immunosuppressant').

Although the two drugs do not affect the immunity we already possess, they do make it harder to develop immunity to new infections. They also have side effects, of which the most harmful is that they can permanently damage the kidneys. To ensure that patients get the right dose, to prevent rejection but minimise side effects, regular blood tests are needed.

Many other drugs "interact" with ciclosporin and tacrolimus. Interaction means that the drugs each affect the way the body absorbs or removes the other, and so drug dosages may need to be adjusted when other medications are given. It is important that patients with organ transplants keep a record of their medications so that all doctors treating them know which medications they are taking, otherwise harmful drug errors may occur; this includes herbal medications, as some of these also cause interactions. Even grapefruit juice can be harmful in people taking tacrolimus as it slows down the body's metabolism of tacrolimus!