6th June 2004

Rapamycin (sirolimus)

Rapamycin is a new drug which is being used for immunosuppression after transplantation. It was first used after liver transplantation at Addenbrooke’s hospital in the mid 1990s in a trial and since then has been used in more patients. It is currently only licensed for use after kidney transplantation but it is also being used in some situations after liver and other organ transplantation. It is a drug which suppresses the immune system in a different way to the other drugs which we normally use (Cyclosporin and Tacrolimus) and therefore has different effects and side effects.

It is available in tablet form and because it is a long acting drug, it is only taken once daily. It is monitored in the same way as Cyclosporin and Tacrolimus with a blood test taken in the morning before the drug dose.

There are currently two reasons why we are using Rapamycin. The first is if patients are suffering from side effects of Cyclosporin or Tacrolimus. Most commonly this is because of the effect that these drugs have on the kidneys. Over a period of several years, they can cause kidney failure. This is not something that you would notice in the early stages, but something that we detect as part of the regular monitoring after transplantation. Other side effects that require a change of drug include fits and difficulty controlling blood pressure, but these are less common. The second reason for using Rapamycin is that we think there may be a positive effect on the transplanted liver. There is evidence that Rapamycin reduces fibrosis (scarring) in various settings and we think that it may reduce fibrosis in the liver where this appears to be becoming a problem. The problem is greatest in hepatitis C, with some patients developing fibrosis much more quickly than they did in their own liver. We are studying the effect of switching drugs to Rapamycin to see if the fibrosis stops getting worse or even improves. If the study which we are doing shows that Rapamycin has a beneficial effect, we will need to study it further in a larger group of patients, perhaps involving other transplant centres.

As with all drugs, Rapamycin has some side effects. These were quite troublesome when the drug was first used at higher doses but as we have been using it more, we have been using lower doses and have seen much fewer side effects. The ones which we do see in some patients are mouth ulcers, diarrhoea, skin rash, bony pains and an increase in the number of infections.
One of the effects of the reduction in fibrosis is a delay in wound healing. As a result of this, we do not use Rapamycin immediately after liver transplantation because of problems with the operation site healing up. There are also some possible problems which may be caused to the liver blood supply. Because of this, we start Rapamycin only after the operation has fully healed, meaning that we usually switch drugs 6 months or longer after the transplant operation. Occasionally when other drugs are not tolerated we use Rapamycin earlier on. In common with Cyclosporin and Tacrolimus there are interactions with other drugs and it is important to tell any doctor or dentist treating you what drugs you are taking. It is also advised that you do not drink grapefruit juice.

In summary, Rapamycin is a new immunosuppressant drug which we are using increasingly. It is particularly useful in patients who are developing problems in their transplanted liver or have side-effects from their other drugs.