Current treatment of transplant rejection utilizes various combinations of immunosuppressive agents. The reason for this strategy is to minimize the dose of a given drug in an effort to decrease the side effects from the drug. Despite these efforts patients continue to struggle with the side effects of immunosuppressant therapy. In order to address the troubling side effects and improve the quality of life for a transplant patient, one area of drug development is to make modifications to the drugs we have available.
There are two new immunosuppresant medications for transplant patients that will soon be available. Both are made by the manufacturer, Novartis. One of the medications recently received approval by the FDA in February 2004. It is enteric-coated mycophenolate sodium with the trade name of Myfortic ®. Myfortic® prevents rejection of your organ the same way as mycophenolate mofetil, which has the trade name of CellCept®. Myfortic® is designed to release mycophenolic acid (MPA), the active form of the drug into the small intestines.
This differs from CellCept® which releases MPA into the stomach. Side effects from CellCept® include nausea, vomiting, ulcers, diarrhea, and abdominal pain. Patients usually respond to spreading out the dose or decreasing the total daily dose of CellCept®, however reducing the dose of immunosuppression may increase the risk of developing acute rejection.
Myfortic® was designed with an enteric coating to have absorption occur in the small intestine rather than in the stomach to help protect the stomach and cause less gastrointestinal side effects. In the United States, Myfortic® has completed two clinical trials. Based on these trials, it appears that both Myfortic® and CellCept® have similar side effects.
The most common side effects were diarrhea and a decrease in white blood cell count. These studies were set up to show that Myfortic® worked as well as CellCept in preventing rejection in kidney transplant patients. The studies were not designed to show a difference in gastrointestinal side effects between Myfortic® and CellCept®. Novartis plans to do a study to compare the gastrointestinal side effects between the two products. For now, Myfortic® is an alternative medication to CellCept®.
A second medication on the horizon is known by the generic name everolimus. The proposed brand or trade name for everolimus is Certican®. Certican® works the same way as sirolimus (Rapamune®) in preventing acute rejection. Both of these medications belong to a group of immunosuppressants known as TOR inhibitors. At this time, the FDA has been given information about the safety and how well Certican® works in kidney and heart transplant patients.
In two large studies involving kidney transplant patients, Certican® worked as well as CellCept® in preventing acute rejection. In studies involving heart transplant patients, acute rejection rates were lower in patients who received Certican® compared to those patients who received azathioprine.
Side effects commonly seen with Certican® occured with higher doses and were reversible when the dose was decreased. These were a decrease in platelets and an increase in cholesterol and triglycerides. Patients will need to have blood levels of Certican® checked on a regular basis.
Certican® is taken twice a day, whereas Rapamune® is usually taken once a day. Certican® should be taken consistently either with or without food. Certican® can also be taken the same time as Neoral ®. This differs from patients taking Rapamune® and Neoral® which must be spaced 4 hour apart.
Everolimus is expected to be approved later in 2004.
- Laura Lees, Ph.D., Transplant Pharmacist
