Anti-Rejection Drugs

Definition

Anti-rejection drugs are daily medications taken by organ transplant patients to prevent organ rejection.

Purpose

Anti-rejection drugs, which are also called immunosuppressants, help to suppress the immune system's response to a new organ. When a new organ is placed inside a patient s body, the patient's immune system recognizes the organ as foreign tissue and tries to reject it.

Description

When a physician prescribes anti-rejection drugs, the patient's risk of rejection and susceptibility to side effects are considered. The most common drugs prescribed to prevent organ rejection are cyclosporine, prednisone, azathioprine, tacrolimus or FK506, mycophenolate mofetil, sirolimus, and OKT3, as well as ATGAM and Thymoglobulin. As is true with all medications, each of these drugs has benefits and drawbacks. Cyclosporine, which is one of the most frequently used anti-rejection drugs, is usually combined with prednisone. An extremely powerful medicine, cyclosporine is usually taken by a patient over the course of his or her lifetime. Cortisol, which is the naturally produced form of prednisone in a person's body, helps the body manage stress, such as infections or organ rejection. Taking prednisone results in less cortisol production in a person's body, thus minimizing the risk of rejection. Azathioprine, which needs to be taken with food to avoid stomach upset, is frequently combined with cyclosporine, prednisone, or tacrolimus. Mycophenolate mofetil is a relatively new immunosuppressant that is similar to azathioprine; therefore, the two drugs should not be taken together. It is preferable to take mycophenolate mofetil on an empty stomach; however, like azathioprine, it can be taken with food because it, too, can cause stomach problems, such as heartburn and nausea. Like azathioprine, mycophenolate mofetil is not a stand-alone drug; instead, it must be used, in combination with other medications. This is also the case with regard to sirolimus.

Physicians prescribe either mycophenolate mofetil or azathioprine (in combination with other immunosuppressant drugs ) to help patients cope with acute bouts of organ rejection. The medications work by interfering with the multiplication process of white blood cells, which is part of the body's natural defense system when foreign invaders, such as a new organ, are detected. However, researchers at Duke University and the University of Florida found that mycophenolate mofetil doesn't work any better than azathioprine, but costs significantly more. Aside from cost, another consideration also needs to be the type of organ transplanted, because acute rejection rates differ. For example, six months after surgery, approximately 15% of kidney recipients will have an acute rejection episode as compared to approximately 60% of lung recipients. And because study results vary depending on the organ transplanted, more research is needed with regard to the success of mycophenolate mofetil as compared to azathioprine.

OKT3 prevents is prescribed to prevent organ rejection immediately after surgery and is also used to treat acute rejection episodes; ATGAM and Thymoglobulin, which are similar to OKT3, are used for the same reasons. All three drugs are given intravenously.

Tacrolimus, which is also known as FK506, is a fairly new drug that is considered by many experts to be as effective as cyclosporine. An alternative drug choice for patients that cannot tolerate cyclosporine, tacrolimus has been the subject of much research in recent years. Used to treat rejection episodes that are acute or chronic in nature, tacrolimus is being studied to see if using it will allow patients to reduce their dosage of prednisone without organ rejection.

In a presentation at the 2003 American Transplant Congress, surgeons from the University of Pittsburgh reported that an innovative clinical protocol developed by Dr. Thomas E. Starzl was implemented, which reduced the dosage of tacrolimus needed by lung transplant patients with excellent success. Patients required lower doses of prednisone as well. In fact, in some cases, patients were taking tacrolimus only once a day (rather than twice a day) or only four times a week. Over the long-term, physicians hope that there will be less risk of lung recipients developing the kinds of complications normally associated with high levels of immunosuppressants, such as kidney dysfunction, which is a common problem faced by lung transplant patients.

Dr. Thomas E. Strazl, the renowned physician often referred to as the modern-day father of transplantation, developed the protocol based on the knowledge that some of his patients had stopped taking their daily pills with no ill effects. Starzl theorized that giving several drugs to a patient immediately after surgery, which was the normal practice, might inhibit the immune system from developing a tolerance for the new organ. Therefore, his new protocol embraced a different approach. Shortly before the transplantation, patients were given a drug that killed their T-cells and after the operation, patients received only one anti-rejection medicine rather than the multi-pill cocktail normally prescribed. In an article published by Lancet in 2003, Starzl and colleagues reported the results of their pilot study involving 82 two kidney, liver, pancreas or small bowel transplant patients treated according to the new drug protocol. Out of the 72 patients with successful transplants after one year, over half the patients were taking anti-rejection medication either every other day, three times per week or twice per week. Amazingly, 11 of the patients were taking only one pill a week and they exhibited no signs of organ rejection or complications. Certainly more research needs to be conducted, but these results are very promising.

Recommended dosage

The dosages vary depending on the drug or drug combination being taken by the patient. In general, cyclosporine is taken every 12 hours in liquid or capsule form. Tacrolimus is generally taken every 12 hours as well. The level of either drug in a patient's blood is monitored carefully and doses are adjusted accordingly in order to not only prevent reject, but also unpleasant side effects. Azathioprine is taken once a day in tablet form, whereas mycophenolate mofetil is generally taken every 12 hours. High doses of prednisone are usually given at first and then tapered down slowly.

Precautions

Patients should discuss proper storage methods with regard to their medications. Sirolimus, for example, should be stored at room temperature with special care taken to keep it out of excessive heat and humidity.

Although pregnant women taking anti-rejection drugs have delivered healthy babies, women planning on becoming pregnant while taking anti-rejection drugs should talk with their physicians regarding any possible complications. For example, the safety of taking mycophenolate mofetil during pregnancy or while breastfeeding is questionable and not advised.

Side effects

Side effects vary depending on the individual and the drug therapy chosen. Patients should talk with their doctors regarding the various side effects they can expect and under what conditions emergency medical care needs to be sought.

Interactions

It is essential that patients talk with their pharmacist and transplant team before taking any medications, regardless of whether they are prescription or over-the-counter drugs to ensure that the combinations will not interact. For example, antacids can diminish the effectiveness of mycophenolate mofetil and drugs used to treat high cholesterol may increase the potency of sirolimus. In addition, certain food products can also alter the potency of some anti-rejection drugs. For example, grapefruit and grapefruit juice can cause cyclosporine blood levels to increase.

Resources

PERIODICALS

Mazariegos, G. V., Zahorchak, A. F., Reyes, J., et al. "Dendritic cell subset ratio in peripheral blood correlates with successful withdrawal of immunosuppression in liver transplant patients." American Journal of Transplantation 3 (2003): 689-696.

Starzl, T. E., Murase, N., Abu-Elmagd, K., et al. "Tolerogenic immunosuppression for organ transplantation." Lancet 361 (2003): 1502-1510.

OTHER

Ross, Melanie Fridl "Duke/UF Researchers compare anti-rejection medicines in lung transplant patients." University of Florida 9 Aug 2001 University of Florida News. 22 Feb 2005 〈http://www.napa.ufl.edu/2001news/antireject.htm〉.

Rossi, Lisa "Studies of liver transplant patients off anti-rejection drugs have altered cell profile." University of Pittsburgh Medical Center 2 June 2003 University of Pittsburgh Medical Center. 22 Feb 2005 〈http://www.eurekalert.org/pub_releases/2003-06/uopm-so1060203.php〉.

Srikameswaran, Anita "Protocol reduces transplant patients need for anti-rejection drugs." Post-Gazette.com Health and Science 2 May 2003 PG Publishing Company, Inc. 22 Feb 2005 〈http://www.post-gazette.com/healthscience/20030502starzlhealth2p2.asp〉.

University of Pittsburgh Medical Center "Our Experts: Thomas E. Starzl, M.D., Ph.D." University of Pittsburgh Medical Center 2005 University of Pittsburgh Medical Center. 22 Feb 2005 〈http://newsbureau.upmc.com/Bios/BioStarzl.htm〉.