Getting to know your transplant drugs

Different transplant centres use different protocols specifying which combination of immunosuppressive medicines are used after transplantation. Often, one or more of these drugs must be taken, sometimes every day, after transplantation to ensure that the immune system is somewhat weakened, so that its ability to destroy the donated organ is minimized. Immunosuppressive medicines, while necessary for the survival of the transplanted organ, can have side effects. Transplant centres try to balance necessary immunosuppression against possible side effects from these drugs. Note that not everyone will get side effects from these drugs. The dose of each of these immunosuppressive drugs will vary from person to person. The transplant team will take blood samples to assess the concentration of these drugs in the blood and make adjustments as necessary. This type of intensive medical surveillance is necessary particularly for HIV-positive people because many medicines used to treat HIV infection also affect transplant drugs and vice versa.

We now report on some commonly used immunosuppressive drugs and summarize their possible side effects. For more information about possible side effects and ways to minimize them, speak to your transplant team and pharmacist.

Corticosteroids

These are commonly called steroids. Methylprednisone is most often used in people with transplants, particularly immediately following a transplant and for treating episodes of rejection (where the immune system begins to attack the donated organ). Steroids are given at an initially high dose and this is gradually reduced over weeks or months. Sometimes steroids may be used for longer periods. Some people taking corticosteroids experience increased weight and blood pressure and can develop higher levels of cholesterol in their blood. This drug may also cause mood swings. Over the long-term, steroids can cause bones to become thinner and more fragile.

Cyclosporine (Neoral, Sandimmune)

This drug belongs to the class of drugs called calcineurin inhibitors. Cyclosporine is very good at suppressing the immune system and is sometimes used together with methylprednisone and another drug called CellCept (mycophenolate mofetil). However, cyclosporine can cause certain side effects, such as the following:

• flushing in the face –this resolves a few hours after you have taken your dose
• increased growth of hair on the face, arms and body (if you are bald, cyclosporine will not reverse this)
• slight tremors of the hands –this is common in the first few months of use but tends to clear over time or if the dose is reduced
• swollen gums and sensitivity of the mouth to heat and cold – keeping your mouth and teeth clean with daily brushing and flossing as well as regular visits to the dentist is important to maintain your oral health
• higher-than-normal blood pressure (hypertension) – your transplant team will prescribe medication to help lower your blood pressure. Advice from a registered dietician is also important. Talk to your dietician about how to reduce excessive intake of salt, which also can raise your blood pressure and affect the health of your kidneys.
• pre-diabetes and diabetes – cyclosporine can increase your risk for developing diabetes. Regular blood tests to assess your blood sugar will be done while you are taking this drug. If you have a parent, brother or sister who has diabetes, let your transplant team know. Signs/symptoms of diabetes can include unexpected and excessive feelings of thirst and/or hunger, frequent urination and blurred vision. If you experience any of these, contact your transplant team right away.
• changes in kidney health – regular blood and urine tests are important for monitoring your overall health and the health of your kidneys. Some cyclosporine users can develop kidney dysfunction (nephrotoxicity). If this happens, your transplant team can reduce your dose of cyclosporine or replace it with a different drug.

Tacrolimus (Prograf)

This drug is also a member of the calcineurin class of transplant medicines. It can cause headache and similar side effects as cyclosporine. However, tacrolimus does not cause swollen gums or extra growth of hair.

Mycophenolate (CellCept, Myfortic)

This drug is a powerful immunosuppressive agent and weakens the ability of T-cells to respond to stimulation from transplanted tissues. It can cause headache and gastrointestinal side effects—including diarrhea and nausea—which are usually mild. Fatigue can also occur in people taking mycophenolate.

Sirolimus (rapamycin, Rapamune)

This drug works by interfering with mTOR (mammalian target of rapamycin). mTOR inhibitors are of particular interest in transplant centres that treat HIV-positive people because these drugs may also have modest anti-HIV activity. Other mTOR inhibitors include everolimus (Certican, Zortress). mTOR inhibitors are as effective as cyclosporine but can have different side effects, such as delayed wound healing and increased cholesterol and triglyceride levels in the blood. Further information about sirolimus appears in later in this issue of TreatmentUpdate.

Antibody therapy

Some antibodies (proteins) infused into transplant recipients can help suppress the immune system. Some antibody therapies such as thymoglobulin attack the body’s T-cells. Other antibody therapies are more specific and attack particular receptors or molecules on the surface of a cell. Examples of these specific antibodies (called monoclonal antibodies) include basiliximab (Simulect) and daclizumab (Zenapax). These two antibodies are not usually associated with side effects in large numbers of people, perhaps because they are only used for brief periods.

REFERENCES:

1. Sánchez-Fueyo A, Strom TB. Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs. Gastroenterology. 2011 Jan;140(1):51-64.
2. Trullas JC, Cofan F, Tuset M, et al. Renal transplantation in HIV-infected patients: 2010 update. Kidney International. 2011 Jan 19. [Epub ahead of print].
3. Dell-Olio D, Kelly DA. Immunosuppressants: what’s new? Current Opinion in Organ Transplantation. 2010 Oct;15(5):594-600.
4. Campistol JM. Long-term maintenance therapy with calcineurin inhibitors: an update. Transplantation Proceedings. 2010 Nov;42(9 Suppl):S21-4.
5. Dandel M, Lehmkuhl HB, Knosalla C, et al. Impact of different long-term maintenance immunosuppressive therapy strategies on patients’ outcome after heart transplantation. Transplant Immunology. 2010 Jul;23(3):93-103.
6. Gaber AO, Monaco AP, Russell JA, et al. Rabbit antithymocyte globulin (thymoglobulin): 25 years and new frontiers in solid organ transplantation and haematology. Drugs. 2010 Apr 16;70(6):691-732.
7. Carpenter CB, Milford EL, Sayegh MH. Chapter 276. Transplantation in the Treatment of Renal Failure. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th ed. McGraw-Hill Companies, Inc.; 2008.
8. Finberg R, Fingeroth J. Chapter 126. Infections in Transplant Recipients. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th ed. McGraw-Hill Companies, Inc.; 2008.
9. Dienstag JL, Chung RT. Chapter 304. Liver Transplantation. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th ed. McGraw-Hill Companies, Inc.; 2008.