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Yesterday we gave an overview of immunosuppressants used for various medical conditions. Among them, immunosuppressants are medications taken by patients who had organ transplantation to avoid organ rejection. As such, immunosuppressants are also known as anti-rejection medications. 

Transplant rejection

Our immune system plays a critical role in transplantation. The complex mechanisms of immunity, which under normal circumstances work to identify foreign bodies (e.g. microorganisms or cells that do not belong to us) and direct the immune system to destroy them, pose a significant barrier to successful transplantation. 

Rejection of a transplant occurs in instances where the immune system identifies the newly transplanted organ as foreign, triggering a response that will ultimately destroy the transplanted organ or tissue. Rejections of the transplanted organ can occur in two ways: rapid rejection (acute) and rejection over a long period of time (chronic). Good news is, with our improved knowledge on handling organ rejection with immunosuppressants today, the number of organ rejection following transplantation has declined ever since.

Immunosuppressants can be further divided into two categories:

  • Induction medications - They’re more powerful anti-rejection medications used at the time of transplant

  • Maintenance medications - They’re anti-rejection medications taken by the patients following a transplantation for a long period of time.

Immunosuppressants used for post-organ transplantation

Here are some commonly used immunosuppressants following an organ transplantation: 

Cyclosporine/CSA

  • Brand name: Sandimmun-Neoral®

  • Available strengths: 

25mg

100mg 

Cyclosporine prevents organ rejection by inhibiting interleukin-2 and lymphocyte activations, both of which are critical players of our immune system. Typically, cyclosporine is taken twice daily (every 12 hours) on an empty stomach, i.e. 1 hour before meal or 2 hours after meal.

You should always strive to take cyclosporine consistently, at the same time every day. If you happen to forget a dose of cyclosporine, take it within 4 to 6 hours of the original prescribed time. If it has been more than 6 hours, skip the missed dose and return to taking your dose at the original schedule next day. Do not take a double dose to make up for the missed dose.

Some potential side effects associated with cyclosporine are:

  • Increase in blood pressure

  • Increased hair growth

  • Fluid retention (leading to swelling)

  • Headache or changes in vision

  • Tremors 

  • Leg cramps

  • Kidney toxicity

Tacrolimus

  • Brand name: Prograf® (immediate-release), Advagraf® (prolonged-release)

  • Available strengths: Prograf® - 0.5mg, 1mg and 5mg; Advagraf® - 0.5mg, 1mg and 5mg

Tacrolimus works similarly as cyclosporine. However, unlike cyclosporine, tacrolimus is available in two different formulations, namely the immediate-release (IR) and prolonged-release (PR). If you’re taking IR tacrolimus, it is typically taken twice daily; whereas it’s an once-daily dosing for PR tacrolimus. Both formulations of tacrolimus should also be taken on an empty stomach.

The appearance of IR and PR tacrolimus can be confusing, make sure you remember correctly which type of tacrolimus you’re taking, as both of them are different and not interchangeable!

Tacrolimus (IR) - Prograf®

Tacrolimus (PR) - Advagraf®

There are a few side effects associated with tacrolimus treatment, such as:

  • Increase in blood sugar level - If you also have diabetes, it’s even more important for you to strictly adhere to your diabetes treatment

  • Increase in potassium level in blood

  • Kidney toxicity

  • Higher level of blood lipid level

  • Higher risk of cardiovascular diseases

  • Nausea and vomiting

  • Headache

  • Numbness and tingling hands

  • Sleep disturbance

  • Hair loss

Everolimus

Brand name: Certican®, Afinitor®, Zortress®

Available strengths: 

0.25mg

0.75mg

 

While cyclosporine and tacrolimus are widely used in organ transplantation, a huge concern of both is kidney toxicity. Everolimus is an eligible alternative to both and has gained increasing popularity recently. Everolimus reduces the activity of immunity by inhibiting interleukin-2 signalling, lymphocyte activation, as well as mammalian target of rapamycin inhibitors (mTORi), thereby reducing risk of organ rejection. 

Similarly, everolimus is usually taken twice daily on an empty stomach, and it needs to be taken within 4 -6 hours of missed dose. Skip the missed dose if more than 6 hours of the prescribed time and resume original dosing time the next day, do not double dose to make it up.

Possible side effects of everolimus include acne, nausea and vomiting, abdominal pain, body swelling, and urinary tract infection (may be manifested as increased sense of urination or burning sensation when urinating). 

Mycophenolate mofetil (MMF) and Mycophenolate sodium

  • Brand name: Cellcept® (MMF); Myfortic® (mycophenolate sodium)

  • Available strengths: Cellcept® - 250mg (capsule) and 500mg (tablet); Myfortic® - 180mg and 360mg (both are tablets)

Mycophenolate is another commonly used medication to reduce risk of organ rejection. It works by inhibiting inosine monophosphate dehydrogenase (IMPDH); as a result, both T- and B-lymphocytes cannot replicate themselves and thus cannot damage the new organ significantly. 

Mycophenolate is available in two different forms that go by the brand names of Cellcept® and Myfortic®. Both are in different salt forms and have different strengths, although eventually they will be converted into mycophenolate in the body. Similarly, they are taken twice daily on an empty stomach, and can be taken within 4 to 6 hours of missed dose. Skip the missed dose if more than 6 hours of the prescribed time and resume original dosing time the next day, do not double dose to make it up.

Mycophenolate has poor oral absorption. Therefore, it is also important to not take any antacids (liquid medication for gastric or heartburn) within 2 hours of taking mycophenolate, as it can significantly reduce the absorption of mycophenolate.

Mycophenolate can lead to the following side effects:

  • Abdominal pain, diarrhea, constipation, flatulence

  • Nausea and vomiting

  • Decreased in appetite 

  • Rash

  • Increase in blood cholesterol level

  • Anemia (reduction in red blood cells, which results in general weakness and tiredness)

  • Leukopenia (reduction in white blood cells, which increase risk of infection)

  • Thrombocytopenia (reduction in platelets, which can increase risk of bleeding)

Azathioprine

  • Brand name: Imuran®

  • Available strength: 50mg

Azathioprine inhibits the purine nucleic acid metabolism, which also helps to reduce the numbers of lymphocytes, thus reducing risk of organ rejection. Azathioprine should be taken in the morning immediately after breakfast to prevent stomach upset. If you missed a dose of azathioprine, take it within 12 hours of the original prescribed time. Skip the dose if it’s more than 12 hours, do not double the dose. Side effects of azathioprine include:

  • Stomach upsets such as loss of appetite, nausea, vomiting and diarrhoea. Taking azathioprine with food or immediately after food can help to relieve such discomfort.

  • Leukopenia (reduction in white blood cells, which increase risk of infection)

  • Thrombocytopenia (reduction in platelets, which can increase risk of bleeding)

  • Anemia (reduction in red blood cells, which results in general weakness and tiredness)

  • Rash

  • Hair loss, although hair often does grow again even if you carry on taking azathioprine.

Azathioprine can interact with some medications, thus affecting its level in your body and how it works. Inform your doctor or pharmacist the other medications you’re taking, such as allopurinol (for gout), Bactrim (an antibiotic), and warfarin (a blood thinner).

Prednisolone

Prednisolone is a corticosteroid that has a wide range of use in medicine, even in preventing organ rejection following transplantation. The strength of prednisolone is 5mg, and is available as a tablet. 

Similar to other types of steroid medications, prednisolone should be taken in the morning immediately after breakfast to prevent stomach upset. If you missed a dose of prednisolone, take it within 12 hours of the original prescribed time. Skip the dose if it’s more than 12 hours, do not double the dose. 

Prednisolone does come with side effects, such as:

  • Weight gain

  • Increased in appetite

  • Stomach upset (take it with food to reduce the side effect)

  • Insomnia (take prednisolone in the morning and limit caffeine intake at the same time)

  • Swelling of face and extremities 

  • Delayed in wound healing

  • Increased in blood sugar level (If you also have diabetes, make sure you strictly adhere to your diabetes treatment)

Other medications

Besides the immunosuppressants mentioned above to prevent organ rejection following transplantation, patients may also require the following medications for reasons other than reducing organ rejection.

  • Tablet Co-trimoxazole (Bactrim®) – To prevent pneumocystis jirovecii infection, a potentially life-threatening lung infection that occurs in immunocompromised individuals such as organ transplant patients. 

  • Medications for gastric pain – To reduce stomach upset caused by immunosuppressants

  • Nystatin suspension – To prevent candida infection in the mouth (white patches)

  • Tablet valganciclovir – To prevent cytomegalovirus (CMV) infection

  • Tablet diltiazem (Herbesser®) – To control blood pressure while also helping to increase tacrolimus level in patient, thereby boosting its effects in reducing risk of organ rejection

Precautions for taking medications after organ transplantation

  1. Know the name of each medication you take and what it does. You’re less likely to forget your medications if you understand what each of them is for.

  2. If there are simply too many medications you need to take every day, get yourself a pill box to set yourself up for a no-brainer daily routine of taking medications at the same time, everyday.

  3. It is very important for you to take your immunosuppressants every day at the same time. This helps to ensure a consistent level of those medications in your blood, which is crucial for a successful prevention of organ rejection.

  4. Grapefruit and grapefruit juice may affect the amount of immunosuppressants and other medications you take. Do not take or drink grapefruit when taking these medications.

Image by Couleur from https://pixabay.com/?utm_source=link-attribution&utm_medium=referral&utm_campaign=image&utm_content=1647688">Pixabay

  1. Do not crush or chew the tablets/open the capsules.

  2. Never skip a dose. Stopping immunosuppressants, even for a short period, may cause you to have an episode of rejection with the possibility of losing the new organ!

  3. Take the medications exactly as prescribed by your doctor. Do not take less or more frequently than directed.

  4. Learn how to manage your missed dose if you happened to forget a dose.

  5. Inform your doctor before taking any new medications, supplements or herbal products, as many of these products can interact with your immunosuppressants.

  6. If you’re taking immunosuppressants, you are considered immunocompromised, i.e. having a lower immunity. Therefore, it’s important for you to take care of your own personal hygiene to prevent any infection in the first place.

  7. Learn from your doctor or pharmacist on how to detect signs of organ rejection, infections as well as how to to handle the side effects of immunosuppressants. This helps to ensure a successful lifelong treatment of preventing organ rejection.

A word from Doc2Us

If you have any questions related to organ transplant, you can consult our professional doctors and healthcare professionals on Doc2Us. Doc2Us is a mobile application that allows you to talk to a doctor or any healthcare professionals via text chat at any time and from anywhere. For better communication, you can even send our online doctor images or voice messages related to your medical inquiry.

Download Doc2Us app on Apple App Store, Google Play Store and Huawei App Gallery; or use our web chat at https://web.doc2us.com/

Note: Doc2Us is not for medical emergencies. In the event of urgent medical conditions, please call 999.

Disclaimer: As a service to our users and general public, Doc2Us provides health education contents. Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.

References

  1. UpToDate - Kidney transplantation in adults: Clinical features and diagnosis of acute renal allograft rejection

  2. UpToDate - Liver transplantation in adults: Overview of immunosuppression

  3. Zdanowicz M. The Pharmacology of Immunosuppression. American Journal of Pharmaceutical Education. 2009;73(8):144.

  4. AJMC - An Overview of Immunosuppression in Solid Organ Transplantation

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Written By

Ms Joyce Toh

Reviewed By

Doc2us Medical Board

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