In order to control rejection a combination of drugs are given which suppress or reduce the effectiveness of the body’s immune system. These drugs are called immunosuppressives and must be taken for life.
Long-term drugs
Life-long immunosuppression is necessary daily. Most patients have to remain on a small dose of prednisone. Currently, most patients also take tacrolimus (Prograf) or cyclosporin (Neoral) twice daily, with the dose being decided on the basis of blood test levels taken just before the morning dose is due. Some patients require a third drug, azathioprine (Imuran) or mycophenolate (Cellcept), taken once or twice a day. All drugs as an outpatient are taken orally.
Side-effects
Any form of long-term immunosuppression brings with it an increased risk from infection. The risk is highest during high-dose prednisone therapy, so during such times patients need to be isolated from anyone suffering from an infection. There is also a slightly increased risk of malignancy in patients taking immunosuppressive drugs. These risks have to be balanced against the necessity to take the drugs that prevent the body from rejecting the liver.
There are three main drugs used for liver transplant patients and your liver specialist will determine which drugs and dosages are best suited to you.
Here is a list of the drugs that may be used after a liver transplant, giving the reasons for their use and possible side effects.
Tacrolimus (FK506) (Prograf)
Stops special white cells (T cells) from becoming active in your blood and attacking your transplanted liver. Tacrolimus and cyclosporine are similar drugs and work in a similar way but have some different side effects. Tacrolimus/Cyclosporin are the mainstay of the immunosuppression post liver transplant. Doses are adjusted according to blood levels. They are never used together because of their shared toxicities.
Side effects of Tacrolimus include:
impaired renal function (picked up on routine blood tests).
increase in blood pressure.
neurological side effects that include headaches, mild tremors, insomnia, possible nightmares. Rarely patients may experience severe side effects including confusion, seizures and coma.
raised blood sugar levels or diabetes.
increased risk of infection.
raised potassium level.
nausea and vomiting.
Cyclosporin (Neoral)
Again Cyclosporin is a strong immunosuppressive drug that stops special white cells (T-cells) from becoming active in your blood and attacking your transplanted liver that normally fight against transplanted tissue introduced into your body. It is almost always given along with prednisone.
Side-effects of Cyclosporin include:
impaired renal function (picked up on routine blood tests).
high blood pressure.
hot flushes or sweating.
numbness or tingling in the hands, feet or mouth.
shaking or trembling hands and feet, but this decreases with the reduction in dose over time.
hair growth, most commonly noted on the face, arms and legs but this decreases with reduction in dose over time.
overgrowth of gums, sometimes associated with soreness, swelling and redness, hence the need for regular mouth care.
sinus drainage, “runny” or “stuffy” nose.
high risk of infection.
How to take your Tacrolimus (Prograf) or Cyclosporin (Neoral).
Tacrolimus/cyclosporin is given in two divided doses 12 hours apart usually taken at 10am and 10pm.
It is very important to take tacrolimus/cyclosporin regularly exactly as prescribed. You must not alter the dose or time taken without medical advice.
DO NOT RUN OUT OF CAPSULES.
Tacrolimus/cyclosporin is usually prescribed through hospital Pharmacies. In patients who are on stable doses, the medication may be available from your local pharmacy using an Authority Script.
Do not take your Tacrolimus or Cyclosporin prior to having your blood taken on the morning of your visit. Bring your morning dose of medication with you and take as soon as possible after the test. Some people taking Cyclosporin will be asked to have their blood tests exactly 2 hours after taking the morning dose.
Prednisone
Prednisone is a steroid hormone similar to cortisol, which your body produces normally. It reduces the number of circulating white cells in the blood by dampening down the inflammatory response. The dose given is initially high post transplant and is gradually tapered down until you are on fairly small dose. It is given in conjunction with other drugs to prevent rejection.
Side-effects include:
Stomach irritation that may occasionally cause stomach ulcers. Never take prednisone on an empty stomach so you should take it after breakfast each day.
Fluid retention, high blood pressure and swelling of the face, hands or ankles.
Weight gain due to an increase in your appetite and subsequent increase in food intake.
Increased risk of infection, especially in the first few months after transplantation while your prednisone dose is high.
High blood sugar (diabetes) may occur with high doses of prednisone therapy. This is called “steroid-induced” diabetes. If you are a diabetic, you may require additional insulin to maintain a normal blood sugar. You will be instructed in a diet that will help you control this side-effect if necessary.
Skin changes such as acne, rashes or bruising.
Mood changes that may swing from feeling “up” to feeling “down”.
Softening of the bones (osteoporosis) can be experienced after long-term use of steroids. A diet high in calcium will help, although prednisone is reduced as soon as possible after transplant.
NEVER STOP OR REDUCE PREDNISONE WITHOUT MEDICAL ADVICE
Imuran (azathioprine)
Imuran is used for the suppression of your immune response. It acts on the bone marrow by decreasing the number of white blood cells which fight infection. With Imuran there is an increased risk of infection and an increased tendency for skin cancers.
Side-effects include:
Bone marrow depression - a low white cell count is the most common problem, but a low platelet count and anaemia may occur.
Nausea or vomiting - so take your Imuran after meals to lessen stomach upset.
Occasionally, people are allergic to azathioprine, and are unable to take it.
Cellcept (Mycophenolate mofetil)
One of the newer immunosuppressant medications similar to Imuran that may be added to some patients drug regime. It is taken twice a day 12 hours apart (as is Tacrolimus/ Cyclosporin).
Side – effects include:
Vomiting
Diarrhoea
Low white cell count
Sirolimus
Another of the newer generation of immunosuppressant drugs. It acts by stopping special white cells (T cells) from becoming active in your blood and attacking your transplanted liver. Unlike tacrolimus/cyclosporin this drug does not have any adverse effect on kidney function. It is taken once a day and the dose given is dependent on the level of the drug in your blood.
Side – effects include:
(i) Hyperlipidemia (high cholesterol levels in the blood)
(ii) Abdominal pain and diarrhoea
(iii) Low red blood cell count (anaemia)
(iii) Low white blood cell count
(iv) Low platelet count (thrombocytopenia)
(v) Acne and rash
Caution-:If you are taking tacrolimus/cyclosporin, your Sirolimus should be taken 4 hours after your morning tacrolimus/cyclosporin dose to prevent absorption complications.
OKT3
OKT3 is a specific antibody directed at cells in the immune process and is used for acute, severe rejection. OKT3 is one of the most powerful anti-rejection drugs and is used where other measures fail or a biopsy shows very severe rejection. It may be used to prevent rejection in very high risk patients. The first dose may cause acute flu-like symptoms.
Valaciclovir (Valtrex)
Valaciclovir is used for prevention and treatment for viruses know as herpes simplex (causing cold sores) and varicella zoster (which causes chickenpox). A large proportion of the population have been exposed to the herpes virus and it may become activated during times of stress, or when a person is immunocompromised (lowered resistance to infection, by medication or disease).
Ganciclovir (Cytovene)
Ganciclovir is used for the prevention and treatment of CMV (cytomegalovirus) viral infection. This is a viral infection transplanted patients may be prone to because of their suppressed immune systems. It may be given as capsules (for prevention) or require intravenous (through a vein) administration (for treatment). When used for prevention, it is usually stopped after 3 months.
Antihypertensives
Antihypertensives are drugs which lower blood pressure. Patients taking Cyclosporin or Tacrolimus often get an increase in their blood pressure. If this occurs, a variety of medications can be used.
Bactrim/Resprim
One Bactrim/Resprim tablet is given three times a week to all patients after transplant to prevent a type of chest infection called Pneumocystis (PCP) which immunosuppressed patients are sometimes prone to. This medication is continued for 12 months.
Pentamidine
This is an alternative drug to Bactrim, which is used as preventative treatment for PCP, for patients who are allergic to Bactrim or those who have a low white cell count. It is inhaled through a nebuliser once a month.
Fluconazole
Fluconazole is a medication used for treatment and prevention of yeast infections. An example of a yeast infection is thrush. Fluconazole may interact with some of the other medications, so it is important not to start or stop fluconazole without direction from your transplant doctor.
Insulin
Insulin may be required for patients who have high blood sugar levels after transplant.
Ranitidine (Zantac) or Omeprazole (Losec)
These drugs help to prevent the possible development of stomach ulcers that can be caused by stress and/or prednisone.
DRUG INTERACTIONS
Many drugs have the potential to interact with your transplant medications.
Please check with your doctor about the possibility of any drug interactions with your transplant medications before commencing any new medication.
Drugs that may increase blood levels of tacrolimus/cyclosporin include macrolide antibiotics such as erythromycin or roxithromycin (Rulide), antifungal medications such as fluconazole, certain blood pressure medication (calcium channel blockers), and grapefruit juice.
Levels may be lowered by other medications, including rifampicin, St John’s Wort, and anti epileptics.
Over-the-counter
drugs
Check with your physician before you take ANY over-the-counter medications, such as cold or cough medications. These medications may mask a serious infection that must be investigated by your doctor. Unless specifically ordered by your physician AVOID taking aspirin, as it may cause stomach irritation.
Paying for your drugs
Once you are discharged you will be responsible for paying for your own drugs. This can be expensive, especially at the beginning. You may be entitled to one of the various concession cards. Check with the Social Worker about this. As well, you will probably be able to take advantage of the Safety Net Scheme. Make sure you keep your Prescription Record up-to-date so that you will know when your safety net total is reached.
You will then be able to get your drugs at a reduced rate. Please talk with the pharmacist or Social Workers if you need further information about these schemes.
Compliance: a crucial factor
When you, as a patient, are said to be “compliant”, it simply means that you are, to the best of your ability, following the instructions of the doctors, nurses, and other professionals responsible for your care. Specific examples of compliance include:
not missing any of your follow-up visits and laboratory tests
exercising regularly and maintaining your weight
learning all you can about the long-term care of your transplant
However, for transplant recipients the most important aspect of compliance is taking your medication exactly as the transplant team instructed you - without missing a single dose - even if you feel fine. For as long as you have a transplant, you will have to take immunosuppressive drugs. Not taking your immunosuppressive medication at the right time and in the correct amount is one of the most common reasons for rejection and transplant failure.