Kidney transplant medications

An overview of the current range of kidney transplant medication, with advice on what contraindications to be aware of and medicines to avoid

After a kidney transplant, patients will need to take immunosuppressant medications to prevent the body from rejecting the new kidney. Additional medications may be prescribed to prevent infection, while the patient must also be aware of what medications can cause issues with their transplant-related medications, and what ‘natural’ or over-the-counter products to potentially avoid, and which are safe to use.

Medications to avoid

Some medications interfere with immunosuppressive drugs. They can include cold, allergy, cough syrup, or antibiotics. Antibiotics to avoid include clarithromycin, erythromycin, and azithromycin. Other drugs to avoid include the antifungal fluconazole and the heart rhythm drug diltiazem.

Avoid grapefruit or grapefruit juice when prescribed cyclosporine, tacrolimus, and sirolimus, as it changes the metabolism of these medications. Avoid magnesium oxide or antacids such as calcium carbonate, etc, within two hours of taking medications, as they may reduce absorption of some drugs such as immunosuppressants and antibiotics.

Herbal preparations and supplements

There are very few scientific studies to indicate whether herbs are effective, safe, or interfere with prescribed medications. Herbs can cause serious interactions and kidney problems for patients with renal failure and those taking medications after a transplant.

Possible issues with herbs are:

• Interactions between herbs and medications, which can include reducing the effectiveness of transplant rejection medication.
• Herbs may not be pure because of unregulated manufacturing procedures. Herbs come from plants that may cause bacterial, fungal, or parasitic infections. There have been reports of herbs containing pesticides and metals, including lead and mercury.
• Some herbs have toxic effects on the liver, kidneys, and heart, especially when taken with other medication, and can result in changes in blood pressure, blood sugar, and potassium levels leading to risk of bleeding and transplant rejection.
• Dosages can vary from pill-to-pill, manufacturer-to-manufacturer, or from what is stated on the label.

To be safe, transplant patients should avoid herbal preparations.

More about transplant medications Immunosuppresants

Cyclosporine

Cyclosporine is a calcineurin inhibitor, used as an immunosuppressant medication in kidney transplant patients. It is available in 100mg and 25mg capsules. If a patient forgets to take a dose of cyclosporine and it is less than six hours since the missed dose, they can take the missed dose and go back to the normal schedule with the next dose. If it has been longer than six hours, skip that one dose and go back to normal schedule with the next dose. Never double-up a dose. If more than one dose is missed because of vomiting, inability to swallow, or any other reason, let the transplant team know immediately.

Possible side-effects include high blood pressure, hand tremors, tingling sensation in hands and feet, increased hair growth on face, and gum problems. Increased creatinine levels can occur due to high cyclosporine blood levels.

Tacrolimus

Tacrolimus is available in 1mg (white), 5mg (pink), and 0.5mg (white) smaller capsules. It must be taken twice a day.

If a patient forgets to take a dose of tacrolimus and it is less than six hours since the missed dose, take the missed dose and get back on schedule with the next dose. If it has been longer than six hours, skip that one dose and get back on schedule with the next one. Do not double-up. If more than one dose is missed due to vomiting, inability to swallow, or any other reason, notify the transplant team immediately.

Some side-effects that have been reported with tacrolimus are hand tremors, burning or tingling of the mouth, hand, or feet (this will likely improve as the dose is reduced), headaches, difficulty sleeping, high blood sugars, high blood pressure, nausea and/or vomiting (if this occurs, try taking with food), and an increase in creatinine.

Prednisone

The steroid prednisone also helps prevent or treat rejection of the new kidney. The dose may be increased or decreased depending on response. High doses of prednisone may be prescribed immediately after the transplant to prevent rejection, with the dose gradually reducing once the transplant is deemed successful. Prednisone may need to be taken long-term. It should be taken with food to prevent stomach irritation. If a patient forgets to take a dose of prednisone, take the missed dose as soon as possible and get back on schedule with the next dose. Never double-up a dose. If more than one dose is missed due to vomiting, inability to swallow, or any other reason, let the transplant team know immediately.

Steroid dependency

The adrenal glands make a hormone called cortisol that is very similar to prednisone and after a few weeks of taking prednisone, the adrenal glands stop making this hormone. Prednisone should never be stopped abruptly; it should be gradually tapered off slowly to give the adrenal glands a chance to start making cortisol again. Sudden withdrawal can cause severe fatigue, weakness, body aches, and joint pains, and possibly even cause life-threatening symptoms. A steroid treatment card alerts any medic who treats a patient that they must keep administering steroids.

Side-effects include:

• Stomach irritation;
• Blurred vision or disturbed eyesight. Long-term use gives risk of cataracts or glaucoma;
• Bone or joint pain, especially in hips;
• Raised blood pressure;
• Diabetes;
• Weight gain;
• Rounded, puffy face (so called ‘moon face’);
• Acne;
• Insomnia;
• Low mood;
• Muscle weakness;
• Slow wound healing;
• Bruising;
• Stretch marks;
• Dry skin.

Sirolimus

Sirolimus may be combined with other immunosuppressive medications to prevent organ rejection. If a dose of sirolimus is forgotten, take the missed dose as soon as possible and get back on schedule with the next dose. Never double up a dose. If more than one dose is missed due to vomiting, inability to swallow, or any other reason, let the transplant team know immediately.

Side-effects include:

• Headache;
• Swelling;
• Tremor;
• Insomnia;
• Diarrhoea, nausea, vomiting;
• Constipation and bloating;
• Low platelet count or anaemia;
• High or low potassium levels;
• Diabetes;
• Back or abdominal pain;
• Cough;
• Rash or acne;
• High cholesterol.

Blood counts (white blood cells, platelets, haemoglobin) need to be monitored while on sirolimus. It can cause anaemia. If it does, the sirolimus dose will be lowered or held for a while and the patient may be prescribed erythropoietin. Erythropoietin is a naturally occurring hormone produced in the kidneys to produce red blood cells. Neupogen may be prescribed if neutrophils are low, as sirolimus can cause neutropaenia. Cholesterol levels can be increased by sirolimus, so a statin may need to be prescribed.

Mycophenolate mofetil

Mycophenolate mofetil may be combined with other immunosuppressive medications to prevent organ rejection following transplant. Mycophenolate comes in 250mg capsules or 500mg tablets. It is usually taken two-to-four times a day and the usual total daily dose is 1,000-2,000mg.

If taking mycophenolate four times a day and a dose is forgotten: If less than two hours since the missed dose, take the missed dose and get back on schedule with the next dose. If it is close to the next dose, skip the missed dose and resume normal schedule.

If taking mycophenolate twice a day and a dose is forgotten: If it is less than six hours since the missed dose, take the missed dose and get back on schedule with the next dose. If more than six hours since missing dose, skip that dose and get back on schedule with the next dose. Never double-up a dose. If more than one dose is missed due to vomiting, inability to swallow, or any other reason, let the transplant team know immediately.

Side-effects include:

• Nausea and vomiting;
• Diarrhoea or constipation;
• Stomach pains and cramps;
• Low white blood cell count;
• Anaemia;
• High or low potassium levels;
• Tremor;
• Headache;
• Diabetes;
• Insomnia.

Blood counts (white blood count and haemoglobin) must be monitored regularly while taking mycophenolate. If blood counts are less than the normal range, mycophenolate may be lowered or held. Neupogen will need to be prescribed to increase white cell count or erythropoietin will need to be prescribed to increase red cell count. Cholesterol levels can be increased by mycophenolate so a statin may need to be prescribed.

Prophylactic medications

Immunosuppressants reduce the body’s ability to fight infections meaning a patient may need to be prescribed medication to prevent infections while on immunosuppressants.

Co-trimoxazole

Co-trimoxazole (a combination of sulfamethoxazole and trimethoprim) is an antibiotic used to prevent and/or treat pneumonia and other bacterial infections. Immunosuppressants increase the risk of pneumonia and other infections as they reduce the body’s ability to fight infections. Patients need to drink plenty of fluids while taking co-trimoxazole.

Side-effects include:

• Nausea;
• Rash;
• Itching;
• Increased risk of sunburn.

Valganciclovir, acyclovir, valacyclovir

These antivirals are used for the treatment and prevention of viral infections, including cytomegalovirus (CMV), which is a type of herpes virus transmitted via bodily fluids. Valaciclovir is used to prevent or treat herpes simplex and shingles. It will not cure herpes virus completely, but it will reduce the pain and help heal the sores.

Valganciclovir or acyclovir are mainly used to treat and prevent CMV. Antivirals are usually prescribed for about three months after transplant.

Side-effects include:

• Headaches;
• Fever;
• Nausea and vomiting;
• Diarrhoea;
• Low blood counts;
• Insomnia.

Taking antivirals with food or milk will increase absorption and reduce stomach irritation. Blood counts must be monitored when taking antivirals and, if lower than expected, the antiviral must be lowered or held. Antivirals should be avoided during pregnancy and women must not become pregnant for 90 days after finishing the antiviral course because of the risk of birth defects. Men should also use barrier contraception (condoms) during and for three months after the course of antivirals.

Fluconazole oral capsules or nystatin oral suspension

Antifungals usually need to be prescribed for about three months. Immunosuppressant medication increases the risk of fungal mouth infections and symptoms include mouth sores, white coating on tongue, or difficulty swallowing. Antifungal medication may need to be recommenced at different stages in the years after the transplant.

Fluconazole and related antifungal medication can interact with some anti-rejection medications, so the doses of anti-rejection medications will need to be adjusted when starting and stopping antifungal medication. Topical nystatin does not interact with the anti-rejection drugs in the same way.

Side-effects include:

• Nausea and vomiting;
• Diarrhoea;
• Mouth and throat irritation;
• Unpleasant taste.

Stomach protectants

Anti-rejection medication can irritate the stomach lining and bring on stomach ulcers.

A proton pump inhibitor (PPI) may be prescribed to reduce stomach acid and protect the stomach and prevent ulcers. PPIs used include lansoprazole, pantoprazole, omeprazole, rabeprazole, and esomeprazole.

Kidney rejection

Rejection is possible even if all precautions are taken. It is reckoned that 50 per cent of kidney transplant patients will suffer at least one rejection episode; however, a rejection episode does not mean the patient will lose the kidney. Swift action from the transplant team (ie, increasing immunosuppressant dose or changing to a different dose) will normally stop the rejection and save the kidney. This is why it is so important to recognise the symptoms of rejection as getting quick treatment will save the kidney in most cases.

The first rejection episode occurs within six months of transplant surgery in most cases. Rejection may be chronic, meaning that it occurs slowly over a long period of time, or it can be acute, which means it occurs suddenly. The patient may feel perfectly well during a rejection episode, which is why it is important to have lab tests checked regularly. High laboratory results (blood, urea, nitrogen, and creatinine) can mean a rejection episode is occurring. An ultrasound or renal scan can help confirm a rejection episode and a kidney biopsy can act as a final confirmation.

Possible symptoms of a rejection episode:

• Temperature of 38.3^oC or higher;
• Urine output halves, ie, if normal fluid intake is about 2,000ml per day and output reduces to 1,000ml. Urine output should roughly equal to fluid intake, so if drinking 2,000ml per 24-hour period, then urine output should also be about 2,000ml (though a 300-to-400ml difference is acceptable);
• Weight increases by five pounds or more within three days;
• Fluid retention, which can show as mild swelling of the face, feet, hands, ankles, and legs;
• If two blood pressure readings (taken at least one hour apart) are outside normal range or below 90/60 or above 170/100;
• Swelling or tenderness around the transplanted kidney;
• Raised blood urea nitrogen (BUN) and creatinine.

How a rejection episode is reversed:

• Increasing prednisone dose;
• Intravenous (IV) steroids;
• Thymoglobulin or OKT3 (anti-rejection serum);
• Reducing cyclosporine or tacrolimus dose;
• Temporary dialysis may be required.

If a rejection occurs, return to dialysis will be necessary. The rejected kidney may remain in place unless fever, pain, swelling, vomiting, etc, occurs. If these symptoms occur, the rejected kidney may need to be removed surgically. Immunosuppressive medications will then be discontinued.

Kidney transplant patients
What OTC medication can be taken?

Some medications interfere with the immunosuppressive medications. They can include meds for cold, allergy, cough syrup, or antibiotics.

What OTC medication is safe?

Headache, fever, and body aches

Paracetamol eases mild pain and fever and is safe for kidney transplant patients. The maximum daily dose of paracetamol is 4,000mg (eight x 500mg tablets).

Non-steroidal anti-inflammatory drugs (NSAIDs) must be avoided, as they can harm the kidneys and interact with some immunosuppressants. Ibuprofen is a common NSAID sold OTC. Aspirin is a relation of NSAIDs, so should also be avoided unless prescribed for medical reasons, ie, low-dose aspirin to prevent clots.

Sneezing, itching, and runny nose

Antihistamines can be safely used by transplant patients. Loratadine and cetirizine are recommended as they cause less drowsiness than other antihistamines. Chlorpheniramine is also safe to use, but is best used at bedtime, as it causes more drowsiness. Antihistamines should be used with caution for those with glaucoma, as they can increase pressure in the eye. They can also cause fluid retention, so are best avoided in those with an enlarged prostate or those experiencing trouble urinating. Sodium cromoglicate eye drops are a safe option to prevent eye allergy symptoms. It works best if begun at least one week before contact with possible allergens.

Avoid combination (multi-symptom) cold, sinus, and flu products. Treat each symptom individually to avoid accidentally taking a drug that can cause kidney problems.

Nasal and sinus congestion

Topical nasal sprays are the safest for congestion problems. Topical decongestants such as xylometazoline should not be used for longer than three days because longer use can cause a rebound effect, making congestion worse.

Sodium chloride 0.9 per cent or salt sprays can ease sinus symptoms by moistening sinus cavities and acting as a natural anti-inflammatory and they can safely be used long-term. Saline solutions are also available as nasal washes through various devices or bottles.

Oral decongestants, such as pseudoephedrine, should be used with care for transplant patients as they can raise blood pressure, which can put pressure on the kidneys. Decongestants are often present in many cough and cold remedies, so check the label before trying.

Sore throat

Most throat lozenges are safe to use and there are sugar-free versions for diabetics.

Chesty cough

Guaifenesin is recommended for chest congestion. Drinking plenty of water can also help loosen chest congestion.

Dry cough

The cough suppressant dextromethorphan is safe to use – use the non-drowsy version during the day, as the night-time version has a sedative antihistamine called diphenhydramine added. Vicks VapoRub can help relieve a cough for a time. For diabetics, use a sugar-free version.

Diarrhoea

Loperamide can be used for short-term relief of diarrhoea. Do not use for longer than 48 hours. For diarrhoea caused by infection, do not treat it with OTC products. If diarrhoea is heavy, bloody, or lasts for more than a day, it is important to get checked by a doctor.

Constipation

Products safe to use for transplant patients include bulk-forming products; stool softeners, such as docusate; stimulants such as bisacodyl or senna; and osmotic laxatives such as lactulose and macrogols.

Do not use stimulant laxatives such as bisacodyl or senna long-term, as this will cause lazy bowel (which causes rebound constipation), prolonged diarrhoea, and loss of important electrolytes (sodium, potassium, etc). Lactulose is a good option if a laxative is needed long-term, as it does not cause long-term problems. If constipation lasts longer than 48 hours, the patient needs to see a doctor.

Indigestion and heartburn

Mild stomach upset can be eased with some OTC remedies such as antacids, famotidine, and pantoprazole. Avoid antacids or magnesium-containing products at the same time as immunosuppressants such as mycophenolate, tacrolimus, or sirolimus as they can reduce absorption of these drugs. Take OTC remedies such as antacids at least one hour before or two hours after the immunosuppressant. If loose stools, avoid products containing magnesium because magnesium can make diarrhoea worse, or worse again, they can cause magnesium levels to become too high, especially if kidneys are not functioning properly.

Gas

Simethicone is recommended for gas, which is a common cause of bloating.

Dry eyes and eye irritation

Artificial tears eye drops (preservative free ideally) should be first choice for the symptoms of dry eyes and eye irritation. They replicate the role of natural tears. Drops are often used during the day (ie, three times daily) and an ointment or gel is used at night, as they are thicker and tend to last for longer while sleeping. There is no evidence that one brand is any more effective than the next. They should not be used for contact lens-associated irritation.

Nausea and vomiting

Domperidone can be used to treat and prevent symptoms of nausea and vomiting, but should only be used short-term and at the lowest possible dose (maximum of one 10mg tablet three times daily). See a doctor if nausea and vomiting last more than 24 hours, as it can be caused by prescription medication.

Skin irritation, insect bites, and poison ivy

Topical corticosteroids, such as hydrocortisone 1 per cent cream, are safe to use for skin irritation, insect bites, and skin rashes. Use of corticosteroids should be short-term (no longer than seven days), as they can thin and mark the skin if used long-term.

Disclaimer: Any brands mentioned in this article are meant as examples only and not meant as preference to other brands.

References on request