Tacrolimus (Prograf, Adoport): anti-rejection medicine and skin ointment explained

Tacrolimus is a calcineurin inhibitor, a type of immunosuppressant. The leaflet for Prograf explains the logic: after an organ transplant such as liver, kidney or heart, the immune system tries to reject the new organ, and tacrolimus controls the immune response so the body can accept it. It is often used in combination with other medicines that also suppress the immune system, and can be used for ongoing rejection or if previous treatment could not control the immune response.

It comes in several forms. Capsules taken twice a day include Prograf, Adoport and other brands; prolonged-release capsules (Advagraf) are listed on the electronic medicines compendium; and a concentrate is available for infusion. A separate ointment is used on the skin. The capsule and ointment have the same active substance but very different purposes and safety considerations.

Do not take it with ciclosporin: the leaflet says Prograf must not be taken with ciclosporin.

NHS Blood and Transplant says people need powerful medicines after a transplant, and that different transplant centres prescribe different combinations. Among the common immunosuppressants it lists tacrolimus, steroids such as prednisolone and mycophenolate mofetil. It says tacrolimus in high doses can impair kidney function, that blood tests are needed to make sure the correct dose is given, that blood sugars can be raised and that tremors can occur.

The leaflet says you will take it every day as long as you need immunosuppression to prevent rejection, and that your doctor may carry out blood, urine, heart function, visual and neurological tests from time to time. It says initial doses are weight-based and are adjusted according to regular blood tests.

On rejection, NHS Blood and Transplant explains that it happens when the immune system recognises the kidney as coming from a different person, and that it can occur even if you take all your medicines, though the risks are higher if you do not take them as prescribed. It gives a figure of between 10 and 15 in every 100 patients in the first year after a kidney transplant. Rejection is suspected when the organ starts to work less well, diagnosis usually needs a biopsy, and treatment is with stronger immunosuppressant medicines. If it is picked up early it can usually be treated successfully.

The practical messages are the same for any transplant: attend all clinic appointments, take your tablets exactly as prescribed, tell the transplant team about missed doses and do not stop your anti-rejection medicines. If you have side effects that bother you, tell the team so they can discuss alternatives.

The leaflet says blood levels can be affected very soon after starting another medicine, and that frequent monitoring may be needed in the first days. Medicines that may change levels include antifungals such as fluconazole and itraconazole, macrolide antibiotics such as erythromycin and clarithromycin, rifampicin, flucloxacillin, HIV and hepatitis C medicines, omeprazole and lansoprazole, metoclopramide, the oral contraceptive pill, calcium channel blockers such as nifedipine and diltiazem, amiodarone, statins, carbamazepine and phenytoin, prednisolone and St John’s wort.

Some combinations can worsen kidney or nerve problems, including ibuprofen, amphotericin B, co-trimoxazole, vancomycin, gentamicin and aciclovir. Potassium supplements, potassium-sparing diuretics, trimethoprim and co-trimoxazole may raise potassium levels. The practical rule is simple: tell every doctor, pharmacist and dentist you take tacrolimus, and check before taking any new prescription, over-the-counter or herbal product.

The leaflet says Prograf is generally taken on an empty stomach, at least 1 hour before or 2 to 3 hours after a meal, and that grapefruit and grapefruit juice should be avoided. It also asks you to limit exposure to sunlight and UV light with protective clothing and a high-factor sunscreen, because of the risk of malignant skin changes with immunosuppressive therapy, and to tell your doctor before any vaccination.

The leaflet notes an increased risk of lymphoproliferative disorders, and asks you to tell your doctor about severe abdominal pain, diarrhoea lasting more than a day, which may require a dose change, or fever with bruising, tiredness, confusion, yellowing of the skin or eyes, reduced urine output, vision loss or seizures, which may indicate damage to the smallest blood vessels.

Do not drive or use machines if you feel dizzy or sleepy or have problems seeing clearly, particularly with alcohol. Prograf is excreted into breast milk, so the leaflet says not to breastfeed while receiving it. It says higher rates of miscarriage were reported among liver and kidney transplant patients treated with tacrolimus in one study, though no increased risk of major birth defects was found, and asks you to seek advice before pregnancy.

NHS Blood and Transplant adds that women who wish to get pregnant and take mycophenolate mofetil should discuss it with their transplant team, which is a separate point but one that applies to combination regimens.

The British Association of Dermatologists describes topical calcineurin inhibitors as creams and ointments that reduce inflammation in the skin, calming itch and soreness. Two are available in the UK: tacrolimus ointment, in 0.03% strength for moderate inflammation in children aged 2 and over and adults and 0.1% for significant inflammation in adults and teens aged 16 and over, and pimecrolimus cream for mild inflammation, suitable from 3 months.

They are alternatives to topical steroids and do not cause skin thinning or stretch marks, so they are valuable on the face, around the eyes or where long-term treatment is needed. They do not cure skin conditions but help control inflammation. They are usually applied as a thin layer twice a day, and once the skin improves use can be cut down to twice a week for maintenance, using the fingertip method.

The leaflet says not to use them on infected skin, if you have a significantly weakened immune system due to medicines such as azathioprine, methotrexate or biologic therapies, or if you have a skin condition such as Netherton syndrome that increases absorption. Burning or itching when first used usually settles within a few days. The BAD says there is no evidence that they damage the immune system or increase the risk of cancer when used as directed. Avoid applying to areas that may touch a baby’s mouth if breastfeeding.

Transplant anti-rejection medicines are prescribed and monitored by NHS transplant centres, often with shared care arrangements. Skin ointment is prescribed by GPs or dermatologists. The checks and brands matter in both settings, and you should always know who to call if you miss doses, are vomiting or have diarrhoea, since these can affect how much medicine you absorb.