Tacrolimus and the nervous system: tremor, headache and rarer neurological effects

Tacrolimus is a medicine that suppresses the immune system. University Hospitals Sussex explains that, after a kidney transplant, it prevents the body rejecting the new organ, and that the dose is adjusted depending on drug levels in the blood. Cambridge University Hospitals (CUH) describes it being given after a liver transplant to stop rejection, in autoimmune hepatitis to stop the immune system attacking the liver, and in some people on steroids to reduce steroid dose and dependence.

Like other drugs of its type it has a range of side effects, which can involve the kidneys, blood pressure, blood sugar and the nervous system. The product information for tacrolimus capsules (the Adoport summary of product characteristics on the electronic medicines compendium) lists nervous system disorders among them. This page concentrates on those, because the term neurotoxicity is used by clinicians to describe nervous system side effects of the drug.

The sources used here are UK hospital leaflets and product information. They do not explain the mechanism in patient terms, so this page does not attempt to.

The product information lists the following nervous system effects, with the frequency categories it uses.

CUH lists the most common side effects as tremor (shaking) of the hands, headache, vivid dreams, upset stomach, hair loss on the head, numb, hot or tingly hands, feet or mouth, diabetes mellitus, high blood pressure and reduced kidney function. It says some of the side effects disappear as the dose of tacrolimus is reduced over time, that not everyone experiences them, and that you should tell the team if you notice any, as there is often a solution.

Sussex lists tremor or pins and needles in the hands or feet, headache, insomnia and vivid dreams, nightmares or hallucinations among the side effects. It says that these might particularly occur in the early weeks after the transplant when the doses and the target level are higher, and that many people do not experience any side effects. It says it is important to tell your doctor of any side effects or unusual symptoms, as these may indicate that your blood concentrations of tacrolimus are too high and the dose may need to be changed.

The product information describes PRES as a condition reported in patients treated with tacrolimus. It says that if patients present with symptoms indicating PRES, such as headache, altered mental status, seizures and visual disturbances, a radiological procedure such as an MRI should be performed. If PRES is diagnosed, it advises adequate blood pressure and seizure control and immediate discontinuation of systemic tacrolimus, and says most patients completely recover after appropriate measures are taken.

The product information also notes that eye disorders, sometimes progressing to loss of vision, have been reported, and that patients should be advised to report changes in visual acuity, colour vision, blurred vision or visual field defects, which should be promptly evaluated, with referral to an ophthalmologist as appropriate.

These are uncommon situations. The decision to stop or switch tacrolimus belongs to the transplant or specialist team, which is why a new neurological symptom should be reported rather than managed alone.

CUH asks you to tell the team straight away about a sore throat, fever or other signs of infection, shortness of breath, unexplained bruising or bleeding, yellowing of the skin or eyes, or any other new symptoms or anything else that concerns you. The same principle applies to nervous system symptoms: a tremor that is getting worse, a persistent or severe headache, confusion, vision changes, a seizure or sudden weakness should be reported to the transplant or specialist team without delay.

The sources used here do not set out an emergency threshold in terms of specific symptoms, so if someone has a seizure, collapses, is very confused or cannot be woken, call 999. The product information notes that suspected adverse reactions can be reported through the MHRA Yellow Card Scheme.

CUH stresses that there are different brands of tacrolimus, some taken once a day and some twice a day, and that it is very important to know which brand and dose you take and to stay on the same brand unless the team tells you to change. It lists medicines that should not be taken with tacrolimus, including the antibiotics erythromycin and clarithromycin, NSAIDs such as ibuprofen or diclofenac, some antifungals and anti-epileptic medication, and asks you to check with a doctor or pharmacist before starting any new medicine, including herbal ones such as St John’s wort.

The product information adds that using strong CYP3A4 inhibitors with tacrolimus can raise blood levels and could lead to serious adverse reactions including nephrotoxicity, neurotoxicity and QT prolongation, and recommends frequent monitoring of blood levels when such combinations cannot be avoided.

Sussex advises that tacrolimus should not be taken with grapefruit, because it affects absorption, and that you should not take the morning dose before a clinic blood test but bring it with you to take afterwards.

Tacrolimus is prescribed and monitored by transplant, renal or liver teams in the NHS, usually with regular blood tests of drug levels, and, as both leaflets note, may be supplied through the hospital rather than a local pharmacy.

If you see a private doctor for a neurological symptom, make sure they know you take tacrolimus and the exact brand and dose, and ensure that the NHS transplant team is informed before any change is made.