Tacrolimus

The tacrolimus test is requested to measure the amount of drug in the blood to find out whether concentrations have reached therapeutic levels and is below toxic levels.  It is important to monitor levels of tacrolimus for several reasons:   

• There is not a good correlation between the dose of tacrolimus given and level of drug in the blood.
• Absorption and metabolism of oral doses of tacrolimus can vary greatly between patients and even in the same patient depending on the time of the dose and what, if any food has been eaten.
• Tacrolimus can cause kidney damage, especially in high doses.  Measuring levels in patients who have had a kidney transplant may help to distinguish between kidney rejection (levels are low) and kidney damage due to tacrolimus toxicity (levels are high).

Tacrolimus monitoring helps ensure that each individual is receiving the right amount of drug needed to treat his or her particular case.

Tacrolimus is requested frequently at the start of therapy, often daily when trying to establish a dosing regimen. Once dosages have been established and shown to be well tolerated then the frequency of tacrolimus testing may be decreased.  The test is performed when dosages are changed and whenever patients have symptoms that suggest side effects, toxicity or organ rejection.  Monitoring at intervals is necessary as long as the patient is taking tacrolimus.

Concentrations that are higher than the established therapeutic range may cause symptoms associated with toxicity.  Concentrations that are too low may lead to rejection of the transplanted organ.  Side effects may be seen at any dosage but tend to be more severe with higher tacrolimus levels.

Some signs and symptoms of tacrolimus toxicity include:

• Kidney damage
• Tremors
• Headache
• High Blood Pressure
• Nausea and vomiting
• Electrolyte disturbances, such as high potassium concentrations (hyperkalaemia)
• Tinnitus—intermittent and/or persistent ringing or roaring in the ears
• Seizures

The therapeutic range established by a laboratory will depend on both the method used to measure the drug and the type of transplant.   Results from different methods are not interchangeable. A doctor will usually have his patient’s samples sent consistently to the same laboratory and will be guided by that laboratory’s therapeutic ranges.

A variety of drugs, such as calcium channel blockers, antifungal drugs, macrolide antibiotics (such as erythromycin), protease inhibitors, chloramphenicol, and another immunosuppressant such as cyclosporine can increase tacrolimus concentrations.  Drugs such as anticonvulsants (carbamazepine, phenytoin), antimicrobials (rifampin), and the immunosuppressant sirolimus can decrease tacrolimus concentrations.

Grapefruit juice and herbal supplements such as St. John’s Wort should be avoided while taking tacrolimus.

Tacrolimus may be given for a period of time to patients who have had bone marrow transplantation.  Topical tacrolimus may be used to treat a variety of skin conditions, such as eczema, that have not responded well to other medications.  This topical use of tacrolimus is intended to be local, not systemic, and is not usually monitored.  In some countries, tacrolimus is also licensed for use as a treatment for myasthenia gravis. 

Patients should not alter their dose or the time that they take their dose without consulting with their doctor.   Tacrolimus should be taken consistently with respect to meals.  Food, especially high fat meals can significantly reduce the bioavailability (amount of the drug that reaches the circulation) compared with fasting.  Women who are pregnant or planning to become pregnant should talk to their doctor about associated risks.