Tacrolimus is a potent immunosuppressant. In experimental studies in vitro and in vivo tacrolimus distinctly reduced the formation of cytotoxic lymphocytes, which play a key role in the graft rejection.
Tacrolimus inhibits the formation of lymphokines (interleukin-2, -3, γ-interferon) that activate T-cells, expression of the receptor of interleukin-2, and dependent on T-helper cells proliferation of B-cells.
Recommendations for achieving the desired concentration of drug in whole blood: in the early postoperative period should be monitored Cmin of tacrolimus in whole blood. Oral application to determine Cmin need to obtain a blood sample within 12 hours after taking tacrolimus, immediately before the next dose. The frequency control Cmin depends on the clinical need. Because tacrolimus has a low ground clearance, correction mode may take a few days before the moment of change of drug concentration in the blood becomes evident. Cmin should be monitored 2 times a week during the early post-transplant period and then periodically during maintenance therapy. It is also necessary to monitor Cmin after modifying the dose of immunosuppressive regime or following a joint application with drugs, which may affect the concentrations of tacrolimus in whole blood. The results of the analysis of clinical studies suggests that successful treatment is achieved at Cmin below 20 ng/ml.
In clinical practice during the early post-transplant period, min in whole blood ranged from 5 to 20 ng/ml in recipients of liver transplant and 10-20 ng/ml – patients with kidney transplant. Therefore, during maintenance therapy of drug concentration in the blood should be 5-15 ng/ml in recipients of liver transplant and the kidneys.
Noted development associated with Epstein-Barr (EBV) lymphoproliferative diseases that may be caused by excessive immunosuppression prior to use of this drug. When translated into therapy with tacrolimus is contraindicated concomitant antilimfocitarnyi therapy. The EBV-seronegative children up to 2 years there is an increased risk of developing lymphoproliferative diseases (before treatment it is necessary serological determination of EBV).
Crosses the placenta and is excreted in breast milk. Safety of use in pregnant women has not been established, therefore it should appoint a drug during pregnancy, except, when the intended benefits to the mother outweighs the potential risk to the fetus. During treatment it is recommended to cancel breastfeeding.
In the initial post-transplant period is necessary to control blood pressure, ECG, neurological and ophthalmological status, concentration of glucose in blood on an empty stomach, proteins in the blood plasma, electrolytes (especially K+), liver function and kidney clinical analysis of blood, indicators of blood coagulation.
Due to the potential risk of malignant skin disease during treatment should limit exposure to sunlight and UV radiation, protecting skin by clothes and using creams with a high protection factor.
Concentrate for preparation of solution for injection contains a polyoxyethylated hydrogenated castor oil which may cause anaphylactic reactions. Risk of anaphylactic reaction can be reduced by introducing the recovered concentrate with a low speed or a pre-injection of antihistamine drugs.
Unused concentrate for on/in the introduction in an open ampoule or restored unused solution should be disposed of immediately to avoid bacterial contamination.
Tacrolimus is incompatible with PVC (polyvinylchloride absorbed by plastics) – pipes, syringes, nasogastric tubes, and other devices that are used for the preparation and introduction of concentrate for infusion or the content of capsules, the probe must not contain polyvinyl chloride.
During treatment should refrain from activities potentially hazardous activities, require high concentration and psychomotor speed reactions (W. driving a car).