Tacrolimus

Mechanism :

Tacrolimus prolongs the survival of the host and transplanted graft in transplant models of liver, kidney, heart, bone marrow, small bowel and pancreas, lung and trachea, skin, cornea, and limb.

Indication :

• Liver transplant
• Renal transplant
• Heart transplant
• Atopic dermatitis

Contraindications :

Contraindicated in patients with a hypersensitivity to tacrolimus, to macrolides or any excipient, particularly polyoxymethylene hydrogenated castor oil, and in pregnancy. Patients with known sensitivity to similar compounds, or who are atopic should be monitored closely on commencing treatment. Particular care required in children <2 years of age who are initially EBV-seronegative—therefore monitor EBV serology before starting and during treatment with tacrolimus. Routine monitoring of cardiovascular, visual, endocrine, renal, hematological and hepatic function is mandatory on commencement of treatment. Dose should be adjusted where clinically relevant changes are identified.

Dosing :

Adverse Effect :

Tremors, headache, infection, paresthesia, impaired renal function, constipation, asthenia, abdominal pain, hyperlipemia, dyspepsia, fever, arthralgia, back pain, diabetes, paresthesia, hypertension and hyperglycemia. Dyspnoea, dizziness, increased cough, rash, pruritus can occur. Susceptibility to bacterial, viral, fungal and/or protozoal infection is increased. EBV-associated lympho-proliferative disorders may occur. Impaired renal function, renal failure, hemolytic uremic syndrome (HUS) and tubular necrosis have been reported. In renal transplant recipients it is important to distinguish tacrolimus toxicity from signs of acute rejection. Anemia, coagulation disorders, thrombocytopenia, leucocytosis, leukopenia, pancytopenia, acidosis, hyper-and hypokalemia, hyperuricemia, hypocalcemia, hypomagnesemia, hypophosphatemia and hyponatremia.

Topical: Skin irritation, burning sensation, erythema, acne, herpes simplex, increased sensitivity to hot and cold, alcohol intolerance.

Interaction :

Cyclosporin: Half-life is increased in patients also receiving tacrolimus. Risk of nephrotoxicity is increased; concurrent use is not recommended.
Clotrimazole, Danazol, Dexamethasone, and Methylprednisolone: Interactions resulting in changes to blood/plasma levels of tacrolimus or the following have been reported.
Aminoglycosides, Amphotericin B, Co-Trimoxazole, Gyrase Inhibitors, NSAIDs and Vancomycin: Nephrotoxicity may be enhanced by concurrent administration.
Potassium-Sparing Diuretics: Risk of hyperkalemia.
Vaccinations: May be less effective. Live attenuated vaccines should be avoided.
Amphotericin B, Barbiturates, Bromocriptine, Carbamazepine, Corticosteroids, Cortisone, Cyclosporin, Diltiazem, Ergotamine, Erythromycin, Ethinylestradiol, Fluconazole, Isoniazid, Ketoconazole, Miconazole, Midazolam, Nifedipine, Phenytoin, Prednisolone, Rifampicin, Tamoxifen and Verapamil: Influence tacrolimus metabolism.
Warfarin and Phenytoin: Interactions with other drugs with a similarly high level of binding to plasma protein, such as warfarin and phenytoin should be considered likely.

Renal Dose :

Hepatic Dose :