Products
Tacrolimus is commercially available in the form of capsules, sustained-release capsules, sustained-release tablets, as a concentrated solution for infusion, as granules, and as an ointment (Prograf, generic, Advagraf, Protopic, generic, Modigraf). It has been approved in many countries since 1996. This article refers to oral use; see also Topical Tacrolimus (Protopic Ointment).
Structure and Properties
Tacrolimus (C44H69NO12 – H2O, Mr = 822.0 g/mol) is a complex macrolide with a 23-membered ring formed by the fungus-like bacterium. It is present in drugs as tacrolimus monohydrate, white crystals, or a crystalline powder that is practically insoluble in water.
Effects
Tacrolimus (ATC D11AX14) has immunosuppressive properties. It inhibits the activation and function of T lymphocytes, T helper cells, and cytotoxic lymphocytes, which are responsible for graft rejection. Furthermore, the formation of lymphokines (e.g., interleukin, interferons) is reduced. The effects are due to intracellular binding to FKBP-12, and the complex forms calcineurin on the phosphatase, thereby inhibiting signal transduction and transcription.
Indications
For the prevention of liver, kidney, and heart transplant rejection. For the treatment of graft rejection and rejection reactions.
Dosage
According to the SmPC. The non-retarded capsules are administered twice daily in the morning and evening; the sustained-release capsules are taken once daily in the morning. The drug must be taken fasting, 1 hour before or 2-3 hours after meals. The sustained-release capsules may be administered only to stable renal or liver transplant patients who have been previously treated with Prograf.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Interactions
Tacrolimus is metabolized primarily by CYP3A4. Appropriate interactions are possible with CYP inhibitors and inducers. Inhibitors may lead to an increase and adverse effects, and inhibitors may cause graft rejection in the worst case. Therefore, attention to drug-drug interactions during therapy is essential. Other interactions have been described because of high protein binding and with nephrotoxic and neurotoxic agents, ciclosporin, potassium, vaccines, and pentobarbital and phenazone.
Adverse effects
The most common potential adverse effects include diarrhea, nausea, high blood pressure, insomnia, tremor, headache, hyperglycemia, glucose intolerance, diabetes mellitus, hyperkalemia, and decreased renal function. Immunosuppressants increase the risk of developing infections and malignancies. Tacrolimus is nephrotoxic and neurotoxic. Numerous other side effects are observed.
