💊 Tacrolimus

Tacrolimus is a macrolide lactone, classified as a calcineurin inhibitor and a potent immunosuppressant.

Tacrolimus binds to the immunophilin FKBP-12, forming a complex that inhibits calcineurin. This inhibition prevents the dephosphorylation of NFAT, thereby blocking the transcription of IL-2 and other pro-inflammatory cytokines, leading to T-cell suppression.

In the UK, its primary use is for the prophylaxis of organ transplant rejection (kidney, liver, heart, lung). It is also indicated for the treatment of organ rejection resistant to other immunosuppressive regimens. Topical formulations are used for severe atopic dermatitis.

Absolute contraindications include hypersensitivity to tacrolimus or macrolides. It is generally contraindicated in uncontrolled infections. Caution is required in patients with pre-existing renal or hepatic impairment, diabetes, or hyperkalaemia.

Common and dose-dependent side effects include nephrotoxicity, neurotoxicity (tremor, headache, paraesthesia), hypertension, and hyperglycaemia (new-onset diabetes). Other serious effects include increased risk of infections, malignancy (skin cancers, lymphoproliferative disorders), and hyperkalaemia.

Regular monitoring of tacrolimus blood trough levels is essential due to its narrow therapeutic index. Renal function (U&Es), blood pressure, liver function tests (LFTs), potassium, and blood glucose levels must be closely monitored.

Always check for drug interactions, especially with CYP3A4 inhibitors/inducers, which can significantly alter tacrolimus levels. Counsel patients on the importance of strict adherence, regular blood tests, and reporting any signs of infection or new symptoms like tremor or increased thirst. Advise on sun protection.

A very potent calcineurin inhibitor, often preferred over ciclosporin in some transplant centres. High yield for its narrow therapeutic index, requiring TDM, and its significant nephrotoxicity, neurotoxicity, and diabetogenic effects. Remember its topical use for atopic dermatitis.

SBAs frequently test the key adverse effects, particularly nephrotoxicity, neurotoxicity, and new-onset diabetes, and the critical need for therapeutic drug monitoring (TDM). Questions may also focus on its role as a primary immunosuppressant in transplant settings.