Immunosuppressant (calcineurin inhibitor)
Tacrolimus is an immunosuppressant medicine used to prevent rejection after organ transplantation (kidney, liver, heart, lung). It reduces the activity of the immune system so the body does not attack the transplanted organ.
Also known as: Tacrolimus, Prograf
Tacrolimus + clarithromycin: clarithromycin reduces tacrolimus metabolism (CYP3A4/P-gp), increasing its levels and the nephrotoxicity risk (QUADRO 2).
Tacrolimus is metabolised by CYP3A4 and is a P-glycoprotein substrate; clarithromycin inhibits both pathways, potentially increasing tacrolimus concentrations several-fold and precipitating nephrotoxicity and neurotoxicity. QUADRO 2 of Annex 7 records this interaction in the cyclosporine and macrolide sections (applicable to calcineurin inhibitors). The risk is higher in transplant patients with already compromised renal function. During clarithromycin, reduce the tacrolimus dose (often by half or more) and monitor serum levels and creatinine; prefer azithromycin when possible.
Tacrolimus + clarithromycin: CYP3A4 and P-gp inhibition — marked tacrolimus increase and nephrotoxicity; reduce dose and monitor levels.
Tacrolimus is a CYP3A4/P-gp substrate; macrolides (clarithromycin, erythromycin) reduce its metabolism, increasing concentrations and toxicity (QUADRO 2, Macrolides/Cyclosporine: "Sirolimus, tacrolimus" among the drugs with increased concentration from enzymatic inhibition).
Monitor tacrolimus blood levels, renal function, potassium and BP during the antibiotic.
Elevated tacrolimus levels, rising creatinine, hyperkalaemia during clarithromycin.
Avoid the combination or monitor tacrolimus levels and adjust the dose (frequent 50-75% reduction).
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Cyclosporine; Macrolides)
Tacrolimus + diltiazem: diltiazem reduces tacrolimus metabolism, increasing its levels and the nephrotoxicity risk (QUADRO 2).
Diltiazem inhibits CYP3A4, the main metabolic pathway of tacrolimus, increasing its plasma concentrations and the risk of nephrotoxicity. QUADRO 2 of Annex 7 records this interaction in the calcium channel blocker section. The rise in levels usually appears within the first days of starting diltiazem; stopping diltiazem has the opposite effect. The risk is higher in renal or hepatic transplant patients with a narrow therapeutic margin. Monitor tacrolimus levels and creatinine when starting, adjusting or stopping diltiazem, and consider reducing the tacrolimus dose (typically 30-50%).
Tacrolimus + diltiazem: CYP3A4 inhibition by diltiazem — increased tacrolimus; reduce dose and monitor levels and renal function.
Diltiazem (CYP3A4/P-gp inhibitor) reduces tacrolimus metabolism — increased concentrations and toxicity (QUADRO 2, Calcium channel blockers: "Tacrolimus: reduced tacrolimus metabolism with diltiazem, nicardipine, verapamil").
Monitor renal function and tacrolimus levels.
Elevated tacrolimus levels and rising creatinine after starting diltiazem.
Monitor tacrolimus levels when starting diltiazem; reduce the dose as needed.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Calcium channel blockers)
No documented food or drink interactions.
No documented disease interactions.
PROGRAF label (8.1): there is a pregnancy registry (Transplantation Pregnancy Registry International — TPRI) that monitors outcomes in transplant recipients exposed to immunosuppressants; insufficient data to quantify the risk.
Potential risk (immunosuppressant, limited data); assess case by case with the transplant team.
Excreted in human milk — breastfeeding during treatment is not recommended (literature data/8.2).
Discuss pregnancy planning and contraception with transplant recipients of reproductive age.
DailyMed/FDA (NIH/NLM) — approved Tacrolimus label (PROGRAF), section 8.1: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7f667de1-9dfa-4bd6-8ba0-15ee2d78873b
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Immunosuppressant (calcineurin inhibitor): binds FKBP-12 and the complex inhibits calcineurin, blocking T-lymphocyte activation; CYP3A4/3A5 and P-gp substrate, with a narrow therapeutic window (PROGRAF label 12.1).
Calcineurin inhibition (via FKBP-12 complex) — prevents NFAT dephosphorylation/translocation and T-lymphocyte activation.
Variable oral absorption (food-influenced); oral bioavailability of approximately 17-25% (section 12.3 data).
Extensive CYP3A4/3A5 metabolism (substrate); CYP3A4/P-gp inhibitors increase levels and inducers decrease them (7.2).
Elimination half-life of approximately 11-19 hours in adults (12.3).
