immunosuppressant
10 interactions related to immunosuppressant
cyclosporine + st. john's wort
St. John's wort is a potent inducer of CYP3A4 and P-glycoprotein, which dramatically accelerates cyclosporine metabolism and efflux. Co-administration reduces cyclosporine blood AUC by roughly 40-50%, producing subtherapeutic levels that have caused documented acute organ rejection in heart, kidney, and liver transplant recipients.
tacrolimus + grapefruit
Grapefruit furanocoumarins irreversibly inhibit intestinal CYP3A4, increasing tacrolimus AUC by roughly 28% and Cmax by up to 73%. Case reports describe trough levels tripling after grapefruit ingestion, producing nephrotoxicity and neurotoxicity.
pomelo + tacrolimus
Pomelo contains furanocoumarins that inhibit intestinal CYP3A4 and P-glycoprotein, the two systems that limit tacrolimus absorption. A documented case in a renal transplant patient showed pomelo consumption nearly doubled tacrolimus blood levels, risking nephrotoxicity and neurotoxicity given tacrolimus's narrow therapeutic window.
seville orange + cyclosporine
Seville orange juice contains furanocoumarins that reduce enterocyte CYP3A4 expression by approximately 40%, although a controlled human study found no significant change in cyclosporine AUC, likely because cyclosporine disposition also depends on intestinal P-glycoprotein, which Seville orange does not inhibit as strongly as grapefruit.
cranberry + tacrolimus
Cranberry juice has been shown to inhibit intestinal CYP3A enzymes, and tacrolimus is heavily metabolized by intestinal CYP3A4 and CYP3A5. The expected direction is an increase in tacrolimus trough levels, raising the risk of nephrotoxicity and tremor, although published cases are scarce and one case unexpectedly reported a decrease.
cbd + tacrolimus
CBD inhibits CYP3A4, CYP3A5, and P-glycoprotein, the main pathways that clear tacrolimus. A published case report documented an approximately 3-fold rise in dose-normalized tacrolimus levels after adding CBD, posing serious nephrotoxicity, neurotoxicity, and over-immunosuppression risk in transplant patients.
cyclosporine + grapefruit
Grapefruit juice contains furanocoumarins that irreversibly inhibit intestinal CYP3A4, raising cyclosporine bioavailability by 35-60% and increasing the risk of nephrotoxicity, hypertension, and neurotoxicity. The effect can persist for 24 hours or longer after a single glass.
tacrolimus + st. john's wort
St. John's wort induces CYP3A4 and P-glycoprotein, slashing tacrolimus blood concentrations and risking acute graft rejection. Conversely, abrupt discontinuation of the herb can unmask tacrolimus nephrotoxicity as levels rebound.
cyclosporine + echinacea
Echinacea is marketed as an immune stimulant and has been shown in vitro and in some animal models to activate macrophages, NK cells, and pro-inflammatory cytokines. While direct pharmacokinetic effects on cyclosporine levels are not well documented in humans, the immunostimulant pharmacology directly opposes the goal of immunosuppression in transplant and autoimmune patients.
grapefruit + sirolimus
Sirolimus is a CYP3A4 and P-glycoprotein substrate with a narrow therapeutic window and high baseline interpatient variability. The FDA-approved Rapamune label states that grapefruit juice inhibits the CYP3A4-mediated metabolism of sirolimus and must not be taken with or used to dilute the drug, because unpredictable, large rises in blood levels can cause nephrotoxicity, infection, and graft injury.