p-glycoprotein
14 interactions related to p-glycoprotein
apixaban + st. john's wort
St. John's wort strongly induces both CYP3A4 (apixaban's primary metabolizing enzyme) and P-glycoprotein (its efflux transporter). Co-use accelerates apixaban metabolism and clearance, lowering plasma concentrations and increasing the risk of stroke or thromboembolism.
verapamil + st. john's wort
St. John's wort is a potent inducer of intestinal CYP3A4 and P-glycoprotein. In a controlled study, two weeks of St. John's wort reduced the AUC of R- and S-verapamil by roughly 78-80%, dramatically lowering systemic drug exposure and likely therapeutic effect.
digoxin + st. john's wort
St. John's wort induces intestinal P-glycoprotein, increasing efflux of digoxin and reducing its absorption. Controlled studies show digoxin AUC falls roughly 25% and peak concentrations around 30-36% after two weeks of St. John's wort, potentially producing therapeutic failure in rate control or heart failure management.
digoxin + hawthorn
Hawthorn (Crataegus) has digoxin-like positive inotropic activity, may modulate P-glycoprotein efflux, and can interfere with serum digoxin immunoassays. Concurrent use raises the risk of additive cardiac effects and erroneous digoxin level readings even though formal pharmacokinetic studies show little change in digoxin AUC.
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.
dabigatran + st. john's wort
St. John's wort is a potent inducer of P-glycoprotein (P-gp), the efflux transporter responsible for dabigatran disposition. Co-administration increases dabigatran efflux and reduces plasma concentrations, potentially leading to subtherapeutic anticoagulation and increased risk of stroke or thrombosis.
simvastatin + st. john's wort
St. John's wort induces intestinal and hepatic CYP3A4 and P-glycoprotein, sharply increasing simvastatin's first-pass metabolism. In a crossover study of healthy adults, the AUC of active simvastatin hydroxy acid was cut roughly in half (to about 48% of placebo).
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.
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.
raloxifene + st. john's wort
Although raloxifene is cleared primarily by glucuronidation rather than CYP3A4, St. John's Wort induces P-glycoprotein and other transporters that may reduce raloxifene exposure. Drug interaction databases list a documented reduction in raloxifene serum concentration with concurrent use, potentially undermining osteoporosis treatment.
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.
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.
black pepper + propranolol
Piperine, the active alkaloid in black pepper, inhibits CYP3A4, CYP2C9, and intestinal P-glycoprotein, increasing the oral bioavailability and serum concentration of propranolol and other beta-blockers, which can amplify blood pressure and heart rate reduction.