Ketoconazole Interactions

St. John's Wort induces CYP3A4 and P-glycoprotein through PXR activation. Because oral ketoconazole is cleared by CYP3A4, regular St. John's Wort use can speed its breakdown, lower antifungal blood levels, and risk reduced effectiveness. The effect is established by mechanism and by analogy with other azole antifungals; topical ketoconazole is not a practical concern.

Calcium carbonate antacids and large calcium supplements neutralize stomach acid and raise gastric pH. Oral ketoconazole needs an acidic stomach to dissolve and be absorbed, so taking the two together can lower ketoconazole blood levels and reduce its antifungal effect.