Rifampicin induces CYP3A4 metabolism of ketoconazole, dramatically reducing ketoconazole levels. Ketoconazole inhibits rifampicin absorption. Bidirectional antagonism.
Management: Avoid combination — both drugs lose efficacy. Use alternative antifungal or alternative antimycobacterial.
Ketoconazole potently inhibits CYP3A4, increasing alprazolam levels 2-3 fold causing excessive prolonged sedation.
Management: Avoid or reduce alprazolam by 50-75%. Use lorazepam instead (glucuronidation pathway — not CYP-dependent).
Budesonide relies on CYP3A4-mediated first-pass metabolism for low systemic bioavailability. Ketoconazole inhibits CYP3A4, dramatically increasing systemic budesonide exposure (up to 6-fold), causing iatrogenic Cushing's syndrome.
Management: Avoid combination. If concurrent antifungal needed with budesonide, use fluconazole (less CYP3A4 inhibition) or terbinafine.
Alfentanil is entirely CYP3A4 metabolized. Ketoconazole inhibits CYP3A4, dramatically increasing alfentanil levels and duration, causing prolonged respiratory depression.
Management: Reduce alfentanil dose by 50-75% if ketoconazole on board. Have ventilatory support ready. Monitor respiratory function closely.
Colchicine is a CYP3A4 and P-glycoprotein substrate. Ketoconazole inhibits both, causing colchicine accumulation and severe toxicity (myelosuppression, multi-organ failure).
Management: Avoid combination. If concurrent use unavoidable, reduce colchicine dose by 50-75% and monitor CBC closely.
Ketoconazole inhibits CYP3A4 metabolism of domperidone, increasing levels. Domperidone causes dose-dependent QT prolongation — elevated levels increase cardiac arrhythmia risk.
Management: Avoid combination. If prokinetic needed with ketoconazole, use metoclopramide (not CYP3A4 substrate).