St. John's Wort

Hyperforin in St. John's Wort strongly induces intestinal and hepatic CYP3A4 and P-glycoprotein, both of which are the primary elimination pathways for cyclosporine. Multiple case reports document cyclosporine plasma levels dropping by 50-70%, leading to acute transplant rejection episodes within days to weeks of initiating St. John's Wort.

Absolutely contraindicated in transplant patients on cyclosporine. Patients must be explicitly warned. If co-administration has occurred, do not abruptly discontinue St. John's Wort (cyclosporine toxicity may result); taper carefully with intensive TDM.

St. John's Wort induces CYP3A4 (primary metabolic pathway for indinavir) and P-glycoprotein, resulting in a documented 57% reduction in indinavir AUC in healthy volunteers. This sub-therapeutic drug exposure risks virological failure and promotes HIV resistance mutations.

Co-administration is absolutely contraindicated. The FDA issued a public health advisory in 2000 warning against this combination. Patients on any antiretroviral regimen (PIs, NNRTIs, INSTIs) must avoid St. John's Wort.

CYP3A4 induction by hyperforin accelerates metabolism of ethinylestradiol and progestins, reducing plasma concentrations. P-gp induction further reduces intestinal absorption. Breakthrough bleeding and contraceptive failure have been documented in women taking St. John's Wort concurrently.

Advise patients that St. John's Wort can cause contraceptive failure. Women should use additional non-hormonal barrier contraception during co-administration and for at least one month after stopping St. John's Wort. Consider alternative contraceptive method.

Hyperforin-mediated PXR activation induces CYP3A4 and P-gp, both critical for tacrolimus elimination. Case reports document up to 50-60% reduction in tacrolimus trough levels, resulting in acute transplant rejection. Tacrolimus has an extremely narrow therapeutic index making even modest CYP3A4 induction dangerous.

Absolutely contraindicated in solid organ transplant patients on tacrolimus. Clinicians must routinely ask about herbal supplement use. If identified, do not abruptly stop; taper SJW with close TDM and adjust tacrolimus dose.

St. John's Wort induces CYP3A4, which metabolizes irinotecan to inactive metabolites, and induces UGT1A1, which glucuronidates its active metabolite SN-38. A clinical study showed a 40% reduction in SN-38 AUC when patients received SJW, potentially leading to treatment failure in cancer patients.

Absolutely contraindicated during chemotherapy. Oncologists must screen all patients for herbal supplement use. Discontinue St. John's Wort at least 2 weeks before initiating irinotecan-based chemotherapy.

Methadone is metabolized primarily by CYP3A4 and to a lesser extent CYP2D6 and CYP2C19. St. John's Wort induction of CYP3A4 can significantly reduce methadone plasma levels. Case reports describe opioid withdrawal in patients on stable methadone maintenance therapy after initiating St. John's Wort.

Avoid in patients on methadone maintenance therapy. Screen opioid-dependent patients for self-medication with St. John's Wort for depression. If identified, coordinate with addiction medicine provider for methadone dose adjustment.

St. John's Wort contains hyperforin, a potent activator of the pregnane X receptor (PXR), which induces CYP2C9, CYP3A4, and P-glycoprotein expression. This accelerates warfarin metabolism (both S-warfarin via CYP2C9 and R-warfarin via CYP3A4), reducing plasma warfarin concentrations by up to 35-50% and significantly decreasing anticoagulant effect. P-gp induction further reduces warfarin bioavailability.

Concurrent use is contraindicated. Patients on warfarin must avoid St. John's Wort entirely. If a patient has been taking both, stopping St. John's Wort abruptly can cause dangerous INR elevation. Monitor INR closely with any change in St. John's Wort use and adjust warfarin dose accordingly.

St. John's Wort induces intestinal P-glycoprotein, the main transporter responsible for limiting digoxin oral bioavailability and promoting tubular secretion. In a pharmacokinetic study, SJW co-administration reduced digoxin AUC by 25% and peak plasma levels by 33%, potentially leading to sub-therapeutic cardiac drug levels.

Avoid concurrent use in patients on digoxin. If unavoidable, monitor digoxin serum levels closely and titrate dose accordingly. Warn patients that discontinuing St. John's Wort may cause sudden rise in digoxin levels and toxicity.

St. John's Wort inhibits synaptic reuptake of serotonin, dopamine, and norepinephrine via hypericin and adhyperforin. Combined with SSRIs, this creates additive serotonergic stimulation, with documented cases of serotonin syndrome (agitation, hyperthermia, tachycardia, neuromuscular abnormalities). May also inhibit CYP2D6 and CYP3A4, further elevating SSRI plasma levels.

Avoid concurrent use. Educate patients not to self-medicate depression with St. John's Wort while on prescription antidepressants. If switching, allow appropriate washout period (2 weeks minimum). Monitor for signs of serotonin syndrome.