St. John's Wort Interactions

St. John's Wort induces cytochrome P450 enzymes and P-glycoprotein, reducing plasma concentrations of SSRIs and increasing the risk of serotonin syndrome when combined due to additive serotonergic effects.

Sertraline is an SSRI that blocks serotonin reuptake, and St. John's wort independently inhibits serotonin reuptake and contains constituents (hyperforin, hypericin) that elevate central serotonin. Combining them can trigger serotonin syndrome, a potentially life-threatening syndrome of altered mental status, autonomic instability, and neuromuscular hyperactivity. St. John's wort also induces CYP3A4 and CYP2C19, which can lower sertraline plasma levels and undermine treatment.

Fluoxetine is an SSRI with a very long half-life (its active metabolite norfluoxetine persists for weeks), and St. John's wort independently raises serotonin via reuptake inhibition. Combined use can precipitate serotonin syndrome and, because of fluoxetine's slow elimination, the risk window extends well beyond the day of last dose.

Paroxetine is an SSRI with potent serotonin reuptake inhibition; St. John's wort independently inhibits serotonin reuptake and induces CYP3A4 and P-glycoprotein. The combination can precipitate serotonin syndrome and is among the most frequently reported SSRI plus St. John's wort interactions in published case series.

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI). St. John's wort independently inhibits serotonin (and to a lesser extent norepinephrine and dopamine) reuptake. Combining them can drive a sharp rise in synaptic serotonin and trigger serotonin syndrome, and St. John's wort can also alter venlafaxine pharmacokinetics through CYP3A4 induction.

Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI), and St. John's wort independently raises central serotonin through reuptake inhibition. Combined use can precipitate serotonin syndrome, and St. John's wort induction of CYP3A4 and P-glycoprotein may also alter duloxetine exposure.

St. John's wort induces CYP3A4 and CYP2D6 enzymes that metabolize amitriptyline, reducing its plasma concentrations by up to 22%, while simultaneously adding serotonergic activity that can trigger serotonin syndrome. The combined result is paradoxical: less antidepressant effect plus higher risk of a potentially fatal serotonin reaction.

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.

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.

St. John's Wort induces CYP3A4 and P-glycoprotein, which accelerates the metabolism of ethinyl estradiol and progestins in combined oral contraceptives. Clinical trials have documented breakthrough bleeding and reduced contraceptive hormone exposure when the two are combined, raising the risk of ovulation and unintended pregnancy.

St. John's Wort inhibits serotonin, dopamine, and norepinephrine reuptake and has weak MAOI activity in vitro. Combined with a prescription MAOI, monoamine clearance is blocked at multiple levels, producing serotonin syndrome and/or hypertensive crisis.

Escitalopram is a highly selective SSRI metabolized largely by CYP2C19 and CYP3A4. St. John's wort independently inhibits serotonin reuptake and strongly induces these same enzymes plus P-glycoprotein. Combined use risks serotonin syndrome and can also lower escitalopram plasma levels, blunting its antidepressant effect.

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.

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.

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).

St. John's Wort potently induces CYP1A2 and CYP2C19 along with CYP3A4 and P-glycoprotein, accelerating the metabolism of propranolol and reducing its plasma levels. Documented cases include loss of intraocular pressure control in glaucoma patients on topical beta-blockers, and the mechanism predicts similar loss of antihypertensive and antiarrhythmic effect with systemic propranolol.

Carvedilol is metabolized by CYP2D6, CYP2C9, CYP3A4, and CYP1A2, and is also a P-glycoprotein substrate. St. John's Wort potently induces several of these enzymes and P-gp, accelerating carvedilol clearance and reducing plasma levels, which can blunt its heart failure and antihypertensive effects.

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.

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.

St. John's Wort is a potent inducer of CYP3A4, CYP2C9, CYP2C19, and P-glycoprotein via activation of the pregnane X receptor. Because phenytoin is heavily metabolized by CYP2C9 and CYP2C19, concurrent St. John's Wort can lower phenytoin plasma concentrations into the subtherapeutic range, increasing the risk of breakthrough seizures.

St. John's wort potently induces CYP3A4 and CYP2C19, the enzymes responsible for omeprazole metabolism. Co-administration significantly lowers omeprazole plasma concentrations, reducing its acid-suppressing efficacy and potentially compromising treatment of GERD, ulcers, or H. pylori eradication.

Tramadol inhibits serotonin and norepinephrine reuptake, and St. John's Wort increases central serotonergic activity, so combining them raises the risk of serotonin syndrome. St. John's Wort also induces CYP3A4 and CYP2B6, which can reduce tramadol's active M1 metabolite and weaken analgesia.

St. John's Wort strongly induces CYP3A4, the main enzyme that metabolizes oxycodone. In a controlled crossover trial, St. John's Wort cut oral oxycodone plasma exposure (AUC) by roughly 50% and significantly reduced its analgesic effect.

Adderall (amphetamine/dextroamphetamine) raises synaptic norepinephrine, dopamine, and serotonin. St. John's Wort inhibits serotonin, dopamine, and norepinephrine reuptake. Combined, the serotonergic load can produce serotonin syndrome and a hypertensive response, while St. John's Wort's CYP3A4 induction may also alter amphetamine metabolism.

Methylphenidate inhibits dopamine and norepinephrine reuptake and modestly affects serotonin signaling. St. John's Wort adds reuptake inhibition of serotonin, dopamine, and norepinephrine, plus weak MAO inhibition. Combination risks serotonin syndrome and a published case series suggests reduced methylphenidate efficacy for ADHD.

Bupropion lowers the seizure threshold and St. John's wort may compound that risk, and the herb's induction of CYP enzymes (particularly the role of CYP2B6 and downstream pathways) can also alter bupropion exposure. Both also influence monoamine signaling, raising the risk of additive CNS effects.

Both carbamazepine and St. John's Wort are strong inducers of CYP3A4, the enzyme that primarily metabolizes carbamazepine. Although healthy-volunteer studies have shown limited additional effect on chronic carbamazepine kinetics (because carbamazepine already maximally autoinduces its own metabolism), starting or stopping St. John's Wort can destabilize carbamazepine levels, and the herb can lower exposure to single carbamazepine doses by up to 21% before autoinduction is established.

St. John's wort induces CYP3A4 and CYP2D6, the enzymes responsible for metabolizing nortriptyline, reducing nortriptyline blood levels and antidepressant effect. The herb also adds serotonergic activity that may increase risk of serotonin syndrome.

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.

St. John's Wort is a potent inducer of CYP3A4 and P-glycoprotein via PXR activation, which can accelerate the metabolism of ketoconazole and reduce its antifungal blood concentrations and clinical effectiveness.

St. John's wort potently induces hepatic and intestinal CYP3A4, accelerating atorvastatin's first-pass metabolism. A controlled study showed roughly a 12% drop in atorvastatin AUC and meaningful increases in LDL and total cholesterol over 4 weeks of co-administration.