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of a rare but serious condition called the serotonin syndrome, which may include symptoms
such as confusion, hallucination, seizure, extreme changes in blood pressure, increased
heart rate, fever, excessive sweating, shivering or shaking, blurred vision, muscle spasm or
stiffness, tremor, incoordination, stomach cramp, nausea, vomiting, and diarrhea. Severe
cases may result in coma and even death.
Triptans (sumatriptan, naratriptan, rizatriptan, zolmitriptan): Potentiation of
serotonin concentration.
Medications changed by the liver (Cytochrome P450 substrates: Certain medications
are metabolized by liver enzymes. St. John’s wort can stimulate these enzymes, leading to
faster breakdown of some drugs. As a result, concurrent use may reduce the
effectiveness of medications that rely on hepatic metabolism for their therapeutic action.

• Cyclosporine: St. John's Wort has been proven to induce the cytochrome P450
enzyme system, the major pathway for cyclosporine metabolism. Heart transplant
rejection has been reported as soon as 3 weeks after St. John's Wort is added to the
drug regimen of heart transplant patients maintained on cyclosporine therap

• Clinicians are warned that St. John's Wort may significantly affect plasma
concentrations of any drug that is metabolized by the cytochrome P450 system.

• Warfarin: It is interesting to note that the combined use of St John’s wort and
warfarin usually causes neutralization of the effect of warfarin by increasing its
metabolism via the P450 enzyme system.

• Benzodiazepines: e.g. Alprazolam.

• Theophylline: The herb decreases theophylline levels on a patient stabilized on
theophylline therapy.

• Medications for HIV/AIDS (Nonnucleoside Reverse Transcriptase Inhibitors
(NNRTIs))

• Medications for HIV/AIDS (protease inhibitors) e.g. Indinavir

coadministration reduces indinavir plasma levels.
• Ethinyloestradiol and desogestrel (combined oral contraceptive): Breakthrough

bleeding has occurred with concomitant use of St. John's Wort.

• Anticonvulsants (carbamazepine, phenobarbitone and phenytoin).

Digoxin: Concurrent administration of St. John’s wort extract with digoxin has been
shown to significantly lower plasma concentrations of digoxin. This interaction may

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