Other DrugSt Johns Wort Interactions

Sugimoto et al. reported interactions of St. John's wort with cholesterol-lowering drugs simvastatin and pravastatin. In a double blind crossover study using 16 healthy male volunteers, the authors demonstrated that use of St. John's wort (900mg/day) for 14 days decreased peak serum concentration of simvastatin hydroxyl acid, the active metabolite of simvastatin, from an average of 2.3 ng/mL in the placebo group to 1.1 ng/mL in the group taking St. John's wort. The AUC was also reduced in the group of volunteers taking St. John's wort compared to the placebo group. Simvastatin is extensively metabolized by CYP3A4 in the intestinal wall and liver, and St. John's wort induces this enzyme. On the other hand, St. John's wort did not influence plasma pravastatin concentration (53). St. John's wort also induces both CYP3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. In a study involving 12 healthy adult men, a group of volunteers received St. John's wort (900 mg/day) for 14 days. Then, both control groups and volunteers taking St. John's wort consumed a single dose of omeprazole (20 mg) orally. Significant decreases in peak plasma concentrations of omeprazole were observed in volunteers taking St. John's wort indicating significant interactions between St. John's wort and omeprazole (54). Tannergren et al. reported that repeated administration of St. John's wort significantly decreases bioavailability of R and S-verapamil. This effect is caused by induction of first pass metabolism by CYP3A4 most likely in the gut (55).

Interestingly, St. John's wort does not interact with carbamazepine. Burstein et al. (56) reported that intake of St. John's wort (900mg/day) for two weeks did not alter pharmacokinetics of the antiepileptic drug carbamazepine. Carbamazepine is metabolized by CYP3A4, but the lack of interaction may be due to the inducing property of carbamazepine itself on cytochrome P 450 enzymes, and therefore, further induction by St. John's wort may not occur.

St. John's wort is as effective as paroxetine for treating mild to moderate depression (57). A patient taking paroxetine (Paxil, 40 mg) for 8 months stopped taking paroxetine and started taking St. John's wort (600 mg per day). She experienced no adverse effect from switching medication. However, one night when she felt tired she took 20 mg of paroxetine and felt lethargic and ended up in a hospital. The authors conclude that St. John's wort is a monoamine oxidase inhibitor and interacted with paroxetine, a selective serotonin reuptake inhibitor (58).

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