MEDICATIONS: ST. JOHN'S WORT MAY DECREASE EFFECTIVENESS OR REQUIRE HIGHER DOSAGE OF SOME MEDS

Sept. 16, 2003 — Use of St. John's wort may result in reduced clinical efficacy or increased dosage requirements for a large and diverse group of medications, according to an article in the Sept. 17 issue of The Journal of the American Medical Association (JAMA).

According to background information in the article, St. John's wort is a popular herbal product available without prescription and used to treat depression. Previous research has indicated that this agent may cause clinically significant, and perhaps dangerous drug interactions.

John S. Markowitz, Pharm.D., and colleagues from the Medical University of South Carolina, Charleston, conducted a study to assess the potential of St. John's wort to alter the activity of the cytochrome P450 (CYP) enzyme systems, which are extensively involved in drug metabolism.

The study, conducted from March 2002 to February 2003, involved 12 healthy individuals (six men and six women) aged 22 to 38 years. Participants were given "probe" drugs (30 mg of dextromethorphan (a cough suppressant) and two mg of alprazolam (an anti-anxiety medication) to establish baseline CYP 2D6 and CYP 3A4 (enzymes) activity. After a minimum seven-day washout period, participants began taking one 300-mg tablet of St. John's wort three times per day. After 14 days of St. John's wort administration, participants were given the probe drugs along with one St. John's wort tablet to establish post-administration CYP activity; the St. John's wort dosing regimen was continued for 48 hours.

The results indicated that alprazolam was eliminated from plasma twice as fast following St. John's wort administration (elimination half-life decreased from 12.4 hours to 6.0 hours). After 36 hours, only seven of 12 St. John 's wort-treated participants had measurable alprazolam concentrations after St. John's wort administration vs. all 12 Participants at baseline. At the 48-hours time point, no participants had measurable alprazolam concentrations after St. John's wort administration compared to 11 of 12 participants during the baseline phase.

"These results indicate that long-term administration of St. John's wort may result in diminished clinical effectiveness or increased dosage requirements for all CYP 3A4 substrates (the specific molecule an enzyme acts upon), which represent at least half of marketed medications. These findings underscore the potential problems associated with the widespread practice of using herbal products (at the same time) with conventional medications," the authors conclude.