Drug Interactions

A probable interaction between warfarin and apanax ginseng product has been reported (13). A 47-year-old man with a St. Jude-type mechanical aortic valve had been controlled on warfarin with an international normalized ratio (INR) of 3.1 (goal 2.5-3.5). He experienced a subtherapeutic INR of 1.5 following 2 weeks of ginseng administration (Ginsana three times daily). Other medications included 30 mg of diltiazem three times daily, nitroglycerin as needed, and 500 mg of salsalate three times daily as needed. He had been on all of these medications for at least 3 years before the abrupt change in his INR. Discontinuation of ginseng resulted in an increase in INR to 3.3 within

2 weeks. In this regard, a randomized, double-blind, placebo-controlled trial was undertaken to study the effects of ginseng on warfarin and INR (70). Coadministration of ginseng statistically significantly reduced the INR by -0.19 (95% confidence interval, -0.36 to -0.07) as well as reduced the INR area under the curve (AUC) and the AUC of warfarin. It should be noted that this study involved healthy volunteers and though they received ginseng for 2 weeks, they only received warfarin for three days prior to administration of ginseng and thus, steady-state warfarin concentrations were not likely achieved. In contrast, an open-label, randomized, three-way crossover study evaluated the effects of 1 week of either ginseng or St. John's wort on the INR and pharmacokinetics of warfarin following a single dose of warfarin 25 mg (71). These investigators found no effect of ginseng on either the INR or the phar-macokinetics of (S)-warfarin (the more active enantiomer) or its (S)-7-hydroxywarfarin metabolite.

In a phenotypic trait measure study of effects of various herbal preparations on cytochrome P450 enzyme activity, Gurley and colleagues evaluated the effects of ginseng administration on CYP1A2, CYP2D6, CYP2E1, and CYP3A4 activity in healthy human volunteers (72). Metabolism of probe drugs for each of these enzymes was studied in the absence and presence of ginseng administered for 28 days. Ginseng administration had no effect on the metabolism of any of the probe drugs, suggesting that ginseng administration will not result in drug interactions with drugs metabolized by CYP1A2, CYP2D6, CYP2E1, or CYP3A4. However, the enzyme that is responsible for the metabolism of (S)-warfarin is CYP2C9 (see previous section) and was not evaluated in this study. These findings of lack of effect on CYP2D6 and CYP3A4 were corroborated by a similar study that found no effect of ginseng administration on the activity of either of these two enzymes (73).

Manic-like symptoms were reported in a patient treated with phenelzine and ginseng. The symptoms disappeared with cessation of the herbal therapy (74). Users should also exercise caution if ginseng is taken in combination with caffeinated beverages; as discussed in Section 5, hypertension and nervousness have been reported when the two are combined (34).

Although Siberian ginseng is not of the same genus as P. ginseng, it may be confused with and substituted for P. ginseng, and thus a discussion of drug interactions with Siberian ginseng is warranted. Siberian ginseng has been reported to inhibit the metabolism of hexobarbital in mice by 66% (75). Siberian ginseng ingestion was associated with elevated digoxin levels in a 74-year-old man whose digoxin levels had been maintained between 0.9 and 2.2 ng/L (normal, 0.6-2.6 ng/L) for more than 10 years. He was asymptomatic for digoxin toxicity despite a level of 5.2 ng/L. Electrocardiogram, potassium level, and serum creatinine level were normal. The level decreased on dechallenge and increased on rechallenge. The product was analyzed for digoxin or digitoxin contamination, but none was found. The product was not analyzed to determine if it did in fact contain Siberian ginseng. It was hypothesized that some component of Siberian ginseng might impair digoxin elimination or interfere with the digoxin assay. The type of digoxin assay used in this case was not specified (76). To this end, the effect of different types of ginseng on assays of digoxin concentration has now been studied extensively (77). These investigators observed that apparent digoxin-like immunoreac-tivity was observed when ginseng was studied with a fluorescence polarization immunoassay (FPIA) technique and modest immunoreactivity with microparticle enzyme immunoassay (MEIA) methods using serum spiked with ginseng. Interestingly, when serum from patients receiving digoxin was studied and ginseng was then spiked into the samples, falsely high digoxin concentrations were measured with FPIA but falsely lower concentrations were measured using MEIA. Using the Tina-quant assay, no interference was noted with any of the ginseng preparations.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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