Goldenseal Drug Interactions John R

MORE @ WWW. PHARMACY For references, go to www RX FOCUS DRUG INTERACTIONS TIMES.COM .PharmacyTimes.com/ publications/issue. Goldenseal Drug Interactions John R. Horn, PharmD, FCCP, and Philip D. Hansten, PharmD

goldenseal inhibits CYP3A4.2-4 Also, a randomized controlled study in 104 trans- John R. Horn, PharmD, plant patients on cyclosporine found that FCCP goldenseal (as berberine) produced sub- stantial increases in cyclosporine levels.5 Goldenseal would also be expected to interact with serolimus and tacrolimus, which are both CYP3A4 substrates. Given the convincing evidence that goldenseal inhibits CYP3A4, it is likely that goldenseal inhibits the metabolism berberine (or goldenseal) is a CYP2C9 Philip D. Hansten, of other CYP3A4 substrates such as alfu- inhibitor. PharmD zosin, calcium channel blockers, carbam- Although the effect of CYP2C9 inhi- azepine, colchicine, ergot alkaloids, phos- bition on the efficacy of losartan is not phodiesterase inhibitors, ranolazine, vinca clear, inhibitors of CYP2C9 are known to alkaloids, and selected members of other increase warfarin response, thus potentially classes, such as benzodiazepines, statins, increasing the bleeding risk if doses are not corticosteroids, opioid analgesics, antipsy- adjusted. Although the effect of golden- chotics, antiarrhythmics, antidiabetics, and seal on CYP2C9 requires more study, one oldenseal is a popular herbal prod- protease inhibitors. should assume that goldenseal can increase uct containing the alkaloids ber- warfarin response until clinical studies Gberine and hydrastine. It is used to CYP2D6 Inhibition of the combination are performed. Other treat infections of various types, inflamma- Pharmacokinetic studies of debrisoquin and CYP2C9 substrates that might interact with tion, hypertension, and many other disor- dextromethorphan (CYP2D6 substrates) goldenseal include phenytoin as well as ders. Evidence is accumulating that gold- in healthy subjects show that goldenseal several oral antidiabetic agents. enseal may have some clinically important inhibits CYP2D6.2,3,6 Although far fewer drug interactions. drugs undergo metabolism by CYP2D6 Summary compared with CYP3A4, one must still Goldenseal is one of the few herbal prod- Interactive Properties consider that reduced CYP2D6 activ- ucts for which we have credible clinical Goldenseal appears to inhibit some cyto- ity can increase the risk of toxicity from information on its interactive properties. chrome P450 (CYP) drug-metabolizing certain members of drug classes, includ- The most important of these properties is isozymes, CYP3A4, CYP2D6, and prob- ing antiarrhythmics, antipsychotics, and the ability of goldenseal to inhibit CYP3A4, ably CYP2C9. Because beta-blockers. Also, some because so many drugs are CYP3A4 sub- CYP3A4 metabolizes more Available clinical drugs such as codeine and strates and some of these drugs have sub- drugs than any other iso- tamoxifen are administered stantial toxicity. zyme, there is a potential for evidence sug- as prodrugs, and CYP2D6 The evidence for CYP2D6 inhibition by numerous interactions with is required for their activa- goldenseal is also substantial, although a goldenseal. Available clini- gests that gold- tion. Thus goldenseal would limited number of drugs are CYP2D6 sub- cal evidence suggests that theoretically reduce the effi- strates. The ability of goldenseal to inhibit goldenseal does not inhibit enseal does not cacy of such medications. CYP2C9 is still under study, but if it proves CYP1A2 or CYP2E1, and to be real, one would expect adverse inter- the lack of an effect of gold- inhibit CYP1A2 CYP2C9 Inhibition actions with warfarin and other CYP2C9 enseal on digoxin pharma- or CYP2E1. In a randomized crossover substrates. cokinetics suggests that it study in 18 healthy sub- does not affect the trans- jects given a single dose of porter, P-glycoprotein (ABCB1).1 losartan 30 mg, berberine administration Drs. Horn and Hansten are both professors doubled the ratio of urinary losartan to of pharmacy at the University of Washington CYP3A4 Inhibition its active metabolite.2 The active metabo- School of Pharmacy. For an electronic version Pharmacokinetic studies of midazolam and lite of losartan is formed by the action of this article, including references if any, visit www.hanstenandhorn.com. cyclosporine in healthy subjects show that of CYP2C9, so this study suggests that

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