There are no known specific drug interactions for CVT-E002/COLD-fX. However, as available evidence is limited, the possibility of significant pharmacological interactions cannot be excluded. Animal model testing for the safety evaluation of CVT-E002 is reassuring, but limited. One experiment in mice evaluated potential effects on cytochrome P450 liver metabolism, an important source of drug-drug and herb-drug interactions.36 Five C57BL/6J mice were fed 5mg/kg/day of CVT-E002 by gastrogavage for 3 days, while 6 mice were given equal volumes of water. Livers were removed and biological samples analyzed for effects on CYP, UGT, and GST pathways within the P450 cytochrome complex. No statistically significant effects between active and control groups were found. It is unclear whether such small sample sizes provided sufficient statistical power to detect such effects.
A published abstract reported that in vitro studies on 6 cytochrome P450 enzymes (human CYP isoenzymes expressed in cells) indicated no effects of CVT-E002.37 By comparison a “ginsenoside-rich extract” apparently “inhibited all of the enzymes to some degree.” However, methods and results were not detailed, so conclusions are considered preliminary until a peer-reviewed journal article becomes available.
Expanding the scope of safety review to P. quinquefolius extracts other than CVT-E002, there are a few potentially relevant reports. For instance, a randomized trial in 20 healthy volunteers, using a preparation derived from P. quinquefolius dosed at 1 gram of unrefined dried root per day, was shown to reduce the anticoagulation effect of warfarin.38 Although this effect may very well be due to phytochemicals that are not present in CVT-E002/COLD-fX (e.g., ginsenosides), it would be helpful to have specific data to evaluate. The manufacturer of CVT-E002/COLD-fX suggests that individuals taking warfarin avoid consumption of the extract as a precaution.
As another example, there have been reports of the effects of ginseng extracts on the measurement of digoxin levels, an effect that seems to occur with extracts from most ginseng species, including P. quinquefolius.39,40 For patients taking digoxin and their clinicians, it might be helpful to know whether these effects occur with COLD-fX, so that clinical decisions made on the basis of potentially false digoxin levels would not be in error.
As noted above in the Contraindications and Precautions section, theoretical concerns may exist for diabetic patients taking oral hypoglycemic drugs or insulin due to a possible hypoglycemic action for the polysaccharides in CVT-E002/COLD-fX. It should be noted that at least one source argues that the ginsenosides in American ginseng root are responsible for this action, thus making this interaction unlikely.29 No interactions of this kind have been reported to date in clinical studies or post-market surveillance.
Finally, there may be a tendency for some researchers to evaluate the relative safety of CVT-E002/COLD-fX by attempting to expand the scope of review to all Panax species. However, as already demonstrated, the CVT-E002/COLD-fX preparation does not contain ginsenosides, universally regarded as the primary active compounds in roots of all Panax species. Hence it is problematic whether case reports based on conventional Panax preparations will actually be relevant to the potential for COLD-fX to interact with the conventional drugs noted as interacting with Panax. The literature contains several case reports, including those cited in safety reviews by Bressler32 and by Coon and Ernst,31 which summarized the reports of adverse events and interactions from clinical trials, reports from manufacturers, the World Health Organization drug reporting centers, etc. These include descriptions of decreased effectiveness of several diuretics (bumetanide, furosemide, torsemide, ethacrynic acid), and potential exacerbation of manic-like side effects from a few medications with known CNS/psychiatric effects (isocarboxazid, tranylcypromine, phenelzine).32 Possible over stimulation with concurrent use of P. ginseng and caffeine or amphetamines has also been cited in a recently published safety review.41 However, as noted in the systematic review of adverse effects and drug interactions on Asian ginseng, “these data suggest that P. ginseng monopreparations are rarely associated with adverse events or drug interactions. The ones that are documented are usually mild and transient.”31 The active agents (oligo- and polysaccharides) in CVT-E002/COLD-fX are pharmacologically unlikely to cause any of the side effects or drug interactions noted in reports on Panax species.