This table lists interactions between selected natural products and prescription and nonprescription drugs. Although many of the listed interactions are theoretical in nature and have not been documented to occur in humans, those involving St. John’s wort are potentially life threatening in nature, depending on the individual drug. Other interactions are based on small studies of healthy volunteers and use pharmaceutical-quality natural products that may or may not be commercially available.
Natural ProductsDrugsInteractionsAndrographisImmune suppressantsAndrographis may stimulate immune function, potentially decreasing the effectiveness of drugs such as cyclosporine, tacrolimus, and prednisone.Antihypertensive agentsAndrographis may lower blood pressure, potentiating the hypotensive effects of antihypertensive agents.Antiplatelet and anticoagulant agentsAndrographis may have antiplatelet activity, potentially increasing the risk of bleeding.Black cohoshHepatotoxic drugsConcern exists that the risk of hepatotoxicity with black cohosh is increased in the presence of hepatotoxic drugs such as acetaminophen.CisplatinAnimal studies suggest that the efficacy of cisplatin against breast cancer cells may be decreased by black cohosh.CYP2D6 substratesBlack cohosh may modestly inhibit CYP2D6 enzyme activity to result in higher drug concentrations.ButterburCYP3A4 inducers (Rifampin, carbamazepine, etc.)Drugs that induce the activity of CYP3A4 increase the risk of the formation of hepatotoxic metabolites from pyrrolizidine alkaloids from some butterbur products.ChamomileCNS depressants (benzodiazepines, opiates, barbiturates, etc.)Chamomile may have additive CNS depressant effects.CYP1A2 substratesChamomile may inhibit CYP1A2 enzyme activity to result in higher drug concentrations.CYP3A4 substratesChamomile may inhibit CYP3A4 enzyme activity to result in higher drug concentrations.EstrogensChamomile may compete for estrogen receptors.TamoxifenChamomile may interfere with the effects of tamoxifen because of its estrogenic effects.Chaste tree berryAntipsychotic agentsChaste tree berry may antagonize the effects of antipsychotic agents through its dopaminergic activity.MetoclopramideChaste tree berry may antagonize the effects of metoclopramide through its dopaminergic activity.Dopamine agonistsChaste tree berry may possess additive effects to drugs such as levodopa and ropinirole through its dopaminergic activity.Oral contraceptives/estrogensChaste tree berry may possess additive hormonal effects.ChondroitinWarfarinHigh-dose chondroitin has structural similarity to a heparinoid and may possess weak anticoagulant effects.CinnamonHypoglycemic agentsCinnamon may possess additive effects on blood glucose to those of hypoglycemic agents.Coenzyme Q10Antihypertensive agentsCoenzyme Q10 may possess additive effects on blood pressure to those of antihypertensive agents.WarfarinCoenzyme Q10 may lessen the anticoagulant effects of warfarin because of its structural similarity to vitamin K.ChemotherapyThe antioxidant effects of coenzyme Q10 may blunt the efficacy of certain chemotherapeutic agents that depend on the formation of free radicals.CranberryCYP2C9 substrates (warfarin)Cranberry may inhibit CYP2C9 enzyme activity to result in higher drug concentrations; evidence with warfarin is contradictory.Dehydroepiandrosterone (DHEA)Tamoxifen and aromatase inhibitors such as anastrozole and exemestaneDHEA may interfere with the antiestrogenic effects of these drugs.CYP3A4 substratesDHEA may slightly inhibit CYP3A4 enzyme activity to result in higher drug concentrations.Devil’s clawAntihypertensive agentsDevil’s claw may possess additive effects on blood pressure to those of antihypertensive agents.Hypoglycemic agentsDevil’s claw may possess additive effects on blood glucose to those of hypoglycemic agents.H2 antagonists and PPIDevil’s claw may raise gastric pH and blunt the efficacy of H2 antagonists and PPI.CYP3A4 substratesDevil’s claw may inhibit CYP3A4 enzyme activity to result in higher drug concentrations.CYP2C9 substratesDevil’s claw may inhibit CYP2C9 enzyme activity to result in higher drug concentrations.CYP2C19 substratesDevil’s claw may inhibit CYP2C19 enzyme activity to result in higher drug concentrations.WarfarinDevil’s claw may inhibit CYP2C9 enzyme activity to result in higher concentrations of warfarin; purpura has been reported.EchinaceaImmune suppressantsEchinacea may stimulate immune function, potentially decreasing the effectiveness of drugs such as cyclosporine, tacrolimus, and prednisone.CYP3A4 substratesEchinacea may modestly induce hepatic CYP3A4 enzyme activity to result in lower drug concentrations.CYP1A2 substratesEchinacea may inhibit CYP1A2 enzyme activity to result in higher drug concentrations.Eleuthero (Siberian ginseng)CNS depressants (benzodiazepines, opiates, barbiturates, etc.)Eleuthero may have additive CNS depressant effects.Antiplatelet and anticoagulant agentsEleuthero may have antiplatelet activity, potentially increasing the risk of bleeding.CYP3A4 substratesEleuthero may inhibit CYP3A4 enzyme activity to result in higher drug concentrations.CYP1A2 substratesEleuthero may modestly inhibit CYP1A2 enzyme activity to result in higher drug concentrations.CYP2C9 substratesEleuthero may modestly inhibit CYP2C9 enzyme activity to result in higher drug concentrations.CYP2D6 substratesEleuthero may inhibit CYP2D6 enzyme activity to result in higher drug concentrations.DigoxinConcentration of digoxin has been reported to increase but without evidence of toxicity.Evening primrose oil (EPO)Antiplatelet and anticoagulant agentsEPO may have anticoagulant activity, potentially increasing the risk of bleeding.FenugreekAntiplatelet and anticoagulant agentsFenugreek may have antiplatelet activity, potentially increasing the risk of bleeding.Hypoglycemic agentsFenugreek may potentially lower blood glucose concentrations and have additive effects with hypoglycemic agents.FeverfewAntiplatelet and anticoagulant agentsFeverfew may have antiplatelet activity, potentially increasing the risk of bleeding.CYP3A4 substratesFeverfew may inhibit CYP3A4 enzyme activity to result in higher drug concentrations.CYP1A2 substratesFeverfew may inhibit CYP1A2 enzyme activity to result in higher drug concentrations.CYP2C9 substratesFeverfew may inhibit CYP2C9 enzyme activity to result in higher drug concentrations.CYP2C19 substratesFeverfew may inhibit CYP2C19 enzyme activity to result in higher drug concentrations.Fish oils (omega-3 fatty acids)Antiplatelet and anticoagulant agentsFish oils may have antiplatelet activity, potentially increasing the risk of bleeding, although this has not been documented in humans.Antihypertensive agents Fish oils may possess additive effects on blood pressure to those of antihypertensive agents.Oral contraceptivesOral contraceptives may potentially interfere with the triglyceride-lowering effects of fish oil.GarlicAntiplatelet and anticoagulant agentsGarlic may have antiplatelet activity, potentially increasing the risk of bleeding.CYP3A4 substratesGarlic may potentially induce CYP3A4 enzyme activity to result in lower drug concentrations; evidence is contradictory.CYP2E1 substratesGarlic may modestly inhibit CYP2E1 enzyme activity to result in higher drug concentrations.GingerAntiplatelet and anticoagulant agentsGinger may have antiplatelet activity, potentially increasing the risk of bleeding.Hypoglycemic agentsGinger may potentially lower blood glucose concentrations and have additive effects with hypoglycemic agents.GinkgoAntiplatelet and anticoagulant agentsGinkgo may have antiplatelet activity, potentially increasing the risk of bleeding.CYP2C19 substratesGinkgo may induce CYP2C19 enzyme activity to result in lower drug concentrations.CYP1A2 substratesGinkgo may modestly inhibit CYP1A2 enzyme activity to result in higher drug levels.CYP2C9 substratesGinkgo may modestly inhibit CYP2C9 enzyme activity to result in higher drug concentrations.CYP2D6 substratesGinkgo may inhibit CYP2D6 enzyme activity to result in higher drug concentrations.Ginseng (Panax)Antiplatelet and anticoagulant agentsPanax ginseng may have antiplatelet properties; American ginseng may decrease the effectiveness (international normalized ration [INR]) of warfarin.CYP2D6 substratesPanax ginseng may modestly inhibit CYP2D6 enzyme activity to result in higher drug concentrations.Immune suppressantsPanax ginseng may stimulate immune function, potentially decreasing the effectiveness of drugs such as cyclosporine, tacrolimus, and prednisone.Hypoglycemic agentsPanax ginseng may potentially lower blood glucose levels and have additive effects with hypoglycemic agents.GlucosamineWarfarinHigh-dose glucosamine (along with high-dose chondroitin) may have additive effects to those of warfarin because of structural similarity to heparin.Green tea extractAntiplatelet agentsGreen tea possesses compounds that may have antiplatelet activity, potentially increasing the risk of bleeding.AmphetaminesCaffeine in green tea may increase the risk of CNS toxicity.CocaineCaffeine in green tea may increase the risk of CNS toxicity.Oral contraceptivesOral contraceptives may decrease the clearance of caffeine in green tea.WarfarinSmall amounts of vitamin K have been reported to be present in green tea, potentially decreasing the effectiveness of warfarin.TheophyllineCaffeine potentially decreases theophylline clearance.VerapamilVerapamil decreases caffeine clearance, resulting in increased concentrations.Quinolone antibioticsSome quinolone antibiotics decrease the clearance of caffeine.Hepatotoxic drugsConcern exists that the risk of hepatotoxicity with green tea is increased in the presence of hepatotoxic drugs such as acetaminophen.Hawthornβ-blockersHawthorn and β-blockers may have additive effects on blood pressure and heart rate.CCB, nitratesHawthorn and CCB (or nitrates) may have additive effects due to coronary vasodilation.Digoxin Hawthorn may have additive effects to those of digoxin.Phosphodiesterase inhibitorsHawthorn may have additive vasodilatory and hypotensive effects with sildenafil, tadalafil, and vardenafil.Horse chestnut seed extract (HCSE)Antiplatelet and anticoagulant agentsHCSE may have antiplatelet activity, potentially increasing the risk of bleeding.Hypoglycemic agentsHCSE may potentially lower blood glucose concentrations and have additive effects with hypoglycemic agents.HuperzineAChE inhibitors (donepezil, etc.)Huperzine may have additive effects when combined with AChE inhibitors.Anticholinergic drugsThe effectiveness of huperzine and/or the anticholinergic drug may be decreased by their concomitant administration.Cholinergic drugs (bethanechol, neostigmine, etc.)Huperzine may have additive effects when combined with cholinergic drugs.KavaCYP3A4 substratesKava may inhibit CYP3A4 enzyme activity to result in higher drug concentrations.CYP1A2 substratesKava may inhibit CYP1A2 enzyme activity to result in higher drug concentrations.CYP2C9 substrates, CYP2C19 substratesKava may inhibit CYP2C9 and CYP2C19 enzyme activity to result in higher drug concentrations.CYP2D6 substratesKava may inhibit CYP2D6 enzyme activity to result in higher drug concentrations.P-glycoprotein substrates (digoxin; etoposide, paclitaxel, vinblastine, vincristine; itraconazole; diltiazem, verapamil; and many other drugs)Kava may inhibit P-glycoprotein transporter systems.Hepatotoxic drugsConcern exists that the risk of hepatotoxicity from kava is increased in the presence of hepatotoxic drugs such as acetaminophen.MelatoninAntiplatelet and anticoagulant agentsMelatonin may potentiate the effects of antiplatelets and anticoagulants, although the mechanism is unknown.CNS depressantsMelatonin may have additive CNS depressant effects.FluvoxamineFluvoxamine may increase levels of melatonin.Immune suppressantsMelatonin may stimulate immune function, potentially decreasing the effectiveness of drugs such as cyclosporine, tacrolimus, and prednisone.Hypoglycemic agentsMelatonin may impair glucose utilization and may decrease the efficacy of hypoglycemic agents.Milk thistleEstrogens (and other drugs that undergo glucuronidation)Silymarin may increase the clearance of estrogens.CYP2C9 substratesMilk thistle may modestly inhibit CYP2C9 enzyme activity to result in higher drug concentrations.Peppermint oilH2 antagonists and proton pump inhibitorsPeppermint oil may raise gastric pH and blunt efficacy of H2 antagonists and PPI.CYP3A4 substratesPeppermint oil may modestly inhibit CYP3A4 enzyme activity to result in higher drug concentrations.CYP1A2 substratesPeppermint oil may modestly inhibit CYP1A2 enzyme activity to result in higher drug concentrations.CYP2C9 substrates, CYP2C19 substratesPeppermint oil may modestly inhibit CYP2C9 and CYP2C19 enzyme activity to result in higher drug concentrations.PolicosanolAntiplatelet and anticoagulant agentsPolicosanol may have antiplatelet activity, potentially increasing the risk of bleeding.ProbioticsAntibioticsAntibiotics may kill the live organisms in different probiotic preparations.Immune suppressantsTheoretically, probiotics may cause bacterial or fungal infections in patients who are taking immune suppressants chronically.Red clover phytoestrogensAntiplatelet and anticoagulant agentsTheoretically, red clover may possess coumarins, which increase the risk of bleeding with antiplatelet and anticoagulants.Tamoxifen/aromatase inhibitorsCYP3A4 substratesRed clover may inhibit CYP3A4 enzyme activity to result in higher drug concentrations.CYP2C9 substrates, CYP2C19 substratesRed clover may inhibit CYP2C9 and CYP2C19 enzyme activity to result in higher drug concentrations.CYP1A2 substratesRed clover may inhibit CYP1A2 enzyme activity to result in higher drug concentrations.Red yeast riceCYP3A4 inhibitorsDrugs that inhibit CYP3A4 may decrease the metabolism of lovastatin in red yeast rice.StatinsRed yeast rice contains lovastatin and increases the risk of myopathy (and hepatotoxicity).Fibrates and niacinFibrates and niacin may increase concentrations of lovastatin in red yeast rice.S-adenosylmethionine (SAM-e)Antidepressants (including MAOIs)Additive effects are possible, and there is potential for toxicity.Serotonergic drugs (triptans, SSRIs, tramadol, meperidine, dextromethorphan, etc.)SAM-e may increase the risk of development of serotonin syndrome when used concomitantly.Soy phytoestrogensAntibioticsAntibiotics may decrease the efficacy of soy because intestinal bacteria convert isoflavones into more active forms.EstrogensSoy potentially may inhibit the effects of estrogen.Tamoxifen/aromatase inhibitorsSoy’s estrogenic effects may antagonize the antitumor effects of tamoxifen/aromatase inhibitors.MAOIsFermented soy products may contain tyramine.St. John’s wortCYP3A4 substratesSt. John’s wort strongly induces CYP3A4 enzyme activity to result in lower drug concentrations.CYP1A2 substratesSt. John’s wort modestly induces CYP1A2 enzyme activity to result in lower drug levels.CYP2C9 substratesSt. John’s wort induces CYP2C9 enzyme activity to result in lower drug concentrations.P-glycoprotein substrates (digoxin; etoposide, paclitaxel, vinblastine, vincristine; itraconazole; diltiazem, verapamil; and other drugs)St. John’s wort induces P-glycoprotein transporter systems.Serotonergic drugs (triptans, SSRIs, tramadol, meperidine, dextromethorphan, etc.)St. John’s wort may increase the risk of development of serotonin syndrome when used concomitantly.ValerianCNS depressants (benzodiazepines, opiates, barbiturates, alcohol, etc.)Valerian may increase the sedative effects of CNS depressants.CYP3A4 substratesValerian may modestly inhibit the CYP3A4 enzyme activity.AChE, Acetylcholinesterase; CCB, calcium channel blockers; CNS, central nervous system; MAOI, monoamine oxidase inhibitor; PPI, proton pump inhibitors; SSRI, selective serotonin reuptake inhibitors.

The following are example drugs that are metabolized through the different cytochrome P450 isoenzymes:

(For a complete list of drugs and their respective metabolic pathways through the cytochrome P450 isoenzyme systems go to flockhart.)

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