Clinical Advanced Joint Care Ingredients & Drug Interactions

Green tea extract seems to reduce the levels and clinical effects of atorvastatin.
In healthy humans, taking green tea extract 300 mg or 600 mg along with atorvastatin reduces plasma levels of atorvastatin by approximately 24%. The elimination of atorvastatin is not affected. Atorvastatin is a substrate of organic anion-transporting polypeptides (OATPs). Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs. Some OATPs are expressed in the small intestine and are responsible for the uptake of drugs and other compounds, which may have resulted in reduced plasma levels of atorvastatin. It is not clear if drinking green tea alters the absorption of atorvastatin.

Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Green tea contains caffeine. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death.

Green tea seems to reduce the levels and clinical effects of nadolol.
Preliminary clinical research shows that green tea consumption reduces plasma concentrations of nadolol. Compared to a control group, both peak levels and total drug exposure (AUC) of nadolol were reduced by approximately 85% in subjects who drank green tea daily for two weeks. Drinking green tea with nadolol also significantly reduced nadolol's systolic blood pressure lowering effect. Other clinical research shows that a single dose of green tea can affect plasma nadolol levels for at least one hour. Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is involved in the uptake of nadolol in the intestine The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea.

Theoretically, high doses of green tea might increase the effects and side effects of 5-fluorouracil.
Animal research shows that taking green tea in amounts equivalent to about 6 cups daily in humans for 4 weeks prior to receiving a single injection of 5-fluorouracil increases the maximum plasma levels of 5-fluorouracil by about 2.5-fold and the area under the curve by 425%.

Theoretically, green tea might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Green tea contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine doesn't seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing.

Theoretically, green tea may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Conflicting reports exist regarding the effect of green tea on bleeding risk when used with anticoagulant or antiplatelet drugs; however, most evidence suggests that drinking green tea in moderate amounts is unlikely to cause a significant interaction. Green tea contains small amounts of vitamin K, approximately 7 mcg per cup. Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea. However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects. Furthermore, the catechins and caffeine in green tea are reported to have antiplatelet activity.

Green tea contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists.

Theoretically, green tea might interfere with the effects of bortezomib.
In vitro research shows that green tea polyphenols, such as epigallocatechin gallate (EGCG), interact with bortezomib and block its proteasome inhibitory action. This prevents the induction of cell death in multiple myeloma or glioblastoma cancer cell lines. Advise patients taking bortezomib, not to take green tea.

Theoretically, green tea might reduce the effects of carbamazepine and increase the risk for convulsions.
Green tea contains caffeine. Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg. Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine 2-fold in healthy individuals.

Theoretically, green tea might reduce the levels and clinical effects of celiprolol.
In a small human study, taking green tea daily for 4 days appears to decrease blood and urine levels of celiprolol by at least 98%. This interaction is possibly due to the inhibition of organic anion transporting polypeptide (OATP). Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is found in the intestine The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea.

Theoretically, concomitant use might increase the effects and adverse effects of caffeine in green tea.
Green tea contains caffeine. Cimetidine can reduce caffeine clearance by 31% to 42%.

Theoretically, green tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Animal research suggests that, although green tea extract does not affect the elimination of clozapine, it delays the time to reach peak concentration and reduces the peak plasma levels. Also, concomitant administration of green tea and clozapine might theoretically cause acute exacerbation of psychotic symptoms due to the caffeine in green tea. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine.

Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in green tea.
Green tea contains caffeine. Oral contraceptives can decrease caffeine clearance by 40% to 65%.

Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Green tea contains caffeine. Caffeine is metabolized by cytochrome P450 1A2 (CYP1A2),. Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from green tea and increase caffeine levels.

Theoretically, green tea might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Green tea contains caffeine. Caffeine might inhibit dipyridamole-induced vasodilation. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing.

Theoretically, disulfiram might increase the risk of adverse effects from caffeine.
In human research, disulfiram decreases the clearance and increases the half-life of caffeine.

Theoretically, using green tea with diuretic drugs might increase the risk of hypokalemia.
Green tea contains caffeine. In excessive amounts, caffeine can reduce potassium levels due to stimulation of the sodium-potassium pump. Diuretics can also cause lower potassium levels.

Theoretically, estrogens might increase the levels and adverse effects of caffeine.
Green tea contains caffeine. Estrogen inhibits caffeine metabolism.

Theoretically, green tea might reduce the effects of ethosuximide and increase the risk for convulsions.
Green tea contains caffeine. Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide. However, this effect has not been reported in humans.

Theoretically, green tea might reduce the effects of felbamate and increase the risk for convulsions.
Green tea contains caffeine. Animal research suggests that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate. However, this effect has not been reported in humans.

Green tea can decrease blood levels of fexofenadine.
Clinical research shows that green tea can significantly decrease blood levels and excretion of fexofenadine. Taking green tea extract with a dose of fexofenadine decreased bioavailability of fexofenadine by about 30%. In vitro, green tea inhibits the cellular accumulation of fexofenadine by inhibiting the organic anion transporting polypeptide (OATP) drug transporter. Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs, specifically OATP1A2, OATP1B1, and OATP2B1. In addition, green tea has been shown to reduce the absorption of some drugs that are OATP substrates.

Theoretically, green tea might increase the levels and adverse effects of flutamide.
Green tea contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide. Theoretically, concomitant use of caffeine and flutamide might increase serum concentrations of flutamide and increase the risk adverse effects.

Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Green tea contains caffeine. Fluvoxamine reduces caffeine metabolism.

Theoretically, concomitant use might have additive adverse hepatotoxic effects.
Green tea extract supplements have been linked to several cases of hepatotoxicity and might have additive hepatotoxic effects with other drugs..

Theoretically, green tea might reduce the levels and clinical effects of imatinib.
In animal research, a single dose of green tea extract reduces the area under the curve (AUC) of imatinib by up to approximately 64% and its main metabolite N-desmethyl imatinib by up to approximately 81%. This interaction has not been shown in humans. The mechanism of action is unclear but may involve multiple pathways.

Theoretically, taking European barberry with anticholinergic drugs might cause additive effects.
In vitro evidence suggests that European barberry might have anticholinergic properties.

Theoretically, European barberry may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal evidence suggest that berberine, a constituent of European barberry, might inhibit platelet aggregation. Theoretically, European barberry might have a similar effect.

Theoretically, taking European barberry with antidiabetes drugs might increase the risk of hypoglycemia.
Preliminary clinical evidence suggests that European barberry juice reduces fasting glucose levels in patients with type 2 diabetes who are also taking antidiabetes drugs. Additionally, some animal studies show that berberine, a constituent of European barberry, has antiglycemic potential. Monitor blood glucose levels closely.

Theoretically, taking European barberry with antihypertensive drugs might increase the risk of hypotension.
Animal and human research suggests that European barberry extracts can have hypotensive effects.

Theoretically, taking European barberry with cholinergic drugs might decrease the effects of cholinergic drugs.
In vitro evidence suggests that European barberry might have anticholinergic properties.

Theoretically, concomitant use with drugs that have sedative properties may cause additive effects.
Animal research suggests that berberine, a constituent of European barberry, might have sedative effects. Theoretically, European barberry might have a similar effect.

Theoretically, concomitant use with cyclosporine may cause additive effects.
Berberine, a constituent of European barberry, can reduce the metabolism and increase serum levels of cyclosporine. This effect is attributed to the ability of berberine to inhibit cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine. Theoretically, European barberry might have a similar effect.

Theoretically, European barberry might increase the levels and clinical effects of CYP3A4 substrates.
There is very preliminary evidence suggesting that berberine, a constituent of European barberry, might inhibit the CYP3A4 enzyme. Theoretically, European barberry might have a similar effect.

Theoretically, phellodendron might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
Phellodendron contains berberine. In vitro and in vivo research suggest that berberine can inhibit platelet aggregation. Theoretically, phellodendron might also inhibit platelet aggregation.

Theoretically, phellodendron may increase the risk of hypoglycemia when taken with antidiabetes drugs.
Phellodendron contains berberine. Clinical research shows that berberine may lower blood glucose levels. Theoretically, phellodendron might also lower blood glucose levels.

Theoretically, phellodendron might have additive effects with antihypertensive drugs.
Phellodendron contains berberine. Animal research suggests that berberine can have hypotensive effects. Also, a clinical study suggests that taking berberine in combination with amlodipine can lower systolic and diastolic blood pressure when compared with amlodipine alone. Theoretically, phellodendron might also reduce blood pressure.

Theoretically, phellodendron might increase the sedative effects of CNS depressants.
Phellodendron contains berberine. Animal research suggests that berberine may have sedative effects. Theoretically, phellodendron might also have CNS depressants effects.

Theoretically, phellodendron might increase blood levels of cyclosporine.
Phellodendron contains berberine. Preliminary clinical research shows that berberine can reduce metabolism of cyclosporine and increase serum levels, likely through inhibition of cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine. Theoretically, phellodendron might also reduce the metabolism of cyclosporine.

Theoretically, phellodendron might increase serum levels of drugs metabolized by CYP2C9.
Phellodendron contains berberine. Preliminary clinical research shows that berberine can inhibit CYP2C9. Theoretically, phellodendron might also inhibit CYP2C9.

Theoretically, phellodendron might increase serum levels of drugs metabolized by CYP2D6.
Phellodendron contains berberine. In vitro research and preliminary clinical evidence show that berberine can inhibit CYP2D6. Theoretically, phellodendron might also inhibit CYP2D6.

Theoretically, phellodendron might increase serum levels of drugs metabolized by CYP3A4.
Phellodendron contains berberine. In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4. Theoretically, phellodendron might also inhibit CYP3A4.

Theoretically, phellodendron may increase serum levels of dextromethorphan.
Phellodendron contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 2D6 (CYP2D6) activity and reduce the metabolism of dextromethorphan. Theoretically, phellodendron may also inhibit the metabolism of dextromethorphan.

Theoretically, phellodendron might reduce the therapeutic effects of losartan by decreasing its conversion to its active form.
Phellodendron contains berberine. Preliminary clinical research suggests that berberine can inhibit cytochrome P450 2C9 (CYP2C9) activity and reduce metabolism of losartan. Theoretically, phellodendron might also inhibit the metabolism of losartan.

Theoretically, phellodendron might increase the therapeutic and adverse effects of metformin.
Phellodendron contains berberine. In vitro and animal studies show that berberine can increase the systemic exposure and half-life of metformin, potentially increasing metformin's effects and side effects. This interaction seems to be most apparent when berberine is administered 2 hours prior to metformin. Taking berberine and metformin at the same time does not appear to increase systemic exposure to metformin. It is unclear if phellodendron might have this same effect.

Theoretically, phellodendron might reduce metabolism of midazolam, which might increase the risk of severe adverse effects.
Phellodendron contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 3A4 (CYP3A4) activity and reduce metabolism of midazolam. Theoretically, phellodendron might also inhibit the metabolism of midazolam.

Theoretically, phellodendron might increase the sedative effect of pentobarbital.
Phellodendron contains berberine. Animal research shows that berberine can prolong pentobarbital-induced sleeping time. Theoretically, phellodendron might increase the sedative effects of pentobarbital.

Theoretically, phellodendron might increase blood levels of tacrolimus.
Phellodendron contains berberine. In a 16-year-old patient with idiopathic nephrotic syndrome who was being treated with tacrolimus 6.5 mg twice daily, intake of berberine 200 mg three times daily increased the blood concentration of tacrolimus from 8 to 22 ng/mL. Following a reduction of the tacrolimus dose to 3 mg daily, blood levels of tacrolimus decreased to 12 ng/mL. It is unclear if phellodendron might have this same effect.

Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
In vitro research suggests that curcumin, a constituent of turmeric, inhibits mechlorethamine-induced apoptosis of breast cancer cells by up to 70%. Also, animal research shows that curcumin inhibits cyclophosphamide-induced tumor regression. However, some in vitro research shows that curcumin does not affect the apoptosis capacity of etoposide. Also, other laboratory research suggests that curcumin might augment the cytotoxic effects of alkylating agents. Reasons for the discrepancies may relate to the dose of curcumin and the specific chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects. More evidence is needed to determine what effect, if any, turmeric might have on alkylating agents.

Taking turmeric with amlodipine may increase levels of amlodipine.
Animal research shows that giving amlodipine 1 mg/kg as a single dose following the use of turmeric extract 200 mg/kg daily for 2 weeks increases the maximum concentration and area under the curve by 53% and 56%, respectively, when compared with amlodipine alone. Additional animal research shows that taking amlodipine 1 mg/kg with a curcumin 2 mg/kg pretreatment for 10 days increases the maximum concentration and area under the curve by about 2-fold when compared with amlodipine alone.

Turmeric may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Curcumin, a constituent of turmeric, has demonstrated antiplatelet effects in vitro. Furthermore, two case reports have found that taking turmeric along with warfarin or fluindione was associated with an increased international normalized ratio (INR). However, one clinical study in healthy volunteers shows that taking curcumin 500 mg daily for 3 weeks, alone or with aspirin 100 mg, does not increase antiplatelet effects or bleeding risk. It is possible that the dose of turmeric used in this study was too low to produce a notable effect.

Theoretically, taking turmeric with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research and case reports suggest that curcumin, a turmeric constituent, can reduce blood glucose levels in patients with diabetes. Furthermore, clinical research in adults with type 2 diabetes shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg decreased postprandial glucose levels for up to 24 hours when compared with glyburide alone, despite the lack of a significant pharmacokinetic interaction. Other clinical studies in patients with diabetes show that taking curcumin daily can reduce blood glucose levels when compared with placebo.

Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
In vitro and animal research shows that curcumin, a constituent of turmeric, inhibits doxorubicin-induced apoptosis of breast cancer cells by up to 65%. However, curcumin does not seem to affect the apoptosis capacity of daunorubicin. In fact, some research shows that curcumin might augment the cytotoxic effects of antitumor antibiotics, increasing their effectiveness. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects. More evidence is needed to determine what effects, if any, antioxidants such as turmeric have on antitumor antibiotics.

Turmeric might increase or decrease levels of drugs metabolized by CYP3A4.
In vitro and animal research show that turmeric and its constituents curcumin and curcuminoids inhibit CYP3A4. Also, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking turmeric and cancer medications that are CYP3A4 substrates, including everolimus, ruxolitinib, ibrutinib, and palbociclib, and bortezomib. In another case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels after consuming turmeric powder at a dose of 15 or more spoonfuls daily for ten days prior. It was thought that turmeric increased levels of tacrolimus due to CYP3A4 inhibition.
Conversely, other in vitro research suggests that turmeric induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates. An animal model suggests that induction of CYP3A4 occurs after daily curcumin use for 1 week. However, the induction of CYP3A4 by turmeric has not been reported in humans.

Theoretically, turmeric might increase the risk of liver damage when taken with hepatotoxic drugs.
There is concern that turmeric might cause hepatotoxicity, especially when highly bioavailable formulations are used in high doses.

Theoretically, turmeric might have additive effects when used with hepatotoxic drugs such as methotrexate.
In one case report, a 39-year-old female taking methotrexate, turmeric, and linseed oil developed hepatotoxicity.

Theoretically, turmeric might increase blood levels of OATP4C1 substrates.
In vitro research shows that the turmeric constituent curcumin competitively inhibits OATP4C1 transport. This transporter is expressed in the kidney and facilitates the renal excretion of certain drugs. Theoretically, taking turmeric might decrease renal excretion of OATP substrates.

Turmeric might increase the effects and adverse effects of sulfasalazine.
Clinical research shows that taking the turmeric constituent, curcumin, can increase blood levels of sulfasalazine by 3.2-fold.

Turmeric might increase the effects and adverse effects of tacrolimus.
In one case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels of 29 ng/mL. The patient previously had tacrolimus levels within the therapeutic range at 9.7 ng/mL. Ten days prior to presenting at the emergency room the patient started consumption of turmeric powder at a dose of 15 or more spoonfuls daily. It was thought that turmeric increased levels of tacrolimus due to cytochrome P450 3A4 (CYP3A4) inhibition. In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4.

Turmeric may reduce the absorption of talinolol in some situations.
Clinical research shows that taking curcumin for 6 days decreases the bioavailability of talinolol when taken together on the seventh day. The clinical significance of this effect is unclear.

Theoretically, turmeric might reduce the levels and clinical effects of tamoxifen.
In a small clinical trial in patients with breast cancer taking tamoxifen 20-30 mg daily, adding curcumin 1200 mg plus piperine 10 mg three times daily reduces the 24-hour area under the curve of tamoxifen and the active metabolite endoxifen by 12.8% and 12.4%, respectively, as well as the maximum concentrations of tamoxifen, when compared with tamoxifen alone. However, in the absence of piperine, the area under the curve for endoxifen and the maximum concentration of tamoxifen were not significantly reduced. Effects were most pronounced in patients who were extensive cytochrome P450 (CYP) 2D6 metabolizers.

Turmeric has antioxidant effects. There is some concern that this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
In vitro research shows that curcumin, a constituent of turmeric, inhibits camptothecin-induced apoptosis of breast cancer cells by up to 71%. However, other in vitro research shows that curcumin augments the cytotoxic effects of camptothecin. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agents. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects. More evidence is needed to determine what effect, if any, turmeric might have.

Theoretically, turmeric might increase or decrease levels of tramadol.
Animal research suggests that a single dose of curcumin, a constituent of turmeric, may increase tramadol's maximum concentration (Cmax) by inhibiting metabolism, while continued daily use for 7 days may reduce the area under the curve (AUC) due to the induction of drug-metabolizing enzymes such as cytochrome P450 3A4 (CYP3A4). However, this interaction has not been reported in humans.

Turmeric might increase the risk of bleeding with warfarin.
One case of increased international normalized ratio (INR) has been reported for a patient taking warfarin who began taking turmeric. Prior to taking turmeric, the patient had stable INR measurements. Within a few weeks of starting turmeric supplementation, the patient's INR increased to 10. Additionally, curcumin, the active constituent in turmeric, has demonstrated antiplatelet effects in vitro, which may produce additive effects when taken with warfarin.

Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.
In vitro and animal research show that the turmeric constituent, curcumin, inhibits CYP1A2. However, other in vitro research suggests that curcumin does not significantly affect CYP1A2.

Theoretically, turmeric might increase blood levels of oral docetaxel.
Animal research suggests that the turmeric constituent, curcumin, enhances the oral bioavailability of docetaxel. However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

Theoretically, large amounts of turmeric might interfere with hormone replacement therapy through competition for estrogen receptors.
In vitro research shows that curcumin, a constituent of turmeric, displaces the binding of estrogen to its receptors.

Theoretically, taking turmeric and glyburide in combination might increase the risk of hypoglycemia.
Clinical research shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg increases blood levels of glyburide by 12% at 2 hours after the dose in patients with type 2 diabetes. While maximal blood concentrations of glyburide were not affected, turmeric modestly decreased postprandial glucose levels for up to 24 hours when compared to glyburide alone, possibly due to the hypoglycemic effect of turmeric demonstrated in animal research.

Theoretically, turmeric might increase the effects of losartan.
Research in hypertensive rats shows that taking turmeric can increase the hypotensive effects of losartan.

Theoretically, turmeric might increase the effects and adverse effects of norfloxacin.
Animal research shows that taking curcumin, a turmeric constituent, can increase blood levels of orally administered norfloxacin.

Theoretically, turmeric might increase the absorption of P-glycoprotein substrates.
In vitro and animal research shows that curcuminoids and other constituents found in turmeric can inhibit P-glycoprotein expression and activity.

Theoretically, turmeric might alter blood levels of paclitaxel, although any effect may not be clinically relevant.
Clinical research in adults with breast cancer receiving intravenous paclitaxel suggests that taking turmeric may modestly alter paclitaxel pharmacokinetics. Patients received paclitaxel on day 1, followed by either no treatment or turmeric 2 grams daily from days 2-22. Pharmacokinetic modeling suggests that turmeric reduces the maximum concentration and area under the curve of paclitaxel by 12.1% and 7.7%, respectively. However, these changes are not likely to be considered clinically relevant. Conversely, animal research suggests that curcumin, a constituent of turmeric, enhances the oral bioavailability of paclitaxel. However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation. However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials. Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.

Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.
Animal and human research suggests that ginger might increase insulin levels and/or decrease blood glucose levels.

Ginger might increase or decrease the levels of CYP3A4 substrates.
In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity. Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration.
Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates. However, this interaction has not been reported in humans.

Theoretically, ginger might increase levels of losartan and the risk of hypotension.
In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan. It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.

Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.
Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone.

Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.
In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates. Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration.

Ginger might increase the risk of bleeding with phenprocoumon.
Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea.

Ginger might increase the risk of bleeding with warfarin.
Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation. In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin. In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen. A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months. However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin. Until more is known, monitor INRs closely in patients taking large amounts of ginger.

Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.
Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects. Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone.

Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.
In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time.

Theoretically, ginger might increase the levels of CYP1A2 substrates.
In vitro research shows that ginger inhibits CYP1A2 activity. However, this interaction has not been reported in humans.

Theoretically, ginger might increase the levels of CYP2B6 substrates.
In vitro research shows that ginger inhibits CYP2B6 activity. However, this interaction has not been reported in humans.

Theoretically, ginger might increase the levels of CYP2C9 substrates.
In vitro research shows that ginger inhibits CYP2C9 activity. However, this interaction has not been reported in humans.

Theoretically, ginger might increase levels of metronidazole.
In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced.

Theoretically, Boswellia serrata might increase the levels of CYP1A2 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP1A2 enzymes.

Theoretically, Boswellia serrata might increase the levels of CYP2C19 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP2C19 enzymes.

Theoretically, Boswellia serrata might increase the levels of CYP2C9 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP2C9 enzymes.

Theoretically, Boswellia serrata might increase the levels of CYP2D6 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP2D6 enzymes.

Theoretically, Boswellia serrata might increase or decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP3A4 enzymes. Other in vitro research shows that Boswellia serrata extract inhibits CYP3A4 enzymes at most concentrations, although it may modestly induce enzyme activity at low concentrations.

Theoretically, Boswellia serrata might alter the effects of immunosuppressive drugs.
Some in vitro research suggests that Boswellia serrata extracts might inhibit mediators of autoimmune disorders such as leukotrienes and reduce production of antibodies and cell-mediated immunity. However, other in vitro research suggests that, when coupled with calcium ions, boswellic acids containing the keto group have immunostimulant properties within specific cell signaling pathways.

Theoretically, feverfew might have additive effects and increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
Laboratory research suggests that feverfew may inhibit platelet aggregation. Additionally, in one case report, a 36-year-old patient taking feverfew 2400 mg daily for 3 months experienced vaginal bleeding and a prolonged menstrual cycle, with a modest increase in partial thromboplastin time (PTT) and prothrombin time (PT).

Theoretically, feverfew might increase levels of drugs metabolized by CYP1A2.
Laboratory research shows that feverfew might inhibit CYP1A2. So far, this interaction has not been reported in humans.

Theoretically, feverfew might increase levels of drugs metabolized by CYP2C19.
Laboratory research shows that feverfew might inhibit CYP2C19. So far, this interaction has not been reported in humans.

Theoretically, feverfew might increase levels of drugs metabolized by CYP2C8.
Laboratory research shows that feverfew might inhibit CYP2C8. So far, this interaction has not been reported in humans.

Theoretically, feverfew might increase levels of drugs metabolized by CYP2C9.
Laboratory research shows that feverfew might inhibit CYP2C9. So far, this interaction has not been reported in humans.

Theoretically, feverfew might increase levels of drugs metabolized by CYP2D6.
Laboratory research shows that feverfew might inhibit CYP2D6. So far, this interaction has not been reported in humans.

Theoretically, feverfew might increase levels of drugs metabolized by CYP3A4.
Laboratory research shows that feverfew might inhibit CYP3A4. So far, this interaction has not been reported in humans.

Theoretically, concomitant use of hops with sedative drugs might cause additive sedation.
Some animal research shows that hops has sedative effects.

Theoretically, concomitant use of large amounts of hops might interfere with hormone replacement therapy due to competition for estrogen receptors.
In vitro research suggests that certain hops constituents can competitively bind to estrogen receptors. However, most hops extracts contain very small amounts of these constituents.

Hops extract does not seem to affect the metabolism of CYP1A2 substrates.
In vitro research suggests that flavonoid constituents of hops inhibit CYP1A2 enzyme activity. However, a pharmacokinetic study in healthy postmenopausal patients shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, does not affect levels of caffeine, a CYP1A2 probe substrate.

Theoretically, hops extract might alter metabolism of CYP3A4 substrates; however, this effect may not be clinically significant.
Animal research suggests that specific constituents of hops, called lupulones, can induce hepatic CYP3A4 enzyme activity. However, a pharmacokinetic study in healthy postmenopausal patients with normal metabolism shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, decreases the concentration of alprazolam, a CYP3A4 probe substrate, by 7.6%. This reduction is unlikely to be clinically relevant.

Resveratrol may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Resveratrol seems to have antiplatelet effects.

Theoretically, resveratrol might increase levels of drugs metabolized by CYP1A2.
In vitro research shows that resveratrol can inhibit CYP1A2 enzymes. However, this interaction has not been reported in humans.

Theoretically, resveratrol might increase levels of drugs metabolized by CYP2C19.
In vitro research shows that resveratrol can inhibit CYP2C19 enzymes. However, this interaction has not been reported in humans.

Resveratrol might increase levels of drugs metabolized by CYP2E1.
In vitro research suggests that resveratrol inhibits CYP2E1 isoenzyme. Also, a pharmacokinetic study shows that taking resveratrol 500 mg daily for 10 days prior to taking a single dose of chlorzoxazone 250 mg increases the maximum concentration of chlorzoxazone by about 54%, the area under the curve of chlorzoxazone by about 72%, and the half-life of chlorzoxazone by about 35%. Chlorzoxazone is used as a probe drug for CYP2E1.

Theoretically, resveratrol might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that resveratrol can inhibit the CYP3A4 enzyme. However, clinical research shows that taking resveratrol 3000 mg daily for 8 weeks does not necessitate dose adjustments to medications metabolized by CYP3A4.

Theoretically, devil's claw might increase levels of drugs metabolized by CYP2C19.
In vitro research shows that devil's claw might inhibit CYP2C19, although this has not been reported in humans.

Theoretically, devil's claw might increase levels of drugs metabolized by CYP2C9.
In vitro research shows that devil's claw might inhibit CYP2C9, although this has not been reported in humans.

Theoretically, devil's claw might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that devil's claw might inhibit CYP3A4, although this has not been reported in humans.

Theoretically, Devil's claw might increase the activity of warfarin.
In one case report, purpura occurred in a patient taking warfarin and devil's claw concurrently. This might indicate over-anticoagulation. It is unclear if this was due to Devil's claw or other contributing factors.

Theoretically, devil's claw might decrease the effectiveness of H2-blockers.
Devil's claw has been reported to increase stomach acid, which might interfere with the effects of H2-blockers.

Theoretically, devil's claw might increase levels of P-glycoprotein substrates.
In vitro research shows that devil's claw inhibits P-glycoprotein, which transports many drugs out of cells. This might increase intracellular levels of P-glycoprotein substrates, although it is unclear if this effect would be clinically important.

Theoretically, devil's claw might decrease the effectiveness of PPIs.
Devil's claw has been reported to increase stomach acid, which might interfere with the effects of PPIs.

Berberine, a constituent of goldthread, can reduce metabolism of cyclosporine and increase serum levels. It might inhibit cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine.

There's very preliminary evidence that berberine, a constituent of goldthread, might inhibit cytochrome P450 3A4 (CYP3A4) enzyme. So far, this interaction has not been reported in humans. However, watch for an increase in the levels of drugs metabolized by CYP3A4 in patients taking goldthread. Some drugs metabolized by CYP3A4 include lovastatin (Mevacor), clarithromycin (Biaxin), indinavir (Crixivan), sildenafil (Viagra), triazolam (Halcion), and numerous others. Use goldthread cautiously or avoid in patients taking these drugs.

Theoretically, rosemary may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research suggests that rosemary inhibits platelet aggregation.

Theoretically, taking rosemary with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research shows that rosemary extract can decrease blood glucose levels in diabetic models. However, research in humans is conflicting. Although rosemary powder decreased blood glucose levels in healthy adults, no change in blood glucose levels was seen in adults with type 2 diabetes, most of whom were taking antidiabetes drugs.

Theoretically, rosemary might have additive effects with salicylate-containing drugs such as aspirin.
Rosemary is reported to contain salicylates.

Theoretically, rosemary might have additive effects with salicylate-containing drugs such as choline magnesium trisalicylate.
Rosemary is reported to contain salicylate.

Theoretically, rosemary might have additive effects with salicylate-containing drugs such as salsalate.
Rosemary is reported to contain salicylate.

Theoretically, rosemary might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that rosemary induces CYP1A2 enzymes. This effect has not been reported in humans.

Theoretically, skullcap can have additive effects when used with other CNS depressants.
Animal and clinical research suggests that skullcap can cause sedation and cognitive impairment.

Theoretically, holy basil seed oil might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
Animal research shows that holy basil seed oil can prolong bleeding time, possibly due to inhibition of platelet aggregation. However, it is not known if this occurs in humans.

Theoretically, holy basil might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Small clinical studies show that taking holy basil can decrease fasting blood glucose and other measures of glycemic control in patients with type 2 diabetes.

Theoretically, holy basil seed oil might increase the sedative effects of pentobarbital.
Animal research shows that holy basil seed oil increases pentobarbitone-induced sleeping time. However, it is not known if this occurs in humans or if this applies to other barbiturates or sedatives.

Theoretically, oregano might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
In vitro research shows that aristolochic acid isolated from oregano leaves has antithrombin activity. It has also been reported that oregano oil inhibits arachidonic acid-induced, and ADP-induced, platelet aggregation.

Theoretically, oregano might increase the risk for hypoglycemia when taken with antidiabetes drugs.
In vitro and animal research shows that oregano extracts might lower blood glucose levels.

Glucosamine might increase the anticoagulant effects of warfarin and increase the risk of bruising and bleeding.
In two individual case reports, glucosamine/chondroitin combinations were associated with a significant increase in international normalized ratio (INR) in patients previously stabilized on warfarin. In one case, the increase in INR occurred only after tripling the dose of a glucosamine/chondroitin supplement from 500 mg/400 mg daily to 1500/1200 mg daily. Additionally, 20 voluntary case reports to the U.S. Food & Drug Administration (FDA) have linked glucosamine plus chondroitin with increased INR, bruising, and bleeding in patients who were also taking warfarin. There have also been 20 additional case reports to the World Health Organization (WHO) that link glucosamine alone to increased INR in patients taking warfarin. The mechanism of this interaction is unclear. Glucosamine is a small component of heparin, but is not thought to have anticoagulant activity; however, animal research suggests that it might have antiplatelet activity.

Theoretically glucosamine may induce resistance to topoisomerase II inhibitors.
In vitro research suggests that glucosamine might induce resistance to etoposide (VP16, VePesid) and doxorubicin (Adriamycin) by reducing inhibition of topoisomerase II, an enzyme required for DNA replication in tumor cells. This effect has not been reported in humans.

Acetaminophen might interfere with the activity of glucosamine sulfate by interacting with the sulfate portion.
Anecdotal reports suggest that adding glucosamine to an acetaminophen regimen might decrease pain control in patients with osteoarthritis. Some research suggests that the sulfate portion of glucosamine sulfate might contribute to its effect in osteoarthritis. Since acetaminophen metabolism requires sulfur and reduces serum sulfate concentrations, acetaminophen could theoretically interfere with the action of glucosamine sulfate. Conversely, the administration of sulfate could theoretically decrease the effectiveness of acetaminophen in sulfate-deficient people by increasing its clearance.

Despite initial concerns, it is unlikely that glucosamine will interfere with the effects of antidiabetes drugs.
In vitro and animal research has suggested that glucosamine might increase insulin resistance or decrease insulin production. This has raised concerns that taking glucosamine might worsen diabetes and decrease the effectiveness of diabetes drugs. However, clinical research suggests that glucosamine does not have adverse effects on blood glucose or glycated hemoglobin (HbA1C) in healthy, obese, or type 2 diabetes patients.

Theoretically, stinging nettle might have additive effects with antidiabetes drugs.
Clinical research shows that stinging nettle might decrease blood glucose levels in patients with diabetes.

Theoretically, combining stinging nettle with diuretic drugs may have additive effects.
Animal research suggests that the above ground parts and roots of stinging nettle may have a diuretic effect.

Theoretically, stinging nettle might reduce excretion and increase levels of lithium.
Animal research suggests that stinging nettle has diuretic and natriuretic properties, which could alter the excretion of lithium. The dose of lithium might need to be decreased.

There is some concern that stinging nettle might decrease the effects of anticoagulant drugs such as warfarin.
Stinging nettle contains a significant amount of vitamin K. When taken in large quantities, this might interfere with the activity of warfarin.

Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
There is one case report of a patient experiencing minor bruising while taking bromelain with naproxen. Bromelain is thought to have antiplatelet activity. Whether this interaction is of concern with topical bromelain is unclear. Interference with coagulation of burn wounds has been reported in a patient receiving bromelain-based enzymatic debridement. However, observational research has found that topical bromelain debridement is not associated with increases or decreases in laboratory markers of coagulation when compared with surgical debridement.

Theoretically, bromelain might increase levels of tetracycline antibiotics.
Laboratory research suggests that bromelain might increase the absorption of tetracycline antibiotics. However, a study in healthy adults reported no difference in tetracycline plasma levels when a 500 mg dose was taken with or without bromelain 80 mg.

Taking chondroitin in combination with glucosamine might increase the anticoagulant effects of warfarin. However, the effect of chondroitin alone is unclear.
There have been multiple reports of increased international normalized ratio (INR) in patients taking warfarin with glucosamine, with or without chondroitin. The lack of reports with chondroitin alone seem to suggest that the interactions occurring in these reports may have been due to glucosamine. In two individual case reports, glucosamine/chondroitin combinations were associated with a significant increase in INR in patients previously stabilized on warfarin. Additionally, 20 voluntary case reports to the US Food & Drug Administration (FDA) have linked glucosamine plus chondroitin with increased INR, bruising, and bleeding in patients who were also taking warfarin. There have also been 20 additional case reports to the World Health Organization (WHO) that link glucosamine alone, without chondroitin, to increased INR in patients taking warfarin.