BrainAid Ingredients & Drug Interactions

Taking ginkgo with talinolol seems to increase blood levels of talinolol.
There is some evidence that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of talinolol by 36% in healthy male individuals. However, single doses of ginkgo do not seem to affect talinolol pharmacokinetics.

Theoretically, ginkgo might decrease the levels and clinical effects of alprazolam.
In clinical research, ginkgo extract (Ginkgold) 120 mg twice daily seems to decrease alprazolam levels by about 17%. However, ginkgo does not appear to decrease the elimination half-life of alprazolam. This suggests that ginkgo is more likely to decrease absorption of alprazolam rather than induce hepatic metabolism of alprazolam.

Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin. Theoretically, ginkgo might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs.
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. Several case reports have documented serious bleeding events in patients taking ginkgo. However, population and clinical studies have produced mixed results. Some evidence shows that short-term use of ginkgo leaf does not significantly reduce platelet aggregation and blood clotting. A study in healthy males who took a specific ginkgo leaf extract (EGb 761) 160 mg twice daily for 7 days found no change in prothrombin time. An analysis of a large medical record database suggests that ginkgo increases the risk of a bleeding adverse event by 38% when taken concurrently with warfarin. It has been suggested that ginkgo has to be taken for at least 2-3 weeks to have a significant effect on platelet aggregation. However, a meta-analysis of 18 studies using standardized ginkgo extracts, 80-480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT. In addition, a single dose of ginkgo plus clopidogrel or ticlopidine does not seem to significantly increase bleeding time or platelet aggregation. Also, taking ginkgo leaf extract daily for 8 days in conjunction with rivaroxaban does not affect anti-factor Xa activity; however, this study did not evaluate bleeding time.

Theoretically, ginkgo might reduce the effectiveness of anticonvulsants.
Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves. Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity. However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy.

Theoretically, taking ginkgo with antidiabetes drugs might alter the response to antidiabetes drugs.
Ginkgo leaf extract seems to alter insulin secretion and metabolism, and might affect blood glucose levels in people with type 2 diabetes. The effect of ginkgo seems to differ depending on the insulin and treatment status of the patient. In diet-controlled diabetes patients with hyperinsulinemia, taking ginkgo does not seem to significantly affect insulin or blood glucose levels. In patients with hyperinsulinemia who are treated with oral hypoglycemic agents, taking ginkgo seems to decrease insulin levels and increase blood glucose following an oral glucose tolerance test. Researchers speculate that this could be due to ginkgo-enhanced hepatic metabolism of insulin. In patients with pancreatic exhaustion, taking ginkgo seems to stimulate pancreatic beta-cells, resulting in increased insulin and C-peptide levels, but with no significant change in blood glucose levels in response to an oral glucose tolerance test.

Theoretically, ginkgo might decrease the levels and clinical effects of atorvastatin.
In humans, intake of ginkgo extract appears to increase atorvastatin clearance, reducing the area under the curve of atorvastatin by 10% to 14% and the maximum concentration by 29%. However, this interaction does not appear to affect cholesterol synthesis and absorption. Further, a model in rats with hyperlipidemia suggests that administering ginkgo extract does not impact blood levels of atorvastatin and leads to lower total cholesterol, low-density lipoprotein cholesterol, and triglycerides when compared with rats given atorvastatin alone.

Theoretically, ginkgo might increase levels of drugs metabolized by CYP1A2.
Laboratory research suggests that ginkgo leaf extract can mildly inhibit CYP1A2 enzymes. However, clinical research suggests ginkgo might not affect CYP1A2. Until more is known, use ginkgo cautiously in patients taking drugs metabolized by these enzymes.

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP2C19.
Some clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce CYP2C19 enzymes and potentially decrease levels of drugs metabolized by these enzymes. However, other clinical research shows that taking ginkgo 120 mg twice daily for 12 days has no effect on levels of drugs metabolized by CYP2C19.

Theoretically, ginkgo might increase levels of drugs metabolized by CYP2C9.
In vitro, a specific standardized extract of ginkgo leaf (EGb 761) inhibits CYP2C9 activity . The terpenoid (ginkgolides) and flavonoid (quercetin, kaempferol, etc.) constituents seem to be responsible for this effect. Most ginkgo extracts contain some amount of these constituents. Therefore, other ginkgo leaf extracts might also inhibit the CYP2C9 enzyme. However, clinical research suggests that ginkgo might not have a significant effect on CYP2C9 in humans. Ginkgo does not seem to significantly affect the pharmacokinetics of CYP2C9 substrates diclofenac or tolbutamide.

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP3A4.
There is conflicting evidence about whether ginkgo induces or inhibits CYP3A4. Ginkgo does not appear to affect hepatic CYP3A4. However, it is not known if ginkgo affects intestinal CYP3A4. Preliminary clinical research suggests that taking ginkgo does not significantly affect levels of donepezil, lopinavir, or ritonavir, which are all CYP3A4 substrates. Other clinical research also suggests ginkgo does not significantly affect CYP3A4 activity. However, there are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4).

Theoretically, ginkgo might decrease the levels and clinical effects of efavirenz.
There are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. In one case, an HIV-positive male experienced over a 50% decrease in efavirenz levels over the course of 14 months while taking ginkgo extract. HIV-1 RNA copies also increased substantially, from less than 50 to more than 1500. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4). In another case report, a patient stable on antiviral therapy including efavirenz for 10 years, had an increase in viral load from <50 copies/mL to 1350 copies/mL after 2 months of taking a combination of supplements including ginkgo. After stopping ginkgo, the viral load was again controlled with the same antiviral therapy regimen.

Theoretically, ginkgo might increase the risk of bleeding when used with ibuprofen.
Ginkgo might have antiplatelet effects and has been associated with several case reports of spontaneous bleeding. In one case, a 71-year-old male had taken a specific ginkgo extract (Gingium, Biocur) 40 mg twice daily for 2.5 years. About 4 weeks after starting ibuprofen 600 mg daily he experienced a fatal intracerebral hemorrhage. However, the antiplatelet effects of ginkgo have been questioned. A meta-analysis and other studies have not found a significant antiplatelet effect with standardized ginkgo extracts, 80 mg to 480 mg taken daily for up to 32 weeks.

Theoretically, taking ginkgo with P-glycoprotein substrates might increase the levels and adverse effects of these substrates.
A small clinical study in healthy volunteers shows that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of the P-glycoprotein substrate, talinolol, by 36% in healthy male individuals. However, single doses of ginkgo do not have the same effect.

Theoretically, taking ginkgo with risperidone might increase the levels and adverse effects of risperidone.
A single case of priapism has been reported for a 26-year-old male with schizophrenia who used risperidone 3 mg daily along with ginkgo extract 160 mg daily. Risperidone is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4. CYP3A4 activity might be affected by ginkgo. Theoretically, ginkgo may inhibit the metabolism of risperidone and increase the risk of adverse effects.

Theoretically, ginkgo might decrease the levels and clinical effects of rosiglitazone.
Animal research shows that ginkgo leaf extract orally 100 or 200 mg/kg daily for 10 days alters the pharmacodynamics of rosiglitazone in a dose-dependent manner. The 100 mg/kg and 200 mg/kg doses reduce the area under the concentration time curve (AUC) of rosiglitazone by 39% and 52%, respectively, and the half-life by 28% and 39%, respectively. It is hypothesized that these changes may be due to induction of cytochrome P450 2C8 by ginkgo.

Theoretically, taking ginkgo with drugs that lower the seizure threshold might increase the risk for convulsions.
Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves. Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity. However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy.

Theoretically, ginkgo might decrease the levels and clinical effects of simvastatin.
Clinical research shows that taking ginkgo extract can reduce the area under the curve and maximum concentration of simvastatin by 32% to 39%. However, ginkgo extract does not seem to affect the cholesterol-lowering ability of simvastatin.

Theoretically, ginkgo might increase the levels and clinical effects of sofosbuvir.
Animal research in rats shows that giving a ginkgo extract 25 mg/kg orally daily for 14 days increases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 11%, increases the half-life by 60%, and increases the plasma concentration at 4 hours by 38%. This interaction appears to be related to the inhibition of intestinal P-glycoprotein by ginkgo.

Theoretically, ginkgo might increase the blood levels of tacrolimus.
In vitro evidence suggests that certain biflavonoids in ginkgo leaves (i.e. amentoflavone, ginkgetin, bilobetin) may inhibit the metabolism of tacrolimus by up to 50%. This interaction appears to be time-dependent and due to inhibition of cytochrome P450 (CYP) 3A4 by these bioflavonoids. In rats given tacrolimus 1 mg/kg orally, amentoflavone was shown to increase the area under the concentration time curve (AUC) of tacrolimus by 3.8-fold.

Theoretically, ginkgo might increase the levels and clinical effects of trazodone.
In a case report, an Alzheimer patient taking trazodone 20 mg twice daily and ginkgo leaf extract 80 mg twice daily for four doses became comatose. The coma was reversed by administration of flumazenil (Romazicon). Coma might have been induced by excessive GABA-ergic activity. Ginkgo flavonoids are thought to have GABA-ergic activity and act directly on benzodiazepine receptors. Ginkgo might also increase metabolism of trazodone to active GABA-ergic metabolites, possibly by inducing cytochrome P450 3A4 (CYP3A4) metabolism.

Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin.
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. Several case reports have documented serious bleeding events in patients taking ginkgo. Information from a medical database suggests that when taken concurrently with warfarin, ginkgo increases the risk of a bleeding adverse event by 38%. There is also some evidence that ginkgo leaf extract can inhibit cytochrome P450 2C9, an enzyme that metabolizes warfarin. This could result in increased warfarin levels. However, population and clinical research has produced mixed results. Clinical research in healthy people suggests that ginkgo has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin. A meta-analysis of 18 studies using standardized ginkgo extracts, 80 mg to 480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT. There is also some preliminary clinical research that suggests ginkgo might not significantly increase the effects of warfarin in patients that have a stable INR.

Theoretically, taking ginkgo with oral, but not intravenous, nifedipine might increase levels and adverse effects of nifedipine.
Animal research and some clinical evidence suggests that taking ginkgo leaf extract orally in combination with oral nifedipine might increase nifedipine levels and cause increased side effects, such as headaches, dizziness, and hot flushes. However, taking ginkgo orally does not seem to affect the pharmacokinetics of intravenous nifedipine.

Theoretically, taking ginkgo with omeprazole might decrease the levels and clinical effects of omeprazole.
Clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce cytochrome P450 (CYP) 2C19 enzymes and decrease levels of omeprazole by about 27% to 42%.

Theoretically, concomitant use of quercetin and antidiabetes drugs might increase the risk of hypoglycemia.

Clinical research suggests that a combination of quercetin, myricetin, and chlorogenic acid reduce levels of fasting glucose in patients with type 2 diabetes, including those already taking antidiabetes agents. The effect of quercetin alone is unknown.

Theoretically, taking quercetin with antihypertensive drugs might increase the risk of hypotension.

Quercetin can modestly decrease blood pressure in people with mild hypertension. Theoretically, it might have additive blood pressure lowering effects when used with antihypertensive drugs.

Theoretically, concomitant use might increase the levels and adverse effects of cyclosporine.

A small study in healthy volunteers shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of a single dose of cyclosporine, possibly due to inhibition of p-glycoprotein or cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporin.

Theoretically, concomitant use might increase the levels and adverse effects of CYP2C8 substrates.

In vitro research shows that quercetin inhibits CYP2C8. Inhibition of paclitaxel (Taxol) metabolism via CYP2C8 has been reported in vitro. However, a small study in humans found no effect of quercetin on rosiglitazone (Avandia), which is also a CYP2C8 substrate.

Theoretically, concomitant use might increase the levels and adverse effects of CYP2C9 substrates.

A small clinical study in healthy volunteers shows that taking quercetin 500 mg twice daily for 10 days prior to taking diclofenac, a CYP2C9 substrate, increases diclofenac plasma levels by 75% and prolongs the half-life by 32.5%. Animal research also shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar), a substrate of CYP2C9. Furthermore, laboratory research shows that quercetin inhibits CYP2C9.

Theoretically, concomitant use might increase the levels and adverse effects of CYP2D6 substrates.

In vitro research show that quercetin inhibits CYP2D6. This effect has not been reported in humans.

Theoretically, concomitant use might alter the effects and adverse effects of CYP3A4 substrates.
A small clinical study in healthy volunteers shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of a single dose of cyclosporine (Neoral, Sandimmune), a substrate of CYP3A4. Animal research also shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar) and quetiapine (Seroquel), substrates of CYP3A4. Other laboratory research also shows that quercetin inhibits CYP3A4. However, one clinical study shows that quercetin can increase the metabolism of midazolam, a substrate of CYP3A4, and decrease serum concentrations of midazolam by about 24% in some healthy individuals, suggesting possible induction of CYP3A4.

Theoretically, concomitant use might increase the levels and adverse effects of diclofenac.

A small clinical study in healthy volunteers shows that taking quercetin 500 mg twice daily for 10 days prior to taking diclofenac increases diclofenac plasma levels by 75% and prolongs the half-life by 32.5%. This is thought to be due to inhibition of CYP2C9 by quercetin.

Theoretically, concomitant use might increase the effects and adverse effects of losartan and decrease the effects of its active metabolite.

Animal research shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar) while decreasing plasma levels of losartan's active metabolite. This metabolite, which is around 10-fold more potent than losartan, is the result of cytochrome P450 (CYP) 2C9- and CYP3A4-mediated transformation of losartan. Additionally, in vitro research shows that quercetin may inhibit P-glycoprotein-mediated efflux of losartan from the intestines, resulting in increased absorption of losartan. These results suggest that concomitant use of quercetin and losartan might increase systemic exposure to losartan while also decreasing plasma concentrations of losartan's active and more potent metabolite.

Theoretically, concomitant use might decrease the levels and effects of midazolam.

A small clinical study in healthy volunteers shows that quercetin can increase the metabolism of midazolam, with a decrease in AUC of about 24%.

Theoretically, quercetin might increase the effects and adverse effects of mitoxantrone.
In vitro research shows that quercetin increases the intracellular accumulation and cytotoxicity of mitoxantrone, possibly through inhibition of breast cancer resistance protein (BCRP), of which mitoxantrone is a substrate. So far, this interaction has not been reported in humans.

Theoretically, concomitant use might increase the effects and adverse effects of OAT1 substrates.

In vitro research shows that quercetin is a strong non-competitive inhibitor of OAT1, with half-maximal inhibitory concentration (IC50) values less than 10 mcM. So far, this interaction has not been reported in humans.

Theoretically, concomitant use might increase the effects and adverse effects of OAT3 substrates.

In vitro research shows that quercetin is a strong non-competitive inhibitor of OAT3, with half-maximal inhibitory concentration (IC50) values as low as 0.75 mcM. So far, this interaction has not been reported in humans.

Theoretically, concomitant use might increase the effects and adverse effects of OATP substrates.

In vitro evidence shows that quercetin can inhibit organic anion-transporting peptide (OATP) 1B1-mediated uptake of estrone-3-sulfate and pravastatin. Furthermore, clinical research in healthy males shows that intake of quercetin along with pravastatin increases the AUC of pravastatin by 24%, prolongs its half-life by 14%, and decreases its apparent clearance by 18%, suggesting that quercetin modestly inhibits the uptake of pravastatin in hepatic cells.

Theoretically, concomitant use might alter the effects and adverse effects of P-glycoprotein substrates.

There is preliminary evidence that quercetin inhibits the gastrointestinal P-glycoprotein efflux pump, which might increase the bioavailability and serum levels of drugs transported by the pump. A small study in healthy volunteers reported that pretreatment with quercetin increased bioavailability and plasma levels after a single dose of cyclosporine (Neoral, Sandimmune). Also, two small studies have shown that quercetin might decrease the absorption of talinolol, a substrate transported by the gastrointestinal P-glycoprotein efflux pump. However, in another small study, several days of quercetin treatment did not significantly affect the pharmacokinetics of saquinavir (Invirase). The reason for these discrepancies is not entirely clear. Until more is known, use quercetin cautiously in combination with P-glycoprotein substrates.

Theoretically, concomitant use might increase the effects and adverse effects of pravastatin.
In vitro evidence shows that quercetin can inhibit OATP 1B1-mediated uptake of pravastatin. Also, preliminary clinical research in healthy males shows that intake of quercetin along with pravastatin increases the maximum concentration of pravastatin by 24%, prolongs its half-life by 14%, and decreases its apparent clearance by 18%, suggesting that quercetin modestly inhibits the uptake of pravastatin in hepatic cells.

Theoretically, quercetin might increase the effects and adverse effects of prazosin.
In vitro research shows that quercetin inhibits the transcellular efflux of prazosin, possibly through inhibition of breast cancer resistance protein (BCRP), of which prazosin is a substrate. BCRP is an ATP-binding cassette efflux transporter in the intestines, kidneys, and liver. So far, this interaction has not been reported in humans.

Theoretically, concomitant use might increase the effects and adverse effects of quetiapine.
Animal research shows that pretreatment with quercetin can increase plasma levels of quetiapine and prolong its clearance, possibly due to inhibition of cytochrome P450 3A4 (CYP3A4) by quercetin. Additionally, the brain-to-plasma ratio of quetiapine concentrations increased, possibly due to inhibition of P-glycoprotein at the blood-brain barrier. This interaction has not been reported in humans.

Theoretically, concomitant use might inhibit the effects of quinolone antibiotics.
In vitro, quercetin binds to the DNA gyrase site on bacteria, which may interfere with the activity of quinolone antibiotics.

Theoretically, quercetin might increase the effects and adverse effects of sulfasalazine.
Animal research shows that quercetin increases the maximum serum concentration (Cmax) and area under the curve (AUC) of sulfasalazine, possibly through inhibition of breast cancer resistance protein (BCRP), of which sulfasalazine is a substrate. So far, this interaction has not been reported in humans.

Theoretically, quercetin may increase the risk of bleeding if used with warfarin.
Animal and in vitro studies show that quercetin might increase serum levels of warfarin. Quercetin and warfarin have the same human serum albumin (HSA) binding site, and in vitro research shows that quercetin has stronger affinity for the HSA binding site and can theoretically displace warfarin, causing higher serum levels of warfarin. Animal research shows that taking quercetin for 2 weeks before initiating warfarin increases the maximum serum level of warfarin by 30%, the half-life by 10%, and the overall exposure by 63% when compared with control. Concomitant administration of quercetin and warfarin, without quercetin pre-treatment, also increased these measures, but to a lesser degree. Researchers theorize that inhibition of CYP3A4 by quercetin may explain these effects. So far, this interaction has not been reported in humans.

Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research shows that a constituent of eleuthero, dihydroxybenzoic acid, appears to inhibit platelet aggregation. Concomitant use with anticoagulant or antiplatelet drugs might increase the risk of bleeding. This effect has not been reported in humans.

Theoretically, eleuthero might have additive effects when used with antidiabetes drugs.
Animal research suggests that certain constituents of eleuthero have hypoglycemic activity in both healthy and diabetic animals. A small study in adults with type 2 diabetes also shows that taking eleuthero for 3 months can lower blood glucose levels. However, one very small study in healthy individuals shows that taking powdered eleuthero 3 grams, 40 minutes prior to a 75-gram oral glucose tolerance test, significantly increases postprandial blood glucose levels when compared with placebo. These contradictory findings might be due to patient-specific variability and variability in active ingredient ratios.

Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.
In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2. This effect has not been reported in humans.

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2C9.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9. This effect has not been reported in humans.

Eleuthero might increase serum digoxin levels and increase the risk of side effects.
In one case report, a 74-year-old male who was stabilized on digoxin presented with an elevated serum digoxin level after starting an eleuthero supplement, without symptoms of toxicity. After stopping the supplement, serum digoxin levels returned to normal. It is not clear whether this was due to a pharmacokinetic interaction or to interference with the digoxin assay. Although the product was found to be free of digoxin and digitoxin, it was not tested for other contaminants.

Theoretically, eleuthero might interfere with immunosuppressive drugs because of its immunostimulant activity.
Animal and in vitro research shows that eleuthero extracts have immunomodulatory effects, including increasing cellular and humoral activity.

Theoretically, eleuthero might increase levels of P-glycoprotein substrates.
In vitro research suggests that eleuthero can inhibit the multi-drug transporter protein, P-glycoprotein. However, it is too soon to tell if this is clinically important. This interaction has not been reported in humans.

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2D6. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP2D6 drug metabolism.

Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP3A4. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP3A4 drug metabolism.

Theoretically, eleuthero might decrease levels of drugs metabolized by OATP.
In vitro research suggests that eleuthero inhibits OATP2B1, which might reduce the bioavailability of oral drugs that are substrates of OATP2B1. Due to the weak inhibitory effect identified in this study, this interaction is not likely to be clinically significant.

Although Panax ginseng has shown antiplatelet effects in the laboratory, it is unlikely to increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that ginsenoside constituents in Panax ginseng might decrease platelet aggregation. However, research in humans suggests that ginseng does not affect platelet aggregation. Animal research indicates low oral bioavailability of Rb1 and rapid elimination of Rg1, which might explain the discrepancy between in vitro and human research. Until more is known, use with caution in patients concurrently taking anticoagulant or antiplatelet drugs.

Theoretically, taking Panax ginseng with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research suggests that Panax ginseng might decrease blood glucose levels. Monitor blood glucose levels closely.

Theoretically, taking Panax ginseng with caffeine might increase the risk of adverse stimulant effects.
Panax ginseng has been shown to have stimulant effects. Theoretically, caffeine might have an additive effect on the stimulant effects of Panax ginseng.

Theoretically, Panax ginseng might increase levels of drugs metabolized by CYP2D6. However, research is conflicting.
There is some evidence that Panax ginseng can inhibit the CYP2D6 enzyme by approximately 6%. In addition, in animal research, Panax ginseng inhibits the metabolism of dextromethorphan, a drug metabolized by CYP2D6, by a small amount. However, contradictory research suggests Panax ginseng might not inhibit CYP2D6. Until more is known, use Panax ginseng cautiously in patients taking drugs metabolized by these enzymes.

Theoretically, Panax ginseng might increase or decrease levels of drugs metabolized by CYP3A4.
Panax ginseng may affect the clearance of drugs metabolized by CYP3A4. One such drug is imatinib. Inhibition of CYP3A4 was believed to be responsible for a case of imatinib-induced hepatotoxicity. In contrast, Panax ginseng has been shown to increase the clearance of midazolam, another drug metabolized by CYP3A4. Clinical research shows that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29%. Midazolam metabolism was also increased in animals given Panax ginseng. Until more is known, use Panax ginseng cautiously in combination with CYP3A4 substrates.

Theoretically, concomitant use of large amounts of Panax ginseng might interfere with hormone replacement therapy.
Laboratory research and some case reports suggest that Panax ginseng can have estrogenic effects due to competition for estrogen receptors. The estrogenic activity is attributed to the ginsenoside constituents of Panax ginseng.

Theoretically, Panax ginseng might reduce the effects of furosemide.
There is some concern that Panax ginseng might contribute to furosemide resistance. There is one case of resistance to furosemide diuresis in a patient taking a germanium-containing ginseng product.

Theoretically, Panax ginseng might increase the effects and adverse effects of imatinib.
A case of imatinib-induced hepatotoxicity has been reported for a 26-year-old male with chronic myelogenous leukemia stabilized on imatinib for 7 years. The patient took imatinib 400 mg along with a Panax ginseng-containing energy drink daily for 3 months. Since imatinib-associated hepatotoxicity typically occurs within 2 years of initiating therapy, it is believed that Panax ginseng affected imatinib toxicity though inhibition of cytochrome P450 3A4. CYP3A4 is the primary enzyme involved in imatinib metabolism.

Theoretically, Panax ginseng use might interfere with immunosuppressive therapy.
Panax ginseng might have immune system stimulating properties.

Theoretically, taking Panax ginseng with insulin might increase the risk of hypoglycemia.
Clinical research suggests that Panax ginseng might decrease blood glucose levels. Insulin dose adjustments might be necessary in patients taking Panax ginseng; use with caution.

Theoretically, Panax ginseng may increase the clearance of midazolam.
Midazolam is metabolized by cytochrome P450 3A4 (CYP3A4). Clinical research suggests that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29%. Midazolam metabolism was also increased in animals given Panax ginseng.

Theoretically, Panax ginseng can interfere with MAOI therapy.
Concomitant use of Panax ginseng with phenelzine (Nardil) is associated with insomnia, headache, tremors, and hypomania.

Theoretically, taking Panax ginseng with nifedipine might increase serum levels of nifedipine and the risk of hypotension.
Preliminary clinical research shows that concomitant use can increase serum levels of nifedipine in healthy volunteers. This might cause the blood pressure lowering effects of nifedipine to be increased when taken concomitantly with Panax ginseng.

Theoretically, Panax ginseng has an additive effect with drugs that prolong the QT interval and potentially increase the risk of ventricular arrhythmias. However, research is conflicting.
Clinical research shows that short-term use of Panax ginseng can increase the QT interval. However, no changes in QT interval have been identified with prolonged use.

Theoretically, taking Panax ginseng with raltegravir might increase the risk of liver toxicity.
A case report suggests that concomitant use of Panax ginseng with raltegravir can increase serum levels of raltegravir, resulting in elevated liver enzymes levels.

Theoretically, Panax ginseng might increase or decrease levels of selegiline, possibly altering the effects and side effects of selegiline.
Animal research shows that taking selegiline with a low dose of Panax ginseng extract (1 gram/kg) reduces selegiline bioavailability, while taking a high dose of Panax ginseng extract (3 grams/kg) increases selegiline bioavailability. More research is needed to confirm these effects.

Theoretically, taking Panax ginseng with stimulant drugs might increase the risk of adverse stimulant effects.
Panax ginseng has been shown to have stimulant effects.

Panax ginseng might affect the clearance of warfarin. However, this interaction appears to be unlikely.
There has been a single case report of decreased effectiveness of warfarin in a patient who also took Panax ginseng. However, it is questionable whether Panax ginseng was the cause of this decrease in warfarin effectiveness. Some research in humans and animals suggests that Panax ginseng does not affect the pharmacokinetics of warfarin. However, other research in humans suggests that Panax ginseng might modestly increase the clearance of the S-warfarin isomer. More evidence is needed to determine whether Panax ginseng causes a significant interaction with warfarin.

Theoretically, Panax ginseng might decrease blood levels of oral or intravenous fexofenadine.
Animal research suggests that taking Panax ginseng in combination with oral or intravenous fexofenadine may reduce the bioavailability of fexofenadine. Some scientists have attributed this effect to the ability of Panax ginseng to increase the expression of P-glycoprotein.

Although Panax ginseng has demonstrated variable effects on cytochrome P450 3A4 (CYP3A4), which metabolizes lopinavir, Panax ginseng is unlikely to alter levels of lopinavir/ritonavir.
Lopinavir is metabolized by CYP3A4 and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Panax ginseng has shown variable effects on CYP3A4 activity in humans. However, taking Panax ginseng (Vitamer Laboratories) 500 mg twice daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in 12 healthy volunteers.

Theoretically, concurrent use might decrease the effectiveness of both agents.
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels, which could counteract the effects of anticholinergic drugs. Similarly, anticholinergic drugs might counteract the cholinergic effects of bacopa.

Theoretically, bacopa might increase the effects and adverse effects of cevimeline.
In one case, a 58-year-old female taking cevimeline long-term for Sjogren syndrome experienced hyperhidrosis, malaise, nausea, and tachycardia shortly after taking a single dose of bacopa. Symptoms resolved after two days. Cevimeline is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, and researchers theorize that bacopa may have inhibited these isoenzymes. However, it is unclear if bacopa causes clinically significant inhibition of either CYP2D6 or CYP3A4.

Theoretically, concurrent use of bacopa with other cholinergic drugs might have additive effects.
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels. Theoretically, this could result in additive cholinergic effects when used with cholinergic drugs.

Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.
Research on the effects of bacopa extracts on CYP1A2 enzymes is conflicting. Some in vitro evidence shows that bacopa extract can moderately and non-competitively inhibit CYP1A2, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.

Theoretically, bacopa might increase the levels and adverse effects of CYP2C19 substrates.
In vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C19 enzymes. It is not known whether this is clinically significant.

Theoretically, bacopa might increase the levels and adverse effects of CYP2C9 substrates.
Research on the effect of bacopa extracts on CYP2C9 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C9, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.

Theoretically, bacopa might increase the levels and adverse effects of CYP3A4 substrates.
Research on the effects of bacopa extracts on CYP3A4 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and competitively inhibit CYP3A4, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.

Theoretically, bacopa might have additive effects when used with thyroid hormone.
Animal research suggests that bacopa increases thyroxine (T4) levels in mice by about 40%.

Theoretically, antioxidant effects of vitamin E might reduce the effectiveness of alkylating agents.
There's concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.

Concomitant use of vitamin E and anticoagulant or antiplatelet agents might increase the risk of bleeding.
Vitamin E seems to inhibit of platelet aggregation and antagonize the effects of vitamin K-dependent clotting factors. These effects appear to be dose-dependent, and are probably only likely to be clinically significant with doses of at least 800 units daily. Mixed tocopherols, such as those found in food, might have a greater antiplatelet effect than alpha-tocopherol. RRR alpha-tocopherol (natural vitamin E) 1000 IU daily antagonizes vitamin K-dependent clotting factors. Advise patients to avoid high doses of vitamin E, especially in people with low vitamin K intake or other risk factors for bleeding.

Theoretically, antioxidant effects of vitamin E might reduce the effectiveness of antitumor antibiotics.
There's concern that antioxidants could reduce the activity of antitumor antibiotic drugs such as doxorubicin, which generate free radicals. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.

A specific form of vitamin E might increase absorption and levels of cyclosporine.
There is some evidence that one specific formulation of vitamin E (D-alpha-tocopheryl-polyethylene glycol-1000 succinate, TPGS, tocophersolan, Liqui-E) might increase absorption of cyclosporine. This vitamin E formulation forms micelles which seems to increase absorption of cyclosporine by 40% to 72% in some patients. However, this interaction is unlikely to occur with the usual forms of vitamin E.

Theoretically, vitamin E might induce metabolism of CYP3A4, possibly reducing the levels CYP3A4 substrates.
Vitamin E appears to bind with the nuclear receptor, pregnane X receptor (PXR), which results in increased expression of CYP3A4. Although the clinical significance of this is not known, use caution when considering concomitant use of vitamin E and other drugs affected by these enzymes.

Taking selumetinib with vitamin E can result in a total daily dose of vitamin E that exceeds safe limits and therefore might increase the risk of bleeding.
Selumetinib contains 48-54 IU vitamin E per capsule. The increased risk of bleeding with vitamin E appears to be dose-dependent. Be cautious when using selumetinib in combination with supplemental vitamin E, especially in patients at higher risk of bleed, such as those with chronic conditions and those taking antiplatelet drugs.

Using vitamin E with warfarin might increase the risk of bleeding.
Due to interference with production of vitamin K-dependent clotting factors, use of more than 400 IU of vitamin E daily with warfarin might increase prothrombin time (PT), INR, and the risk of bleeding,. At a dose of 1000 IU per day, vitamin E can antagonize vitamin K-dependent clotting factors even in people not taking warfarin. Limited clinical evidence suggests that doses up to 1200 IU daily may be used safely by patients taking warfarin, but this may not be applicable in all patient populations.

Vitamin E might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
A combination of niacin and simvastatin (Zocor) effectively raises high-density lipoprotein (HDL) cholesterol levels in people with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50%. Vitamin E alone combined with a statin does not seem to decrease HDL levels. It is not known whether the adverse effect on HDL is due to one of the other antioxidants or to the combination. It also is not known whether it will occur in other patient populations.

Concomitant use of alcohol and niacin might increase the risk of flushing and hepatotoxicity.
Alcohol can exacerbate the flushing and pruritus associated with niacin. Large doses of niacin might also exacerbate liver dysfunction associated with chronic alcohol use. A case report describes delirium and lactic acidosis in a patient taking niacin 3 grams daily who ingested 1 liter of wine. Advise patients to avoid large amounts of alcohol while taking niacin.

Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as allopurinol.
Large doses of niacin can reduce urinary excretion of uric acid, potentially resulting in hyperuricemia. Doses of uricosurics such as allopurinol might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.

Theoretically, niacin may have additive effects when used with anticoagulant or antiplatelet drugs.
Several cases of clotting factor synthesis deficiency and coagulopathy have been reported in patients taking sustained-release niacin. Also, thrombocytopenia has been reported in patients treated with niacin or niacin plus lovastatin.

Niacin can increase blood glucose levels and may diminish the effects of antidiabetes drugs.
Niacin impairs glucose tolerance in a dose-dependent manner, probably by causing or aggravating insulin resistance and increasing hepatic production of glucose. In diabetes patients, niacin 4.5 grams daily for 5 weeks can increase plasma glucose by an average of 16% and glycated hemoglobin (HbA1c) by 21%. However, lower doses of 1.5 grams daily or less appear to have minimal effects on blood glucose. In some patients, glucose levels increase when niacin is started, but then return to baseline when a stable dose is reached. Up to 35% of patients with diabetes may need adjustments in hypoglycemic therapy when niacin is added.

Theoretically, niacin may increase the risk of hypotension when used with antihypertensive drugs.
The vasodilating effects of niacin can cause hypotension. Furthermore, some clinical evidence suggests that a one-hour infusion of niacin can reduce systolic, diastolic, and mean blood pressure in hypertensive patients. This effect is not observed in normotensive patients.

Bile acid sequestrants can bind niacin and decrease absorption. Separate administration by 4-6 hours to avoid an interaction.
In vitro studies show that colestipol (Colestid) binds about 98% of available niacin and cholestyramine (Questran) binds 10% to 30%.

Theoretically, concomitant use of niacin and gemfibrozil might increase the risk of myopathy in some patients.
A case of myopathy from concomitant use of niacin and gemfibrozil has been reported. Niacin alone has also been associated with cases of myopathy. Using gemfibrozil with niacin might further increase the risk of developing myopathy.

Theoretically, concomitant use of niacin and hepatotoxic drugs might increase the risk of hepatotoxicity.
Niacin has been associated with cases of liver toxicity, especially when used in pharmacologic doses. Sustained-release niacin preparations appear to be associated with a higher risk of hepatotoxicity than immediate-release niacin.

Theoretically, concomitant use of niacin and statins might increase the risk of myopathy and rhabdomyolysis in some patients.
Some case reports have raised concerns that niacin might increase the risk of myopathy and rhabdomyolysis when combined with statins. However, a significantly increased risk of myopathy has not been demonstrated in clinical trials, including those using an FDA-approved combination of lovastatin and niacin (Advicor).

Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as probenecid.
Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia. Doses of uricosurics such as probenecid might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.

Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as sulfinpyrazone.
Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia. Doses of uricosurics such as sulfinpyrazone might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.

Theoretically, niacin might antagonize the therapeutic effects of thyroid hormones.
Clinical research and case reports suggests that taking niacin can reduce serum levels of thyroxine-binding globulin by up to 25% and moderately reduce levels of thyroxine (T4). Patients taking thyroid hormone for hypothyroidism might need dose adjustments when using niacin.

Theoretically, concomitant use of niacin and transdermal nicotine might increase the risk of flushing and dizziness.
Niacin and nicotine can both cause flushing and dizziness.

There is limited evidence that niacin may increase the anticoagulant effects of warfarin.
In a case report, a patient on warfarin developed an elevated international normalized ratio (INR) of 3.9 after taking niacin for two weeks. The patient's INR was previously stable, ranging between 2 and 3 in recent months, and no other medication changes were identified. The elevated INR returned to therapeutic range within 4 days following the discontinuation of niacin.

Large doses of aspirin might alter the clearance of niacin.
Aspirin is often used with niacin to reduce niacin-induced flushing. Doses of 80-975 mg aspirin have been used, but 325 mg appears to be optimal. Aspirin also seems to reduce the clearance of niacin by competing for glycine conjugation. Taking aspirin 1 gram seems to reduce niacin clearance by 45%. This is probably a dose-related effect and not clinically significant with the more common aspirin dose of 325 mg.

Theoretically, taking gotu kola might increase the sedative effects of CNS depressants.
In vitro research suggests that gotu kola may have sedative effects via binding of GABA receptors.

Theoretically, taking gotu kola with hepatotoxic drugs might have additive adverse effects.
There are at least four case reports of hepatotoxicity associated with the use of gotu kola. However, more information is needed to determine if gotu kola was the causative factor in these cases.

Concomitant use of retinoids with vitamin A supplements might produce supratherapeutic vitamin A levels.
Retinoids, which are vitamin A derivatives, could have additive toxic effects when taken with vitamin A supplements.

Theoretically, taking high doses of vitamin A in combination with other potentially hepatotoxic drugs might increase the risk of liver disease.
The tolerable upper intake level (UL) is the highest level of intake that is likely to pose no risk of adverse effects. Doses of vitamin A above the UL can cause hepatotoxicity, ranging from elevated liver enzymes to liver failure.

Theoretically, taking tetracycline antibiotics with high doses of vitamin A can increase the risk of pseudotumor cerebri.
Benign intracranial hypertension (pseudotumor cerebri) can occur with tetracyclines and with acute or chronic vitamin A toxicity. Case reports suggest that taking tetracyclines and vitamin A concurrently can increase the risk of this condition. Avoid high doses of vitamin A in people taking tetracyclines chronically.

Theoretically, high doses of vitamin A could increase the risk of bleeding with warfarin.
Vitamin A toxicity is associated with hemorrhage and hypoprothrombinemia, possibly due to vitamin K antagonism. Advise patients taking warfarin to avoid doses of vitamin A above the tolerable upper intake level of 10,000 IU/day for adults.

Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity. Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation.

Theoretically, selenium might prolong the sedating effects of barbiturates.
Laboratory research suggests that selenium can inhibit the hepatic metabolism of barbiturates. Selenium seems to prolong the sedative effect of pentobarbital in animal models.

Theoretically, selenium supplementation may reduce the effectiveness of immunosuppressant therapy.
In vitro research and preliminary clinical evidence suggests that selenium may stimulate the immune system.

Theoretically, selenium might interfere with warfarin activity.
Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors. Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity.

Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.
Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels. It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium.

Selenium might reduce the beneficial effects of niacin on high-density lipoprotein (HDL) levels.
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease. It is not known whether this adverse effect is due to a single antioxidant such as selenium, or to the combination. It also is not known whether it will occur in other patient populations.

Theoretically, capsicum may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro research shows that capsicum might increase the effects of antiplatelet drugs. Also, population research shows that capsicum is associated with an increased risk of self-reported bleeding in patients taking warfarin. However, clinical research shows that taking a single dose of capsaicin (Asian Herbex Ltd.), the active ingredient in capsicum, 400-800 mcg orally in combination with aspirin 500 mg does not decrease platelet aggregation when compared with taking aspirin 500 mg alone. Also, there was no notable effect on measures of platelet aggregation with capsaicin. It is unclear whether capsaicin must be used in more than a single dose to affect platelet aggregation.

Theoretically, taking capsicum with antidiabetes drugs might increase the risk of hypoglycemia.
Preliminary clinical research shows that consuming capsicum 5 grams along with a glucose drink attenuates the rise in plasma glucose after 30 minutes by 21%, decreases the 2-hour postprandial area under the curve of plasma glucose by 11%, and increases the 2-hour postprandial area under the curve of plasma insulin by 58% in healthy individuals when compared with placebo. Other clinical research shows that taking capsicum 5 mg daily for 28 days significantly reduces postprandial blood glucose and insulin levels, but not fasting blood glucose and insulin levels, in patients with gestational diabetes.

Theoretically, taking capsicum with aspirin might reduce the bioavailability of aspirin.
Animal research shows that acute or chronic intake of capsicum pepper reduces oral aspirin bioavailability. This has not been shown in humans.

Theoretically, taking capsicum with theophylline might increase the levels and adverse effects of theophylline.
In animal research, oral administration of capsicum reduced excretion of theophylline. However, capsicum does not seem to affect the pharmacokinetics of theophylline when administered intravenously.

Theoretically, using topical capsaicin may increase the risk of ACE inhibitor-induced cough.
There is one case report of a topically applied capsaicin cream contributing to the cough reflex in a patient using an ACEI. However, it is unclear if this interaction is clinically significant.

Theoretically, taking capsicum with ciprofloxacin might increase levels and adverse effects of ciprofloxacin.
Animal research shows that concomitant use of capsaicin, the active constituent of capsicum, and ciprofloxacin increases the bioavailability of ciprofloxacin by up to 70%.

Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
Despite initial case reports suggesting that pyridoxine may have a protective effect against amiodarone-induced photosensitivity, preliminary clinical research suggests that pyridoxine may actually exacerbate this adverse effect.

Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure. Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine.

High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenobarbital, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenobarbital to avoid high doses of vitamin B6.

High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenytoin, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenytoin to avoid high doses of vitamin B6.

Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people.

Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.

Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.
Research in animals and humans shows that vitamin C increases aluminum absorption, theoretically by chelating aluminum and keeping it in solution where it is available for absorption. In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely. Patients with renal failure who take aluminum-containing compounds such as phosphate binders should avoid vitamin C supplements in doses above the recommended dietary allowances.

Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as doxorubicin. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.

Vitamin C might increase blood levels of estrogens.
Increases in plasma estrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products. It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall. When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. Increases in plasma estrogen levels may occur when patients who are deficient in vitamin C take supplements. Monitor these patients for estrogen-related side effects.

Theoretically, vitamin C might decrease levels of fluphenazine.
In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started. The mechanism is not known, and there is no further data to confirm this interaction.

Vitamin C can modestly reduce indinavir levels.
One pharmacokinetic study shows that taking vitamin C 1 gram orally once daily along with indinavir 800 mg orally three times daily reduces the area under the concentration-time curve of indinavir by 14%. The mechanism of this interaction is unknown, but it is unlikely to be clinically significant in most patients. The effect of higher doses of vitamin C on indinavir levels is unknown.

Vitamin C can increase levothyroxine absorption.
Two clinical studies in adults with poorly controlled hypothyroidism show that swallowing levothyroxine with a glass of water containing vitamin C 500-1000 mg in solution reduces thyroid stimulating hormone (TSH) levels and increases thyroxine (T4) levels when compared with taking levothyroxine alone. This suggests that vitamin C increases the oral absorption of levothyroxine, possibly due to a reduction in pH.

High-dose vitamin C might reduce the levels and effectiveness of warfarin.
Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption. There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time. Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant. However, a case of warfarin resistance has been reported for a patient who took vitamin C 500 mg twice daily. Cessation of vitamin C supplementation resulted in a rapid increase in international normalized ratio (INR). Tell patients taking warfarin to avoid taking vitamin C in excessively high doses (greater than 10 grams daily). Lower doses may be safe, but the anticoagulation activity of warfarin should be monitored. Patients who are stabilized on warfarin while taking vitamin C should avoid adjusting vitamin C dosage to prevent the possibility of warfarin resistance.

High-dose vitamin C might slightly prolong the clearance of acetaminophen.
A small pharmacokinetic study in healthy volunteers shows that taking high-dose vitamin C (3 grams) 1.5 hours after taking acetaminophen 1 gram slightly increases the apparent half-life of acetaminophen from around 2.3 hours to 3.1 hours. Ascorbic acid competitively inhibits sulfate conjugation of acetaminophen. However, to compensate, elimination of acetaminophen glucuronide and unconjugated acetaminophen increases. This effect is not likely to be clinically significant.

Acidification of the urine by vitamin C might increase aspirin levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction is not clinically significant.

Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Vitamin C might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease. It is not known whether this adverse effect is due to a single antioxidant such as vitamin C, or to the combination. It also is not known whether it will occur in other patient populations.

Acidification of the urine by vitamin C might increase salsalate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of acenocoumarol.
L-carnitine, the parent compound of acetyl-L-carnitine, might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant that is similar to warfarin, but shorter-acting. There are at least two case reports of INR elevation when L-carnitine was taken with acenocoumarol. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product. It is unclear if such an interaction would also occur with acetyl-L-carnitine.

Theoretically, acetyl-L-carnitine might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders, when taken with serotonergic drugs.
Animal research shows that acetyl-L-carnitine can increase levels of serotonin in the brain.

Theoretically, acetyl-L-carnitine might decrease the effectiveness of thyroid hormone replacement.
L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells. Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism. It is unclear if such an interaction would occur with acetyl-L-carnitine.

Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of warfarin.
L-carnitine, the parent compound of acetyl-L-carnitine, might increase the anticoagulant effects of acenocoumarol, a shorter-acting oral anticoagulant similar to warfarin. There is not enough information to know whether this interaction occurs with acetyl-L-carnitine and warfarin.

Theoretically, chromium may have additive effects with antidiabetic agents and increase the risk of hypoglycemia.
Some research shows that taking chromium might lower blood glucose levels, especially in patients with poorly controlled type 2 diabetes.

Theoretically, concomitant use of chromium and insulin might increase the risk of hypoglycemia.
In clinical research, chromium has been shown to increase insulin sensitivity,

Chromium might bind levothyroxine in the intestinal tract and decrease levothyroxine absorption.
Clinical research in healthy volunteers shows that taking chromium picolinate 1000 mcg with levothyroxine 1 mg decreases serum levels of levothyroxine by 17% when compared to taking levothyroxine alone. Advise patients to take levothyroxine at least 30 minutes before or 3-4 hours after taking chromium.

Theoretically, aspirin might increase chromium absorption.
Animal research suggests that aspirin may increase chromium absorption and chromium levels in the blood.

NSAIDs might increase chromium levels in the body.
Drugs that are prostaglandin inhibitors, such as NSAIDs, seem to increase chromium absorption and retention.

Theoretically, taking inositol with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research shows that inositol lowers blood glucose levels and glycated hemoglobin (HbA1c) levels in patients with diabetes.

Theoretically, zinc might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide should be taken at least 2 hours before or 6 hours after zinc containing products.

Zinc might decrease cephalexin levels by chelating with cephalexin in the gut and preventing its absorption.
A pharmacokinetic study shows that zinc sulfate 250 mg taken concomitantly with cephalexin 500 mg decreases peak levels of cephalexin by 31% and reduces the exposure to cephalexin by 27%. Also, taking zinc sulfate 3 hours before cephalexin decreases peak levels of cephalexin by 11% and reduces the exposure to cephalexin by 18%. By decreasing cephalexin levels, zinc might increase the risk of treatment failure. This effect does not occur when zinc is taken 3 hours after the cephalexin dose. To avoid an interaction, advise patients take zinc sulfate 3 hours after taking cephalexin.

Theoretically, zinc might interfere with the therapeutic effects of cisplatin.
Animal research suggests that zinc stimulates tumor cell production of the protein metallothionein, which binds and inactivates cisplatin. It is not known whether zinc supplements or high dietary zinc intake can cause clinically significant interference with cisplatin therapy. Cisplatin might also increase zinc excretion.

Theoretically, taking zinc along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Zinc is a divalent cation. Pharmacokinetic studies have shown that other divalent cations such as calcium and iron can decrease blood levels of the integrase inhibitor dolutegravir through chelation.

Zinc might reduce the levels and clinical effects of penicillamine.
By forming an insoluble complex with penicillamine, zinc interferes with penicillamine absorption and activity. Zinc supplements reduce the efficacy of low-dose penicillamine (0.5-1 gram/day), but do not seem to affect higher doses (1-2.75 gram/day), provided dosing times are separated. Advise patients to take zinc and penicillamine at least 2 hours apart.

Zinc can decrease the levels and clinical effects of quinolones antibiotics.
Quinolones form complexes with zinc in the gastrointestinal tract, reducing absorption of both the quinolone and zinc if taken at the same time. Advise patients to take these drugs at least 2 hours before, or 4-6 hours after, zinc supplements.

Zinc modestly reduces levels of ritonavir.
Clinical research shows that zinc might reduce serum ritonavir levels by chelating with ritonavir in the gut and preventing its absorption. In patients with HIV, ritonavir is taken with atazanavir to prevent the metabolism and increase the effects of atazanavir. A pharmacokinetic study shows that, in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate (Solvazinc tablets) 125 mg as a single dose or as multiple daily doses for 2 weeks reduces plasma levels of ritonavir by about 16%. However, atazanavir levels still remains high enough to prevent HIV virus replication. Therefore, the decrease in ritonavir levels is not likely to be clinically significant.

Zinc might reduce levels of tetracycline antibiotics.
Tetracyclines form complexes with zinc in the gastrointestinal tract, which can reduce absorption of both the tetracycline and zinc when taken at the same time. Taking zinc sulfate 200 mg with tetracycline reduces absorption of the antibiotic by 30% to 40%. Demeclocycline and minocycline cause a similar interaction. However, doxycycline does not seem to interact significantly with zinc. Advise patients to take tetracyclines at least 2 hours before, or 4-6 hours after, zinc supplements to avoid any interactions.

Amiloride can modestly reduce zinc excretion and increase zinc levels.
Clinical research shows that amiloride can reduce urinary zinc excretion, especially at doses of 10 mg per day or more. This zinc-sparing effect can help to counteract zinc losses caused by thiazide diuretics, but it is unlikely to cause zinc toxicity at usual amiloride doses. The other potassium-sparing diuretics, spironolactone (Aldactone) and triamterene (Dyrenium), do not seem to have a zinc-sparing effect.

Zinc modestly reduces levels of atazanavir, although this effect does not seem to be clinically significant.
Clinical research shows that zinc might decrease serum atazanavir levels by chelating with atazanavir in the gut and preventing its absorption. Although a single dose of zinc sulfate (Solvazinc tablets) 125 mg orally does not affect atazanavir concentrations in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate 125 mg daily for 2 weeks reduces plasma levels of atazanavir by about 22% in these patients. However, despite this decrease, atazanavir levels still remain at high enough concentrations for the prevention of HIV virus replication.

Theoretically, glutamine might antagonize the effects of anticonvulsant medications.
Glutamine is metabolized to the excitatory neurotransmitter glutamate. Glutamate might have antagonistic effects with anticonvulsant drugs. However, this interaction has not yet been reported in humans.

Theoretically, taking copper with penicillamine might decrease the absorption of penicillamine; separate dosing by at least 2 hours.
Copper chelates penicillamine, which decreases its absorption and may reduce its clinical effects.

Theoretically, taking copper with contraceptive drugs might increase the levels and toxic effects of copper.
A meta-analysis of clinical studies suggests that chronic use of oral contraceptives increases serum copper levels by a mean of 57 mcg/dL. In most people, this resulted in levels above the normal reference range for copper.

Theoretically, tyrosine might decrease the effectiveness of levodopa.
Tyrosine and levodopa compete for absorption in the proximal duodenum by the large neutral amino acid (LNAA) transport system. Advise patients to separate doses of tyrosine and levodopa by at least 2 hours.

Theoretically, tyrosine might have additive effects with thyroid hormone medications.
Tyrosine is a precursor to thyroxine and might increase levels of thyroid hormones.

Metformin, a common medication used to manage type 2 diabetes, has been associated with lower vitamin B12 levels in some individuals. Prolonged use of metformin can interfere with the absorption of B12 in the digestive system, potentially leading to a deficiency in this essential vitamin.

Theoretically, taking riboflavin with tetracycline antibiotics may decrease the potency of these antibiotics.
In vitro research suggests that riboflavin may inhibit the potency of tetracycline antibiotics. It is not clear if this effect is clinically significant, as this interaction has not been reported in humans.

Theoretically, choline might decrease the effects of atropine in the brain.
Animal research shows that administering choline one hour before administering atropine can attenuate atropine-induced decreases in brain levels of acetylcholine. Theoretically, concomitant use of choline and atropine may decrease the effects of atropine.

Trimethoprim might increase blood levels of thiamine.
In vitro, animal, and clinical research suggest that trimethoprim inhibits intestinal thiamine transporter ThTR-2, hepatic transporter OCT1, and renal transporters OCT2, MATE1, and MATE2, resulting in paradoxically increased thiamine plasma concentrations.