Go Greens Natural Green Apple Flavor 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, 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, taking pomegranate with ACEIs might increase the risk of adverse effects.
Pomegranate juice is thought to have ACE inhibitor-like effects.

Theoretically, taking pomegranate with antihypertensive drugs might increase the risk of hypotension.
Consuming pomegranate juice can modestly lower blood pressure.

Theoretically, pomegranate might increase levels of drugs metabolized by CYP2D6.
In vitro, pomegranate juice inhibits CYP2D6. However, the clinical significance of this potential interaction in humans is not known.

Theoretically, taking pomegranate with rosuvastatin might increase the risk of adverse effects.
In one case, a patient taking rosuvastatin 5 mg every other day in combination with ezetimibe 10 mg daily developed rhabdomyolysis after drinking pomegranate juice 200 mL twice weekly for 3 weeks. This patient had a history of elevated creatine kinase levels while not receiving any statin treatment. This suggests a possible underlying myopathy and predisposition to rhabdomyolysis.

Theoretically, pomegranate might increase warfarin levels and increase the risk of bleeding. Also, discontinuing regular consumption of pomegranate juice might decrease warfarin levels.
In one case report, a patient had a stable, therapeutic bleeding time, as measured by international normalized ratio (INR), while taking warfarin in combination with pomegranate juice 2-3 times per week. The patient became subtherapeutic within about 10 days after discontinuing pomegranate juice, which required a warfarin dose increase. In another case report, a patient with a stable INR for over one year presented with an INR of 14. The patient noted no changes to medications or diet but did report consuming around 3 liters of pomegranate juice over the previous week. The patient's INR stabilized upon moderation of pomegranate juice consumption. The mechanism of this potential interaction is unclear.

Theoretically, taking pomegranate with carbamazepine might increase the risk of adverse effects, although research suggests this interaction is unlikely to be clinically significant.
Animal research shows that pomegranate juice may inhibit cytochrome P450 3A4 (CYP3A4) metabolism of carbamazepine and increase levels of carbamazepine by 1.5 times without prolonging the elimination half-life. This suggests that pomegranate juice inhibits intestinal CYP3A4, but might not inhibit hepatic CYP3A4. However, some human research suggests that pomegranate does not significantly inhibit CYP3A4 drug metabolism in humans.

Theoretically, pomegranate might increase levels of drugs metabolized by CYP2C9.
Some animal and in vitro research shows that pomegranate juice inhibits intestinal, but not hepatic, CYP2C9 isoenzyme activity. However, clinical research shows that neither pomegranate juice nor pomegranate extract have a significant effect on CYP2C9 activity in humans.

Theoretically, pomegranate might increase levels of drugs metabolized by CYP3A4, but most research suggests this interaction is unlikely to be clinically significant.
Pomegranate contains several polyphenols that have individually been shown to inhibit CYP3A4. However, there is contradictory evidence about the effect of whole pomegranate juice on CYP3A4 activity. In vitro, pomegranate juice significantly inhibits the CYP3A4 enzyme, with comparable inhibition to grapefruit juice. In an animal model, pomegranate juice inhibits CYP3A4 metabolism of carbamazepine and increases levels of carbamazepine by 1.5 times; however, in human volunteers, drinking a single glass of pomegranate juice 240 mL or taking 200 mL daily for 2 weeks does not significantly affect levels of the CYP3A4 substrate midazolam after oral or intravenous administration. Another study in healthy volunteers shows that consuming pomegranate juice 300 mL three times daily for three days also does not significantly affect levels of simvastatin, a CYP3A4 substrate This suggests that pomegranate is unlikely to significantly affect levels of CYP3A4 substrates in humans.

Theoretically, pomegranate might increase levels of tolbutamide, although research suggests this interaction is unlikely to be clinically significant.
Animal research shows that pomegranate juice inhibits the cytochrome P450 2C9 (CYP2C9) metabolism of tolbutamide. Pomegranate juice increased tolbutamide levels by 1.2 times without prolonging the elimination half-life. This suggests that pomegranate juice inhibits intestinal CYP2C9, but might not inhibit hepatic CYP2C9. Despite this evidence, clinical research shows that neither pomegranate juice nor pomegranate extract have a significant effect on CYP2C9 activity in humans. This interaction does not appear to be clinically significant in humans.

Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that grape extracts might decrease platelet aggregation.

Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.
A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water. Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.

Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2.

Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes. However, this interaction has not been reported in humans.

Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes. However, this interaction has not been reported in humans.

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have not been reported in humans.

Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.
Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination.

Grape juice might decrease phenacetin absorption.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2).

It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes. However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism. The effects of continued grape juice consumption are unclear.

Theoretically, beet might increase the levels of CYP3A4 substrates.
In vitro research suggests that betanin, the major pigment in beet, competitively inhibits CYP3A4 in a dose-dependent manner similarly to strong CYP3A4 inhibitor ketoconazole.

Beet and beetroot contain nitrates, which can cause vasodilation, potentially leading to lower blood pressure. However, a study published in the European Journal of Clinical Nutrition using concentrated beetroot juice found no significant impact on blood pressure or heart rate in different age groups. Other small clinical studies suggest that while beet consumption might transiently lower blood pressure due to vessel dilation, there's no consistent evidence of a lasting effect. Overall, the theoretical risk of reduced blood pressure due to beet's nitrate content exists, but studies generally indicate a low and temporary impact rather than a sustained decrease.

Theoretically, beet might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research suggests that beet induces CYP1A2 enzymes.

Theoretically, cranberry might increase levels and adverse effects of atorvastatin.
In one case report, a patient taking atorvastatin experienced upper back pain, rhabdomyolysis, and abnormal liver function after drinking cranberry juice 16 ounces daily for 2 weeks. Theoretically, this may have been caused by inhibition of cytochrome P450 3A4 (CYP3A4) enzymes by cranberry juice, as atorvastatin is a CYP3A4 substrate. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice. Patients taking atorvastatin should avoid large quantities of cranberry juice.

Theoretically, cranberry might increase the levels and adverse effects of CYP3A4 substrates.
A case of upper back pain, rhabdomyolysis, and abnormal liver function has been reported for a patient taking atorvastatin, a CYP3A4 substrate, in combination with cranberry juice 16 ounces daily for 2 weeks. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice. Also, animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine, a CYP3A4 substrate, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control.

Theoretically, cranberry might increase the levels and adverse effects of nifedipine.
Animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine treatment, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control. This interaction has not been reported in humans.

Theoretically, cranberry might increase the levels and adverse effects of warfarin. However, research is conflicting.
There is contradictory evidence about the effect of cranberry juice on warfarin. Case reports have linked cranberry juice consumption to increases in the international normalized ratio (INR) in patients taking warfarin, resulting in severe spontaneous bleeding and excessive postoperative bleeding. Daily consumption of cranberry sauce for one week has also been linked to an increase in INR in one case report. In a small study in healthy young males, taking a high dose of 3 grams of cranberry juice concentrate capsules, equivalent to 57 grams of fruit daily, for 2 weeks produced a 30% increase in the area under the INR-time curve after a single 25-mg dose of warfarin. However, 3 very small clinical studies in patients stabilized on warfarin reported that cranberry juice 250 mL once or twice daily for 7 days (27% cranberry juice or pure cranberry juice) or 240 mL once daily for 14 days does not significantly increase INR or affect plasma warfarin levels. The reasons for these discrepant findings are unclear. It is possible that the form and dose of cranberry may play a role, as cranberry extracts and juices contain different constituents. Additionally, an in vitro study evaluating 5 different cranberry juices found varying effects, with only a cranberry concentrate, and not diluted cranberry juices, inhibiting CYP2C9. However, this concentrate did not inhibit CYP2C9 activity in humans.

Theoretically, cranberry might increase the levels and adverse effects of CYP2C9 substrates. However, research is conflicting.
There is contradictory evidence about the effect of cranberry on CYP2C9 enzymes. In vitro evidence suggests that flavonoids in cranberry inhibit CYP2C9 enzymes. However, clinical research shows that cranberry juice does not significantly affect the levels, metabolism, or elimination of the CYP2C9 substrates flurbiprofen or diclofenac. Also, in patients stabilized on warfarin, drinking cranberry juice 250 mL daily for 7 days does not significantly increase the anticoagulant activity of warfarin, a CYP2C9 substrate. Additional pharmacokinetic research shows that cranberry juice does not increase peak plasma concentrations or area under the concentration-time curve of warfarin.

Theoretically, cranberry might modestly increase the levels and adverse effects of diclofenac.
In vitro evidence suggests that cranberry juice inhibits diclofenac metabolism by human liver microsomes. However, drinking cranberry juice does not seem to affect diclofenac metabolism in humans.

Theoretically, aloe latex might increase the risk of adverse effects when taken with cardiac glycosides.
Overuse of aloe latex can increase the risk of adverse effects from cardiac glycoside drugs, such as digoxin, due to potassium depletion. Overuse of aloe, along with cardiac glycoside drugs, can increase the risk of toxicity.

Theoretically, aloe gel might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
In vitro research shows that aloe gel can inhibit platelet aggregation. This inhibition was greater than that seen with celecoxib, but less than that seen with aspirin.

Aloe might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Preliminary clinical research suggests aloe gel might lower blood glucose levels and have additive effects when used with antidiabetes drugs. Monitor blood glucose levels closely.

Theoretically, aloe latex might increase the risk of hypokalemia when taken with diuretic drugs.
Overuse of aloe latex might compound diuretic-induced potassium loss, increasing the risk of hypokalemia.

Theoretically, aloe latex might increase the risk for fluid and electrolyte loss when taken with stimulant laxatives.
Due to cathartic laxative effects of aloe latex, concomitant use with other stimulant laxatives might compound fluid and electrolyte loss.

Theoretically, aloe latex might increase the risk of bleeding when taken with warfarin.
Aloe latex has stimulant laxative effects. In some people aloe latex can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. Advise patients who take warfarin not to take excessive amounts of aloe vera.

Theoretically, aloe might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that aloe extract induces CYP1A2 enzymes.

Theoretically, cassia cinnamon may have additive effects with antidiabetes drugs.
Cassia cinnamon may lower blood glucose levels, and have additive effects in patients treated with antidiabetic agents. Dose adjustments to diabetes medications might be necessary.

Theoretically, large doses of cassia cinnamon might cause additive effects when used with hepatotoxic drugs.
There is some concern that ingesting large amounts of cassia cinnamon for an extended duration might cause hepatotoxicity in some people. Cassia cinnamon contains coumarin, which can cause hepatotoxicity in animal models. In humans, very high doses of coumarin from 50-7000 mg/day can result in hepatotoxicity that resolves when coumarin use is discontinued. Lower amounts might also cause liver problems in sensitive people, such as those with liver disease or those taking potentially hepatotoxic agents.

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.

Theoretically, chlorella might have additive effects with photosensitizing drugs.
Chlorella has been reported to cause photosensitization. In five case reports, patients who had ingested chlorella exhibited swelling followed by erythematopurpuric lesions on sun-exposed areas of the body. Theoretically, concomitant use with photosensitizing drugs may exacerbate effects.

Theoretically, chlorella might reduce the clinical effects of warfarin.
Chlorella contains significant amounts of vitamin K. There is at least one case report of warfarin therapy becoming sub-therapeutic after initiation of chlorella supplements.

Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of OATP substrates.
Research shows that consuming apple juice inhibits OATP, which reduces bioavailability of oral drugs that are substrates of OATP. Fexofenadine, atenolol, and aliskiren are substrates of OATP. Clinical research shows that coadministration of apple juice decreases bioavailability of fexofenadine by up to 78%, aliskiren by 63%, and atenolol by up to 82%. These effects appear to increase with larger quantities of apple juice. It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction.

Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of aliskiren.
Pharmacokinetic research shows that coadministration of apple juice 200 mL along with aliskiren 150 mg decreases the bioavailability of aliskiren by 63%. Apple juice seems to inhibit organic anion transporting polypeptide (OATP), which is involved in drug uptake in the gut, liver, and kidney. It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction.

Theoretically, consuming apple juice with antidiabetes drugs might interfere with blood glucose control.
Clinical research suggests that consuming apples or drinking apple juice can raise blood glucose levels, with the effects of drinking apple juice being more significant than consuming apples.

Consuming apple juice with antihypertensive drugs might interfere with blood pressure control.
Some clinical evidence suggests that consuming apple and cherry juice can increase blood pressure in elderly patients.

Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of atenolol.
Pharmacokinetic research shows that coadministration of apple juice 600-1200 mL decreases levels of atenolol by 58% to 82% in a dose-dependent manner. Apple juice seems to inhibit organic anion transporting polypeptide (OATP), which is involved in drug uptake in the gut, liver, and kidney. It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction.

Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of fexofenadine.
Pharmacokinetic research shows that coadministration of apple juice 400-1200 mL along with fexofenadine 60-120 mg decreases bioavailability of fexofenadine by up to 78%. Coadministration with smaller quantities of apple juice (150 mL or less) does not appear to affect the bioavailability of fexofenadine. Apple juice seems to inhibit organic anion transporting polypeptide (OATP), which is involved in drug uptake in the gut, liver, and kidney. It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction.

There is some concern that concomitant consumption of apple juice might decrease oral absorption and blood levels of lithium.
In one case report, a patient had an undetectable serum lithium level when lithium citrate was administered with apple juice. When lithium was administered with an alternative beverage, the lithium level became detectable and the patient demonstrated clinical improvement.

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, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.
High intake of dietary sodium can increase systolic and diastolic blood pressure. Also, high intake of sodium may necessitate increased use of antihypertensive medications to achieve blood pressure control in some patients, such as those with chronic kidney disease.

Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.
Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone.

Concomitant use of didanosine with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia.
Didanosine formulations contain a significant amount of sodium.

Altering dietary intake of sodium might alter the levels and clinical effects of lithium.
High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion. Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate. Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L. Patients taking lithium should avoid significant alterations in their dietary intake of sodium.

Theoretically, concomitant use of sodium phosphate with sodium supplements might increase the risk of hypernatremia.
Use of high doses (> 45 mL in 24 hours) of sodium phosphate, such as those used for bowel cleansing before surgery, can lead to serious electrolyte disturbances, including hypernatremia. The risk of hypernatremia is highest in the elderly and people with other risk factors for electrolyte disturbances.

Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.
The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population. Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.

Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.
Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia. Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.

Theoretically, broccoli might reduce the levels and effects of drugs metabolized by CYP1A2.
Pharmacokinetic research in humans shows that eating 500 grams of fresh broccoli daily for 6-12 days can increase CYP1A2 activity by 10% to 200%. Induction of CYP1A2 activity by broccoli is attributed to its glucosinolate constituents.

Theoretically, broccoli might reduce the levels and effects of drugs metabolized by CYP2A6.
Pharmacokinetic research in humans shows that eating 500 grams of broccoli daily for 6 days increases CYP2A6 activity by 135% to 550%. Induction of CYP2A6 activity is attributed to its glucosinolate constituents.

Co-administration of intravenous calcium and ceftriaxone can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys.
Avoid administering intravenous calcium in any form, such as parenteral nutrition or Lactated Ringers, within 48 hours of intravenous ceftriaxone. Case reports in neonates show that administering intravenous ceftriaxone and calcium can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys. In several cases, neonates have died as a result of this interaction. So far there are no reports in adults; however, there is still concern that this interaction might occur in adults.

Calcium seems to reduce levels of dolutegravir.
Advise patients to take dolutegravir either 2 hours before or 6 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium carbonate 1200 mg concomitantly with dolutegravir 50 mg reduces plasma levels of dolutegravir by almost 40%. Calcium appears to decrease levels of dolutegravir through chelation.

Calcium seems to reduce levels of elvitegravir.
Advise patients to take elvitegravir either 2 hours before or 2 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium along with elvitegravir can reduce blood levels of elvitegravir through chelation.

Calcium citrate might increase aluminum absorption and toxicity. Other types of calcium do not increase aluminum absorption.
Calcium citrate can increase the absorption of aluminum when taken with aluminum hydroxide. The increase in aluminum levels may become toxic, particularly in individuals with kidney disease. However, the effect of calcium citrate on aluminum absorption is due to the citrate anion rather than calcium cation. Calcium acetate does not appear to increase aluminum absorption.

Calcium might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption when taken in a fasting state.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide and calcium can be taken together if taken with food. However, if taken on an empty stomach, bictegravir/emtricitabine/tenofovir alafenamide should not be taken with, or 2 hours after, calcium containing products.

Calcium reduces the absorption of bisphosphonates.
Advise patients to take bisphosphonates at least 30 minutes before calcium, but preferably at a different time of day. Calcium supplements decrease absorption of bisphosphonates.

Taking calcipotriene with calcium might increase the risk for hypercalcemia.
Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia. Theoretically, combining calcipotriene with calcium supplements might increase the risk of hypercalcemia.

Using intravenous calcium with digoxin might increase the risk of fatal cardiac arrhythmias.
Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. However, one retrospective analysis of clinical data suggests that intravenous calcium does not increase the risk of dysrhythmias or mortality in patients receiving digoxin.

Theoretically, calcium may reduce the therapeutic effects of diltiazem.
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically, calcium might increase this risk of hypercalcemia and reduce the effectiveness of diltiazem.

Calcium seems to reduce the absorption and effectiveness of levothyroxine.
Advise patients to take levothyroxine and calcium supplements at least 4 hours apart. Calcium reduces levothyroxine absorption, probably by forming insoluble complexes. Calcium carbonate supplements reduce effectiveness of levothyroxine in patients with hypothyroidism.

Theoretically, concomitant use of calcium and lithium may increase this risk of hypercalcemia.
Clinical research suggests that long-term use of lithium may cause hypercalcemia in 10% to 60% of patients. Theoretically, concomitant use of lithium and calcium supplements may further increase this risk.

Calcium seems to reduce the absorption of quinolone antibiotics.
Advise patients to take oral quinolones at least 2 hours before or 4-6 hours after calcium supplements or calcium-fortified foods. Taking calcium at the same time as oral quinolones can reduce quinolone absorption. Calcium binds to quinolones in the gut.

Calcium may reduce levels of raltegravir.
Pharmacokinetic research shows that taking a single dose of calcium carbonate 3000 mg along with raltegravir 400 mg twice daily modestly decreases the mean area under the curve of raltegravir, but the decrease does not necessitate a dose adjustment of raltegravir. However, a case of elevated HIV-1 RNA levels and documented resistance to raltegravir has been reported for a patient taking calcium carbonate 1 gram three times daily plus vitamin D3 (cholecalciferol) 400 IU three times daily in combination with raltegravir 400 mg twice daily for 11 months. It is thought that calcium reduced raltegravir levels by chelation, leading to treatment failure.

Calcium seems to reduce the absorption of sotalol.
Advise patients to separate doses by at least 2 hours before or 4-6 hours after calcium. Calcium appears to reduce the absorption of sotalol, probably by forming insoluble complexes.

Calcium seems to reduce the absorption of tetracycline antibiotics.
Advise patients to take oral tetracyclines at least 2 hours before, or 4-6 hours after calcium supplements. Taking calcium at the same time as oral tetracyclines can reduce tetracycline absorption. Calcium binds to tetracyclines in the gut.

Taking calcium along with thiazides might increase the risk of hypercalcemia and renal failure.
Thiazides reduce calcium excretion by the kidneys. Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal failure). Patients may need to have their serum calcium levels and/or parathyroid function monitored regularly.

Theoretically, calcium may reduce the therapeutic effects of verapamil.
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically, use of calcium supplements may increase this risk of hypercalcemia and reduce the effectiveness of verapamil.

Intravenous calcium may decrease the effects of calcium channel blockers; oral calcium is unlikely to have this effect.
Intravenous calcium is used to decrease the effects of calcium channel blockers in the management of overdose. Intravenous calcium gluconate has been used before intravenous verapamil (Isoptin) to prevent or reduce the hypotensive effects without affecting the antiarrhythmic effects. But there is no evidence that dietary or supplemental calcium when taken orally interacts with calcium channel blockers.

Theoretically, the antioxidant effects of acerola might reduce the effectiveness of alkylating agents.
Acerola contains vitamin C, an antioxidant. There is concern that antioxidants might reduce the activity of chemotherapy drugs that generate free radicals, such as alkylating agents. In contrast, other researchers theorize that antioxidants might make alkylating 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.

Theoretically, the antioxidant effects of acerola might reduce the effectiveness of antitumor antibiotics.
Acerola contains vitamin C, an antioxidant. There is concern that antioxidants might reduce the activity of chemotherapy drugs that generate free radicals, such as antitumor antibiotics. In contrast, other researchers theorize that antioxidants might make antitumor antibiotic 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 antitumor antibiotic chemotherapy.

Theoretically, concomitant use of acerola with aluminum salts might increase the amount of aluminum absorbed.
Acerola contains vitamin C. It is thought that vitamin C chelates aluminum, keeping it in solution and available for absorption. In people with normal renal function, urinary excretion of aluminum likely increases, making aluminum retention and toxicity unlikely. However, patients with renal failure who take aluminum-containing compounds, such as phosphate binders, should avoid acerola in doses that provide more vitamin C than the recommended dietary allowances.

Theoretically, acerola might reduce the clearance of aspirin; however, its vitamin C content is likely too low to produce clinically significant effects.
Acerola contains vitamin C. It has been suggested that acidification of the urine by vitamin C can decrease the urinary excretion of salicylates, increasing 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. The vitamin C content of acerola is typically about 2000 mg per 100 grams. Thus, a clinically significant interaction between acerola and aspirin is unlikely.

Theoretically, concomitant use of acerola with estrogens might increase estrogenic effects.
Acerola contains vitamin C. Increases in plasma estrogen levels of up to 55% have occurred 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. However, increases in plasma estrogen levels may occur when women who are deficient in vitamin C take supplements.

Theoretically, acerola might reduce the effectiveness of warfarin; however, its vitamin C content is likely too low to produce clinically significant effects.
Acerola contains vitamin C. High doses of vitamin C may reduce the response to warfarin, possibly by causing diarrhea and reducing warfarin absorption. This occurred in two people who took up to 16 grams daily of vitamin C, and resulted in decreased prothrombin time. Lower doses of 5-10 grams daily of vitamin C can also reduce warfarin absorption, but this does not seem to be clinically significant. The vitamin C content of acerola is typically about 2000 mg per 100 grams. Thus, a clinically significant interaction between acerola and warfarin is unlikely.

There are claims that spinach leaves have hypoglycemic effects. Evidence from clinical research suggests that consumption of a spinach-rich meal reduces post-meal blood glucose levels. Theoretically, spinach might have additive effects with antidiabetes drugs and increase the risk of hypoglycemia. Monitor blood glucose levels closely. Dose adjustments might be necessary. Some antidiabetes drugs include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), and others.

Spinach contains vitamin K, which can interfere with the activity of warfarin.
In human research, although eating spinach with one meal does not result in coagulation test results outside the therapeutic range, daily consumption for one week necessitates dose adjustment of warfarin. Individuals using anticoagulants should consume a consistent daily amount of spinach to maintain the effect of anticoagulant therapy.

Theoretically, blueberries or blueberry leaf extracts might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal and in vitro research suggests that blueberry and/or blueberry leaf extracts can lower blood glucose levels.

Theoretically, blueberry juice might increase blood levels of buspirone.
In vitro research shows that blueberry juice can inhibit the metabolism of buspirone, possibly by inhibiting cytochrome P450 3A (CYP3A) enzymes. However, pharmacokinetic research in humans shows that drinking 300 mL of blueberry juice 30 minutes before taking buspirone hydrochloride 10 mg does not significantly affect the concentration or clearance of buspirone.

Theoretically, blueberry juice might increase blood levels of flurbiprofen.
In vitro research shows that blueberry juice can inhibit the metabolism of flurbiprofen, possibly by inhibiting cytochrome P450 2C9 (CYP2C9) enzymes. However, pharmacokinetic research in humans shows that drinking 300 mL of blueberry juice 30 minutes before taking flurbiprofen 100 mg does not significantly affect the concentration or clearance of flurbiprofen.

Theoretically, taking rutin with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research suggests that rutin has hypoglycemic effects.

Theoretically, taking acai with antidiabetes drugs might interfere with glycemic control.
Preliminary clinical research in healthy adults has shown that taking acai may increase or decrease levels of fasting blood glucose.

Theoretically, laminaria might increase the risk of hyperkalemia when taken with ACEIs.
Laminaria contains potassium.

Theoretically, combining laminaria with amiodarone might cause excessively high iodine levels.
Amiodarone contains 37.3% iodine and can increase iodine levels. Concomitant use with laminaria supplements, some of which may contain as much as 1000 mcg iodine, might increase the risk of adverse effects from iodine, including altered thyroid function.

Due to its iodine content, laminaria might alter the effects of antithyroid drugs.
Some laminaria supplements contain up to 1000 mcg of iodine. Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking laminaria could theoretically alter the effects of antithyroid drugs.

Theoretically, laminaria might increase the risk of hyperkalemia, which could increase the effects and adverse effects of digoxin.
Laminaria contains potassium.

Theoretically, laminaria might increase the risk of hyperkalemia when taken with potassium-sparing diuretics.
Laminaria contains potassium.

Due to its iodine content, laminaria might alter the effects of thyroid hormone.
Some laminaria supplements contain up to 1000 mcg of iodine. Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking laminaria could theoretically alter the effects of thyroid hormone.

Using ACEIs with high doses of potassium increases the risk of hyperkalemia.
ACEIs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion. Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia. However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels.

Using ARBs with high doses of potassium increases the risk of hyperkalemia.
ARBs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion. Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia. However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels.

Concomitant use increases the risk of hyperkalemia.
Using potassium-sparing diuretics with potassium supplements increases the risk of hyperkalemia.

Vitamin K can antagonize and reverse the therapeutic effects of warfarin.
Vitamin K antagonizes the effects of warfarin. Excessive vitamin K intake, either from supplements or from changes in the diet, can reduce the anticoagulant effect of warfarin.

Theoretically, barley might decrease the clinical effects of triclabendazole.
Animal research suggests that a diet supplemented with barley can reduce the bioavailability of triclabendazole when taken concomitantly. This effect has not been shown in humans.

Theoretically, taking itraconazole capsules or tablets with a beverage containing lemon might increase the levels and clinical effects of itraconazole.
In one case report, dissolving itraconazole tablets in a small amount of specific beverages containing lemon prior to administration increased the level of itraconazole in a lung transplant patient. In this case, the increased bioavailability was desirable and was likely due to improved tablet dissolution in the acidic beverage.