Now Whey Protein Ingredients & Drug Interactions

Theoretically, licorice might reduce the effects of antihypertensive drugs.
In human research, licorice increases blood pressure in a dose-dependent manner.

Theoretically, licorice might reduce the effects of cisplatin.
In animal research, licorice diminished the therapeutic efficacy of cisplatin.

Theoretically, concomitant use of licorice and corticosteroids might increase the side effects of corticosteroids.
Case reports suggest that concomitant use of licorice and oral corticosteroids, such as hydrocortisone, can potentiate the duration of activity and increase blood levels of corticosteroids. Additionally, in one case report, a patient with neurogenic orthostatic hypertension stabilized on fludrocortisone 0.1 mg twice daily developed pseudohyperaldosteronism after recent consumption of large amounts of black licorice.

Theoretically, licorice might increase levels of drugs metabolized by CYP2B6.
In vitro research shows that licorice extract and glabridin, a licorice constituent, inhibit CYP2B6 isoenzymes. Licorice extract from the species G. uralensis seems to inhibit CYP2B6 isoenzymes to a greater degree than G. glabra extract in vitro. Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2B6; however, these interactions have not yet been reported in humans.

Theoretically, licorice might increase levels of drugs metabolized by CYP2C19.
In vitro, licorice extracts from the species G. glabra and G. uralensis inhibit CYP2C19 isoenzymes in vitro. Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C19; however, this interaction has not yet been reported in humans.

Theoretically, licorice might increase levels of drugs metabolized by CYP2C8.
In vitro, licorice extract from the species G. glabra and G. uralensis inhibits CYP2C8 isoenzymes. Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C8; however, this interaction has not yet been reported in humans.

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP2C9.
There is conflicting evidence about the effect of licorice on CYP2C9 enzyme activity. In vitro research shows that extracts from the licorice species G. glabra and G. uralensis moderately inhibit CYP2C9 isoenzymes. However, evidence from an animal model shows that licorice extract from the species G. uralensis can induce hepatic CYP2C9 activity. Until more is known, licorice should be used cautiously in people taking CYP2C9 substrates.

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.
Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity. Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity. However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species. Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.

Theoretically, concomitant use of licorice with digoxin might increase the risk of cardiac toxicity.
Overuse or misuse of licorice with cardiac glycoside therapy might increase the risk of cardiac toxicity due to potassium loss.

Theoretically, concomitant use of licorice with diuretic drugs might increase the risk of hypokalemia.
Overuse of licorice might compound diuretic-induced potassium loss. In one case report, a 72-year-old male with a past medical history of hypertension, type 2 diabetes, hyperlipidemia, arrhythmia, stroke, and hepatic dysfunction was hospitalized with severe hypokalemia and uncontrolled hypertension due to pseudohyperaldosteronism. This was thought to be provoked by concomitant daily consumption of a product containing 225 mg of glycyrrhizin, a constituent of licorice, and hydrochlorothiazide 12.5 mg for 1 month.

Theoretically, licorice might increase or decrease the effects of estrogen therapy.
Theoretically, licorice might interfere with estrogen therapy due to estrogenic and anti-estrogenic effects.

Theoretically, loop diuretics might increase the mineralocorticoid effects of licorice.
Theoretically, loop diuretics might enhance the mineralocorticoid effects of licorice by inhibiting the enzyme that converts cortisol to cortisone; however, bumetanide (Bumex) does not appear to have this effect.

Theoretically, licorice might decrease levels of midazolam.
In humans, the licorice constituent glycyrrhizin appears to moderately induce the metabolism of midazolam. This is likely due to induction of cytochrome P450 3A4 by licorice. Until more is known, licorice should be used cautiously in people taking midazolam.

Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.
In vitro research shows that licorice can increase P-glycoprotein activity.

Theoretically, licorice might decrease plasma levels and clinical effects of paclitaxel.
Multiple doses of licorice taken concomitantly with paclitaxel might reduce the effectiveness of paclitaxel. Animal research shows that licorice 3 grams/kg given orally for 14 days before intravenous administration of paclitaxel decreases the exposure to paclitaxel and increases its clearance. Theoretically, this occurs because licorice induces cytochrome P450 3A4 enzymes, which metabolize paclitaxel. Notably, a single dose of licorice did not affect exposure or clearance of paclitaxel.

Theoretically, licorice might decrease plasma levels and clinical effects of warfarin.
Licorice seems to increase metabolism and decrease levels of warfarin in animal models. This is likely due to induction of cytochrome P450 2C9 (CYP2C9) metabolism by licorice. Advise patients taking warfarin to avoid taking licorice.

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

Theoretically, licorice might increase levels of methotrexate.
Animal research suggests that intravenous administration of glycyrrhizin, a licorice constituent, and high-dose methotrexate may delay methotrexate excretion and increase systemic exposure, leading to transient elevations in liver enzymes and total bilirubin. This interaction has not yet been reported in humans.

Garlic may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Raw garlic and a variety of garlic extracts have antiplatelet activity and can increase prothrombin time.

Theoretically, taking garlic with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research suggests that garlic and garlic extract lower blood glucose levels in healthy and diabetic individuals.

Theoretically, taking garlic with antihypertensive drugs might increase the risk of hypotension.
In human research, both garlic and garlic extracts have blood pressure-lowering effects.

Theoretically, garlic might decrease levels and effects of atazanavir.
In a case report, a patient consuming six stir-fried garlic cloves three times weekly developed suboptimal atazanavir levels and increases in HIV viral load. While the exact cause of this interaction is unclear, there is speculation that garlic might decrease the intestinal absorption of atazanavir or increase its metabolism by inducing cytochrome P450 3A4 (CYP3A4). Until more is known, advise patients not to consume large amounts of garlic while taking atazanavir.

Garlic might increase levels of drugs metabolized by CYP2E1.
Clinical research suggests garlic oil can inhibit the activity of CYP2E1 by 39%. Use garlic oil cautiously in patients taking drugs metabolized by these enzymes.

Theoretically, garlic products containing allicin might induce intestinal CYP3A4 and inhibit hepatic CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
Some human research suggests that garlic may induce INTESTINAL CYP3A4, reducing levels of drugs metabolized by this enzyme. This is primarily based on a study showing that taking a specific allicin-containing garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induced CYP3A4 in the gut mucosa. Another study shows that giving docetaxel intravenously, bypassing the CYP3A4 enzymes in the gut mucosa, along with the same specific garlic product for 12 consecutive days, does not affect docetaxel levels. Conversely, there is concern that garlic may inhibit HEPATIC CYP3A4. In a single case report, increased tacrolimus levels and liver injury occurred in a liver transplant patient after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days. Several other studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin.

Theoretically, garlic might decrease levels of isoniazid.
Animal research suggests that an aqueous extract of garlic reduces isoniazid levels by about 65%. Garlic reduced the maximum concentration (Cmax) and area under the curve (AUC), but not the half-life, of isoniazid. This suggests that garlic extract might inhibit isoniazid absorption across the intestinal mucosa; however, the exact mechanism of this potential interaction is not known.

Theoretically, garlic products containing allicin might decrease levels of PIs.
Protease inhibitors are metabolized by cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4, reducing plasma levels of protease inhibitors. This is primarily based on a study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces levels of saquinavir, a PI, by approximately 50%. It is speculated that the allicin constituent induce CYP3A4 in the gut mucosa. Several studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin.

Theoretically, garlic containing allicin might decrease levels of saquinavir.
Saquinavir is a substrate of cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4 and cause subtherapeutic levels of saquinavir. This is primarily based on a pharmacokinetic study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induces CYP3A4 in the gut mucosa. Several pharmacokinetic studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin. Until more is known about this potential interaction, use garlic containing allicin cautiously in patients taking saquinavir.

Theoretically, taking garlic with sofosbuvir might decrease its effectiveness.
Animal research in rats shows that giving aged garlic extract 120 mg/kg orally daily for 14 days decreases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 36%, increases the clearance by 63%, and decreases the plasma concentrations at 1 and 8 hours by 35% and 58%, respectively. This interaction is hypothesized to be due to induction of intestinal P-glycoprotein expression by garlic.

Theoretically, garlic might increase levels of tacrolimus.
In one case report, a liver transplant patient taking tacrolimus experienced increased tacrolimus levels and liver injury after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days. It is speculated that garlic inhibited hepatic cytochrome P450 3A4 (CYP3A4), which increased plasma levels of tacrolimus.

Theoretically, garlic might increase the risk of bleeding with warfarin.
Raw garlic and a variety of garlic extracts have antiplatelet activity and can increase prothrombin time. In addition, there is a report of two patients who experienced an increase in a previously stabilized international normalized ratio (INR) with concomitant garlic and warfarin use. However, this report has been subsequently debated due to limited clinical information. Other clinical studies have not identified an effect of garlic on INR, warfarin pharmacokinetics, or bleeding risk. More evidence is needed to determine the safety of using garlic with warfarin.

Theoretically, combining Fucus vesiculosus with amiodarone might cause excessively high iodine levels.
Fucus vesiculosus contains high concentrations of iodine. Amiodarone contains 37.3% iodine and can increase iodine levels. Concomitant use might increase the risk of having excessive iodine levels and adversely affecting thyroid function. Monitor thyroid function.

Due to its iodine content, Fucus vesiculosus might alter the effects of antithyroid drugs.
Fucus vesiculosus contains high concentrations of iodine. Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking Fucus vesiculosus while using antithyroid drugs could alter the effects of the antithyroid drugs.

Concomitant use of Fucus vesiculosus and lithium has resulted in hyperthyroidism.
There is a case of hyperthyroidism occurring in a patient taking Fucus vesiculosus and lithium. Monitor thyroid hormones closely in patients taking lithium and Fucus vesiculosus concomitantly.

Due to its iodine content, Fucus vesiculosus might alter the effects of thyroid hormone.
Fucus vesiculosus contains high concentrations of iodine. Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking Fucus vesiculosus while using thyroid hormone could alter the effects of thyroid hormone.

Theoretically, taking Fucus vesiculosus with antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding.
In vitro evidence suggests that a constituent of Fucus vesiculosus, known as fucoidan, has anticoagulant effects. However, in clinical research, fucoidan does not seem to have significant anticoagulant activity when taken orally, possibly due to poor absorption.

Theoretically, concomitant use of Fucus vesiculosus with CYP2C8 substrates might increase the risk for adverse effects.
In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, inhibits CYP2C8. This interaction has not been reported in humans.

Theoretically, concomitant use of Fucus vesiculosus with CYP2C9 substrates might increase the risk for adverse effects.
In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, inhibits CYP2C9. This interaction has not been reported in humans.

Theoretically, concomitant use of Fucus vesiculosus with CYP2D6 substrates might alter the effects of these substrates.
In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, both inhibits and induces CYP2D6. This interaction has not been reported in humans.

Theoretically, concomitant use of Fucus vesiculosus with CYP3A4 substrates might increase the risk for adverse effects.
In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, inhibits CYP3A4. This interaction has not been reported in humans.

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.

Vitamin D might increase aluminum absorption and toxicity, but this has only been reported in people with renal failure.
The protein that transports calcium across the intestinal wall can also bind and transport aluminum. This protein is stimulated by vitamin D, which may therefore increase aluminum absorption. This mechanism may contribute to increased aluminum levels and toxicity in people with renal failure, when they take vitamin D and aluminum-containing phosphate binders chronically.

Vitamin D might reduce absorption of atorvastatin.
A small, low-quality clinical study shows that taking vitamin D reduces levels of atorvastatin and its active metabolites by up to 55%. However, while atorvastatin levels decreased, total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels did not substantially change. Atorvastatin is metabolized in the gut by CYP3A4 enzymes, and researchers theorized that vitamin D might induce CYP3A4, causing reduced levels of atorvastatin. However, this proposed mechanism was not specifically studied.

Taking calcipotriene with vitamin D increases 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 vitamin D supplements might increase the risk of hypercalcemia.

Theoretically, hypercalcemia induced by high-dose vitamin D can increase the risk of arrhythmia from digoxin.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and digoxin concurrently.

Theoretically, hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of diltiazem for arrhythmia.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically this could also occur with diltiazem. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and diltiazem concurrently.

Theoretically, taking thiazide diuretics and high-dose vitamin D can increase the risk of hypercalcemia.
Thiazide diuretics decrease urinary calcium excretion, which could lead to hypercalcemia if vitamin D supplements are taken concurrently. This has been reported in people being treated with vitamin D for hypoparathyroidism, and also in elderly people with normal parathyroid function who were taking a thiazide, vitamin D, and calcium-containing antacids daily.

Hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of verapamil for arrhythmia.
Hypercalcemia due to high doses of vitamin D can reduce the effectiveness of verapamil in atrial fibrillation. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and verapamil concurrently.

Vitamin D might induce CYP3A4 enzymes and reduce the bioavailability of CYP3A4 substrates.
There is some concern that vitamin D might induce CYP3A4. In vitro research suggests that vitamin D induces CYP3A4 transcription. Additionally, observational research has found that increased UV light exposure and serum vitamin D levels are associated with decreased serum levels of CYP3A4 substrates such as tacrolimus and sirolimus, while no association between UV light exposure or vitamin D levels and levels of mycophenolic acid, a non-CYP3A4 substrate, was found. A small, low-quality clinical study shows that taking vitamin D reduces levels of the CYP3A4 substrate atorvastatin and its active metabolites by up to 55%; however, the clinical effects of atorvastatin were not reduced. While researchers theorized that vitamin D might induce CYP3A4, this proposed mechanism was not specifically studied.

Theoretically, frequent and high doses of rhubarb might increase the risk of hypokalemia when taken with corticosteroids.
Rhubarb has stimulant laxative effects. Overuse of rhubarb might compound corticosteroid-induced potassium loss.

Theoretically, taking rhubarb with cyclosporine might reduce cyclosporine levels.
Animal research shows that co-administration of rhubarb decoction 0.25 or 1 gram/kg with cyclosporine 2.5 mg/kg, decreases cyclosporine maximum plasma concentration and overall exposure levels when compared with taking cyclosporine alone. The authors theorize that rhubarb might reduce cyclosporine bioavailability by inducing of P-glycoprotein and/or cytochrome P450 3A4. However, since rhubarb was administered as a single oral dose and enzyme induction usually occurs after multiple doses, it is possible that cyclosporine absorption was actually reduced via rhubarb's stimulant laxative effects. Also, the composition of the rhubarb decoction was not described.

Theoretically, overuse of rhubarb might increase the risk of adverse effects when taken with digoxin.
Rhubarb has stimulant laxative effects. Overuse of rhubarb might cause potassium depletion, increasing the risk of digoxin toxicity.

Theoretically, frequent and high doses of rhubarb might increase the risk of hypokalemia.
Rhubarb has stimulant laxative effects. Overuse of rhubarb might cause potassium depletion and compound diuretic-induced potassium loss.

Theoretically, concomitant use of rhubarb with potentially hepatotoxic drugs might increase the risk of developing liver damage.
Some animal research suggests that anthraquinones in rhubarb might have hepatotoxic effects. Also, rhubarb use has been linked to at least 24 cases of liver injury, although details on the dose of rhubarb and duration of use in these cases is unclear.

Theoretically, long-term use of anthraquinones from rhubarb might increase the risk of nephrotoxicity when used with nephrotoxic drugs.
The anthraquinone constituents of rhubarb have been shown to induce nephrotoxicity in animal research. Additionally, in a case report, a 23-year old female presented with kidney failure after taking 6 tablets of a proprietary slimming agent (found to contain the anthraquinones emodin and aloe-emodin from rhubarb) daily for 6 weeks and then adding diclofenac 25 mg 4 times daily for 2 days. The authors postulate that the anthraquinone constituents of rhubarb contributed to the renal dysfunction, and the addition of diclofenac, a nephrotoxic drug, led to renal failure. Until more is known, advise patients to avoid taking rhubarb if they are taking other potentially nephrotoxic drugs.

Theoretically, rhubarb might increase the risk for fluid and electrolyte loss when taken with other stimulant laxatives.
Rhubarb has stimulant laxative effects. Concomitant use with stimulant laxatives might compound fluid and electrolyte loss.

Theoretically, excessive use of rhubarb might increase the risk of bleeding when taken with warfarin.
Rhubarb has stimulant laxative effects and 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 rhubarb.

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, maritime pine bark extract might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
Clinical research suggests that maritime pine bark extract inhibits platelet aggregation. However, the clinical significance of this effect is unclear.

Theoretically, maritime pine bark extract might increase the risk of hypoglycemia when used with antidiabetes drugs.
One clinical study shows that maritime pine bark extract decreases blood sugar in patients with diabetes being treated with antidiabetes agents. Monitor blood glucose levels closely. Dose adjustments might be necessary.

Theoretically, maritime pine bark extract might decrease the effectiveness of immunosuppressant therapy.
In vitro and animal research suggests that maritime pine bark extract has immunostimulant activity. This effect has not been reported in humans.

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.

Magnesium can reduce the bioavailability of levodopa/carbidopa.
Clinical research in healthy volunteers shows that taking magnesium oxide 1000 mg with levodopa 100 mg/carbidopa 10 mg reduces the area under the curve (AUC) of levodopa by 35% and of carbidopa by 81%. In vitro and animal research shows that magnesium produces an alkaline environment in the digestive tract, which might lead to degradation and reduced bioavailability of levodopa/carbidopa.

Concomitant use of aminoglycoside antibiotics and magnesium can increase the risk for neuromuscular weakness.
Both aminoglycosides and magnesium reduce presynaptic acetylcholine release, which can lead to neuromuscular blockade and possible paralysis. This is most likely to occur with high doses of magnesium given intravenously.

Use of acid reducers may reduce the laxative effect of magnesium oxide.
A retrospective analysis shows that, in the presence of H2 receptor antagonists (H2RAs) or proton pump inhibitors (PPIs), a higher dose of magnesium oxide is needed for a laxative effect. This may also occur with antacids. Under acidic conditions, magnesium oxide is converted to magnesium chloride and then to magnesium bicarbonate, which has an osmotic laxative effect. By reducing acidity, antacids may reduce the conversion of magnesium oxide to the active bicarbonate salt.

Magnesium 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 magnesium containing products.

Magnesium can decrease absorption of bisphosphonates.
Cations, including magnesium, can decrease bisphosphonate absorption. Advise patients to separate doses of magnesium and these drugs by at least 2 hours.

Magnesium can have additive effects with calcium channel blockers, although evidence is conflicting.
Magnesium inhibits calcium entry into smooth muscle cells and may therefore have additive effects with calcium channel blockers. Severe hypotension and neuromuscular blockades may occur when nifedipine is used with intravenous magnesium, although some contradictory evidence suggests that concurrent use of magnesium with nifedipine does not increase the risk of neuromuscular weakness. High doses of magnesium could theoretically have additive effects with other calcium channel blockers.

Magnesium salts may reduce absorption of digoxin.
Clinical evidence suggests that treatment with oral magnesium hydroxide or magnesium trisilicate reduces absorption of digoxin from the intestines. This may reduce the blood levels of digoxin and decrease its therapeutic effects.

Potassium-sparing diuretics decrease excretion of magnesium, possibly increasing magnesium levels.
Potassium-sparing diuretics also have magnesium-sparing properties, which can counteract the magnesium losses associated with loop and thiazide diuretics. Theoretically, increased magnesium levels could result from concomitant use of potassium-sparing diuretics and magnesium supplements.

Magnesium decreases absorption of quinolones.
Magnesium can form insoluble complexes with quinolones and decrease their absorption. Advise patients to take these drugs at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

Parenteral magnesium alters the pharmacokinetics of skeletal muscle relaxants, increasing their effects and accelerating the onset of effect.
Parenteral magnesium shortens the time to onset of skeletal muscle relaxants by about 1 minute and prolongs the duration of action by about 2 minutes. Magnesium potentiates the effects of skeletal muscle relaxants by decreasing calcium-mediated release of acetylcholine from presynaptic nerve terminals, reducing postsynaptic sensitivity to acetylcholine, and having a direct effect on the membrane potential of myocytes. Magnesium also has vasodilatory actions and increases cardiac output, allowing a greater amount of muscle relaxant to reach the motor end plate. A clinical study found that low-dose rocuronium (0.45 mg/kg), when given after administration of magnesium 30 mg/kg over 10 minutes, has an accelerated onset of effect, which matches the onset of effect seen with a full-dose rocuronium regimen (0.6 mg/kg). In another clinical study, onset times for rocuronium doses of 0.3, 0.6, and 1.2 mg/kg were 86, 76, and 50 seconds, respectively, when given alone, but were reduced to 66, 44, and 38 seconds, respectively, when the doses were given after a 15-minute infusion of magnesium sulfate 60 mg/kg. Giving intraoperative intravenous magnesium sulfate, 50 mg/kg loading dose followed by 15 mg/kg/hour, reduces the onset time of rocuronium, enhances its clinical effects, reduces the dose of intraoperative opiates, and prolongs the spontaneous recovery time. It does not affect the activity of subsequently administered neostigmine.

Magnesium increases the systemic absorption of sulfonylureas, increasing their effects and side effects.
Clinical research shows that administration of magnesium hydroxide with glyburide increases glyburide absorption, increases maximal insulin response by 35-fold, and increases the risk of hypoglycemia, when compared with glyburide alone. A similar interaction occurs between magnesium hydroxide and glipizide. The mechanism of this effect appears to be related to the elevation of gastrointestinal pH by magnesium-based antacids, increasing solubility and enhancing absorption of sulfonylureas.

Magnesium decreases absorption of tetracyclines.
Magnesium can form insoluble complexes with tetracyclines in the gut and decrease their absorption and antibacterial activity. Advise patients to take these drugs 1 hour before or 2 hours after magnesium supplements.

Theoretically, magnesium may have antiplatelet effects, but the evidence is conflicting.
In vitro evidence shows that magnesium sulfate inhibits platelet aggregation, even at low concentrations. Some preliminary clinical evidence shows that infusion of magnesium sulfate increases bleeding time by 48% and reduces platelet activity. However, other clinical research shows that magnesium does not affect platelet aggregation, although inhibition of platelet-dependent thrombosis can occur.

Gabapentin absorption can be decreased by magnesium.
Clinical research shows that giving magnesium oxide orally along with gabapentin decreases the maximum plasma concentration of gabapentin by 33%, time to maximum concentration by 36%, and area under the curve by 43%. Advise patients to take gabapentin at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

Sevelamer may increase serum magnesium levels.
In patients on hemodialysis, sevelamer use was associated with a 0.28 mg/dL increase in serum magnesium. The mechanism of this interaction remains unclear.

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, the antioxidant effects of rose hip might reduce the effectiveness of alkylating agents but might also reduce the oxidative damage caused by certain alkylating agents.
Rose hip contains vitamin C. 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. Further, some animal research suggests that the antioxidant effects of rose hip might attenuate cyclophosphamide-induced testicular toxicity. More evidence is needed to determine what effect, if any, antioxidants found in rose hip, such as vitamin C, have on the effectiveness and adverse effects of chemotherapy.

Theoretically, rose hip might increase the amount of aluminum absorbed from aluminum compounds.
Rose hip contains vitamin C. Theoretically, vitamin C increases the absorption of aluminum. Concomitant use might increase aluminum absorption, but the clinical significance of this is unknown. Administer rose hip two hours before or four hours after antacids.

Theoretically, rose hip might reduce the effectiveness of anticoagulant or antiplatelet drugs.
In vitro and animal research suggests that a constituent of rose hip, rugosin E, can induce platelet aggregation. This has not been shown in humans. Theoretically, concomitant use of rose hip might reduce the effectiveness of antiplatelet or anticoagulant drugs.

Theoretically, the antioxidant effects of rose hip might reduce the effectiveness of antitumor antibiotics.
Rose hip contains the antioxidant vitamin C. 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, rose hip might increase blood levels of estrogens.
Rose hip contains vitamin C. Increases in plasma estrogen levels of up to 55% have occured 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, rose hip might increase blood levels of lithium.
Rose hip is thought to have diuretic properties. Theoretically, due to these potential diuretic effects, rose hip might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

Theoretically, rose hip might reduce the clearance of aspirin; however, its vitamin C content is likely too low to produce clinically significant effects.
Rose hip 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 rose hip is typically about 500 mg per 100 grams. Thus, a clinically significant interaction between rose hip and aspirin is unlikely.

Theoretically, rose hip might reduce the effectiveness of warfarin; however, its vitamin C content is likely too low to produce clinically significant effects.
Rose hip 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 rose hip is typically about 500 mg per 100 grams. Thus, a clinically significant interaction between rose hip and warfarin is unlikely.

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, 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.