ARM Plus+ Watermelon Splash Ingredients & Drug Interactions

Theoretically, black psyllium might reduce the effects of carbamazepine and increase the risk for convulsions.
Theoretically, black psyllium might reduce carbamazepine absorption. A preliminary study using blond psyllium reported decreased carbamazepine bioavailability due to binding of the drug to psyllium, as well as reduction of available fluid in the gut for dissolution of the drug. This interaction may also occur with black psyllium.

Theoretically, taking black psyllium at the same time as lithium might reduce lithium absorption.
The fiber in black psyllium might reduce lithium absorption and plasma levels. Some case reports describe a reduction in plasma lithium levels with concomitant administration of blond psyllium. This was reversed when psyllium was stopped. This interaction may also occur with black psyllium.

Theoretically, black psyllium might increase the therapeutic and adverse effects of metformin.
Animal research shows that concurrent consumption of blond psyllium with metformin slows and increases the absorption of metformin. This interaction may also occur with black psyllium. To avoid changes in absorption, take psyllium 30-60 minutes after metformin.

Theoretically, taking black psyllium at the same time as olanzapine might reduce olanzapine absorption.
The fiber in black psyllium might decrease the absorption of olanzapine. A single case report describes a reduction in the effectiveness of olanzapine when it was concomitantly administered with an unspecified type of psyllium 3 grams orally twice daily. This effect was reversed when psyllium was stopped.

Theoretically, taking black psyllium at the same time as digoxin might reduce digoxin absorption and decrease digoxin levels.
Psyllium might bind digoxin in the gut. However, some clinical evidence suggests that psyllium does not impact digoxin absorption.

Theoretically, taking black psyllium at the same time as ethinyl estradiol might alter levels of estradiol.
Concurrent use of blond psyllium with ethinyl estradiol results in a slight increase in the extent of ethinyl estradiol absorption and a slower rate of absorption. This is unlikely to be clinically significant.

Theoretically, psyllium might increase, decrease, or have no effect on the absorption of oral drugs.
Psyllium seems to have variable effects on drug absorption. To avoid changes in absorption, take psyllium 30-60 minutes after oral medications. Animal research shows that blond psyllium delays and increases the absorption of metformin and ethinyl estradiol. Case reports and animal research suggest that blond psyllium might reduce absorption of lithium, digoxin, olanzapine, and carbamazepine. Finally, some pharmacokinetic studies show that psyllium does not affect the absorption of levothyroxine or warfarin. Although many of these studies evaluated blond psyllium, the fiber content in black psyllium may have similar effects.

Theoretically, taking rhodiola with antidiabetes drugs might increase the risk of hypoglycemia.
In vitro and animal research shows that rhodiola extract can decrease blood glucose due to alpha-glucosidase activity.

Theoretically, taking rhodiola with antihypertensive drugs might increase the risk of hypotension.
In vitro and animal research shows that rhodiola extract inhibits angiotensin-converting enzyme (ACE) and might lower blood pressure.

Theoretically, rhodiola might increase levels of drugs metabolized by CYP2C9.
In vitro research shows that rhodiola inhibits CYP2C9. This effect is highly variable and appears to be dependent on the rhodiola product studied. Also, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours.

Theoretically, rhodiola use might interfere with immunosuppressive therapy.
In vitro and animal research show that rhodiola has immunostimulatory effects.

Rhodiola might increase the levels and adverse effects of losartan.
A clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours.

Theoretically, rhodiola might increase levels of P-glycoprotein substrates.
In vitro research shows that rhodiola inhibits P-glycoprotein. Theoretically, using rhodiola with P-glycoprotein substrates might increase drug levels and potentially increase the risk of adverse effects.

Theoretically, rhodiola might increase the risk of adverse effects when taken with antidepressants.
A review of adverse event reports in Poland identified cases of tachyarrhythmias, myalgia, arthralgia, gum pain, restless leg syndrome, swallowing disorders, and changes in consciousness when rhodiola was taken in combination with paroxetine, escitalopram, fluoxetine, sertraline, trazodone, and/or duloxetine.

Theoretically, rhodiola might increase the risk of adverse effects when taken with CNS depressants.
A review of adverse event reports in Poland identified cases of excessive sedation, myoclonus, hypotension, and hallucinations when rhodiola was taken with haloperidol, diazepam, or alprazolam.

Theoretically, rhodiola might increase levels of drugs metabolized by CYP1A2.
In vitro research shows that rhodiola inhibits CYP1A2. This effect is highly variable and appears to be dependent on the rhodiola product studied. However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of caffeine, a CYP1A2 substrate.

Theoretically, rhodiola might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that rhodiola inhibits CYP3A4. This effect is highly variable and appears to be dependent on the rhodiola product studied. However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of midazolam, a CYP3A4 substrate.

Theoretically, combining peony with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
In vitro research suggests that peony might have antiplatelet, anticoagulant, and antithrombotic effects.

Theoretically, peony might increase the levels and clinical effects of clozapine.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on cytochromes P450 (CYP) 1A2 and CYP3A4. This effect has not been reported in humans.

Theoretically, peony might interfere with contraceptive drugs due to competition for estrogen receptors.
In vitro and animal research shows that peony extract has estrogenic activity. Concomitant use might also increase the risk for estrogen-related adverse effects.

Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4. This effect has not been reported in humans.

Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4. This effect has not been reported in humans.

Theoretically, concomitant use of large amounts of peony might interfere with hormone replacement therapy and/or increase the risk for estrogen-related adverse effects.
In vitro and animal research shows that peony extract has estrogenic activity. Theoretically, peony might compete for estrogen receptors and/or cause additive estrogenic effects.

Theoretically, peony might reduce the levels and clinical effects of phenytoin.
Animal research shows that taking peony root reduces levels of phenytoin. Some researchers suggest that peony root might affect cytochrome P450 (CYP) 2C9, which metabolizes phenytoin. However, preliminary research in humans shows that peony root does not alter levels of losartan (Cozaar), which is also metabolized by CYP2C9.

Theoretically, schisandra might increase the levels and clinical effects of cyclophosphamide.
In vitro research shows that schisandra increases the concentration of cyclophosphamide, likely through inhibition of cytochrome P450 3A4. After multiple doses of the schisandra constituents schisandrin A and schisantherin A, the maximum concentration of cyclophosphamide was increased by 7% and 75%, respectively, while the overall exposure to cyclophosphamide was increased by 29% and 301%, respectively.

Schisandra can increase the levels and clinical effects of cyclosporine.
A small observational study in children with aplastic anemia found that taking schisandra with cyclosporine increased cyclosporine trough levels by 93% without increasing the risk of adverse events. However, the dose of cyclosporine was reduced in 9% of children to maintain appropriate cyclosporine blood concentrations.

Theoretically, schisandra might increase the levels and clinical effects of CYP2C19 substrates.
In vitro research shows that schisandra inhibits CYP2C19, and animal research shows that schisandra increases the concentration of voriconazole, a CYP2C19 substrate. Theoretically, schisandra may also inhibit the metabolism of other CYP2C19 substrates. This effect has not been reported in humans.

Theoretically, schisandra might decrease the levels and clinical effects of CYP2C9 substrates.
In vitro and animal research suggests that schisandra induces CYP2C9 enzymes. This effect has not been reported in humans.

Schisandra can increase the levels and clinical effects of drugs metabolized by CYP3A4.
Most clinical and laboratory research shows that schisandra, administered either as a single dose or up to twice daily for 14 days, inhibits CYP3A4 and increases the concentration of CYP3A4 substrates such as cyclophosphamide, midazolam, tacrolimus, and talinolol. Although one in vitro and animal study shows that schisandra may induce CYP3A4 metabolism, this effect appears to be overpowered by schisandra's CYP3A4 inhibitory activity and has not been reported in humans.

Schisandra can increase the levels and clinical effects of midazolam.
A small pharmacokinetic study in healthy adults shows that taking schisandra extract (Hezheng Pharmaceutical Co.) containing deoxyschizandrin 33.75 mg twice daily for 8 days and a single dose of midazolam 15 mg on day 8 increases the overall exposure to midazolam by about 119%, increases the peak plasma level of midazolam by 86%, and decreases midazolam clearance by about 52%. This effect has been attributed to inhibition of CYP3A4 by schisandra.

Schisandra might increase the levels and clinical effects of P-glycoprotein substrates.
In vitro research shows that schisandra extracts and constituents such as schisandrin B inhibit P-glycoprotein mediated efflux in intestinal cells and in P-glycoprotein over-expressing cell lines. Additionally, a small clinical study shows that schisandra increases the peak concentration and overall exposure to talinolol, a P-glycoprotein probe substrate. Theoretically, schisandra might inhibit the efflux of other P-glycoprotein substrates.

Schisandra can increase the levels and clinical effects of sirolimus.
A small pharmacokinetic study in healthy volunteers shows that taking 3 capsules of schisandra (Hezheng Pharmaceutical Company) containing a total of 33.75 mg deoxyschizandrin twice daily for 13 days and then taking a single dose of sirolimus 2 mg increases the overall exposure and peak level of sirolimus by two-fold. This effect is thought to be due to inhibition of cytochrome P450 3A4 by schisandra, as well as possible inhibition of the P-glycoprotein drug transporter.

Schisandra can increase the levels and clinical effects of tacrolimus.
Clinical research in healthy children and adults, transplant patients, and patients with nephrotic syndrome and various rheumatic immunologic disorders shows that taking schisandra with tacrolimus increases tacrolimus peak levels by 183% to 268%, prolongs or delays time to peak tacrolimus concentrations, increases overall exposure to tacrolimus by 126% to 343%, and decreases tacrolimus clearance by 19% to 73%. This effect is thought to be due to inhibition of P-glycoprotein drug transporter and CYP3A4 and CYP3A5 by schisandra. Some clinical and observational studies suggest that schisandra increases tacrolimus levels similarly in both expressors and non-expressors of CYP3A5, while other studies suggest it does so to a greater degree in CYP3A5 expressors than non-expressors. Animal research suggests that the greatest increase in tacrolimus levels occurs when schisandra is taken either concomitantly or up to 2 hours before tacrolimus, and clinical and observational research in humans suggests that schisandra may increase whole blood levels of tacrolimus and decrease clearance of tacrolimus in a dose-dependent manner.

Schisandra can increase the levels and clinical effects of talinolol.
A small pharmacokinetic study in healthy volunteers shows that taking schisandra extract 300 mg twice daily for 14 days with a single dose of talinolol 100 mg on day 14 increases the peak talinolol level by 51% and the overall exposure to talinolol by 47%. This effect is thought to be due to the possible inhibition of cytochrome P450 3A4 and P-glycoprotein by schisandra. tly.

Theoretically, schisandra might increase the levels and clinical effects of voriconazole.
Animal research shows that oral schisandra given daily for 1 or 14 days increases levels of intravenously administered voriconazole, a cytochrome P450 (CYP) 2C19 substrate. This effect is thought to be due to inhibition of CYP2C19 by schisandra. However, this interaction has not been reported in humans.

Theoretically, schisandra might decrease the levels and clinical effects of warfarin.
Animal research suggests that oral schisandra extract, given daily for 6 days, reduces levels of intravenously administered warfarin. This effect might be due to the induction of cytochrome P450 (CYP) 2C9 metabolism by schisandra. However, this interaction has not been reported in humans.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Theoretically, concomitant use of L-arginine and ACE inhibitors may increase the risk for hypotension and hyperkalemia.
Combining L-arginine with some antihypertensive drugs, especially ACE inhibitors, seems to have additive vasodilating and blood pressure-lowering effects. Furthermore, ACE inhibitors can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients. Theoretically, concomitant use of ACE inhibitors with L-arginine may increases the risk of hyperkalemia.

Theoretically, concomitant use of L-arginine and ARBs may increase the risk of hypotension and hyperkalemia.
L-arginine increases nitric oxide, which causes vasodilation. Combining L-arginine with ARBs seems to increase L-arginine-induced vasodilation. Furthermore, ARBs can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients. Theoretically, concomitant use of ARBs with L-arginine may increases the risk of hyperkalemia.

Theoretically, concomitant use of L-arginine with anticoagulant and antiplatelet drugs might have additive effects and increase the risk of bleeding.
Preliminary research suggests that L-arginine infusions reduce platelet aggregation in humans. The clinical significance of this effect is unclear.

Theoretically, concomitant use of L-arginine might have additive effects with antidiabetes drugs.
Preliminary clinical research shows that L-arginine decreases blood glucose levels in patients with type 2 diabetes.

Theoretically, concomitant use of L-arginine and antihypertensive drugs may increase the risk of hypotension.
L-arginine increases nitric oxide, which causes vasodilation. Clinical evidence shows that L-arginine can reduce blood pressure in some individuals with hypertension. Furthermore, combining L-arginine with some antihypertensive drugs seems to have additive vasodilating and blood pressure-lowering effects.

Theoretically, concurrent use of isoproterenol and L-arginine might result in additive effects and hypotension.
Preliminary clinical evidence suggests that L-arginine enhances isoproterenol-induced vasodilation in patients with essential hypertension or a family history of essential hypertension.

Theoretically concomitant use of potassium-sparing diuretics with L-arginine may increases the risk of hyperkalemia.
Potassium-sparing diuretics can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients.

Theoretically, concurrent use of sildenafil and L-arginine might increase the risk for hypotension.
In vivo, concurrent use of L-arginine and sildenafil has resulted in increased vasodilation. Theoretically, concurrent use might have additive vasodilatory and hypotensive effects. However, in studies evaluating the combined use of L-arginine and sildenafil for erectile dysfunction, hypotension was not reported.

Theoretically, concomitant use of L-arginine and testosterone might have additive effects.
In clinical research, L-arginine increases the level of testosterone in male patients with erectile dysfunction. The clinical significance of this finding is unclear.

Theoretically, fenugreek might have additive effects when used with anticoagulant or antiplatelet drugs.
Some of the constituents in fenugreek have antiplatelet effects in animal and in vitro research. However, common fenugreek products might not contain sufficient concentrations of these constituents for clinical effects. A clinical study in patients with coronary artery disease or diabetes shows that taking fenugreek seed powder 2.5 grams twice daily for 3 months does not affect platelet aggregation, fibrinolytic activity, or fibrinogen levels .

Theoretically, fenugreek seed might have additive hypoglycemic effects when used with antidiabetes drugs.
Clinical research shows that fenugreek seed can reduce fasting blood glucose and 2-hour postprandial glucose levels in adults with type 2 diabetes.

Theoretically, fenugreek seed might alter the clinical effects of clopidogrel by inhibiting its conversion to the active form.
Animal research shows that fenugreek seed 200 mg/kg daily for 14 days increases the maximum serum concentration of clopidogrel by 21%. It is unclear how this affects the pharmacokinetics of the active metabolite of clopidogrel; however, this study found that concomitant use of fenugreek seed and clopidogrel prolonged bleeding time by an additional 11%.

Theoretically, fenugreek seed might have additive hypotensive effects when used with metoprolol.
Animal research shows that fenugreek seed 300 mg/kg daily for 2 weeks decreases systolic and diastolic blood pressure by 9% and 11%, respectively, when administered alone, and by 15% and 22%, respectively, when given with metoprolol 10 mg/kg.

Theoretically, fenugreek might decrease plasma levels of phenytoin.
Animal research shows that taking fenugreek seeds for 1 week decreases maximum concentrations and the area under the curve of a single dose of phenytoin by 44% and 72%, respectively. This seems to be related to increased clearance. So far, this interaction has not been reported in humans.

Theoretically, concurrent use of sildenafil and fenugreek might reduce levels and therapeutic effects of sildenafil.
Animal research shows that taking fenugreek seeds for 1 week reduces maximum concentrations and the area under the curve of a single dose of sildenafil by 27% and 48%, respectively. So far, this interaction has not been reported in humans.

Theoretically, fenugreek may reduce the levels and clinical effects of theophylline.
Animal research shows that fenugreek 50 grams daily for 7 days reduces the maximum serum concentration (Cmax) of theophylline by 28% and the area under the plasma drug concentration-time curve (AUC) by 22%.

Theoretically, fenugreek might have additive effects with warfarin and increase the international normalized ratio (INR).
Some fenugreek constituents have antiplatelet effects, although these might not be present in concentrations that are clinically significant. In one case report, a patient taking warfarin experienced an increased INR when starting to take fenugreek in combination with boldo.

Fenugreek may also have an additive effect on blood pressure-lowering medications. Studies on animals have shown that fenugreek seed can decrease both systolic and diastolic blood pressure by up to 22% when combined with metoprolol. Therefore, it is essential to monitor your blood pressure regularly if you are taking fenugreek and metoprolol together or any other antihypertensive drugs.

Theoretically, concomitant use of banaba and hypoglycemic drugs might have additive effects.
Human and animal research suggests that banaba can lower blood glucose levels.

Theoretically, concomitant use of banaba and antihypertensive drugs might cause additive effects.
Human and animal research suggests that banaba can lower blood pressure.

Theoretically, concomitant use of banaba with substrates of OATP might reduce the bioavailability of the OATP substrate.
In vitro research shows that banaba inhibits OATP, particularly OATP2B1. OATPs are expressed in the small intestine and liver and are responsible for the absorption of drugs and other compounds.

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, bilberry fruit extract might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
In vitro, animal, and clinical research suggest that anthocyanidin extracts from bilberry can inhibit platelet aggregation.

Theoretically, bilberry leaf or fruit extract may increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal research suggests that bilberry leaf extract might have blood glucose-lowering activity. Also, one small clinical trial in patients with type 2 diabetes shows that taking bilberry fruit extract 470 mg as a single dose prior to an oral glucose tolerance test lowers plasma glucose levels when compared with placebo.

Theoretically, bilberry fruit extract might decrease levels of drugs metabolized by CYP2E1.
Animal research shows that exposure to small concentrations of bilberry extract in drinking water for around one month increased CYP2E1 activity by 31%. However, exposure over a 2-month period did not increase CYP2E1 activity. This effect has not been reported in humans.

Theoretically, bilberry fruit extract might reduce the efficacy of erlotinib.
In vitro research suggests that bilberry fruit extract and its constituents, delphinidin and delphinidin-3-O-glucoside, inhibit the activity of erlotinib. This interaction has not been reported in humans.

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, Indian gooseberry may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs; however, research is conflicting.
Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking Indian gooseberry 500 mg along with clopidogrel 75 mg or ecosprin 75 mg, as a single dose or for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with clopidogrel 75 mg or ecosprin 75 mg alone. Until more is known, use caution when taking Indian gooseberry in combination with anticoagulant/antiplatelet drugs.

Taking Indian gooseberry with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research shows that taking Indian gooseberry fruit or fruit extract alone or in conjunction with antidiabetes medications can lower blood glucose levels. Dose adjustments to diabetes medications might be necessary.

Theoretically, Indian gooseberry may increase the risk of bleeding if used with aspirin; however, research is conflicting.
Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking a single dose of Indian gooseberry 500 mg along with ecosprin 75 mg, or taking a combination of Indian gooseberry 500 mg twice daily plus ecosprin 75 mg once daily for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with ecosprin 75 mg alone.

Theoretically, Indian gooseberry may increase the risk of bleeding if used with clopidogrel; however, research is conflicting.
Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking a single dose of Indian gooseberry 500 mg along with clopidogrel 75 mg, or taking a combination of Indian gooseberry 500 mg twice daily plus clopidogrel 75 mg once daily for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with clopidogrel 75 mg alone.

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

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

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

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

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

Theoretically, concomitant use of L-citrulline with antihypertensive drugs might have additive effects and increase the chance of hypotension.
L-citrulline is converted to L-arginine, which can increase nitric oxide and cause vasodilation. However, a meta-analysis of 5 small clinical studies suggests that taking L-citrulline 3-6 grams daily for 1-8 weeks does not lower blood pressure when compared with control.

Theoretically, concurrent use of phosphodiesterase-5 (PDE-5) inhibitors and L-citrulline might result in additive vasodilation.
L-citrulline is converted to L-arginine, which can increase nitric oxide and cause vasodilation. Theoretically, taking L-arginine with PDE-5 inhibitors might have additive vasodilatory and hypotensive effects. However, in studies evaluating the combined use of L-arginine and sildenafil for erectile dysfunction, hypotension was not reported.

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 risk for manganese toxicity might increase when taken with antipsychotic drugs.
Hallucinations and behavioral changes have been reported in a patient with liver disease who was taking haloperidol and manganese. Researchers speculate that taking manganese along with haloperidol, phenothiazine-derivatives, or other antipsychotic medications might increase the risk of manganese toxicity in some patients.

Theoretically, manganese might reduce the absorption of quinolone antibiotics.
Manganese is a multivalent cation. Interactions resulting in reduced quinolone absorption have been reported between quinolones and other multivalent cations, such as calcium and iron.

Theoretically, manganese might reduce the absorption of tetracycline antibiotics.
Manganese is a multivalent cation. Interactions resulting in reduced tetracycline absorption have been reported between tetracyclines and other multivalent cations, such as calcium and iron.

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

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

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

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

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

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

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

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

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

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

Theoretically, whey protein might decrease levodopa absorption.
Small clinical studies show that concomitant ingestion of protein or high doses of leucine or isoleucine (100 mg/kg) and levodopa can exacerbate tremor, rigidity, and the "on-off" syndrome in patients with Parkinson disease.

Theoretically, whey protein might reduce the absorption of bisphosphonates.
Whey protein contains minerals such as calcium that bind bisphosphonates in the gut. Advise patients to take bisphosphonates at least 30 minutes before whey protein, but preferably at a different time of day.

Theoretically, whey protein might decrease quinolone absorption.
Whey protein contains minerals, such as calcium, that can bind to quinolones in the gut. To avoid this interaction, advise patients to take oral quinolones at least 2 hours before or 4-6 hours after whey protein.

Theoretically, whey protein might decrease tetracycline absorption.
Whey protein contains minerals, such as calcium, that bind to tetracyclines in the gut. To avoid this interaction, advise patients to take oral tetracyclines at least 2 hours before or 4-6 hours after whey protein.

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

Theoretically, high doses of folic acid might increase the toxicity of 5-fluorouracil.
Increases in gastrointestinal side effects of 5-fluorouracil, such as stomatitis and diarrhea, have been described in two clinical studies when leucovorin, a form of folic acid, was administered with 5-fluorouracil.

Use of high-dose folic acid might contribute to capecitabine toxicity.
Clinical research suggests that higher serum folate levels are associated with an increased risk for moderate or severe toxicity during capecitabine-based treatment for colorectal cancer. Additionally, in one case report, taking folic acid 15 mg daily might have contributed to increased toxicity, including severe diarrhea, vomiting, edema, hand-foot syndrome, and eventually death, in a patient prescribed capecitabine.

Folic acid might reduce the efficacy of methotrexate as a cancer treatment when given concurrently.
Methotrexate exerts its cytotoxic effects by preventing conversion of folic acid to the active form needed by cells. There is some evidence that folic acid supplements reduce the efficacy of methotrexate in the treatment of acute lymphoblastic leukemia, and theoretically they could reduce its efficacy in the treatment of other cancers. Advise cancer patients to consult their oncologist before using folic acid supplements. In patients treated with long-term, low-dose methotrexate for rheumatoid arthritis (RA) or psoriasis, folic acid supplements can reduce the incidence of side effects, without reducing efficacy.

Folic acid might have antagonistic effects on phenobarbital and increase the risk for seizures.
Folic acid can have direct convulsant activity in some people, reversing the effects of phenobarbital and worsening seizure control. Monitor closely for increased seizure activity.

Folic acid might reduce serum levels of phenytoin in some patients.
Folic acid may be a cofactor in phenytoin metabolism. Folic acid, in doses of 1 mg daily or more, can reduce serum levels of phenytoin in some patients. Increases in seizure frequency have been reported. If folic acid supplements are added to established phenytoin therapy, monitor serum phenytoin levels closely. If phenytoin and folic acid are started at the same time and continued together, adverse changes in phenytoin pharmacokinetics are avoided. Note that phenytoin also reduces serum folate levels.

Folic acid might have antagonistic effects on primidone and increase the risk for seizures.
Folic acid can have direct convulsant activity in some people, reversing the effects of primidone and worsening seizure control. Monitor closely for increased seizure activity. Note that primidone also reduces serum folate levels.

Folic acid might antagonize the effects of pyrimethamine.
Folic acid can antagonize the antiparasitic effects of pyrimethamine against toxoplasmosis and Pneumocystis carinii pneumonia. Folic acid doesn't antagonize the effects of pyrimethamine in the treatment of malaria, because malarial parasites cannot use exogenous folic acid. Use folinic acid as an alternative to folic acid when indicated.

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

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

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

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

Theoretically, L-carnitine might increase the anticoagulant effects of acenocoumarol.
L-carnitine might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant similar to warfarin, but shorter-acting. There are at least two case reports of INR elevation with concomitant use. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product.

Theoretically, L-carnitine might decrease the effectiveness of thyroid hormone replacement.
L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells. Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism.

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

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