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

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

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

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

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

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

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

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

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

Theoretically, 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.

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

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

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

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

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

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

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, DHA may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Although some clinical evidence suggests that DHA might reduce collagen-stimulated platelet aggregation and thromboxane release, most clinical evidence suggests that DHA alone does not affect blood clotting. However, theoretically, when given in combination with EPA as fish oil, concomitant use with anticoagulant or antiplatelet drugs (including aspirin) might increase risk of bleeding.

Theoretically, taking DHA with antidiabetes drugs might reduce the effects of these medications.
In people with type 2 diabetes, including those taking oral hypoglycemic medications, DHA seems to increase fasting blood glucose levels.

Theoretically, taking DHA with antihypertensive drugs might increase the risk of hypotension.
Fish oils containing DHA can lower blood pressure and might have additive effects in patients treated with antihypertensives; use with caution.

In vitro and animal research suggests that strawberry extract can inhibit platelet aggregation due to its phenolic content. Theoretically, strawberry might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
Some anticoagulant or antiplatelet drugs include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), warfarin (Coumadin), and others.

In vitro research suggests that strawberry extract can inhibit p-glycoprotein efflux. Theoretically, strawberry might inhibit p-glycoprotein mediated drug efflux and potentially increase levels of drugs that are substrates of p-glycoprotein. Until more is known, strawberry should be used cautiously in people taking p-glycoprotein substrates.
Drugs that might be affected include some chemotherapeutic agents (etoposide, paclitaxel, vinblastine, vincristine, vindesine), antifungals (ketoconazole, itraconazole), protease inhibitors (amprenavir, indinavir, nelfinavir, saquinavir), H2 antagonists (cimetidine, ranitidine), some calcium channel blockers (diltiazem, verapamil), corticosteroids, erythromycin, cisapride (Propulsid), fexofenadine (Allegra), cyclosporine, loperamide (Imodium), quinidine, and others.

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, concomitant use of anticoagulant or antiplatelet drugs with onion might increase the risk of bleeding.
In vitro research shows that onion inhibits platelet aggregation.

Concomitant use of antidiabetes drugs with onion may increase the risk of hypoglycemia.
Animal research and clinical research shows that taking onion can lower blood glucose levels. Monitor blood glucose levels closely.

Concomitant use of aspirin with onion may worsen onion allergy.
In one case report, a patient with a mild onion allergy reported worsening allergy, including swelling and severe urticaria, after taking aspirin.

Theoretically, taking onion might increase the levels and clinical effects of drugs metabolized by CYP2E1.
Animal research shows that taking onion powder inhibits CYP2E1. However, this interaction has not been reported in humans.

Onion is thought to have diuretic properties. Theoretically, due to these potential diuretic effects, onion might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

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.

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

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

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

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

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

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

Theoretically, taking Bifidobacterium breve with antibiotic drugs might decrease the effectiveness of B. breve.
Since B. breve preparations usually contain live and active organisms, simultaneously taking antibiotics might kill a significant number of the organisms. Tell patients to separate administration of antibiotics and B. breve preparations by at least 2 hours.

Theoretically, taking Lactobacillus acidophilus with antibiotic drugs might decrease the effectiveness of L. acidophilus.
L. acidophilus preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms. Tell patients to separate administration of antibiotics and L. acidophilus preparations by at least two hours.

Theoretically, taking Bifidobacterium lactis with antibiotic drugs might decrease the effectiveness of B. lactis.
Since B. lactis preparations usually contain live and active organisms, simultaneously taking antibiotics might kill a significant number of the organisms. Tell patients to separate administration of antibiotics and B. lactis preparations by at least 2 hours.

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, niacinamide may have additive effects when used with anticoagulant or antiplatelet drugs, especially in patients on hemodialysis.
Several cases of thrombocytopenia have been reported for hemodialysis patients treated with niacinamide 1 gram daily. Hemodialysis patients receiving niacinamide had almost a three-fold higher risk of developing thrombocytopenia when compared with those receiving placebo.

Niacinamide might increase the levels and adverse effects of carbamazepine.
Plasma levels of carbamazepine were increased in two children given high-dose niacinamide, 60-80 mg/kg/day. This might be due to inhibition of the cytochrome P450 enzymes involved in carbamazepine metabolism. There is not enough data to determine the clinical significance of this interaction.

Niacinamide might increase the levels and adverse effects of primidone.
Case reports in children suggest niacinamide 60-100 mg/kg/day reduces hepatic metabolism of primidone to phenobarbital, and reduces the overall clearance rate of primidone; however, there is not enough data to determine the clinical significance of this potential interaction.

There is limited evidence that niacinamide may increase the anticoagulant effects of warfarin.
In a case report, a patient on warfarin developed an elevated international normalized ratio (INR) of 8.4 after taking niacinamide 500 mg twice daily for 10 days. The patient's INR was previously stable, ranging between 2 and 3, with no other changes to current medications or diet reported. The elevated INR returned to the therapeutic range after receiving vitamin K and discontinuing niacinamide.

Theoretically, plum juice might have antiplatelet effects.
Consuming plum juice while taking anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding. In healthy volunteers, drinking plum juice 200 mL daily for 28 days prolonged clotting time and inhibited platelet aggregation.

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

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

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

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

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

Iron 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 iron 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, iron containing products.

Iron reduces the absorption of bisphosphonates.
Advise patients that doses of bisphosphonates should be separated by at least two hours from doses of all other medications, including supplements such as iron. Divalent cations, including iron, can decrease absorption of bisphosphonates by forming insoluble complexes in the gastrointestinal tract.

Administration of intravenous iron within one month of denosumab administration might increase the risk of severe hypophosphatemia and hypocalcemia.
A case of severe hypocalcemia (albumin corrected calcium 6.88 mg/dL, ionized calcium 3.68 mg/dL) and hypophosphatemia (<0.5 mg/dL) with respiratory acidosis, QT interval prolongation, and nonsustained ventricular tachycardia was reported in a 76-year-old male who had received an iron polymaltose infusion within 2 weeks of a subcutaneous injection of denosumab. Serum parathyroid hormone was also elevated (348 pg/mL). Subsequent iron infusions with iron polymaltose and ferric carboxymaltose were followed by transient hypophosphatemia, but without hypocalcemia. Additionally, a literature review describes 6 additional cases of hypophosphatemia and hypocalcemia in patients 52-92 years of age who had been administered intravenous iron as either ferric carboxymaltose or iron polymaltose and subcutaneous denosumab within 1-4 weeks of each other.

Iron might decrease dolutegravir levels by reducing its absorption.
Advise patients to take dolutegravir at least 2 hours before or 6 hours after taking iron. Pharmacokinetic research shows that iron can decrease the absorption of dolutegravir from the gastrointestinal tract through chelation. When taken under fasting conditions, a single dose of ferrous fumarate 324 mg orally along with dolutegravir 50 mg reduces overall exposure to dolutegravir by 54%.

Theoretically, taking iron along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Iron is a divalent cation. There is concern that iron may decrease the absorption of integrase inhibitors from the gastrointestinal tract through chelation. One pharmacokinetic study shows that iron can decrease blood levels of the specific integrase inhibitor dolutegravir through chelation. Also, other pharmacokinetic research shows that other divalent cations such as calcium can decrease the absorption and levels of some integrase inhibitors through chelation.

Iron might decrease levodopa levels by reducing its absorption.
Advise patients to separate doses of levodopa and iron as much as possible. There is some evidence in healthy people that iron forms chelates with levodopa, reducing the amount of levodopa absorbed by around 50%. The clinical significance of this hasn't been determined.

Iron might decrease levothyroxine levels by reducing its absorption.
Advise patients to separate levothyroxine and iron doses by at least 2 hours. Iron can decrease the absorption and efficacy of levothyroxine by forming insoluble complexes in the gastrointestinal tract.

Iron might decrease methyldopa levels by reducing its absorption.
Advise patients to separate methyldopa and iron doses by at least 2 hours. Iron can decrease the absorption of methyldopa from the gastrointestinal tract through chelation, resulting in increases in blood pressure.

Theoretically, iron might decrease mycophenolate mofetil levels by reducing its absorption.
Advise patients to take iron 4-6 hours before, or 2 hours after, mycophenolate mofetil. It has been suggested that a decrease of absorption is possible, probably by forming nonabsorbable chelates. However, mycophenolate pharmacokinetics are not affected by iron supplementation in available clinical research.

Iron might decrease penicillamine levels by reducing its absorption.
Advise patients to separate penicillamine and iron doses by at least 2 hours. Oral iron supplements can reduce absorption of penicillamine by 30% to 70%, probably due to chelate formation. In people with Wilson's disease, this interaction has led to reduced efficacy of penicillamine.

Iron might decrease levels of quinolone antibiotics by reducing their absorption.
Advise patients to separate quinolone antibiotics and iron doses by at least 2 hours. Iron decreases the absorption of quinolones due to formation of insoluble complexes in the gastrointestinal tract.

Iron might decrease levels of tetracycline antibiotics by reducing their absorption.
Advise patients to take iron at least 2 hours before or 4 hours after tetracycline antibiotics. Concomitant use can decrease absorption of tetracycline antibiotics from the gastrointestinal tract by 50% to 90%.

Theoretically, taking chloramphenicol with iron might reduce the response to iron therapy in iron deficiency anemia.
Chloramphenicol interferes with erythrocyte maturation. However, since chloramphenicol isn't usually taken for prolonged periods, this isn't likely to be clinically significant.

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.

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

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

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

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.

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

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

Combining iodine with lithium might have additive hypothyroid effects.
Lithium can inhibit thyroid function. Several case reports suggest that concomitant use of lithium and potassium iodide can reduce thyroid function in otherwise healthy adults. Monitor thyroid function.