InflamAid Plus 60t

Orthoplex

Orthoplex Green InflamAid Plus contains herbs traditionally used for the temporary symptomatic relief of minor headaches, lower back pain, gout, mild joint, muscle and rheumatic pain, digestive disturbances and inflammation.

Gluten Free
Egg Free
Dairy Free
Vegan
Vegetarian
    Product Details

    Pack Size
    60 Tablet

    Adult Dose
    Take 2-4 tablets daily, or as recommended by your registered healthcare practitioner.

    BIO

    Storage
    Store below 30°C in a cool, dry place, away from direct sunlight.

    Indications

      • Contains herbs traditionally used in herbal medicine:
        • As anti-inflammatories
        • To provide temporary relief of headaches and lower back pain
        • To help relieve mild rheumatic complaints as well as joint and muscular pain and inflammation
        • To help relieve minor digestive disturbances
        • To help relieve symptoms of gout
      • Vitamin C supports the healthy functioning of the immune system

    Excipients
    Calcium hydrogen phosphate dihydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, colloidal anhydrous silica, maltodextrin, povidone, hypromellose, macrogol 400, carnauba wax

    Warning
    If symptoms persist consult your healthcare practitioner. Vitamin and mineral supplements should not replace a balanced diet.

    Ingredients

    Each tablet contains

    Salix alba stem bark (Dry Herb Equiv) 80.0mg
    Prunus cerasus fruit (Dry Herb Equiv) 200.0mg
    Boswellia serrata sap (Dry Herb Equiv) 100.0mg
    Curcuma longa rhizome (Dry Herb Equiv) 100.0mg
    equiv. Curcuminoids 65.0mg
    Apium graveolens seed (Dry Herb Equiv) 150.0mg
    Zingiber officinale root (Dry Herb Equiv) 45.5mg
    Magnesium citrate 100.0mg
    equiv. Magnesium 16.2mg
    Potassium citrate 50.0mg
    Ascorbic acid 50.0mg
    Drug Interactions
    Significance
    Ingredient
    Interaction Descriptions
    Major
    MAGNESIUM
    (Magnesium, Magnesium amino acid chelate, Magnesium aspartate, Magnesium citrate, Magnesium orotate dihydrate, Magnesium oxide, Heavy magnesium oxide, Magnesium chloride hexahydrate, Magnesium phosphate pentahydrate, Magnesium glycinate dihydrate, Magnesium orotate)
    Do not take this combination.
    View Interactions:
    Major

    LEVODOPA/CARBIDOPA (Sinemet)

    Do not take this combination.

    Major

    LEVODOPA/CARBIDOPA (Sinemet)

    Do not take this combination.

    Major

    LEVODOPA/CARBIDOPA (Sinemet)

    Do not take this combination.

    Severity: high
    Occurrence: probable
    Level of Evidence: B

    Magnesium can reduce the bioavailability of levodopa/carbidopa.<br> 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 (100265).

    References

    100265

    Kashihara Y, Terao Y, Yoda K, et al. Effects of magnesium oxide on pharmacokinetics of L-dopa/carbidopa and assessment of pharmacodynamic changes by a model-based simulation. Eur J Clin Pharmacol. 2019;75(3):351-361.

    Moderate

    AMINOGLYCOSIDE ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    AMINOGLYCOSIDE ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    AMINOGLYCOSIDE ANTIBIOTICS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Concomitant use of aminoglycoside antibiotics and magnesium can increase the risk for neuromuscular weakness.<br> 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 (13362).

    References

    13362

    L'Hommedieu CS, Nicholas D, Armes DA, et al. Potentiation of magnesium sulfate--induced neuromuscular weakness by gentamicin, tobramycin, and amikacin. J Pediatr 1983;102:629-31..

    Moderate

    CALCIUM CHANNEL BLOCKERS

    Be cautious with this combination.

    Moderate

    CALCIUM CHANNEL BLOCKERS

    Be cautious with this combination.

    Moderate

    CALCIUM CHANNEL BLOCKERS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Magnesium can have additive effects with calcium channel blockers, although evidence is conflicting.<br> 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 (3046,20264,20265,20266), although some contradictory evidence suggests that concurrent use of magnesium with nifedipine does not increase the risk of neuromuscular weakness (60831). High doses of magnesium could theoretically have additive effects with other calcium channel blockers.

    References

    3046

    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.

    20264

    Koontz SL, Friedman SA, Schwartz ML. Symptomatic hypocalcemia after tocolytic therapy with magnesium sulfate and nifedipine. Am J Obstet Gynecol. 2004;190(6):1773-6.

    20265

    Snyder SW, Cardwell MS. Neuromuscular blockade with magnesium sulfate and nifedipine. Am J Obstet Gynecol. 1989;161(1):35-6.

    20266

    Waisman GD, Mayorga LM, Cámera MI, et al. Magnesium plus nifedipine: potentiation of hypotensive effect in preeclampsia? Am J Obstet Gynecol. 1988;159(2):308-9.

    60831

    Magee, L. A., Miremadi, S., Li, J., Cheng, C., Ensom, M. H., Carleton, B., Cote, A. M., and von Dadelszen, P. Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium-related maternal side effects in women with preeclampsia. Am.J Obstet.Gynecol. 2005;193(1):153-163.

    Moderate

    BISPHOSPHONATES

    Be cautious with this combination.

    Moderate

    BISPHOSPHONATES

    Be cautious with this combination.

    Moderate

    BISPHOSPHONATES

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Magnesium can decrease absorption of bisphosphonates.<br> Cations, including magnesium, can decrease bisphosphonate absorption. Advise patients to separate doses of magnesium and these drugs by at least 2 hours (13363).

    References

    13363

    Dunn CJ, Goa KL. Risedronate: a review of its pharmacological properties and clinical use in resorptive bone disease. Drugs 2001;61:685-712..

    Moderate

    SULFONYLUREAS

    Be cautious with this combination.

    Moderate

    SULFONYLUREAS

    Be cautious with this combination.

    Moderate

    SULFONYLUREAS

    Be cautious with this combination.

    Severity: mild
    Occurrence: probable
    Level of Evidence: B

    Magnesium increases the systemic absorption of sulfonylureas, increasing their effects and side effects.<br> 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 (20307). A similar interaction occurs between magnesium hydroxide and glipizide (20308). 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 (22364).

    References

    20307

    Neuvonen PJ, Kivistö KT. The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations. Br J Clin Pharmacol. 1991;32(2):215-20.

    20308

    Kivistö KT, Neuvonen PJ. Enhancement of absorption and effect of glipizide by magnesium hydroxide. Clin Pharmacol Ther. 1991;49(1):39-43.

    22364

    Neuvonen PJ, Kivistö KT. Enhancement of drug absorption by antacids. An unrecognised drug interaction. Clin Pharmacokinet. 1994;27(2):120-8.

    Moderate

    ANTACIDS

    Be cautious with this combination.

    Moderate

    ANTACIDS

    Be cautious with this combination.

    Moderate

    ANTACIDS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Use of acid reducers may reduce the laxative effect of magnesium oxide.<br> 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 (90033). 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.

    References

    90033

    Yamasaki M, Funakoshi S, Matsuda S, Imazu T, Takeda Y, Murakami T, Maeda Y. Interaction of magnesium oxide with gastric acid secretion inhibitors in clinical pharmacotherapy. Eur J Clin Pharmacol 2014;70(8):921-4.

    Moderate

    TETRACYCLINE ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    TETRACYCLINE ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    TETRACYCLINE ANTIBIOTICS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: D

    Magnesium decreases absorption of tetracyclines.<br> Magnesium can form insoluble complexes with tetracyclines in the gut and decrease their absorption and antibacterial activity (12586). Advise patients to take these drugs 1 hour before or 2 hours after magnesium supplements.

    References

    12586

    Sompolinsky D, Samra Z. Influence of magnesium and manganese on some biological and physical properties of tetracycline. J Bacteriol 1972;110:468-76..

    Moderate

    QUINOLONE ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    QUINOLONE ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    QUINOLONE ANTIBIOTICS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: D

    Magnesium decreases absorption of quinolones.<br> Magnesium can form insoluble complexes with quinolones and decrease their absorption (3046). Advise patients to take these drugs at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

    References

    3046

    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.

    Moderate

    SKELETAL MUSCLE RELAXANTS

    Be cautious with this combination.

    Moderate

    SKELETAL MUSCLE RELAXANTS

    Be cautious with this combination.

    Moderate

    SKELETAL MUSCLE RELAXANTS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: A

    Parenteral magnesium alters the pharmacokinetics of skeletal muscle relaxants, increasing their effects.<br> 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 acetylcholine release from motor nerve terminals (3046,97492). A clinical study found that low-dose rocuronium (0.45 mg/kg), when given after administration of magnesium 30 mg/kg over 10 minutes, undergoes an accelerated onset of effect, which matches the onset of effect seen with a full-dose rocuronium regimen (0.6 mg/kg) (96485).

    References

    3046

    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.

    96485

    Choi ES, Jeong WJ, Ahn SH, Oh AY, Jeon YT, Do SH. Magnesium sulfate accelerates the onset of low-dose rocuronium in patients undergoing laryngeal microsurgery. J Clin Anesth. 2017 Feb;36:102-106.

    97492

    Rodríguez-Rubio L, Solis Garcia Del Pozo J, Nava E, Jordán J. Interaction between magnesium sulfate and neuromuscular blockers during the perioperative period. A systematic review and meta-analysis. J Clin Anesth. 2016;34:524-34.

    Moderate

    DIGOXIN

    Be cautious with this combination.

    Moderate

    DIGOXIN

    Be cautious with this combination.

    Moderate

    DIGOXIN

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: B

    Magnesium salts may reduce absorption of digoxin.<br> Clinical evidence suggests that treatment with oral magnesium hydroxide or magnesium trisilicate reduces absorption of digoxin from the intestines (198,20268,20270). This may reduce the blood levels of digoxin and decrease its therapeutic effects.

    References

    198

    Rodin SM, Johnson BF. Pharmacokinetic interactions with digoxin. Clin Pharmacokinet 1988;15:227-44.

    20268

    Brown DD, Juhl RP. Decreased bioavailability of digoxin due to antacids and kaolin-pectin. N Engl J Med. 1976;295(19):1034-7.

    20270

    Allen MD, Greenblatt DJ, Harmatz JS, et al. Effect of magnesium--aluminum hydroxide and kaolin--pectin on absorption of digoxin from tablets and capsules. J Clin Pharmacol. 1981;21(1):26-30.

    Moderate

    POTASSIUM-SPARING DIURETICS

    Be cautious with this combination.

    Moderate

    POTASSIUM-SPARING DIURETICS

    Be cautious with this combination.

    Moderate

    POTASSIUM-SPARING DIURETICS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: D

    Potassium-sparing diuretics decrease excretion of magnesium, possibly increasing magnesium levels.<br> Potassium-sparing diuretics also have magnesium-sparing properties, which can counteract the magnesium losses associated with loop and thiazide diuretics (9613,9614,9622). Theoretically, increased magnesium levels could result from concomitant use of potassium-sparing diuretics and magnesium supplements.

    References

    9613

    Ryan MP. Diuretics and potassium/magnesium depletion. Directions for treatment. Am J Med 1987;82:38-47..

    9614

    Hollifield JW. Magnesium depletion, diuretics, and arrhythmias. Am J Med 1987;82:30-7..

    9622

    Heidenreich O. Mode of action of conventional and potassium-sparing diuretics--aspects with relevance to Mg-sparing effects. Magnesium 1984;3:248-56..

    Minor

    GABAPENTIN (Neurontin)

    Be watchful with this combination.

    Minor

    GABAPENTIN (Neurontin)

    Be watchful with this combination.

    Minor

    GABAPENTIN (Neurontin)

    Be watchful with this combination.

    Severity: mild
    Occurrence: unlikely
    Level of Evidence: B

    Gabapentin absorption can be decreased by magnesium.<br> 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% (90032). Advise patients to take gabapentin at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

    References

    90032

    Yagi T, Naito T, Mino Y, Umemura K, Kawakami J. Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects. Drug Metab Pharmacokinet 2012;27(2):248-54.

    Minor

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be watchful with this combination.

    Minor

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be watchful with this combination.

    Minor

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be watchful with this combination.

    Severity: moderate
    Occurrence: unlikely
    Level of Evidence: B

    Theoretically, magnesium may have antiplatelet effects, but the evidence is conflicting.<br> In vitro evidence shows that magnesium sulfate inhibits platelet aggregation, even at low concentrations (20304,20305). Some preliminary clinical evidence shows that infusion of magnesium sulfate increases bleeding time by 48% and reduces platelet activity (20306). However, other clinical research shows that magnesium does not affect platelet aggregation, although inhibition of platelet-dependent thrombosis can occur (60759).

    References

    20304

    Ravn HB, Vissinger H, Kristensen SD, et al. Magnesium inhibits platelet activity--an in vitro study. Thromb Haemost. 1996;76(1):88-93.

    20305

    Ravn HB, Kristensen SD, Vissinger H, et al. Magnesium inhibits human platelets. Blood Coagul Fibrinolysis. 1996;7(2):241-4.

    20306

    Ravn HB, Vissinger H, Kristensen SD, et al. Magnesium inhibits platelet activity--an infusion study in healthy volunteers. Thromb Haemost. 1996;75(6):939-44.

    60759

    Shechter, M., Merz, C. N., Paul-Labrador, M., Meisel, S. R., Rude, R. K., Molloy, M. D., Dwyer, J. H., Shah, P. K., and Kaul, S. Beneficial antithrombotic effects of the association of pharmacological oral magnesium therapy with aspirin in coronary heart disease patients. Magnes.Res. 2000;13(4):275-284.

    Minor

    SEVELAMER (Renagel, Renvela)

    Be watchful with this combination.

    Minor

    SEVELAMER (Renagel, Renvela)

    Be watchful with this combination.

    Minor

    SEVELAMER (Renagel, Renvela)

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: B

    Sevelamer may increase serum magnesium levels. <br> 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 (96486).

    References

    96486

    Ikee R, Toyoyama T, Endo T, Tsunoda M, Hashimoto N. Impact of sevelamer hydrochloride on serum magnesium concentrations in hemodialysis patients. Magnes Res. 2016 Apr 1;29(4):184-90.

    Major
    WILLOW BARK
    (Beta tocotrienol, Salix alba stem bark (Dry Herb Equiv))
    Do not take this combination.
    View Interactions:
    Major

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Do not take this combination.

    Major

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Do not take this combination.

    Major

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Do not take this combination.

    Severity: high
    Occurrence: probable
    Level of Evidence: D

    Theoretically, willow bark might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.<br> Willow bark has antiplatelet effects, but less so than aspirin (12810).

    References

    12810

    Krivoy N, Pavlotzky E, Chrubasik S, et al. Effect of salicis cortex extract on human platelet aggregation. Planta Med 2001;67:209-12.

    Moderate

    ACETAZOLAMIDE

    Be cautious with this combination.

    Moderate

    ACETAZOLAMIDE

    Be cautious with this combination.

    Moderate

    ACETAZOLAMIDE

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, willow bark might result in additive adverse effects associated with acetazolamide.<br> Willow bark contains salicin, a plant salicylate. Human case reports suggests that a combination of acetazolamide and salicylate increases unbound plasma levels of acetazolamide, as well as adverse effects related to acetazolamide (86481).

    References

    86481

    Sweeney, K. R., Chapron, D. J., Brandt, J. L., Gomolin, I. H., Feig, P. U., and Kramer, P. A. Toxic interaction between acetazolamide and salicylate: case reports and a pharmacokinetic explanation. Clin Pharmacol Ther 1986;40(5):518-524.

    Moderate

    ASPIRIN

    Be cautious with this combination.

    Moderate

    ASPIRIN

    Be cautious with this combination.

    Moderate

    ASPIRIN

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: D

    Theoretically, willow bark might increase the effects and adverse effects of aspirin.<br> Willow bark contains salicin, a plant salicylate. It might have an additive effect when taken with other salicylate-containing drugs such as aspirin (12808).

    References

    12808

    Schmid B, Kotter I, Heide L. Pharmacokinetics of salicin after oral administration of a standardised willow bark extract. Eur J Clin Pharmacol. 2001;57:387-91.

    Moderate

    SALSALATE (Disalcid)

    Be cautious with this combination.

    Moderate

    SALSALATE (Disalcid)

    Be cautious with this combination.

    Moderate

    SALSALATE (Disalcid)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: D

    Theoretically, willow bark might increase the effects and adverse effects of salsalate.<br> Willow bark contains salicin, a plant salicylate. It might have an additive effect when taken with other salicylate-containing drugs such as salsalate (12808).

    References

    12808

    Schmid B, Kotter I, Heide L. Pharmacokinetics of salicin after oral administration of a standardised willow bark extract. Eur J Clin Pharmacol. 2001;57:387-91.

    Moderate

    CHOLINE MAGNESIUM TRISALICYLATE (Trilisate)

    Be cautious with this combination.

    Moderate

    CHOLINE MAGNESIUM TRISALICYLATE (Trilisate)

    Be cautious with this combination.

    Moderate

    CHOLINE MAGNESIUM TRISALICYLATE (Trilisate)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: D

    Theoretically, willow bark might increase the effects and adverse effects of choline magnesium trisalicylate.<br> Willow bark contains salicin, a plant salicylate. It might have an additive effect when taken with other salicylate-containing drugs such as choline magnesium trisalicylate (12808).

    References

    12808

    Schmid B, Kotter I, Heide L. Pharmacokinetics of salicin after oral administration of a standardised willow bark extract. Eur J Clin Pharmacol. 2001;57:387-91.

    Moderate
    VITAMIN C
    (Calcium ascorbate, Magnesium ascorbate, Magnesium ascorbate monohydrate, Sodium ascorbate, Ascorbic acid, Calcium ascorbate dihydrate, Ascorbic acid (in liposomal form) ZEAL® )
    Be cautious with this combination.
    View Interactions:
    Moderate

    ALKYLATING AGENTS

    Be cautious with this combination.

    Moderate

    ALKYLATING AGENTS

    Be cautious with this combination.

    Moderate

    ALKYLATING AGENTS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.<br> 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 (391). 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 (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.

    References

    391

    Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.

    14012

    Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S.

    14013

    Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S.

    Moderate

    LEVOTHYROXINE (Synthroid, others)

    Be cautious with this combination.

    Moderate

    LEVOTHYROXINE (Synthroid, others)

    Be cautious with this combination.

    Moderate

    LEVOTHYROXINE (Synthroid, others)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Vitamin C can increase levothyroxine absorption. <br> 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 (102978).

    References

    102978

    Skelin M, Lucijanic T, Amidzic Klaric D, et al. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017 Feb;39(2):378-403.

    Moderate

    ALUMINUM

    Be cautious with this combination.

    Moderate

    ALUMINUM

    Be cautious with this combination.

    Moderate

    ALUMINUM

    Be cautious with this combination.

    Severity: mild
    Occurrence: probable
    Level of Evidence: B

    Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.<br> 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 (10549,10550,10551,21556). In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely (10549). 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.

    References

    10549

    Domingo JL, Gomez M, Llobet JM, Richart C. Effect of ascorbic acid on gastrointestinal aluminum absorption (letter). Lancet 1991;338:1467.

    10550

    Domingo JL, Gomez M, Llobet JM, Corbella J. Influence of some dietary constituents on aluminum absorption and retention in rats. Kidney Int 1991;39:598-601.

    10551

    Partridge NA, Regnier FE, White JL, Hem SL. Influence of dietary constituents on intestinal absorption of aluminum. Kidney Int 1989;35:1413-7.

    21556

    Fairweather-Tait S, Hickson K, McGaw B, et al. Orange juice enhances aluminium absorption from antacid preparation. Eur J Clin Nutr. 1994;48(1):71-3.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    High-dose vitamin C might reduce the levels and effectiveness of warfarin.<br> Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption (11566). There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time (9804,9806). Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant (9805,9806,11566,11567). 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) (90942). 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.

    References

    9804

    Rosenthal G. Interaction of ascorbic acid and warfarin. JAMA 1971;215:1671.

    9805

    Hume R, Johnstone JM, Weyers E. Interaction of ascorbic acid and warfarin. JAMA 1972;219:1479.

    9806

    Smith EC, Skalski RJ, Johnson GC, Rossi GV. Interaction of ascorbic acid and warfarin. JAMA 1972;221:1166.

    11566

    Feetam CL, Leach RH, Meynell MJ. Lack of a clinically important interaction between warfarin and ascorbic acid. Toxicol Appl Pharmacol 1975;31:544-7.

    11567

    Weintraub M, Griner PF. Warfarin and ascorbic acid: lack of evidence for a drug interaction. Toxicol Appl Pharmacol 1974;28:53-6.

    90942

    Sattar A, Willman JE, Kolluri R. Possible warfarin resistance due to interaction with ascorbic acid: case report and literature review. Am J Health Syst Pharm. 2013;70(9):782-6.

    Moderate

    ESTROGENS

    Be cautious with this combination.

    Moderate

    ESTROGENS

    Be cautious with this combination.

    Moderate

    ESTROGENS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Vitamin C might increase blood levels of estrogens. <br> 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 (129,130,11161). 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 (129,11161). 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 women who are deficient in vitamin C take supplements (11161). Monitor these patients for estrogen-related side effects.

    References

    129

    Back DJ, Breckenridge AM, MacIver M, et al. Interaction of ethinyloestradiol with ascorbic acid in man. Br Med J (Clin Res Ed) 1981;282:1516.

    130

    Morris JC, Beeley L, Ballantine N. Interaction of ethinyloestradiol with ascorbic acid in man [letter]. Br Med J (Clin Res Ed) 1981;283:503.

    11161

    Vihtamaki T, Parantainen J, Koivisto AM, et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002;42:129-35.

    Moderate

    INDINAVIR (Crixivan)

    Be cautious with this combination.

    Moderate

    INDINAVIR (Crixivan)

    Be cautious with this combination.

    Moderate

    INDINAVIR (Crixivan)

    Be cautious with this combination.

    Severity: mild
    Occurrence: probable
    Level of Evidence: B

    Vitamin C can modestly reduce indinavir levels. <br> 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 (11300,93578).

    References

    93578

    Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15.

    11300

    Slain D, Amsden JR, Khakoo RA, et al. Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. Pharmacotherapy 2005;25:165-70.

    Moderate

    FLUPHENAZINE (Prolixin)

    Be cautious with this combination.

    Moderate

    FLUPHENAZINE (Prolixin)

    Be cautious with this combination.

    Moderate

    FLUPHENAZINE (Prolixin)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, vitamin C might decrease levels of fluphenazine. <br> In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started (11017). The mechanism is not known, and there is no further data to confirm this interaction.

    References

    11017

    Dysken MW, Cumming RJ, Channon RA, Davis JM. Drug interaction between ascorbic acid and fluphenazine. JAMA 1979;241:2008.

    Moderate

    ANTITUMOR ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    ANTITUMOR ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    ANTITUMOR ANTIBIOTICS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.<br> 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 (391). 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 (14012,14013). More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.

    References

    391

    Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.

    14012

    Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S.

    14013

    Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S.

    Minor

    ACETAMINOPHEN (Tylenol, others)

    Be watchful with this combination.

    Minor

    ACETAMINOPHEN (Tylenol, others)

    Be watchful with this combination.

    Minor

    ACETAMINOPHEN (Tylenol, others)

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: probable
    Level of Evidence: B

    High dose vitamin C might slightly prolong the clearance of acetaminophen.<br> 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 (6451). This effect is not likely to be clinically significant.

    References

    6451

    Houston JB, Levy G. Drug biotransformation interactions in man VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218-21.

    Minor

    NIACIN

    Be watchful with this combination.

    Minor

    NIACIN

    Be watchful with this combination.

    Minor

    NIACIN

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: A

    Vitamin C might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.<br> 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 (7388,11537). 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.

    References

    7388

    Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93.

    11537

    Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6.

    Minor

    ASPIRIN

    Be watchful with this combination.

    Minor

    ASPIRIN

    Be watchful with this combination.

    Minor

    ASPIRIN

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: possible
    Level of Evidence: B

    Acidification of the urine by vitamin C might increase aspirin levels.<br> 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 (3046). However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction is not clinically significant.

    References

    3046

    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.

    10588

    Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413.

    10589

    Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31.

    Minor

    CHOLINE MAGNESIUM TRISALICYLATE (Trilisate)

    Be watchful with this combination.

    Minor

    CHOLINE MAGNESIUM TRISALICYLATE (Trilisate)

    Be watchful with this combination.

    Minor

    CHOLINE MAGNESIUM TRISALICYLATE (Trilisate)

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: possible
    Level of Evidence: B

    Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.<br> 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 (3046,4531). However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction probably is not clinically significant.

    References

    3046

    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.

    4531

    Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.

    10588

    Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413.

    10589

    Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31.

    Minor

    SALSALATE (Disalcid)

    Be watchful with this combination.

    Minor

    SALSALATE (Disalcid)

    Be watchful with this combination.

    Minor

    SALSALATE (Disalcid)

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: possible
    Level of Evidence: B

    Acidification of the urine by vitamin C might increase salsalate levels. <br> 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 (3046). However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction probably is not clinically significant.

    References

    3046

    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.

    10588

    Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413.

    10589

    Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31.

    Moderate
    POTASSIUM
    (Potassium aspartate monohydrate, Potassium, Potassium citrate, Potassium sulfate, Monobasic potassium phosphate, Potassium acetate)
    Be cautious with this combination.
    View Interactions:
    Moderate

    ANGIOTENSIN RECEPTOR BLOCKERS (ARBs)

    Be cautious with this combination.

    Moderate

    ANGIOTENSIN RECEPTOR BLOCKERS (ARBs)

    Be cautious with this combination.

    Moderate

    ANGIOTENSIN RECEPTOR BLOCKERS (ARBs)

    Be cautious with this combination.

    Severity: mild
    Occurrence: likely
    Level of Evidence: C

    Using ARBs with high doses of potassium increases the risk of hyperkalemia. <br> ARBs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion (95628). Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia (15,23207). However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels (95628).

    References

    15

    McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

    23207

    Phillips, C. O., Kashani, A., Ko, D. K., Francis, G., and Krumholz, H. M. Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials. Arch Intern Med 10-8-2007;167(18):1930-1936.

    95628

    Malta D, Arcand J, Ravindran A, Floras V, Allard JP, Newton GE. Adequate intake of potassium does not cause hyperkalemia in hypertensive individuals taking medications that antagonize the renin angiotensin aldosterone system. Am J Clin Nutr 2016 Oct;104(4):990-94.

    Moderate

    POTASSIUM-SPARING DIURETICS

    Be cautious with this combination.

    Moderate

    POTASSIUM-SPARING DIURETICS

    Be cautious with this combination.

    Moderate

    POTASSIUM-SPARING DIURETICS

    Be cautious with this combination.

    Severity: mild
    Occurrence: likely
    Level of Evidence: C

    Concomitant use increases the risk of hyperkalemia. <br> Using potassium-sparing diuretics with potassium supplements increases the risk of hyperkalemia (15).

    References

    15

    McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

    Moderate

    ACE INHIBITORS (ACEIs)

    Be cautious with this combination.

    Moderate

    ACE INHIBITORS (ACEIs)

    Be cautious with this combination.

    Moderate

    ACE INHIBITORS (ACEIs)

    Be cautious with this combination.

    Severity: mild
    Occurrence: likely
    Level of Evidence: C

    Using ACEIs with high doses of potassium increases the risk of hyperkalemia. <br> ACEIs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion (95628). Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia (15,23207). However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels (95628).

    References

    15

    McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

    23207

    Phillips, C. O., Kashani, A., Ko, D. K., Francis, G., and Krumholz, H. M. Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials. Arch Intern Med 10-8-2007;167(18):1930-1936.

    95628

    Malta D, Arcand J, Ravindran A, Floras V, Allard JP, Newton GE. Adequate intake of potassium does not cause hyperkalemia in hypertensive individuals taking medications that antagonize the renin angiotensin aldosterone system. Am J Clin Nutr 2016 Oct;104(4):990-94.

    Moderate
    GINGER
    (Zingiber officinale root (Dry Herb Equiv))
    Be cautious with this combination.
    View Interactions:
    Moderate

    LOSARTAN (Cozaar)

    Be cautious with this combination.

    Moderate

    LOSARTAN (Cozaar)

    Be cautious with this combination.

    Moderate

    LOSARTAN (Cozaar)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, ginger might increase levels of losartan and the risk of hypotension. <br> Animal research in rats with laboratory-induced hypertension shows that a single administration of ginger with losartan modestly increases losartan concentrations and increases hypotensive effects when compared with a single administration of losartan alone (102459). It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.

    References

    102459

    Ahad A, Raish M, Bin Jardan YA, Alam MA, Al-Mohizea AM, Al-Jenoobi FI. Effect of Hibiscus sabdariffa and Zingiber officinale on the antihypertensive activity and pharmacokinetic of losartan in hypertensive rats. Xenobiotica. 2020:1-11.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: B

    Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting. <br> Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation (7622,12634,20321,20322,20323,96257). However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials (96257). Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.

    References

    7622

    Srivastava KC. Effect of onion and ginger consumption on platelet thromboxane production in humans. Prostaglandins Leukot Essent Fatty Acids 1989;35:183-5.

    12634

    Thomson M, Al-Qattan KK, Al-Sawan SM, et al. The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent. Prostaglandins Leukot Essent Fatty Acids 2002;67:475-8.

    20321

    Backon J. Ginger as an antiemetic: possible side effects due to its thromboxane synthetase activity. Anaesthesia. 1991;46(8):705-6..

    20322

    Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin Pharm Ther. 2002;27:391-401.

    20323

    Argento A, Tiraferri E, Marzaloni M. [Oral anticoagulants and medicinal plants. An emerging interaction]. Ann Ital Med Int. 2000;15:139-43.

    96257

    Marx W, McKavanagh D, McCarthy AL, Bird R, Ried K, Chan A, Isenring L. The effect of ginger (Zingiber officinale) on platelet aggregation: A systematic literature review. PLoS One. 2015;10(10):e0141119.

    Moderate

    NIFEDIPINE (Procardia)

    Be cautious with this combination.

    Moderate

    NIFEDIPINE (Procardia)

    Be cautious with this combination.

    Moderate

    NIFEDIPINE (Procardia)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: B

    Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.<br> Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone (20324).

    References

    20324

    Young HY, Liao JC, Chang YS, et al. Synergistic effect of ginger and nifedipine on human platelet aggregation: a study in hypertensive patients and normal volunteers. Am J Chin Med. 2006;34:545-51.

    Moderate

    PHENPROCOUMON (Marcoumar, others)

    Be cautious with this combination.

    Moderate

    PHENPROCOUMON (Marcoumar, others)

    Be cautious with this combination.

    Moderate

    PHENPROCOUMON (Marcoumar, others)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Ginger might increase the risk of bleeding with phenprocoumon. <br> Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea (12880).

    References

    12880

    Kruth P, Brosi E, Fux R, et al. Ginger-associated overanticoagulation by phenprocoumon. Ann Pharmacother 2004;38:257-60.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: B

    Ginger might increase the risk of bleeding with warfarin.<br> Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation (7622,12634,20321,20322,20323). In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin (12880). In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen (20349). A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months (20348). However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin (12881,15176). Until more is known, monitor INRs closely in patients taking large amounts of ginger.

    References

    15176

    Jiang X, Blair EY, McLachlan AJ. Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach. J Clin Pharmacol 2006;46:1370-8.

    20348

    Shalansky S, Lynd L, Richardson K, et al. Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. 2007;27:1237-47.

    7622

    Srivastava KC. Effect of onion and ginger consumption on platelet thromboxane production in humans. Prostaglandins Leukot Essent Fatty Acids 1989;35:183-5.

    12634

    Thomson M, Al-Qattan KK, Al-Sawan SM, et al. The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent. Prostaglandins Leukot Essent Fatty Acids 2002;67:475-8.

    12880

    Kruth P, Brosi E, Fux R, et al. Ginger-associated overanticoagulation by phenprocoumon. Ann Pharmacother 2004;38:257-60.

    20321

    Backon J. Ginger as an antiemetic: possible side effects due to its thromboxane synthetase activity. Anaesthesia. 1991;46(8):705-6..

    20322

    Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin Pharm Ther. 2002;27:391-401.

    20323

    Argento A, Tiraferri E, Marzaloni M. [Oral anticoagulants and medicinal plants. An emerging interaction]. Ann Ital Med Int. 2000;15:139-43.

    20349

    Lesho EP, Saullo L, Udvari-Nagy S. A 76-year-old woman with erratic anticoagulation. Cleve Clin J Med. 2004;71:651-6.

    12881

    Jiang X, Williams KM, Liauw WS, et al. Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2005;59:425-32.

    Minor

    METRONIDAZOLE (Flagyl)

    Be watchful with this combination.

    Minor

    METRONIDAZOLE (Flagyl)

    Be watchful with this combination.

    Minor

    METRONIDAZOLE (Flagyl)

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: D

    Theoretically, ginger might increase levels of metronidazole.<br> In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced (20350).

    References

    20350

    Okonta JM, Uboh M, Obonga WO. Herb-Drug Interaction: A Case Study of Effect of Ginger on the Pharmacokinetic of Metronidazole in Rabbit. Indian Journal of Pharmaceutical Sciences (India) 2008;70(230):232.

    Minor

    CYCLOSPORINE (Neoral, Sandimmune)

    Be watchful with this combination.

    Minor

    CYCLOSPORINE (Neoral, Sandimmune)

    Be watchful with this combination.

    Minor

    CYCLOSPORINE (Neoral, Sandimmune)

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: D

    Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.<br> In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time (20401).

    References

    20401

    Chiang HM, Chao PD, Hsiu SL, et al. Ginger significantly decreased the oral bioavailability of cyclosporine in rats. Am J Chin Med. 2006;34:845-55.

    Minor

    ANTIDIABETES DRUGS

    Be watchful with this combination.

    Minor

    ANTIDIABETES DRUGS

    Be watchful with this combination.

    Minor

    ANTIDIABETES DRUGS

    Be watchful with this combination.

    Severity: moderate
    Occurrence: unlikely
    Level of Evidence: D

    Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.<br> Animal and human research suggests that ginger might increase insulin levels and/or decrease blood glucose levels (12636,20402,20403,20404,20405,89895,89896).

    References

    12636

    Akhani SP, Vishwakarma SL, Goyal RK. Anti-diabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats. J Pharm Pharmacol 2004;56:101-5.

    20402

    Bhandari U, Kanojia R, Pillai KK. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats. J Ethnopharmacol. 2005;97:227-30.

    20403

    Ojewole JA. Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats. Phytother Res. 2006;20:764-72.

    20404

    Al-Amin ZM, Thomson M, Al-Qattan KK, et al. Anti-diabetic and hypolipidaemic properties of ginger (Zingiber officinale) in streptozotocin-induced diabetic rats. Br J Nutr. 2006;96:660-6.

    20405

    Islam MS, Choi H. Comparative effects of dietary ginger (Zingiber officinale) and garlic (Allium sativum) investigated in a type 2 diabetes model of rats. J Med Food. 2008;11:152-9.

    89895

    Mahluji S, Attari VE, Mobasseri M, Payahoo L, Ostadrahimi A, Golzari SE. Effects of ginger (Zingiber officinale) on plasma glucose level, HbA1c and insulin sensitivity in type 2 diabetic patients. Int J Food Sci Nutr 2013;64(6):682-6.

    89896

    Mozaffari-Khosravi H, Talaei B, Jalali BA, Najarzadeh A, Mozayan MR. The effect of ginger powder supplementation on insulin resistance and glycemic indices in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Complement Ther Med 2014;22(1):9-16.

    Minor

    CALCIUM CHANNEL BLOCKERS

    Be watchful with this combination.

    Minor

    CALCIUM CHANNEL BLOCKERS

    Be watchful with this combination.

    Minor

    CALCIUM CHANNEL BLOCKERS

    Be watchful with this combination.

    Severity: moderate
    Occurrence: unlikely
    Level of Evidence: D

    Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension. <br> Laboratory research suggests ginger might have hypotensive and calcium channel-blocking effects (12633).

    References

    12633

    Ghayur MN, Gilani AH. Ginger lowers blood pressure through blockade of voltage-dependent calcium channels. J Cardiovasc Pharmacol 2005;45:74-80.

    Moderate
    CELERY
    (Apium graveolens seed (Dry Herb Equiv))
    Be cautious with this combination.
    View Interactions:
    Moderate

    CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    In vitro and animal research suggests that celery can inhibit cytochrome P450 1A2 (CYP1A2) (68176). Theoretically concomitant use may increase the levels of CYP1A2 substrates. Some drugs metabolized by CYP1A2 include amitriptyline (Elavil), haloperidol (Haldol), ondansetron (Zofran), propranolol (Inderal), theophylline (Theo-Dur, others), verapamil (Calan, Isoptin, others), and others.

    References

    68176

    Peterson, S., Lampe, J. W., Bammler, T. K., Gross-Steinmeyer, K., and Eaton, D. L. Apiaceous vegetable constituents inhibit human cytochrome P-450 1A2 (hCYP1A2) activity and hCYP1A2-mediated mutagenicity of aflatoxin B1. Food Chem.Toxicol. 2006;44(9):1474-1484.

    Moderate

    LITHIUM

    Be cautious with this combination.

    Moderate

    LITHIUM

    Be cautious with this combination.

    Moderate

    LITHIUM

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: D

    Celery is thought to have diuretic properties (4,6). Theoretically, due to these potential diuretic effects, celery might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

    References

    4

    Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

    6

    The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.

    Moderate

    LEVOTHYROXINE (Synthroid, others)

    Be cautious with this combination.

    Moderate

    LEVOTHYROXINE (Synthroid, others)

    Be cautious with this combination.

    Moderate

    LEVOTHYROXINE (Synthroid, others)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Celery has been associated with case reports of both hypothyroidism and hyperthyroidism (10646,102912,102914). Be cautious or avoid using in patients stabilized on levothyroxine.<br> Some drugs containing levothyroxine include Armour Thyroid, Eltroxin, Estre, Euthyrox, Levo-T, Levothroid, Levoxyl, Synthroid, Unithroid, and others.

    References

    10646

    Moses, G. Thyroxine interacts with celery seed tablets? Australian Prescriber 2001;24:6-7.

    102912

    Maljaei MB, Moosavian SP, Mirmosayyeb O, Rouhani MH, Namjoo I, Bahreini A. Effect of celery extract on thyroid function; is herbal therapy safe in obesity? Int J Prev Med 2019;10:55. doi: 10.4103/ijpvm.IJPVM_209_17.

    102914

    Rouhi-Boroujeni H, Hosseini M, Gharipour M, Rouhi-Boroujeni H. Is herbal therapy safe in obesity? A case of Apium graveolens (Celery) induced hyperthyroidism. ARYA Atheroscler 2016;12(5):248-9.

    Moderate

    VENLAFAXINE (Effexor)

    Be cautious with this combination.

    Moderate

    VENLAFAXINE (Effexor)

    Be cautious with this combination.

    Moderate

    VENLAFAXINE (Effexor)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Some evidence suggests that taking celery root along with venlafaxine might increase levels of venlafaxine. There is one case report of a patient who experienced medication-induced bipolar disorder after beginning to take celery root extract 1000 mg daily along with venlafaxine 75 mg daily and St. John's Wort 600 mg. Symptoms included confusion, speech abnormalities, manic affect, and visual hallucinations. The plasma level of venlafaxine was 476.8 ng/mL (normal range 195-400 ng/mL). The patient was treated with IV fluids and oral haloperidol and discontinued use of the celery root. Twenty-four hours later, the patient's mental status improved and visual hallucinations ceased. It is theorized that celery root increased venlafaxine levels by inhibiting cytochrome P450 2D6 (92854).

    References

    92854

    Khalid Z, Osuagwu FC, Shah B, Roy N, Dillon JE, Bradley R. Celery root extract as an inducer of mania induction in a patient on venlafaxine and St John's Wort. Postgrad Med. 2016;128(7):682-3.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Celery contains the constituents falcarinol and falcarindiol. Laboratory research suggests that falcarinol and falcarindiol can inhibit platelet aggregation (6048,40991). Theoretically, celery might also inhibit platelet aggregation and increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs. Some of these drugs include aspirin; clopidogrel (Plavix); nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others); dalteparin (Fragmin); enoxaparin (Lovenox); heparin; warfarin (Coumadin); and others.

    References

    6048

    Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7.

    40991

    Christensen, L. P. and Brandt, K. Bioactive polyacetylenes in food plants of the Apiaceae family: occurrence, bioactivity and analysis. J Pharm.Biomed.Anal. 6-7-2006;41(3):683-693.

    Moderate

    CNS DEPRESSANTS

    Be cautious with this combination.

    Moderate

    CNS DEPRESSANTS

    Be cautious with this combination.

    Moderate

    CNS DEPRESSANTS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, concomitant use of celery with CNS depressants may cause additive effects (4)<br> Some CNS depressants include clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem (Ambien), and others.

    References

    4

    Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Anecdotal evidence suggests that celery can decrease blood pressure (41175). Theoretically, concomitant use with antihypertensive drugs might have additive blood pressure lowering effects and increase the risk of hypotension; use with caution. Some antihypertensive drugs include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), Amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.

    References

    41175

    Fraser L and et al. Stalking hypertension. Health 1992;6(5):11.

    Minor

    ACETAMINOPHEN (Tylenol, others)

    Be watchful with this combination.

    Minor

    ACETAMINOPHEN (Tylenol, others)

    Be watchful with this combination.

    Minor

    ACETAMINOPHEN (Tylenol, others)

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: D

    Animal research suggests that concomitant use of celery juice plus acetaminophen prolongs the effects of acetaminophen. This effect has been attributed to a decrease in hepatic cytochrome P450 activity (25362). Theoretically concomitant use of celery juice plus acetaminophen might increase the effects and side effects of acetaminophen.

    References

    25362

    Jakovljevic, V., Raskovic, A., Popovic, M., and Sabo, J. The effect of celery and parsley juices on pharmacodynamic activity of drugs involving cytochrome P450 in their metabolism. Eur.J Drug Metab Pharmacokinet. 2002;27(3):153-156.

    Minor

    PHOTOSENSITIZING DRUGS

    Be watchful with this combination.

    Minor

    PHOTOSENSITIZING DRUGS

    Be watchful with this combination.

    Minor

    PHOTOSENSITIZING DRUGS

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: D

    Laboratory research has shown that celery contains photosensitizing agents such as phenols and psoralens (6178,40894,40917,41073,41121). Theoretically, concomitant use with photosensitizing drugs might further increase photosensitivity.<br> Some photosensitizing drugs include naproxen (Aleve), amiodarone (Cordarone), amitriptyline (Elavil), ciprofloxacin (Cipro), levofloxacin (Levaquin), moxifloxacin (Avelox), trimethoprim/sulfamethoxazole (Septra), tetracycline, methoxsalen (Oxsoralen), glipizide (Glucotrol), lamotrigine (Lamictal), and others.

    References

    6178

    Gral N, Beani JC, Bonnot D, et al. [Plasma levels of psoralens after celery ingestion]. Ann Dermatol Venereol 1993;120:599-603.

    41073

    Gorgus, E., Lohr, C., Raquet, N., Guth, S., and Schrenk, D. Limettin and furocoumarins in beverages containing citrus juices or extracts. Food Chem.Toxicol. 2010;48(1):93-98.

    40894

    Weber, I. C., Davis, C. P., and Greeson, D. M. Phytophotodermatitis: the other "lime" disease. J Emerg.Med 1999;17(2):235-237.

    40917

    Lombaert, G. A., Siemens, K. H., Pellaers, P., Mankotia, M., and Ng, W. Furanocoumarins in celery and parsnips: method and multiyear Canadian survey. J AOAC Int 2001;84(4):1135-1143.

    41121

    Beier, R. C., Ivie, G. W., Oertli, E. H., and Holt, D. L. HPLC analysis of linear furocoumarins (psoralens) in healthy celery (Apium graveolens). Food Chem.Toxicol. 1983;21(2):163-165.

    Moderate
    TURMERIC
    (Curcuma longa rhizome (Dry Herb Equiv), Curcuminoids, Curcumin (including curcumin, demethoxycurcumin and bisdemethoxycurcumin))
    Be cautious with this combination.
    View Interactions:
    Moderate

    TOPOISOMERASE I INHIBITORS

    Be cautious with this combination.

    Moderate

    TOPOISOMERASE I INHIBITORS

    Be cautious with this combination.

    Moderate

    TOPOISOMERASE I INHIBITORS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Turmeric has antioxidant effects. There is some concern that this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting. <br> In vitro research shows that curcumin, a constituent of turmeric, inhibits camptothecin-induced apoptosis of breast cancer cells by up to 71% (96126). However, other in vitro research shows that curcumin augments the cytotoxic effects of camptothecin. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agents. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have.

    References

    96125

    Mitchell TM. Correspondence re: Somasundaram et al., Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2003;63(16):5165-6; author reply 5166-7.

    96126

    Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2002;62(13):3868-75.

    Moderate

    AMLODIPINE (Norvasc)

    Be cautious with this combination.

    Moderate

    AMLODIPINE (Norvasc)

    Be cautious with this combination.

    Moderate

    AMLODIPINE (Norvasc)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Taking turmeric with amlodipine may increase levels of amlodipine. <br> Animal research shows that taking amlodipine 1 mg/kg with curcumin 2 mg/kg increases the maximum concentration and area under the curve by about 2-fold when compared with amlodipine taken alone (103099).

    References

    103099

    Jiang N, Zhang M, Meng X, Sun B. Effects of Curcumin on the Pharmacokinetics of Amlodipine in Rats and Its Potential Mechanism. Pharm Biol. 2020;58(1):465-468.

    Moderate

    HEPATOTOXIC DRUGS

    Be cautious with this combination.

    Moderate

    HEPATOTOXIC DRUGS

    Be cautious with this combination.

    Moderate

    HEPATOTOXIC DRUGS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, turmeric might increase the risk of liver damage when taken with hepatotoxic drugs. <br> There is concern that turmeric might cause hepatotoxicity, especially when highly bioavailable formulations are used in high doses (103633).

    References

    103633

    Lombardi N, Crescioli G, Maggini V, et al. Acute liver injury following turmeric use in Tuscany: an analysis of the Italian Phytovigilance database and systematic review of case reports. Br J Clin Pharmacol. 2020.

    Moderate

    CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, turmeric might increase levels of drugs metabolized by CYP3A4. <br> In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4 (21497,21498,21499). In one case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels of 29 ng/mL. The patient previously had tacrolimus levels within the therapeutic range at 9.7 ng/mL. Ten days prior to presenting to the emergency room the patient started consumption of turmeric powder at a dose of 15 or more spoonfuls daily. It was thought that turmeric increased levels of tacrolimus due to CYP3A4 inhibition (93544).

    References

    21497

    Appiah-Opong, R., Commandeur, J. N., Vugt-Lussenburg, B., and Vermeulen, N. P. Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products. Toxicology 6-3-2007;235(1-2):83-91.

    21498

    Hou, X. L., Takahashi, K., Kinoshita, N., Qiu, F., Tanaka, K., Komatsu, K., Takahashi, K., and Azuma, J. Possible inhibitory mechanism of Curcuma drugs on CYP3A4 in 1alpha,25 dihydroxyvitamin D3 treated Caco-2 cells. Int.J Pharm 6-7-2007;337(1-2):169-177.

    21499

    Valentine, S. P., Le Nedelec, M. J., Menzies, A. R., Scandlyn, M. J., Goodin, M. G., and Rosengren, R. J. Curcumin modulates drug metabolizing enzymes in the female Swiss Webster mouse. Life Sci. 4-11-2006;78(20):2391-2398.

    93544

    Nayeri A, Wu S, Adams E, et al. Acute Calcineurin Inhibitor Nephrotoxicity Secondary to Turmeric Intake: A Case Report. Transplant Proc. 2017;49(1):198-200.

    Moderate

    ANTIDIABETES DRUGS

    Be cautious with this combination.

    Moderate

    ANTIDIABETES DRUGS

    Be cautious with this combination.

    Moderate

    ANTIDIABETES DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: B

    Theoretically, taking turmeric with antidiabetes drugs might increase the risk of hypoglycemia. <br> Animal research and case reports suggest that curcumin, a turmeric constituent, can reduce blood glucose levels in patients with diabetes (79692,79984,80155,80313,80315,80476,80553,81048,81219). Furthermore, clinical research in adults with type 2 diabetes shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg decreased postprandial glucose levels for up to 24 hours when compared with glyburide alone, despite the lack of a significant pharmacokinetic interaction (96133). Another clinical study in patients with diabetes on hemodialysis shows that taking curcumin 80 mg daily for 12 weeks can reduce blood glucose levels when compared with placebo (104149).

    References

    79692

    Mahesh, T., Balasubashini, M. S., and Menon, V. P. Effect of photo-irradiated curcumin treatment against oxidative stress in streptozotocin-induced diabetic rats. J Med.Food 2005;8(2):251-255.

    79984

    Patumraj, S., Wongeakin, N., Sridulyakul, P., Jariyapongskul, A., Futrakul, N., and Bunnag, S. Combined effects of curcumin and vitamin C to protect endothelial dysfunction in the iris tissue of STZ-induced diabetic rats. Clin Hemorheol.Microcirc. 2006;35(4):481-489.

    80155

    Murugan, P. and Pari, L. Influence of tetrahydrocurcumin on erythrocyte membrane bound enzymes and antioxidant status in experimental type 2 diabetic rats. J Ethnopharmacol. 9-25-2007;113(3):479-486.

    80313

    Seo, K. I., Choi, M. S., Jung, U. J., Kim, H. J., Yeo, J., Jeon, S. M., and Lee, M. K. Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Mol.Nutr.Food Res 2008;52(9):995-1004.

    80315

    Weisberg, S. P., Leibel, R., and Tortoriello, D. V. Dietary curcumin significantly improves obesity-associated inflammation and diabetes in mouse models of diabesity. Endocrinology 2008;149(7):3549-3558.

    80476

    Jain, S. K., Rains, J., Croad, J., Larson, B., and Jones, K. Curcumin supplementation lowers TNF-alpha, IL-6, IL-8, and MCP-1 secretion in high glucose-treated cultured monocytes and blood levels of TNF-alpha, IL-6, MCP-1, glucose, and glycosylated hemoglobin in diabetic rats. Antioxid.Redox.Signal. 2009;11(2):241-249.

    80553

    Yu, Y., Hu, S. K., and Yan, H. [The study of insulin resistance and leptin resistance on the model of simplicity obesity rats by curcumin]. Zhonghua Yu Fang Yi.Xue.Za Zhi. 2008;42(11):818-822.

    81048

    Madkor, H. R., Mansour, S. W., and Ramadan, G. Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats. Br J Nutr 2011;105(8):1210-1217.

    81219

    Srinivasan, M. Effect of curcumin on blood sugar as seen in a diabetic subject. Indian J Med Sci 1972;26(4):269-270.

    96133

    Neerati P, Devde R, Gangi AK. Evaluation of the effect of curcumin capsules on glyburide therapy in patients with type-2 diabetes mellitus. Phytother Res. 2014;28(12):1796-800.

    104149

    Shafabakhsh R, Asemi Z, Reiner Z, Soleimani A, Aghadavod E, Bahmani F. The effects of nano-curcumin on metabolic status in patients with diabetes on hemodialysis, a randomized, double blind, placebo-controlled trial. Iran J Kidney Dis. 2020;14(4):290-9.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Turmeric might increase the risk of bleeding with warfarin. <br> One case of increased international normalized ratio (INR) has been reported for a patient taking warfarin who began taking turmeric. Prior to taking turmeric, the patient had stable INR measurements. Within a few weeks of starting turmeric supplementation, the patient's INR increased to 10 (100906). Additionally, curcumin, the active constituent in turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271), which may produce additive effects when taken with warfarin.

    References

    11143

    Shah BH, Nawaz Z, Pertani SA. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol 1999;58:1167-72..

    81204

    Srivastava, R., Puri, V., Srimal, R. C., and Dhawan, B. N. Effect of curcumin on platelet aggregation and vascular prostacyclin synthesis. Arzneimittelforschung. 1986;36(4):715-717.

    81271

    Srivastava, K. C., Bordia, A., and Verma, S. K. Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins Leukot.Essent.Fatty Acids 1995;52(4):223-227.

    100906

    Medsafe Safety Communication- Turmeric/Curcumin Interaction with Warfarin. April 30, 2018. Accessed at: https://medsafe.govt.nz/safety/EWS/2018/Turmeric.asp.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: B

    Turmeric may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. <br> Curcumin, a constituent of turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271). Furthermore, two case reports have found that taking turmeric along with warfarin or fluindione was associated with an increased international normalized ratio (INR) (89718,100906). However, one clinical study in healthy volunteers shows that taking curcumin 500 mg daily for 3 weeks, alone or with aspirin 100 mg, does not increase antiplatelet effects or bleeding risk (96137). It is possible that the dose of turmeric used in this study was too low to produce a notable effect.

    References

    96137

    Fung FY, Wong WH, Ang SK, et al. A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng. Phytomedicine. 2017;32:88-96.

    11143

    Shah BH, Nawaz Z, Pertani SA. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol 1999;58:1167-72..

    81204

    Srivastava, R., Puri, V., Srimal, R. C., and Dhawan, B. N. Effect of curcumin on platelet aggregation and vascular prostacyclin synthesis. Arzneimittelforschung. 1986;36(4):715-717.

    81271

    Srivastava, K. C., Bordia, A., and Verma, S. K. Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins Leukot.Essent.Fatty Acids 1995;52(4):223-227.

    100906

    Medsafe Safety Communication- Turmeric/Curcumin Interaction with Warfarin. April 30, 2018. Accessed at: https://medsafe.govt.nz/safety/EWS/2018/Turmeric.asp.

    89718

    Daveluy A, Géniaux H, Thibaud L, Mallaret M, Miremont-Salamé G, Haramburu F. Probable interaction between an oral vitamin K antagonist and turmeric (Curcuma longa). Therapie. 2014 Nov-Dec;69(6):519-20.

    Moderate

    ANTITUMOR ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    ANTITUMOR ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    ANTITUMOR ANTIBIOTICS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.<br> In vitro and animal research shows that curcumin, a constituent of turmeric, inhibits doxorubicin-induced apoptosis of breast cancer cells by up to 65% (96126). However, curcumin does not seem to affect the apoptosis capacity of daunorubicin. In fact, some research shows that curcumin might augment the cytotoxic effects of antitumor antibiotics, increasing their effectiveness. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effects, if any, antioxidants such as turmeric have on antitumor antibiotics.

    References

    96125

    Mitchell TM. Correspondence re: Somasundaram et al., Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2003;63(16):5165-6; author reply 5166-7.

    96126

    Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2002;62(13):3868-75.

    Moderate

    ALKYLATING AGENTS

    Be cautious with this combination.

    Moderate

    ALKYLATING AGENTS

    Be cautious with this combination.

    Moderate

    ALKYLATING AGENTS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting. <br> In vitro research suggests that curcumin, a constituent of turmeric, inhibits mechlorethamine-induced apoptosis of breast cancer cells by up to 70%. Also, animal research shows that curcumin inhibits cyclophosphamide-induced tumor regression (96126). However, some in vitro research shows that curcumin does not affect the apoptosis capacity of etoposide. Also, other laboratory research suggests that curcumin might augment the cytotoxic effects of alkylating agents. Reasons for the discrepancies may relate to the dose of curcumin and the specific chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have on alkylating agents.

    References

    96125

    Mitchell TM. Correspondence re: Somasundaram et al., Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2003;63(16):5165-6; author reply 5166-7.

    96126

    Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2002;62(13):3868-75.

    Moderate

    SULFASALAZINE (Azulfidine)

    Be cautious with this combination.

    Moderate

    SULFASALAZINE (Azulfidine)

    Be cautious with this combination.

    Moderate

    SULFASALAZINE (Azulfidine)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Turmeric might increase the effects and adverse effects of sulfasalazine.<br> Clinical research shows that taking the turmeric constituent, curcumin, can increase blood levels of sulfasalazine by 3.2-fold (81131).

    References

    81131

    Kusuhara, H., Furuie, H., Inano, A., Sunagawa, A., Yamada, S., Wu, C., Fukizawa, S., Morimoto, N., Ieiri, I., Morishita, M., Sumita, K., Mayahara, H., Fujita, T., Maeda, K., and Sugiyama, Y. Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP. Br J Pharmacol 2012;166(6):1793-1803.

    Moderate

    TALINOLOL

    Be cautious with this combination.

    Moderate

    TALINOLOL

    Be cautious with this combination.

    Moderate

    TALINOLOL

    Be cautious with this combination.

    Severity: mild
    Occurrence: probable
    Level of Evidence: B

    Turmeric may reduce the absorption of talinolol in some situations.<br> Clinical research shows that taking curcumin for 6 days decreases the bioavailability of talinolol when taken together on the seventh day (80079). The clinical significance of this effect is unclear.

    References

    80079

    Juan, H., Terhaag, B., Cong, Z., Bi-Kui, Z., Rong-Hua, Z., Feng, W., Fen-Li, S., Juan, S., Jing, T., and Wen-Xing, P. Unexpected effect of concomitantly administered curcumin on the pharmacokinetics of talinolol in healthy Chinese volunteers. Eur.J Clin Pharmacol 2007;63(7):663-668.

    Moderate

    TACROLIMUS (Prograf)

    Be cautious with this combination.

    Moderate

    TACROLIMUS (Prograf)

    Be cautious with this combination.

    Moderate

    TACROLIMUS (Prograf)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Turmeric might increase the effects and adverse effects of tacrolimus.<br> In one case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels of 29 ng/mL. The patient previously had tacrolimus levels within the therapeutic range at 9.7 ng/mL. Ten days prior to presenting at the emergency room the patient started consumption of turmeric powder at a dose of 15 or more spoonfuls daily. It was thought that turmeric increased levels of tacrolimus due to cytochrome P450 3A4 (CYP3A4) inhibition (93544). In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4 (21497,21498,21499).

    References

    21497

    Appiah-Opong, R., Commandeur, J. N., Vugt-Lussenburg, B., and Vermeulen, N. P. Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products. Toxicology 6-3-2007;235(1-2):83-91.

    21498

    Hou, X. L., Takahashi, K., Kinoshita, N., Qiu, F., Tanaka, K., Komatsu, K., Takahashi, K., and Azuma, J. Possible inhibitory mechanism of Curcuma drugs on CYP3A4 in 1alpha,25 dihydroxyvitamin D3 treated Caco-2 cells. Int.J Pharm 6-7-2007;337(1-2):169-177.

    21499

    Valentine, S. P., Le Nedelec, M. J., Menzies, A. R., Scandlyn, M. J., Goodin, M. G., and Rosengren, R. J. Curcumin modulates drug metabolizing enzymes in the female Swiss Webster mouse. Life Sci. 4-11-2006;78(20):2391-2398.

    93544

    Nayeri A, Wu S, Adams E, et al. Acute Calcineurin Inhibitor Nephrotoxicity Secondary to Turmeric Intake: A Case Report. Transplant Proc. 2017;49(1):198-200.

    Minor

    CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

    Be watchful with this combination.

    Minor

    CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

    Be watchful with this combination.

    Minor

    CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: D

    Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. <br> In vitro and animal research show that the turmeric constituent, curcumin, inhibits CYP1A2 (15823,21497,81304). However, other in vitro research suggests that curcumin does not significantly affect CYP1A2 (22000).

    References

    21497

    Appiah-Opong, R., Commandeur, J. N., Vugt-Lussenburg, B., and Vermeulen, N. P. Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products. Toxicology 6-3-2007;235(1-2):83-91.

    15823

    Thapliyal R, Deshpande SS, Maru GB. Mechanism(s) of turmeric-mediated protective effects against benzo(a)pyrene-derived DNA adducts. Cancer Lett 2002;175:79-88.

    22000

    Price, R. J., Scott, M. P., Giddings, A. M., Walters, D. G., Stierum, R. H., Meredith, C., and Lake, B. G. Effect of butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole on cytochrome P450 forms in cultured human hepatocytes. Xenobiotica 2008;38(6):574-586.

    81304

    Oetari, S., Sudibyo, M., Commandeur, J. N., Samhoedi, R., and Vermeulen, N. P. Effects of curcumin on cytochrome P450 and glutathione S-transferase activities in rat liver. Biochem Pharmacol 1-12-1996;51(1):39-45.

    Minor

    GLYBURIDE (Diabeta, others)

    Be watchful with this combination.

    Minor

    GLYBURIDE (Diabeta, others)

    Be watchful with this combination.

    Minor

    GLYBURIDE (Diabeta, others)

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: B

    Theoretically, taking turmeric and glyburide in combination might increase the risk of hypoglycemia.<br> Clinical research shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg increases blood levels of glyburide by 12% at 2 hours after the dose in patients with type 2 diabetes. While maximal blood concentrations of glyburide were not affected, turmeric modestly decreased postprandial glucose levels for up to 24 hours when compared to glyburide alone, possibly due to the hypoglycemic effect of turmeric demonstrated in animal research (96133).

    References

    96133

    Neerati P, Devde R, Gangi AK. Evaluation of the effect of curcumin capsules on glyburide therapy in patients with type-2 diabetes mellitus. Phytother Res. 2014;28(12):1796-800.

    Minor

    NORFLOXACIN (Noroxin)

    Be watchful with this combination.

    Minor

    NORFLOXACIN (Noroxin)

    Be watchful with this combination.

    Minor

    NORFLOXACIN (Noroxin)

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: D

    Theoretically, turmeric might increase the effects and adverse effects of norfloxacin. <br> Animal research shows that taking curcumin, a turmeric constituent, can increase blood levels of orally administered norfloxacin (80863).

    References

    80863

    Pavithra, B. H., Prakash, N., and Jayakumar, K. Modification of pharmacokinetics of norfloxacin following oral administration of curcumin in rabbits. J Vet.Sci. 2009;10(4):293-297.

    Minor

    ESTROGENS

    Be watchful with this combination.

    Minor

    ESTROGENS

    Be watchful with this combination.

    Minor

    ESTROGENS

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: D

    Theoretically, large amounts of turmeric might interfere with hormone replacement therapy through competition for estrogen receptors.<br> In vitro research shows that curcumin, a constituent of turmeric, displaces the binding of estrogen to its receptors (21486).

    References

    21486

    Shenouda, N. S., Zhou, C., Browning, J. D., Ansell, P. J., Sakla, M. S., Lubahn, D. B., and MacDonald, R. S. Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro. Nutr.Cancer 2004;49(2):200-208.

    Minor

    DOCETAXEL (Taxotere)

    Be watchful with this combination.

    Minor

    DOCETAXEL (Taxotere)

    Be watchful with this combination.

    Minor

    DOCETAXEL (Taxotere)

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: D

    Theoretically, turmeric might increase blood levels of oral docetaxel. <br> Animal research suggests that the turmeric constituent, curcumin, enhances the oral bioavailability of docetaxel (80999). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

    References

    80999

    Yan, Y. D., Kim, D. H., Sung, J. H., Yong, C. S., and Choi, H. G. Enhanced oral bioavailability of docetaxel in rats by four consecutive days of pre-treatment with curcumin. Int J Pharm 10-31-2010;399(1-2):116-120.

    Minor

    PACLITAXEL (Abraxane, Onxol)

    Be watchful with this combination.

    Minor

    PACLITAXEL (Abraxane, Onxol)

    Be watchful with this combination.

    Minor

    PACLITAXEL (Abraxane, Onxol)

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: D

    Theoretically, turmeric might increase blood levels of oral paclitaxel. <br> Animal research suggests that curcumin, a constituent of turmeric, enhances the oral bioavailability of paclitaxel (22005). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

    References

    22005

    Ganta, S., Devalapally, H., and Amiji, M. Curcumin enhances oral bioavailability and anti-tumor therapeutic efficacy of paclitaxel upon administration in nanoemulsion formulation. J Pharm Sci 2010;99(11):4630-4641.

    Minor

    P-GLYCOPROTEIN SUBSTRATES

    Be watchful with this combination.

    Minor

    P-GLYCOPROTEIN SUBSTRATES

    Be watchful with this combination.

    Minor

    P-GLYCOPROTEIN SUBSTRATES

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: D

    Theoretically, turmeric might increase the absorption of P-glycoprotein substrates.<br> In vitro and animal research shows that curcuminoids and other constituents found in turmeric can inhibit P-glycoprotein expression and activity (21472,21473,21474,21475,21476,21477,21478,21479,21480)(21482,21484).

    References

    21472

    Junyaprasert, V. B., Soonthornchareonnon, N., Thongpraditchote, S., Murakami, T., and Takano, M. Inhibitory effect of Thai plant extracts on P-glycoprotein mediated efflux. Phytother.Res 2006;20(1):79-81.

    21473

    Ampasavate, C., Sotanaphun, U., Phattanawasin, P., and Piyapolrungroj, N. Effects of Curcuma spp. on P-glycoprotein function. Phytomedicine. 2010;17(7):506-512.

    21474

    Hou, X. L., Takahashi, K., Tanaka, K., Tougou, K., Qiu, F., Komatsu, K., Takahashi, K., and Azuma, J. Curcuma drugs and curcumin regulate the expression and function of P-gp in Caco-2 cells in completely opposite ways. Int.J Pharm 6-24-2008;358(1-2):224-229.

    21475

    Choi, B. H., Kim, C. G., Lim, Y., Shin, S. Y., and Lee, Y. H. Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NF kappa B pathway. Cancer Lett. 1-18-2008;259(1):111-118.

    21476

    Zhang, W., Tan, T. M., and Lim, L. Y. Impact of curcumin-induced changes in P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral celiprolol and midazolam in rats. Drug Metab Dispos. 2007;35(1):110-115.

    21477

    Limtrakul, P., Chearwae, W., Shukla, S., Phisalphong, C., and Ambudkar, S. V. Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCC1) by tetrahydrocurcumin, a major metabolite of curcumin. Mol.Cell Biochem. 2007;296(1-2):85-95.

    21478

    Holland, M. L., Panetta, J. A., Hoskins, J. M., Bebawy, M., Roufogalis, B. D., Allen, J. D., and Arnold, J. C. The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells. Biochem.Pharmacol 4-14-2006;71(8):1146-1154.

    21479

    Tang, X. Q., Bi, H., Feng, J. Q., and Cao, J. G. Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR. Acta Pharmacol Sin. 2005;26(8):1009-1016.

    21480

    Nabekura, T., Kamiyama, S., and Kitagawa, S. Effects of dietary chemopreventive phytochemicals on P-glycoprotein function. Biochem.Biophys.Res Commun. 2-18-2005;327(3):866-870.

    21482

    Romiti, N., Tongiani, R., Cervelli, F., and Chieli, E. Effects of curcumin on P-glycoprotein in primary cultures of rat hepatocytes. Life Sci. 1998;62(25):2349-2358.

    21484

    Yue, G. G., Cheng, S. W., Yu, H., Xu, Z. S., Lee, J. K., Hon, P. M., Lee, M. Y., Kennelly, E. J., Deng, G., Yeung, S. K., Cassileth, B. R., Fung, K. P., Leung, P. C., and Lau, C. B. The role of turmerones on curcumin transportation and P-glycoprotein activities in intestinal Caco-2 cells. J Med Food 2012;15(3):242-252.

    Moderate
    BOSWELLIA SERRATA
    (Boswellic acid, Boswellia serrata sap (Dry Herb Equiv))
    Be cautious with this combination.
    View Interactions:
    Moderate

    CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, Boswellia serrata might increase the levels of CYP1A2 substrates. <br> In vitro research shows that Boswellia serrata gum resin inhibits CYP1A2 enzymes (21178).

    References

    21178

    Frank A, Unger M. Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction. J Chromatogr A 2006;1112:255-62.

    Moderate

    IMMUNOSUPPRESSANTS

    Be cautious with this combination.

    Moderate

    IMMUNOSUPPRESSANTS

    Be cautious with this combination.

    Moderate

    IMMUNOSUPPRESSANTS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, Boswellia serrata might alter the effects of immunosuppressive drugs.<br> Some in vitro research suggests that Boswellia serrata extracts might inhibit mediators of autoimmune disorders such as leukotrienes and reduce production of antibodies and cell-mediated immunity (12432,12435,12437,12438). However, other in vitro research suggests that, when coupled with calcium ions, boswellic acids containing the keto group have immunostimulant properties within specific cell signaling pathways (21180).

    References

    21180

    Altmann A, Poeckel D, Fischer L, et al. Coupling of boswellic acid-incuded Ca2+ mobilisation and MAPK activation to lipid metabolism and peroxide formation in human leucocytes. Br J Pharmacol 2004;141:223-32.

    12432

    Kimmatkar N, Thawani V, Hingorani L, et al. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Phytomedicine 2003;10:3-7.

    12435

    Liu JJ, Nilsson A, Oredsson S, et al. Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells. Carcinogenesis 2002;23:2087-93.

    12437

    Wildfeuer A, Neu IS, Safayhi H, et al. Effects of boswellic acids extracted from a herbal medicine on the biosynthesis of leukotrienes and the course of experimental autoimmune encephalomyelitis. Arzneimittelforschung 1998;48:668-74.

    12438

    Gupta I, Parihar A, Malhotra P, et al. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Med 2001;67:391-5.

    Moderate

    CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, Boswellia serrata might increase the levels of CYP2C9 substrates.<br> In vitro research shows that Boswellia serrata gum resin inhibits CYP2C9 enzymes (21178).

    References

    21178

    Frank A, Unger M. Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction. J Chromatogr A 2006;1112:255-62.

    Moderate

    CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, Boswellia serrata might increase the levels of CYP3A4 substrates.<br> In vitro research shows that Boswellia serrata gum resin inhibits CYP3A4 enzymes (21178).

    References

    21178

    Frank A, Unger M. Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction. J Chromatogr A 2006;1112:255-62.

    Moderate

    CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, Boswellia serrata might increase the levels of CYP2D6 substrates.<br> In vitro research shows that Boswellia serrata gum resin inhibits CYP2D6 enzymes (21178).

    References

    21178

    Frank A, Unger M. Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction. J Chromatogr A 2006;1112:255-62.

    Moderate

    CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, Boswellia serrata might increase the levels of CYP2C19 substrates. <br> In vitro research shows that Boswellia serrata gum resin inhibits CYP2C19 enzymes (21178).

    References

    21178

    Frank A, Unger M. Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction. J Chromatogr A 2006;1112:255-62.


    Full Reference List

    12810
    Krivoy N, Pavlotzky E, Chrubasik S, et al. Effect of salicis cortex extract on human platelet aggregation. Planta Med 2001;67:209-12.
    12808
    Schmid B, Kotter I, Heide L. Pharmacokinetics of salicin after oral administration of a standardised willow bark extract. Eur J Clin Pharmacol. 2001;57:387-91.
    86481
    Sweeney, K. R., Chapron, D. J., Brandt, J. L., Gomolin, I. H., Feig, P. U., and Kramer, P. A. Toxic interaction between acetazolamide and salicylate: case reports and a pharmacokinetic explanation. Clin Pharmacol Ther 1986;40(5):518-524.
    21178
    Frank A, Unger M. Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction. J Chromatogr A 2006;1112:255-62.
    21180
    Altmann A, Poeckel D, Fischer L, et al. Coupling of boswellic acid-incuded Ca2+ mobilisation and MAPK activation to lipid metabolism and peroxide formation in human leucocytes. Br J Pharmacol 2004;141:223-32.
    12432
    Kimmatkar N, Thawani V, Hingorani L, et al. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Phytomedicine 2003;10:3-7.
    12435
    Liu JJ, Nilsson A, Oredsson S, et al. Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells. Carcinogenesis 2002;23:2087-93.
    12437
    Wildfeuer A, Neu IS, Safayhi H, et al. Effects of boswellic acids extracted from a herbal medicine on the biosynthesis of leukotrienes and the course of experimental autoimmune encephalomyelitis. Arzneimittelforschung 1998;48:668-74.
    12438
    Gupta I, Parihar A, Malhotra P, et al. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Med 2001;67:391-5.
    21497
    Appiah-Opong, R., Commandeur, J. N., Vugt-Lussenburg, B., and Vermeulen, N. P. Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products. Toxicology 6-3-2007;235(1-2):83-91.
    21498
    Hou, X. L., Takahashi, K., Kinoshita, N., Qiu, F., Tanaka, K., Komatsu, K., Takahashi, K., and Azuma, J. Possible inhibitory mechanism of Curcuma drugs on CYP3A4 in 1alpha,25 dihydroxyvitamin D3 treated Caco-2 cells. Int.J Pharm 6-7-2007;337(1-2):169-177.
    21499
    Valentine, S. P., Le Nedelec, M. J., Menzies, A. R., Scandlyn, M. J., Goodin, M. G., and Rosengren, R. J. Curcumin modulates drug metabolizing enzymes in the female Swiss Webster mouse. Life Sci. 4-11-2006;78(20):2391-2398.
    93544
    Nayeri A, Wu S, Adams E, et al. Acute Calcineurin Inhibitor Nephrotoxicity Secondary to Turmeric Intake: A Case Report. Transplant Proc. 2017;49(1):198-200.
    80079
    Juan, H., Terhaag, B., Cong, Z., Bi-Kui, Z., Rong-Hua, Z., Feng, W., Fen-Li, S., Juan, S., Jing, T., and Wen-Xing, P. Unexpected effect of concomitantly administered curcumin on the pharmacokinetics of talinolol in healthy Chinese volunteers. Eur.J Clin Pharmacol 2007;63(7):663-668.
    21472
    Junyaprasert, V. B., Soonthornchareonnon, N., Thongpraditchote, S., Murakami, T., and Takano, M. Inhibitory effect of Thai plant extracts on P-glycoprotein mediated efflux. Phytother.Res 2006;20(1):79-81.
    21473
    Ampasavate, C., Sotanaphun, U., Phattanawasin, P., and Piyapolrungroj, N. Effects of Curcuma spp. on P-glycoprotein function. Phytomedicine. 2010;17(7):506-512.
    21474
    Hou, X. L., Takahashi, K., Tanaka, K., Tougou, K., Qiu, F., Komatsu, K., Takahashi, K., and Azuma, J. Curcuma drugs and curcumin regulate the expression and function of P-gp in Caco-2 cells in completely opposite ways. Int.J Pharm 6-24-2008;358(1-2):224-229.
    21475
    Choi, B. H., Kim, C. G., Lim, Y., Shin, S. Y., and Lee, Y. H. Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NF kappa B pathway. Cancer Lett. 1-18-2008;259(1):111-118.
    21476
    Zhang, W., Tan, T. M., and Lim, L. Y. Impact of curcumin-induced changes in P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral celiprolol and midazolam in rats. Drug Metab Dispos. 2007;35(1):110-115.
    21477
    Limtrakul, P., Chearwae, W., Shukla, S., Phisalphong, C., and Ambudkar, S. V. Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCC1) by tetrahydrocurcumin, a major metabolite of curcumin. Mol.Cell Biochem. 2007;296(1-2):85-95.
    21478
    Holland, M. L., Panetta, J. A., Hoskins, J. M., Bebawy, M., Roufogalis, B. D., Allen, J. D., and Arnold, J. C. The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells. Biochem.Pharmacol 4-14-2006;71(8):1146-1154.
    21479
    Tang, X. Q., Bi, H., Feng, J. Q., and Cao, J. G. Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR. Acta Pharmacol Sin. 2005;26(8):1009-1016.
    21480
    Nabekura, T., Kamiyama, S., and Kitagawa, S. Effects of dietary chemopreventive phytochemicals on P-glycoprotein function. Biochem.Biophys.Res Commun. 2-18-2005;327(3):866-870.
    21482
    Romiti, N., Tongiani, R., Cervelli, F., and Chieli, E. Effects of curcumin on P-glycoprotein in primary cultures of rat hepatocytes. Life Sci. 1998;62(25):2349-2358.
    21484
    Yue, G. G., Cheng, S. W., Yu, H., Xu, Z. S., Lee, J. K., Hon, P. M., Lee, M. Y., Kennelly, E. J., Deng, G., Yeung, S. K., Cassileth, B. R., Fung, K. P., Leung, P. C., and Lau, C. B. The role of turmerones on curcumin transportation and P-glycoprotein activities in intestinal Caco-2 cells. J Med Food 2012;15(3):242-252.
    22005
    Ganta, S., Devalapally, H., and Amiji, M. Curcumin enhances oral bioavailability and anti-tumor therapeutic efficacy of paclitaxel upon administration in nanoemulsion formulation. J Pharm Sci 2010;99(11):4630-4641.
    81131
    Kusuhara, H., Furuie, H., Inano, A., Sunagawa, A., Yamada, S., Wu, C., Fukizawa, S., Morimoto, N., Ieiri, I., Morishita, M., Sumita, K., Mayahara, H., Fujita, T., Maeda, K., and Sugiyama, Y. Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP. Br J Pharmacol 2012;166(6):1793-1803.
    80999
    Yan, Y. D., Kim, D. H., Sung, J. H., Yong, C. S., and Choi, H. G. Enhanced oral bioavailability of docetaxel in rats by four consecutive days of pre-treatment with curcumin. Int J Pharm 10-31-2010;399(1-2):116-120.
    21486
    Shenouda, N. S., Zhou, C., Browning, J. D., Ansell, P. J., Sakla, M. S., Lubahn, D. B., and MacDonald, R. S. Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro. Nutr.Cancer 2004;49(2):200-208.
    80863
    Pavithra, B. H., Prakash, N., and Jayakumar, K. Modification of pharmacokinetics of norfloxacin following oral administration of curcumin in rabbits. J Vet.Sci. 2009;10(4):293-297.
    96125
    Mitchell TM. Correspondence re: Somasundaram et al., Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2003;63(16):5165-6; author reply 5166-7.
    96126
    Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2002;62(13):3868-75.
    96133
    Neerati P, Devde R, Gangi AK. Evaluation of the effect of curcumin capsules on glyburide therapy in patients with type-2 diabetes mellitus. Phytother Res. 2014;28(12):1796-800.
    96137
    Fung FY, Wong WH, Ang SK, et al. A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng. Phytomedicine. 2017;32:88-96.
    11143
    Shah BH, Nawaz Z, Pertani SA. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol 1999;58:1167-72..
    81204
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    Rating System Description

    Level of Significance: Stop‑Light Rating System Occurrence/Severity
    Major

    Do not use combination; contraindicated; strongly discourage patients from using this combination; a serious adverse outcome could occur.

    Moderate

    Use cautiously or avoid combination; warn patients that a significant interaticon or adverse outcome could occur.

    Minor

    Be aware that there is a chance of an interaction; advise patients to watch for warning signs of a potential interaction.

    Likelihood of Occurrence

    Likely: Well‑controlled human studies have demonstrated existence of this interaction.

    Probable: Interaction has not been documented in well‑controlled studies, however interaction has been demonstrated in human studies or in controlled animal studies plus multiple case reports.

    Possible: Interaction has been documented in animal or in vitro research, or interaction has been documented in humans but is limited to case reports or conflicting clinical research.

    Unlikely: Interaction has been demonstrated in animal or in vitro research but has been shown not to occur in humans.

    Severity

    High: Life threatening or requires medical intervention to prevent a serious adverse event.

    Moderate: Worsened clinical status and/or requires medication adjustment.

    Mild: May cause minor clinical side effects. Unlikely to require medication adjustment.

    Insignificant: Drug or supplement levels may be affected but will not cause clinical effects.

    Level of Evidence

    A: High-quality randomized controlled trial(RCT).

    A: High-quality meta-analysis (quantitative systematic review)

    B: Nonrandomized clinical trial

    B: Nonquantitative systematic review

    B: Lower quality RCT

    B: Clinical cohort study

    B: Case-control study

    B: Historical control

    B: Epidemoilogic study

    C: Consensus

    C: Expert opinion

    D: Acecdotal evidence

    D: In vitro or animal study

    D: Theoretical based on pharmacology


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    TRC and all associated names and service marks including TRC are restricted and reserved for Therapeutic Research Center use.
    Natural Medicines™ and associated Natural Medicines product marks are trademarks of Therapeutic Research Center.

    Disclaimer: This information on interactions is licensed from the TRC Natural Medicines Database. Neither Bio Concepts nor TRC are providing medical, clinical or other advice and nothing should be interpreted as constituting such advice. Currently this does not check for drug-drug or supplementsupplement interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgement is necessary.