Mito Xcell Powder 150g

Orthoplex

Orthoplex Mito Xcell is a classically innovative formula aimed at supporting energy and mood through the intricate relationships that are connected by the mitochondria.

By combining therapeutic doses of magnesium citrate, acetyl-l-carnitine and inositol with mitochondrial-specific nutrients, Mito Xcell targets the previously unknown complexities of this organelle.

Gluten Free
Egg Free
Dairy Free
Soy Protein Free
Vegan
Vegetarian
    Product Details

    Pack Size
    150g

    Adult Dose
    Mix 1 scoop (1 level included scoop contains approx. 8g) into water and consume immediately. Take once or twice daily, or as recommended by your registered healthcare practitioner. Do not exceed the recommended daily usage.

    Storage
    Store below 25°C in a cool, dry place.

    Indications

      • Supports energy levels and healthy mood balance
      • Supports glucose metabolism and healthy thyroid function
      • Supports sperm motility and production

    Excipients
    Manufacturing Excipients: Colloidal anhydrous silica, orange flavour, glycine, malic acid, Stevia rebaudiana leaf extract.

    Warning
    Keep out of reach of children. This health supplement is not to be used as a substitute for a varied diet. This product is exclusively a HEALTH SUPPLEMENT and NOT INTENDED TO DIAGNOSE, TREAT, CURE OR CORRECT ANY DISEASE. This product contains selenium which is toxic in high doses. A daily dose of 150 micrograms for adults of selenium from dietary supplements should not be exceeded. Do not take while on warfarin therapy without medical advice. Contains sulfites. Advise your doctor of any medicine you take during pregnancy, particularly in your first trimester.

    Ingredients

    Each 8g (1 level included scoop) Contains

    Magnesium citrate 1.85g
    equiv. Magnesium 300.0g
    Acetyl levocarnitine hydrochloride 1.0g
    Inositol 1.0g
    Rutoside 750.0mg
    Levocarnitine 250.0mg
    Alpha lipoic acid 50.0mg
    Ubidecarenone (Coenzyme Q10) 30.0mg
    Riboflavin sodium phosphate 10.0mg
    Nicotinamide 50.0mg
    Calcium pantothenate 100.0mg
    Biotin 3.0mg
    Manganese amino acid chelate 20.0mg
    equiv. Manganese 2.0mg
    Selenomethionine 148.8mcg
    equiv. Selenium 60.0mcg
    Zinc citrate dihydrate 31.9mg
    equiv. Zinc 10.0mg
    Palm tocotrienols complex (EVNolMax™) 5.0mg
    Reynoutria japonica root (Dry Herb Equiv) 20.0g
    equiv. Resveratrol 100.0mg
    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, Magnesium (as Magnesium citrate), Magnesium (as Magnesium amino acid chelate), Magnesium (as Magnesium citrate nonahydrate), Magnesium (as Magnesium orotate dihydrate), Magnesium (as Magnesium phosphate pentahydrate), Total elemental Magnesium, Magnesium , Magnesium Citrate, Magnesium (as Magnesium glycinate dihydrate), Magnesium (as 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

    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

    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

    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..

    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

    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

    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

    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

    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 and accelerating the onset of effect.<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 calcium-mediated release of acetylcholine from presynaptic nerve terminals, reducing postsynaptic sensitivity to acetylcholine, and having a direct effect on the membrane potential of myocytes (3046,97492,107364). Magnesium also has vasodilatory actions and increases cardiac output, allowing a greater amount of muscle relaxant to reach the motor end plate (107364). A clinical study found that low-dose rocuronium (0.45 mg/kg), when given after administration of magnesium 30 mg/kg over 10 minutes, has an accelerated onset of effect, which matches the onset of effect seen with a full-dose rocuronium regimen (0.6 mg/kg) (96485). In another clinical study, onset times for rocuronium doses of 0.3, 0.6, and 1.2 mg/kg were 86, 76, and 50 seconds, respectively, when given alone, but were reduced to 66, 44, and 38 seconds, respectively, when the doses were given after a 15-minute infusion of magnesium sulfate 60 mg/kg (107364). Giving intraoperative intravenous magnesium sulfate, 50 mg/kg loading dose followed by 15 mg/kg/hour, reduces the onset time of rocuronium, enhances its clinical effects, reduces the dose of intraoperative opiates, and prolongs the spontaneous recovery time (112781,112782). It does not affect the activity of subsequently administered neostigmine (112782).

    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.

    107364

    Almeida CED, Carvalho LR, Andrade CVC, Nascimento PD Jr, Barros GAM, Modolo NSP. Effects of magnesium sulphate on the onset time of rocuronium at different doses: a randomized clinical trial. Braz J Anesthesiol. 2021;71(5):482-8.

    112781

    Su YH, Luo DC, Pang Y. Effects of intraoperative Magnesium sulfate infusion on emergency agitation during general anesthesia in patients undergoing radical mastectomy: a randomized controlled study. BMC Anesthesiol 2023;23(1):326.

    112782

    Han J, Park HY, Shin HJ, Chung SH, Do SH. Effects of magnesium sulphate on neostigmine-induced recovery from moderate neuromuscular blockade with rocuronium: a randomized controlled trial. Magnes Res 2023;36(2):31-39.

    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.

    Moderate
    HU ZHANG
    (Resveratrol, Reynoutria japonica root (Dry Herb Equiv), Reynoutria japonica root ext dry conc std, From Reynoutria japonica root dry)
    Be cautious with this combination.
    View Interactions:
    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, hu zhang might increase levels of drugs metabolized by CYP2C19.<br> Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP2C19 enzyme (70896). This interaction has not been reported in humans.

    References

    70896

    Yu, C., Shin, Y. G., Kosmeder, J. W., Pezzuto, J. M., and van Breemen, R. B. Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate. Rapid Commun.Mass Spectrom. 2003;17(4):307-313.

    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, hu zhang might increase levels of drugs metabolized by CYP3A4.<br> Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP3A4 enzyme (7864,70896). However, a clinical study in adults with NAFLD found that adding resveratrol 3000 mg daily for 8 weeks did not necessitate dose adjustments to any established medications metabolized by CYP3A4 (91327).

    References

    7864

    Piver B, Berthou F, Dreano Y, Lucas D. Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Toxicol Lett 2001;125:83-91.

    70896

    Yu, C., Shin, Y. G., Kosmeder, J. W., Pezzuto, J. M., and van Breemen, R. B. Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate. Rapid Commun.Mass Spectrom. 2003;17(4):307-313.

    91327

    Chachay VS, Macdonald GA, Martin JH, Whitehead JP, O'Moore-Sullivan TM, Lee P, Franklin M, Klein K, Taylor PJ, Ferguson M, Coombes JS, Thomas GP, Cowin GJ, Kirkpatrick CM, Prins JB, Hickman IJ. Resveratrol does not benefit patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2014 Dec;12(12):2092-103.e1-6.

    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, hu zhang might increase levels of drugs metabolized by CYP1A2.<br> Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP1A2 enzyme (21733). This interaction has not been reported in humans.

    References

    21733

    Chang, T. K., Chen, J., and Lee, W. B. Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism-based inactivation of CYP1A2. J.Pharmacol.Exp.Ther. 2001;299(3):874-882.

    Moderate

    CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, hu zhang might increase levels of drugs metabolized by CYP2E1.<br> Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP2E1 enzyme (7864,70896). Also, a pharmacokinetic study shows that taking resveratrol 500 mg daily for 10 days prior to taking a single dose of chlorzoxazone 250 mg increases the maximum concentration of chlorzoxazone by about 54%, the area under the curve of chlorzoxazone by about 72%, and the half-life of chlorzoxazone by about 35% (95824). Chlorzoxazone is used as a probe drug for CYP2E1.

    References

    7864

    Piver B, Berthou F, Dreano Y, Lucas D. Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Toxicol Lett 2001;125:83-91.

    70896

    Yu, C., Shin, Y. G., Kosmeder, J. W., Pezzuto, J. M., and van Breemen, R. B. Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate. Rapid Commun.Mass Spectrom. 2003;17(4):307-313.

    95824

    Bedada SK, Neerati P. Resveratrol Pretreatment Affects CYP2E1 Activity of Chlorzoxazone in Healthy Human Volunteers. Phytother Res. 2016;30(3):463-8.

    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: D

    Theoretically, hu zhang might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.<br> Hu zhang contains the constituent resveratrol. Resveratrol seems to have antiplatelet effects (2949,2950,2951,2952,2961,70813,70828,70831,70892,70968,71106).

    References

    2949

    Pace-Asciak CR, Rounova O, Hahn SE, et al. Wines and grape juices as modulators of platelet aggregation in healthy human subjects. Clin Chim Acta 1996;246:163-82.

    2950

    Bertelli AA, Giovannini L, Bernini W, et al. Antiplatelet activity of cis-resveratrol. Drugs Exp Clin Res 1996;22:61-3.

    2951

    Pace-Asciak CR, Hahn S, Diamandis EP, et al. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta 1995;235:207-19.

    2952

    Bertelli A, Bertelli AA, Gozzini A, Giovannini L. Plasma and tissue resveratrol concentrations and pharmacological activity. Drugs Exp Clin Res 1998;24:133-8.

    2961

    Bertelli AA, Giovannini L, Giannessi D, et al. Antiplatelet activity of synthetic and natural resveratrol in red wine. Int J Tissue React 1995;17:1-3.

    70892

    Olas, B., Wachowicz, B., Saluk-Juszczak, J., and Zielinski, T. Effect of resveratrol, a natural polyphenolic compound, on platelet activation induced by endotoxin or thrombin. Thromb.Res 8-15-2002;107(3-4):141-145.

    70813

    Dobrydneva, Y., Williams, R. L., and Blackmore, P. F. trans-Resveratrol inhibits calcium influx in thrombin-stimulated human platelets. Br.J.Pharmacol. 1999;128(1):149-157.

    70828

    Kirk, R. I., Deitch, J. A., Wu, J. M., and Lerea, K. M. Resveratrol decreases early signaling events in washed platelets but has little effect on platalet in whole food. Blood Cells Mol.Dis. 2000;26(2):144-150.

    70831

    Zbikowska, H. M. and Olas, B. Antioxidants with carcinostatic activity (resveratrol, vitamin E and selenium) in modulation of blood platelet adhesion. J Physiol Pharmacol. 2000;51(3):513-520.

    70968

    Ma, Z. H. and Ma, Q. Y. Resveratrol: a medical drug for acute pancreatitis. World J Gastroenterol. 6-7-2005;11(21):3171-3174.

    71106

    Pendurthi, U. R., Williams, J. T., and Rao, L. V. Resveratrol, a polyphenolic compound found in wine, inhibits tissue factor expression in vascular cells : A possible mechanism for the cardiovascular benefits associated with moderate consumption of wine. Arterioscler.Thromb.Vasc.Biol 1999;19(2):419-426.

    Moderate

    ESTROGENS

    Be cautious with this combination.

    Moderate

    ESTROGENS

    Be cautious with this combination.

    Moderate

    ESTROGENS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, hu zhang might competitively inhibit the effects of estrogen replacement therapy. <br> In vitro research shows that hu zhang might have estrogenic activity (13124,16061).

    References

    16061

    Zhang CZ, Wang SX, Zhang Y, et al. In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms. J Ethnopharmacol 2005;98:295-300.

    13124

    Matsuda H, Shimoda H, Morikawa T, Yoshikawa M. Phytoestrogens from the roots of Polygonum cuspidatum (Polygonaceae): structure-requirement of hydroxyanthraquinones for estrogenic activity. Bioorg Med Chem Lett 2001;11:1839-42.

    Minor

    CARBAMAZEPINE (Tegretol)

    Be watchful with this combination.

    Minor

    CARBAMAZEPINE (Tegretol)

    Be watchful with this combination.

    Minor

    CARBAMAZEPINE (Tegretol)

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: D

    Theoretically, hu zhang might increase the effects and adverse effects of carbamazepine. <br> In animals, blood and tissue levels of carbamazepine were increased when given in combination with hu zhang. It is thought that increased levels of carbamazepine are due to cytochrome P450 3A4 (CYP3A4) inhibition (101418). This interaction has not been reported in humans.

    References

    101418

    Chi YC, Lin SP, Hou YC. A new herb-drug interaction of Polygonum cuspidatum, a resveratrol-rich nutraceutical, with carbamazepine in rats. Toxicol Appl Pharmacol 2012;263(3):315-22.

    Moderate
    ZINC
    (Polaprezinc (Zinc carnosine), Zinc, Zinc amino acid chelate, Zinc citrate, Zinc citrate dihydrate, Zinc gluconate, Zinc picolinate, Zinc sulfate heptahydrate, Zinc (as Zinc citrate dihydrate), Zinc (as Zinc amino acid chelate), Zinc (as Zinc citrate))
    Be cautious with this combination.
    View Interactions:
    Moderate

    PENICILLAMINE (Cuprimine, Depen)

    Be cautious with this combination.

    Moderate

    PENICILLAMINE (Cuprimine, Depen)

    Be cautious with this combination.

    Moderate

    PENICILLAMINE (Cuprimine, Depen)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Zinc might reduce the levels and clinical effects of penicillamine. <br> By forming an insoluble complex with penicillamine, zinc interferes with penicillamine absorption and activity. Zinc supplements reduce the efficacy of low-dose penicillamine (0.5-1 gram/day), but do not seem to affect higher doses (1-2.75 gram/day), provided dosing times are separated (2678,4534,11605). Advise patients to take zinc and penicillamine at least 2 hours apart.

    References

    2678

    Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, et al. Treatment of Wilson's disease with zinc: XI. Interaction with other anticopper agents. J Am Coll Nutr 1993;12:26-30.

    4534

    Seelig MS. Auto-immune complications of D-penicillamine - A possible result of zinc and magnesium depletion and of pyridoxine inactivation. J Am Coll Nutr 1982;1:207-14.

    11605

    Mery C, Delrieu F, Ghozlan R, et al. Controlled trial of D-penicillamine in rheumatoid arthritis. Dose effect and the role of zinc. Scand J Rheumatol 1976;5:241-7.

    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: B

    Zinc might reduce levels of tetracycline antibiotics.<br> Tetracyclines form complexes with zinc in the gastrointestinal tract, which can reduce absorption of both the tetracycline and zinc when taken at the same time (3046,4945). Taking zinc sulfate 200 mg with tetracycline reduces absorption of the antibiotic by 30% to 40% (11615). Demeclocycline and minocycline cause a similar interaction (4945). However, doxycycline does not seem to interact significantly with zinc (11615). Advise patients to take tetracyclines at least 2 hours before, or 4-6 hours after, zinc supplements to avoid any interactions.

    References

    3046

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

    4945

    Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs 1976;11:45-54..

    11615

    Penttila O, Hurme H, Neuvonen PJ. Effect of zinc sulfate on the absorption of tetracycline and doxycycline in man. Eur J Clin Pharmacol 1975;9:131-4.

    Moderate

    CEPHALEXIN (Keflex)

    Be cautious with this combination.

    Moderate

    CEPHALEXIN (Keflex)

    Be cautious with this combination.

    Moderate

    CEPHALEXIN (Keflex)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Zinc might decrease cephalexin levels by chelating with cephalexin in the gut and preventing its absorption. <br> A pharmacokinetic study shows that zinc sulfate 250 mg taken concomitantly with cephalexin 500 mg decreases peak levels of cephalexin by 31% and reduces the exposure to cephalexin by 27%. Also, taking zinc sulfate 3 hours before cephalexin decreases peak levels of cephalexin by 11% and reduces the exposure to cephalexin by 18%. By decreasing cephalexin levels, zinc might increase the risk of treatment failure. This effect does not occur when zinc is taken 3 hours after the cephalexin dose (94163). To avoid an interaction, advise patients take zinc sulfate 3 hours after taking cephalexin.

    References

    94163

    Ding Y, Jia YY, Li F, et al. The effect of staggered administration of zinc sulfate on the pharmacokinetics of oral cephalexin. Br J Clin Pharmacol. 2012 Mar;73(3):422-7.

    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: B

    Zinc can decrease the levels and clinical effects of quinolones antibiotics. <br> Quinolones form complexes with zinc in the gastrointestinal tract, reducing absorption of both the quinolone and zinc if taken at the same time (828,2682,3046,11600). Advise patients to take these drugs at least 2 hours before, or 4-6 hours after, zinc supplements.

    References

    3046

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

    828

    Blondeau JM. Expanded activity and utility of the new fluoroquinolones: a review. Clin Ther 1999;21:3-40.

    2682

    Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf 1995;12:314-33.

    11600

    Polk RE, Healy DP, Sahai J, et al. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother 1989;33:1841-4.

    Moderate

    RITONAVIR (Norvir)

    Be cautious with this combination.

    Moderate

    RITONAVIR (Norvir)

    Be cautious with this combination.

    Moderate

    RITONAVIR (Norvir)

    Be cautious with this combination.

    Severity: mild
    Occurrence: probable
    Level of Evidence: B

    Zinc modestly reduces levels of ritonavir.<br> Clinical research shows that zinc might reduce serum ritonavir levels by chelating with ritonavir in the gut and preventing its absorption (93578). In patients with HIV, ritonavir is taken with atazanavir to prevent the metabolism and increase the effects of atazanavir. A pharmacokinetic study shows that, in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate (Solvazinc tablets) 125 mg as a single dose or as multiple daily doses for 2 weeks reduces plasma levels of ritonavir by about 16% (90216). However, atazanavir levels still remains high enough to prevent HIV virus replication. Therefore, the decrease in ritonavir levels is not likely to be clinically significant.

    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.

    90216

    Moyle G, Else L, Jackson A, Back D, Yapa MH, Seymour N, Ringner-Nackter L, Karolia Z, Gazzard B, Boffito M. Coadministration of atazanavir-ritonavir and zinc sulfate: impact on hyperbilirubinemia and pharmacokinetics. Antimicrob Agents Chemother. 2013 Aug;57(8):3640-4.

    Moderate

    CISPLATIN (Platinol-AQ)

    Be cautious with this combination.

    Moderate

    CISPLATIN (Platinol-AQ)

    Be cautious with this combination.

    Moderate

    CISPLATIN (Platinol-AQ)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, zinc might interfere with the therapeutic effects of cisplatin.<br> Animal research suggests that zinc stimulates tumor cell production of the protein metallothionein, which binds and inactivates cisplatin (11624,11625). It is not known whether zinc supplements or high dietary zinc intake can cause clinically significant interference with cisplatin therapy. Cisplatin might also increase zinc excretion.

    References

    11624

    Kondo Y, Yamagata K, Satoh M, et al. Optimal administration schedule of cisplatin for bladder tumor with minimal induction of metallothionein. J Urol 2003;170:2467-70.

    11625

    Doz F, Berens ME, Deschepper CF, et al. Experimental basis for increasing the therapeutic index of cis-diamminedicarboxylatocyclobutaneplatinum(II) in brain tumor therapy by a high-zinc diet. Cancer Chemother Pharmacol 1992;29:219-26.

    Moderate

    INTEGRASE INHIBITORS

    Be cautious with this combination.

    Moderate

    INTEGRASE INHIBITORS

    Be cautious with this combination.

    Moderate

    INTEGRASE INHIBITORS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, taking zinc along with integrase inhibitors might decrease the levels and clinical effects of these drugs.<br> Zinc is a divalent cation. Pharmacokinetic studies have shown that other divalent cations such as calcium and iron can decrease blood levels of the integrase inhibitor dolutegravir through chelation (93578,93579).

    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.

    93579

    Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents: Drug Interactions between Integrase Inhibitors and Other Drugs. AIDSinfo. July 14, 2016. Available at: https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/287/insti-drug-interactions. (Accessed: 4/12/2017).

    Minor

    ATAZANAVIR (Reyataz)

    Be watchful with this combination.

    Minor

    ATAZANAVIR (Reyataz)

    Be watchful with this combination.

    Minor

    ATAZANAVIR (Reyataz)

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: probable
    Level of Evidence: B

    Zinc modestly reduces levels of atazanavir, although this effect does not seem to be clinically significant.<br> Clinical research shows that zinc might decrease serum atazanavir levels by chelating with atazanavir in the gut and preventing its absorption (93578). Although a single dose of zinc sulfate (Solvazinc tablets) 125 mg orally does not affect atazanavir concentrations in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate 125 mg daily for 2 weeks reduces plasma levels of atazanavir by about 22% in these patients. However, despite this decrease, atazanavir levels still remain at high enough concentrations for the prevention of HIV virus replication (90216).

    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.

    90216

    Moyle G, Else L, Jackson A, Back D, Yapa MH, Seymour N, Ringner-Nackter L, Karolia Z, Gazzard B, Boffito M. Coadministration of atazanavir-ritonavir and zinc sulfate: impact on hyperbilirubinemia and pharmacokinetics. Antimicrob Agents Chemother. 2013 Aug;57(8):3640-4.

    Minor

    AMILORIDE (Midamor)

    Be watchful with this combination.

    Minor

    AMILORIDE (Midamor)

    Be watchful with this combination.

    Minor

    AMILORIDE (Midamor)

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: probable
    Level of Evidence: B

    Amiloride can modestly reduce zinc excretion and increase zinc levels. <br> Clinical research shows that amiloride can reduce urinary zinc excretion, especially at doses of 10 mg per day or more. This zinc-sparing effect can help to counteract zinc losses caused by thiazide diuretics, but it is unlikely to cause zinc toxicity at usual amiloride doses (830,11626,11627,11634). The other potassium-sparing diuretics, spironolactone (Aldactone) and triamterene (Dyrenium), do not seem to have a zinc-sparing effect.

    References

    830

    Reyes AJ, Olhaberry JV, Leary WP, et al. Urinary zinc excretion, diuretics, zinc deficiency and some side-effects of diuretics. S Afr Med J 1983;64:936-41.

    11626

    Wester PO. Urinary zinc excretion during treatment with different diuretics. Acta Med Scand 1980;208:209-12.

    11627

    Golik A, Modai D, Weissgarten J, et al. Hydrochlorothiazide-amiloride causes excessive urinary zinc excretion. Clin Pharmacol Ther 1987;42:42-4.

    11634

    Leary WP, Reyes AJ, Van der Byl K. Urinary magnesium and zinc excretion after two different single doses of amiloride in healthy adults. Curr Ther Res 1983;34:205-16.

    Moderate
    SELENIUM
    (Sodium selenite, Selenium, Selenomethionine, Selenium (as Selenomethionine))
    Be cautious with this combination.
    View Interactions:
    Moderate

    BARBITURATES

    Be cautious with this combination.

    Moderate

    BARBITURATES

    Be cautious with this combination.

    Moderate

    BARBITURATES

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, selenium might prolong the sedating effects of barbiturates.<br> Laboratory research suggests that selenium can inhibit the hepatic metabolism of barbiturates (14601,14602). Selenium seems to prolong the sedative effect of pentobarbital in animal models (14601).

    References

    14601

    Debski B, Milner JA. Dietary selenium supplementation prolongs pentobarbital induced hypnosis. J Nutr Biochem 2004;15:548-53.

    14602

    Ishikawa M, Sasaki M, Koiwai K, et al. Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium. J Pharmacobiodyn 1992;15:377-85.

    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

    Theoretically, selenium might interfere with warfarin activity. <br> Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors (14541). Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity (14540).

    References

    14540

    Schiavon R, Freeman GE, Guidi GC, et al. Selenium enhances prostacyclin production by cultured endothelial cells: possible explanation for increased bleeding times in volunteers taking selenium as a dietary supplement. Thromb Res 1984;34:389-96.

    14541

    Davila JC, Edds GT, Osuna O, Simpson CF. Modification of the effects of aflatoxin B1 and warfarin in young pigs given selenium. Am J Vet Res 1983;44:1877-83.

    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: D

    Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.<br> Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity (14540). Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation (74406).

    References

    14540

    Schiavon R, Freeman GE, Guidi GC, et al. Selenium enhances prostacyclin production by cultured endothelial cells: possible explanation for increased bleeding times in volunteers taking selenium as a dietary supplement. Thromb Res 1984;34:389-96.

    74406

    Salonen, J. T., Salonen, R., Seppanen, K., Rinta-Kiikka, S., Kuukka, M., Korpela, H., Alfthan, G., Kantola, M., and Schalch, W. Effects of antioxidant supplementation on platelet function: a randomized pair-matched, placebo-controlled, double-blind trial in men with low antioxidant status. Am.J Clin.Nutr. 1991;53(5):1222-1229.

    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, selenium supplementation may reduce the effectiveness of immunosuppressant therapy. <br> In vitro research and preliminary clinical evidence suggests that selenium may stimulate the immune system (74483,74445).

    References

    74445

    Peretz, A., Neve, J., Desmedt, J., Duchateau, J., Dramaix, M., and Famaey, J. P. Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast. Am.J Clin.Nutr. 1991;53(5):1323-1328.

    74483

    Kiremidjian-Schumacher, L., Roy, M., Wishe, H. I., Cohen, M. W., and Stotzky, G. Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells. Biol.Trace Elem.Res. 1994;41(1-2):115-127.

    Minor

    CONTRACEPTIVE DRUGS

    Be watchful with this combination.

    Minor

    CONTRACEPTIVE DRUGS

    Be watchful with this combination.

    Minor

    CONTRACEPTIVE DRUGS

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: possible
    Level of Evidence: B

    Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.<br> Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels (14544,14545,14546,101343). It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium (14545).

    References

    14544

    Heese HD, Lawrence MA, Dempster WS, Pocock F. Reference concentrations of serum selenium and manganese in healthy nulliparas. S Afr Med J 1988;73:163-5.

    14545

    Lloyd B, Lloyd RS, Clayton BE. Effect of smoking, alcohol and other factors on the selenium status of a healthy population. J Epidemiol Commun Health 1983;37:213-7.

    14546

    Capel ID, Jenner M, Williams DC, et al. The effect of prolonged oral contraceptive steroid use on erythrocyte glutathione peroxidase activity. J Steroid Biochem 1981;14:729-32.

    101343

    Fallah S, Sani FV, Firoozrai M. Effect of contraceptive pill on the selenium and zinc status of healthy subjects. Contraception. 2009;80(1):40-3.

    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

    Selenium might reduce the beneficial effects of niacin on high-density lipoprotein (HDL) 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 selenium, 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.

    Moderate
    MANGANESE
    (Manganese amino acid chelate, Manganese, Manganese chloride tetrahydrate, Manganese (as Manganese amino acid chelate))
    Be cautious with this combination.
    View Interactions:
    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

    Theoretically, manganese might reduce the absorption of quinolone antibiotics.<br> Manganese is a multivalent cation. Interactions resulting in reduced quinolone absorption have been reported between quinolones and other multivalent cations, such as calcium and iron (488).

    References

    488

    Hansten PD, Horn JR. Hansten and Horn's Drug Interactions Analysis and Management. Vancouver, CAN:Appl Therapeut, 1999.

    Moderate

    ANTIPSYCHOTIC DRUGS

    Be cautious with this combination.

    Moderate

    ANTIPSYCHOTIC DRUGS

    Be cautious with this combination.

    Moderate

    ANTIPSYCHOTIC DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, the risk for manganese toxicity might increase when taken with antipsychotic drugs.<br> Hallucinations and behavioral changes have been reported in a patient with liver disease who was taking haloperidol and manganese. Researchers speculate that taking manganese along with haloperidol, phenothiazine-derivatives, or other antipsychotic medications might increase the risk of manganese toxicity in some patients (61493).

    References

    61493

    Mehta, R. and Reilly, J. J. Manganese levels in a jaundiced long-term total parenteral nutrition patient: potentiation of haloperidol toxicity? Case report and literature review. JPEN J Parenter.Enteral Nutr 1990;14(4):428-430.

    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

    Theoretically, manganese might reduce the absorption of tetracycline antibiotics.<br> Manganese is a multivalent cation. Interactions resulting in reduced tetracycline absorption have been reported between tetracyclines and other multivalent cations, such as calcium and iron (488).

    References

    488

    Hansten PD, Horn JR. Hansten and Horn's Drug Interactions Analysis and Management. Vancouver, CAN:Appl Therapeut, 1999.

    Moderate
    NIACINAMIDE
    (Nicotinamide)
    Be cautious with this combination.
    View Interactions:
    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: unlikely
    Level of Evidence: D

    Theoretically, niacinamide may have additive effects when used with anticoagulant or antiplatelet drugs, especially in patients on hemodialysis.<br> Several cases of thrombocytopenia have been reported for hemodialysis patients treated with niacinamide 1 gram daily. Hemodialysis patients receiving niacinamide had almost a three-fold higher risk of developing thrombocytopenia when compared with those receiving placebo (25563,98940).

    References

    25563

    Rottembourg JB, Launay-Vacher V, Massard J. Thrombocytopenia induced by nicotinamide in hemodialysis patients. Kidney Int. 2005;68(6):2911-2.

    98940

    Zhang Y, Ma T, Zhang P. Efficacy and safety of nicotinamide on phosphorus metabolism in hemodialysis patients: A systematic review and meta-analysis. Medicine (Baltimore). 2018;97(41):e12731.

    Moderate

    CARBAMAZEPINE (Tegretol)

    Be cautious with this combination.

    Moderate

    CARBAMAZEPINE (Tegretol)

    Be cautious with this combination.

    Moderate

    CARBAMAZEPINE (Tegretol)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Niacinamide might increase the levels and adverse effects of carbamazepine.<br> Plasma levels of carbamazepine were increased in two children given high-dose niacinamide, 60-80 mg/kg/day. This might be due to inhibition of the cytochrome P450 enzymes involved in carbamazepine metabolism (14506). There is not enough data to determine the clinical significance of this interaction.

    References

    14506

    Bourgeois BF, Dodson WE, Ferrendelli JA. Interactions between primidone, carbamazepine, and nicotinamide. Neurology 1982;32:1122-6.

    Moderate

    PRIMIDONE (Mysoline)

    Be cautious with this combination.

    Moderate

    PRIMIDONE (Mysoline)

    Be cautious with this combination.

    Moderate

    PRIMIDONE (Mysoline)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Niacinamide might increase the levels and adverse effects of primidone.<br> Case reports in children suggest niacinamide 60-100 mg/kg/day reduces hepatic metabolism of primidone to phenobarbital, and reduces the overall clearance rate of primidone (14506); however, there is not enough data to determine the clinical significance of this potential interaction.

    References

    14506

    Bourgeois BF, Dodson WE, Ferrendelli JA. Interactions between primidone, carbamazepine, and nicotinamide. Neurology 1982;32:1122-6.

    Moderate
    RIBOFLAVIN
    (Riboflavin, Riboflavin sodium phosphate)
    Be cautious with this combination.
    View Interactions:
    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: possible
    Level of Evidence: D

    Theoretically, taking riboflavin with tetracycline antibiotics may decrease the potency of these antibiotics.<br> In vitro research suggests that riboflavin may inhibit the potency of tetracycline antibiotics (23372). It is not clear if this effect is clinically significant, as this interaction has not been reported in humans.

    References

    23372

    Leeson LJ, Weidenheimer JF. Stability of tetracycline and riboflavin. J Pharm Sci. 1969;58(3):355-7.

    Moderate
    COENZYME Q10
    (Ubidecarenone (Coenzyme Q10))
    Be cautious with this combination.
    View Interactions:
    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

    Coenzyme Q10 is chemically similar to menaquinone and might have vitamin K-like procoagulant effects, which could decrease the effects of warfarin.<br> Concomitant use of coenzyme Q10 and warfarin might reduce the anticoagulant effects of warfarin (2128,6048,6199). Four cases of decreased warfarin efficacy thought to be due to coenzyme Q10 have been reported (2128,6048,11048). However, there is some preliminary clinical research that suggests coenzyme Q10 might not significantly decrease the effects of warfarin in patients who have a stable INR (11905).

    References

    6048

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

    2128

    Spigset O. Reduced effect of warfarin caused by ubidecarenone. Lancet 1994;334:1372-3.

    6199

    Landbo C, Almdal TP. [Interaction between warfarin and coenzyme Q10]. Ugeskr Laeger 1998;160:3226-7.

    11048

    Porterfield LM. Why did the response to warfarin change? RN 2000;63:107.

    11905

    Engelsen J, Nielsen JD, Winther K. Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial. Thromb Haemost 2002;87:1075-6.

    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: moderate
    Occurrence: possible
    Level of Evidence: D

    Coenzyme Q10 has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals.<br> Theoretically, antioxidants such as coenzyme Q10 might protect tumor cells from chemotherapeutic agents that work by inducing oxidative stress, such as alkylating agents (e.g., cyclophosphamide) and radiation therapy (5158,5159). The clinical importance of this interaction is unknown.

    References

    5158

    Portakal O, Ozkaya O, Erden Inal M, et al. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 2000;33:279-84.

    5159

    Lund EL, Quistorff B, Spang-Thomsen M, Kristjansen PE. Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake. Folia Microbiol (Praha) 1998;43:505-6.

    Minor

    ANTIHYPERTENSIVE DRUGS

    Be watchful with this combination.

    Minor

    ANTIHYPERTENSIVE DRUGS

    Be watchful with this combination.

    Minor

    ANTIHYPERTENSIVE DRUGS

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: B

    Theoretically, coenzyme Q10 might have additive effects with antihypertensive drugs.<br> Some clinical research shows that coenzyme Q10 can significantly lower blood pressure (2122,3365,8907,9890,17702,17650,17651,44343,96541), although other studies have shown conflicting results (17651,44211,95607).

    References

    2122

    Langsjoen P, Willis R, Folkers K. Treatment of essential hypertension with coenzyme Q10. Mol Aspects Med 1994;S265-72.

    9890

    Hodgson JM, Watts GF, Playford DA, et al. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 2002;56:1137-42.

    17702

    Ho MJ, Bellusci A, Wright JM. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension (review). Cochrane Database Syst Rev 2009;(4):CD007435.

    3365

    Singh RB, Niaz MA, Rastogi SS, et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens 1999;13:203-8.

    8907

    Burke BE, Neuenschwander R, Olson RD. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. South Med J 2001;94:1112-7.

    17650

    Digiesi V, Cantini F, Oradei A, et al. Coenzyme Q10 in essential hypertension. Mol Aspects Med 1994;15 Suppl:s257-63.

    17651

    Yamagami T, Takagi M, Akagami H, et al. Effect of coenzyme Q10 on essential hypertension, a double blind controlled study. In: Folkers KA, Yamamura Y, eds. Biomedical and Clinical Aspects of Coenzyme Q, Vol. 5. Amsterdam: Elsevier Science Publications, 1986:337-43.

    44211

    Young, J. M., Florkowski, C. M., Molyneux, S. L., McEwan, R. G., Frampton, C. M., Nicholls, M. G., Scott, R. S., and George, P. M. A randomized, double-blind, placebo-controlled crossover study of coenzyme Q10 therapy in hypertensive patients with the metabolic syndrome. Am J Hypertens. 2012;25(2):261-270.

    44343

    Digiesi V, Cantini F, and Brodbeck B. Effect of coenzyme Q10 on essential arterial hypertension. Current Therapeutic Research 1990;47(5):841-845.

    95607

    Ho MJ, Li EC, Wright JM. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension. Cochrane Database Syst Rev. 2016 Mar 3;3:CD007435. doi: 10.1002/14651858.CD007435.pub3.

    96541

    Tabrizi R, Akbari M, Sharifi N, Lankarani KB, Moosazadeh M, Kolahdooz F, et al. The effects of coenzyme Q10 supplementation on blood pressures among patients with metabolic diseases: a systematic review and meta-analysis of randomized controlled trials. High Blood Press Cardiovasc Prev. 2018;25(1):41-50. doi: 10.1007/s40292-018-0247-2.

    Moderate
    ALPHA-LIPOIC ACID
    (Alpha lipoic acid)
    Be cautious with this combination.
    View Interactions:
    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, alpha-lipoic acid might decrease the effects of thyroid hormone drugs.<br> Animal research suggests that co-administration of thyroxine with alpha-lipoic acid reduces conversion into the active T3 form (8946).

    References

    8946

    Segermann J, Hotze A, Ulrich H, Rao GS. Effect of alpha-lipoic acid on the peripheral conversion of thyroxine to triiodothyronine and on serum lipid-, protein- and glucose levels. Arzneimittelforschung 1991;41:1294-8.

    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

    Theoretically, alpha-lipoic acid may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.<br> In vitro, alpha-lipoic acid inhibits platelet aggregation (98682).

    References

    98682

    Karkabounas S, Papadopoulos N, Anastasiadou C, et al. Effects of a-lipoic Acid, carnosine, and thiamine supplementation in obese patients with type 2 diabetes mellitus: A randomized, double-blind study. J Med Food. 2018;21(12):1197-1203.

    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 alpha-lipoic acid might alter the effectiveness of antitumor antibiotics.<br> The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of antitumor antibiotic drugs, which work by generating free radicals (391). However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using alpha-lipoic acid.

    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

    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, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of alkylating agents. <br> The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals (391). However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy. Advise patients to consult their oncologist before using alpha-lipoic acid.

    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

    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: B

    Theoretically, taking alpha-lipoic acid with antidiabetes drugs might increase the risk of hypoglycemia.<br> Although some small clinical studies have suggested that alpha-lipoic acid can lower blood glucose levels (3545,3874,3875,3876,20490,20493,104650), larger clinical studies in patients with diabetes have shown no clinically meaningful effect (20494,20495,20496,90443,90445,110118). Additionally, co-administration of single doses of alpha-lipoic acid and glyburide or acarbose did not cause detectable drug interactions in healthy volunteers (3870).

    References

    3545

    Konrad T, Vicini P, Kusterer K, et al. Alpha-lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with Type 2 diabetes. Diabetes Care 1999;22:280-7.

    3870

    Gleiter CH, Schreeb KH, Freudenthaler S, et al. Lack of interaction between thioctic acid, glibenclamide and acarbose. Br J Clin Pharmacol 1999;48:819-25.

    3874

    Jacob S, Henriksen EJ, Tritschler HJ, et al. Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid. Exp Clin Endocrinol Diabet 1996;104:284-8.

    3875

    Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung 1995;45:872-4.

    3876

    Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled, pilot trial. Free Rad Biol Med 1999;27:309-14.

    20490

    Porasuphatana S., Suddee S., Nartnampong A., Konsil J., Harnwong B., Santaweesuk A. Glycemic and oxidative status of patients with type 2 diabetes mellitus following oral administration of alpha-lipoic acid: a randomized double-blinded placebo-controlled study. Asia Pac J Clin Nutr 2012;21(1):12-21.

    20493

    Ansar H., Mazloom Z., Kazemi F., Hejazi N. Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients. Saudi Med J 2011;32(6):584-588.

    20494

    de Oliveira A. M., Rondó P. H., Luzia L. A., D'Abronzo F. H., Illison V. K. The effects of lipoic acid and a-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Diabetes Res Clin Pract 2011;92(2):253-260.

    20495

    Mazloom Z., Ansar H. The Effect of Alpha-Lipoic Acid on Blood Pressure in Type 2 Diabetics. Iranian Journal of Endocrinology and Metabolism 2009;11(3):245-250.

    20496

    Volchegorskii I. A., Rassokhina L. M., Koliadich M. I., Alekseev M. I. [Comparative study of alpha-lipoic acid and mexidol effects on affective status, cognitive functions and quality of life in diabetes mellitus patients]. Eksp Klin Farmakol 2011;74(11):17-23.

    90443

    Hegazy SK, Tolba OA, Mostafa TM, Eid MA, El-Afify DR. Alpha-lipoic acid improves subclinical left ventricular dysfunction in asymptomatic patients with type 1 diabetes. Rev Diabet Stud 2013;10(1):58-67.

    90445

    Huang Z, Wan X, Liu J, et al. Short-term continuous subcutaneous insulin infusion combined with insulin sensitizers rosiglitazone, metformin, or antioxidant a-lipoic acid in patients with newly diagnosed type 2 diabetes mellitus. Diabetes Technol Ther 2013;15(10):859-69.

    104650

    Derosa G, D'Angelo A, Preti P, Maffioli P. Safety and efficacy of alpha lipoic acid during 4 years of observation: A retrospective, clinical trial in healthy subjects in primary prevention. Drug Des Devel Ther. 2020;14:5367-5374.

    110118

    Jibril AT, Jayedi A, Shab-Bidar S. Efficacy and safety of oral alpha-lipoic acid supplementation for type 2 diabetes management: a systematic review and dose-response meta-analysis of randomized trials. Endocr Connect 2022;11(10):e220322.

    Moderate
    L-CARNITINE
    (Levocarnitine, Levocarnitine fumarate)
    Be cautious with this combination.
    View Interactions:
    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Theoretically, L-carnitine might decrease the effectiveness of thyroid hormone replacement.<br> L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells (12761). Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism (8047).

    References

    8047

    Benvenga S, Ruggeri RM, Russo A, et al. Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab 2001;86:3579-94.

    12761

    12761 Benvenga S, Amato A, Calvani M, Trimarchi F. Effects of carnitine on thyroid hormone action. Ann N Y Acad Sci 2004;1033:158-67.

    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

    Theoretically, L-carnitine might increase the anticoagulant effects of warfarin.<br> L-carnitine might increase the anticoagulant effects of acenocoumarol, a shorter-acting oral anticoagulant similar to warfarin (9878,12165). There is not enough information to know whether this interaction occurs with L-carnitine and warfarin.

    References

    9878

    Martinez E, Domingo P, Roca-Cusachs A. Potentiation of acenocoumarol action by L-carnitine. J Intern Med 1993;233:94.

    12165

    Bachmann HU, Hoffmann A. Interaction of food supplement L-carnitine with oral anticoagulant acenocoumarol. Swiss Med Wkly 2004;134:385.

    Moderate

    ACENOCOUMAROL (Sintrom)

    Be cautious with this combination.

    Moderate

    ACENOCOUMAROL (Sintrom)

    Be cautious with this combination.

    Moderate

    ACENOCOUMAROL (Sintrom)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, L-carnitine might increase the anticoagulant effects of acenocoumarol. <br> L-carnitine might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant similar to warfarin, but shorter-acting (9878,12165). There are at least two case reports of INR elevation with concomitant use. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product (12165).

    References

    9878

    Martinez E, Domingo P, Roca-Cusachs A. Potentiation of acenocoumarol action by L-carnitine. J Intern Med 1993;233:94.

    12165

    Bachmann HU, Hoffmann A. Interaction of food supplement L-carnitine with oral anticoagulant acenocoumarol. Swiss Med Wkly 2004;134:385.

    Moderate
    RUTIN
    (Rutoside)
    Be cautious with this combination.
    View Interactions:
    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: D

    Theoretically, taking rutin with antidiabetes drugs might increase the risk of hypoglycemia.<br> Animal research suggests that rutin has hypoglycemic effects (105299).

    References

    105299

    Sun C, Wang L, Sun J, Wang Z, Tang Z. Hypoglycemic and hypolipidemic effects of rutin on hyperglycemic rats. J Tradit Chin Med. 2020;40(4):640-645.

    Moderate
    INOSITOL
    (Inositol)
    Be cautious with this combination.
    View Interactions:
    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: A

    Theoretically, taking inositol with antidiabetes drugs might increase the risk of hypoglycemia. <br> Clinical research shows that inositol lowers blood glucose levels and glycated hemoglobin (HbA1c) levels in patients with diabetes (95083,95084,95088).

    References

    95083

    Zheng X, Liu Z, Zhang Y, et al. Relationship Between Myo-Inositol Supplementary and Gestational Diabetes Mellitus: A Meta-Analysis. Medicine (Baltimore). 2015;94(42):e1604.

    95084

    Crawford TJ, Crowther CA, Alsweiler J, Brown J. Antenatal dietary supplementation with myo-inositol in women during pregnancy for preventing gestational diabetes. Cochrane Database Syst Rev. 2015;(12):CD011507.

    95088

    Maurizi AR, Menduni M, Del Toro R, et al. A pilot study of D-chiro-inositol plus folic acid in overweight patients with type 1 diabetes. Acta Diabetol. 2017;54(4):361-65.

    Moderate
    ACETYL-L-CARNITINE
    (Acetyl levocarnitine hydrochloride)
    Be cautious with this combination.
    View Interactions:
    Moderate

    ACENOCOUMAROL (Sintrom)

    Be cautious with this combination.

    Moderate

    ACENOCOUMAROL (Sintrom)

    Be cautious with this combination.

    Moderate

    ACENOCOUMAROL (Sintrom)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of acenocoumarol. <br> L-carnitine, the parent compound of acetyl-L-carnitine, might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant that is similar to warfarin, but shorter-acting (9878,12165). There are at least two case reports of INR elevation when L-carnitine was taken with acenocoumarol. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product (12165). It is unclear if such an interaction would also occur with acetyl-L-carnitine.

    References

    9878

    Martinez E, Domingo P, Roca-Cusachs A. Potentiation of acenocoumarol action by L-carnitine. J Intern Med 1993;233:94.

    12165

    Bachmann HU, Hoffmann A. Interaction of food supplement L-carnitine with oral anticoagulant acenocoumarol. Swiss Med Wkly 2004;134:385.

    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

    Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of warfarin. <br> L-carnitine, the parent compound of acetyl-L-carnitine, might increase the anticoagulant effects of acenocoumarol, a shorter-acting oral anticoagulant similar to warfarin (9878,12165). There is not enough information to know whether this interaction occurs with acetyl-L-carnitine and warfarin.

    References

    9878

    Martinez E, Domingo P, Roca-Cusachs A. Potentiation of acenocoumarol action by L-carnitine. J Intern Med 1993;233:94.

    12165

    Bachmann HU, Hoffmann A. Interaction of food supplement L-carnitine with oral anticoagulant acenocoumarol. Swiss Med Wkly 2004;134:385.

    Moderate

    SEROTONERGIC DRUGS

    Be cautious with this combination.

    Moderate

    SEROTONERGIC DRUGS

    Be cautious with this combination.

    Moderate

    SEROTONERGIC DRUGS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, acetyl-L-carnitine might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders, when taken with serotonergic drugs.<br> Animal research shows that acetyl-L-carnitine can increase levels of serotonin in the brain (95065).

    References

    95065

    Veronese N, Stubbs B, Solmi M, Ajnakina O, Carvalho AF, Maggi S. Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis. Psychosom Med. 2018;80(2):154-9.

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Theoretically, acetyl-L-carnitine might decrease the effectiveness of thyroid hormone replacement.<br> L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells (12761). Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism (8047). It is unclear if such an interaction would occur with acetyl-L-carnitine.

    References

    8047

    Benvenga S, Ruggeri RM, Russo A, et al. Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab 2001;86:3579-94.

    12761

    12761 Benvenga S, Amato A, Calvani M, Trimarchi F. Effects of carnitine on thyroid hormone action. Ann N Y Acad Sci 2004;1033:158-67.

    Minor
    TOCOTRIENOLS
    (Mixed tocotrienols, Alpha tocotrienol, Beta tocotrienol, Gamma tocotrienol, Delta tocotrienol, Palm tocotrienols complex (EVNolMax™), Palm tocotrienols complex, Tocotrienols complex - palm (sustainably sourced))
    Be watchful with this combination.
    View Interactions:
    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

    Concomitant use of tocotrienols with anticoagulant or antiplatelet agents might increase the risk of bleeding. However, this has not been reported in humans. <br> Taking tocotrienols orally inhibits experimentally-induced platelet aggregation in humans (3237,104429). Theoretically tocotrienols might increase the risk of bleeding if taken with antiplatelet or anticoagulant drugs. However, tocotrienols 400-800 mg daily have been used with aspirin and/or clopidogrel for 1 year with no clear cumulative antiplatelet effects and no reports of bleeding (104429).

    References

    3237

    Mensink RP, van Houwelingen AC, Kromhout D, Hornstra G. A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations. Am J Clin Nutr 1999;69:213-9.

    104429

    Slivka A, Rink C, Paoletto D, Sen CK. Platelet function in stroke/transient ischemic attack patients treated with tocotrienol. FASEB J. 2020;34(9):11838-11843.


    Full Reference List

    3046
    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
    96485
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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.

    Factsheets Pregnancy & Lactation

    Contraindications*:

    Pregnancy & Lactation: Contact Supplier

    *Information taken from Natural Medicines Database regarding “Major” contraindications related to active ingredients only and accurate as of October 2021. Please refer to Natural Medicines Database for more information.