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Drug Interactions between E-Gems and selumetinib

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

vitamin E selumetinib

Applies to: E-Gems (vitamin e) and selumetinib

GENERALLY AVOID: Selumetinib capsules contain vitamin E. Coadministration of selumetinib with additional vitamin E supplementation resulting in daily vitamin E intake that exceeds recommended or safe limits may increase the risk of bleeding. Vitamin E is thought to inhibit the oxidation of reduced vitamin K and interfere with the functions of vitamin K-dependent clotting factors. These effects appear to be dose-dependent and greater in individuals with preexisting vitamin K deficiency. In addition, data from in vitro and ex vivo human studies suggest that vitamin E can inhibit collagen-induced platelet activation and protein kinase C-dependent platelet aggregation. Clinically significant antiplatelet effects have not been consistently observed in published studies, particularly at dosages below 400 units/day. However, there have been isolated reports of excessive bleeding in surgical patients who had taken vitamin E regularly prior to surgery, and one controlled clinical trial found that supplementation with only 50 mg/day of vitamin E resulted in an increase in subarachnoid hemorrhage in male smokers aged 55 to 74 years (n=409). In a random sampling of that same population of male smokers, gingival bleeding was also more common in subjects who received vitamin E with aspirin compared to those who received either agent alone or neither. Selumetinib 10 mg capsules contain 32 mg vitamin E as the excipient, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), while 25 mg capsules contain 36 mg vitamin E as TPGS.

MANAGEMENT: Patients should consult a healthcare provider before taking any nutritional supplements like vitamin E. Supplemental vitamin E is not recommended during selumetinib therapy if total daily vitamin E intake will exceed recommended or safe limits.

References (13)
  1. (1983) "Megavitamin E supplementation and vitamin K-dependent carboxylation." Nutr Rev, 41, p. 268-70
  2. Helson L (1984) "The effect of intravenous vitamin E and menadiol sodium diphosphate on vitamin K dependent clotting factors." Thromb Res, 35, p. 11-8
  3. Celestini A, Pulcinelli FM, Pignatelli P, et al. (2002) "Vitamin E potentiates the antiplatelet activity of aspirin in collagen-stimulated platelets." Haematologica, 87, p. 420-6
  4. Kakishita E, Suehiro A, Oura Y, Nagai K (1990) "Inhibitory effect of vitamin E (alpha-tocopherol) on spontaneous platelet aggregation in whole blood." Thromb Res, 60, p. 489-99
  5. Mardla V, Kobzar G, Samel N (2004) "Potentiation of antiaggregating effect of prostaglandins by alpha-tocopherol and quercetin." Platelets, 15, p. 319-24
  6. Gonzalez-Correa JA, Arrebola MM, Guerrero A, et al. (2005) "Influence of vitamin E on the antiplatelet effect of acetylsalicylic acid in human blood." Platelets, 16(3-4), p. 171-9
  7. Booth SL, Golly I, Sacheck JM, Roubenoff R, Dallal GE, et al. (2004) "Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status." Am J Clin Nutr, 80, p. 143-8
  8. Freedman JE, Farhat JH, Loscalzo J, Keaney JF (1996) "Alpha-tocopherol inhibits aggregation of human platelets by a protein kinase C--dependent mechanism." Circulation, 94, p. 2434-40
  9. Stampfer MJ, Jakubowski JA, Faigel D, Vaillancourt R, Deykin D (1988) "Vitamin E supplementation effect on human platelet function, arachidonic acid metabolism, and plasma prostacyclin levels." Am J Clin Nutr, 47, p. 700-6
  10. Murohara T, Ikeda H, Otsuka Y, Aoki M, Takajo Y, et al. (2004) "Inhibition of platelet adherence to Mononuclear cells by alpha-tocopherol: role of P-selection." Circulation, 110, p. 141-8
  11. Jandak J, Steiner M, Richardson PD (1989) "Alpha-tocopherol, an effective inhibitor of platelet adhesion." Blood, 73, p. 141-9
  12. Liu M, Wallmon A, Olsson-Mortlock C, Wallin R, Saldeen T (2003) "Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms." Am J Clin Nutr, 77, p. 700-6
  13. (2020) "Product Information. Koselugo (selumetinib)." Astra-Zeneca Pharmaceuticals

Drug and food interactions

Major

selumetinib food

Applies to: selumetinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of selumetinib, which undergoes metabolism primarily by CYP450 3A4 and to a lesser extent by CYP450 2C19, 1A2, 2C9, 2E1 and 3A5, as well as glucuronidation by UGT1A1 and UGT1A3. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. When coadministered with itraconazole, a potent CYP450 3A4 inhibitor, selumetinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 19% and 49%, respectively. When coadministered with fluconazole, a potent CYP450 2C19 and moderate CYP450 3A4 inhibitor, selumetinib Cmax and AUC increased by 26% and 53%, respectively. Concomitant use of erythromycin, a moderate CYP450 3A4 inhibitor, is predicted to increase selumetinib Cmax and AUC by 23% and 41%, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to selumetinib may increase the risk and/or severity of serious adverse effects such as cardiomyopathy (decrease in left ventricular ejection fraction by 10% or more below baseline), ocular toxicity (blurred vision, photophobia, cataracts, ocular hypertension, retinal pigment epithelial detachment, retinal vein occlusion), gastrointestinal toxicity (diarrhea, colitis), skin toxicity (dermatitis acneiform, maculopapular rash, eczema), and musculoskeletal toxicity (creatine phosphokinase elevations, myalgia, rhabdomyolysis).

MANAGEMENT: Patients should avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with selumetinib.

References (2)
  1. (2024) "Product Information. Koselugo (selumetinib)." Alexion Pharmaceuticals Inc
  2. (2024) "Product Information. Koselugo (selumetinib)." AstraZeneca UK Ltd

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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