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Ezetimibe-Simvastatin

Drug Information

Common brand names:

Vytorin

Summary of Interactions with Vitamins, Herbs, & Foods

Types of interactions: Beneficial Adverse Check

Replenish Depleted Nutrients

  • none

Reduce Side Effects

  • Creatine Monohydrate
    In a preliminary study, ten patients who had to discontinue statin drugs because of muscle-related side effects were given creatine (as creatine monohydrate) in the amount of 5 grams twice a day for five days, then 5 grams per day. Eight of the ten patients experienced no muscle symptoms upon resuming the statin drug.1
  • Vitamin D
    In a preliminary trial, supplementation with vitamin D appeared to prevent muscle-related side effects in patients taking statin drugs.2 The amount of vitamin D used in this study was very large (up to 50,000 IU twice a week) and potentially toxic. People taking statin drugs should consult with their doctor regarding how much vitamin D can be taken.

Support Medicine

  • Fish Oil

    The omega-3 fatty acid EPA, present in fish oil, may improve the cholesterol- and triglyceride-lowering effect of simvastatin. In a preliminary trial, people with high cholesterol who had been taking simvastatin for about three years were able to significantly lower their triglyceride levels and raise their levels of HDL (“good”) cholesterol by supplementing with either 900 mg or 1800 mg of EPA for three months in addition to simvastatin.3 The authors of the study concluded that the combination of simvastatin and EPA may prevent coronary heart disease better than simvastatin alone.

  • Psyllium

    In one study, supplementation with 15 grams of psyllium per day for eight weeks enhanced the cholesterol-lowering effect of simvastatin.4

  • Sitostanol

    A synthetic molecule related to beta-sitosterol, sitostanol, is available in a special margarine and has been shown to lower cholesterol levels. In one study, supplementing with 1.8 grams of sitostanol per day for six weeks enhanced the cholesterol-lowering effect of various statin drugs.5

Reduces Effectiveness

  • St. John’s Wort
    In patients taking simvastatin, treatment with St. John's wort increased serum cholesterol levels, apparently because St. John's wort interfered with the effect of the medication.6

Potential Negative Interaction

  • Grapefruit

    Grapefruit contains substances that may inhibit the body’s ability to break down simvastatin; consuming grapefruit or grapefruit juice might therefore increase the potential toxicity of the drug. In a study of healthy volunteers, ingesting 200 ml of grapefruit juice along with simvastatin increased blood levels of the drug, compared with taking simvastatin with water.7 There is one case report of a woman developing severe muscle damage from simvastatin after she began eating one grapefruit per day.8 Although there have been no reports of a grapefruit–simvastatin interaction, to be on the safe side, people taking simvastatin should not eat grapefruit or drink grapefruit juice.

  • Antioxidants
    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Pomegranate

    Pomegranate juice has been shown to inhibit the same enzyme that is inhibited by grapefruit juice.9 , 10 The degree of inhibition is about the same for each of these juices. Therefore, it would be reasonable to expect that pomegranate juice might interact with simvastatin in the same way that grapefruit juice does.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Red Yeast Rice
    A supplement containing red yeast rice (Cholestin) has been shown to effectively lower cholesterol and triglycerides in people with moderately elevated levels of these blood lipids.11 This extract contains small amounts of naturally occurring HMG-CoA reductase inhibitors such as lovastatin and should not be used if you are currently taking a statin medication.
    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Explanation Required 

  • Coenzyme Q10

    In patients with high cholesterol, simvastatin therapy results in decreased serum coenzyme Q10 (CoQ10) levels.12 , 13 Several trials, including double-blind trials, have confirmed this effect of simvastatin and other HMG-CoA reductase inhibitors, such as lovastatin and pravastatin.14 , 15 , 16 Supplementation with 100 mg per day or 10 mg three times daily of CoQ10 has been shown to prevent reductions in blood levels of CoQ10 due to simvastatin.17 , 18 In the latter study, people taking CoQ10 along with simvastatin increased their blood CoQ10 concentration by 63%. In a preliminary study, supplementing with 100 mg of CoQ10 per day reduced the severity of muscle pain by 40% in people with muscle pain caused by a statin drug.19 However, in a double-blind trial, supplementation with 200 mg of CoQ10 per day did not improve muscle symptoms or tolerance to simvastatin.20 Because low CoQ10 levels are undesirable in people who have or are at risk for developing heart disease, many doctors recommend that people taking HMG-CoA reductase inhibitor drugs such as simvastatin also supplement with approximately 100 mg CoQ10 per day, although lower amounts, such as 10 to 30 mg per day might conceivably be effective in preventing the decline in CoQ10 levels.

  • Vitamin B3

    Niacin is the form of vitamin B3 used to lower cholesterol. Taking large amounts of niacin along with HMG-CoA reductase inhibitors may cause muscle disorders (myopathy) that can become serious (rhabdomyolysis).21 , 22 Such problems appear to be uncommon.23 , 24 Moreover, concurrent use of niacin has been reported to enhance the cholesterol-lowering effect of HMG-CoA reductase inhibitors.25 , 26 Individuals taking simvastatin should consult a doctor before taking niacin.

  • Vitamin A

    A study of 37 people with high cholesterol treated with diet and HMG-CoA reductase inhibitors found blood vitamin A levels increased over two years of therapy.27 Until more is known, people taking HMG-CoA reductase inhibitors, including simvastatin, should have blood levels of vitamin A monitored if they intend to supplement vitamin A.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Vitamin E

    In a study of seven patients with hypercholesterolemia, eight weeks of simvastatin plus vitamin E 300 IU improved markers of blood vessel elasticity more than simvastatin alone.28

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers’ package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a new supplement with your doctor or pharmacist.

References

1. Shewmon DA, Craig JM. Creatine supplementation prevents statin-induced muscle toxicity. Ann Intern Med 2010;153:690–2.

2. Glueck CJ, Budhani SB, Masineni SS, et al. Vitamin D deficiency, myositis-myalgia, and reversible statin intolerance. Curr Med Res Opin 2011;27:1683–90.

3. Nakamura N, Hamazaki T, Ohta M, et al. Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia. Int J Clin Lab Res 1999;29:22–5.

4. Moreyra AE, Wilson AC, Koraym A. Effect of combining psyllium fiber with simvastatin in lowering cholesterol. Arch Intern Med 2005;165:1161–6.

5. Goldberg AC, Ostlund RE Jr, Bateman JH, et al. Effect of plant stanol tablets on low-density lipoprotein cholesterol lowering in patients on statin drugs. Am J Cardiol 2006;97:376–9.

6. Eggertsen R, Andreasson A, Andren L. Effects of treatment with a commercially available St John's Wort product (Movina) on cholesterol levels in patients with hypercholesterolemia treated with simvastatin. Scand J Prim Health Care 207;25:154–9.

7. Lilja JJ, Neuvonen M, Neuvonen PJ. Effects of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin. Br J Clin Pharmacol 2004;58:56–60.

8. Dreier JP, Endres M. Statin-associated rhabdomyolysis triggered by grapefruit consumption. Neurology 2004;62:670 [Letter].

9. Sorokin AV, Duncan B, Panetta R, Thompson PD. Rhabdomyolysis associated with pomegranate juice consumption. Am J Cardiol 2006;98:705–6.

10. Summers KM. Potential drug-food interactions with pomegranate juice. Ann Pharmacother 2006;40:1472–3.

11. Heber D, Yip I, Ashley JM, et al. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr 1999;69:231–6.

12. Laaksonen R, Jokelainen K, Sahi T, et al. Decreases in serum ubiquinone concentrations do not result in reduced levels in muscle tissue during short-term simvastatin treatment in humans. Clin Pharmacol Ther 1995;57:62–6.

13. Laaksonen R, Ojala JP, Tikkanen MJ, et al. Serum ubiquinone concentrations after short- and long-term treatment with HMG-CoA reductase inhibitors. Eur J Clin Pharmacol 1994;46:313–7.

14. Ghirlanda G, Oradei A, Manto A, et al. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol 1993;33:226–9.

15. Watts GF, Cummings MH, Umpleby M, et al. Simvastatin decreases the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in heterozygous familial hypercholesterolaemia: pathophysiological and therapeutic implications. Eur J Clin Invest 1995;25:559–67.

16. Folkers K, Langsjoen P, Willis R, et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci USA 1990;87:8931–4.

17. Bargossi AM, Grossi G, Fiorella PL, et al. Exogenous CoQ10 supplementation prevents plasma ubiquinone reduction induced by HMG-CoA reductase inhibitors. Molec Aspects Med 1994;15(suppl):s187–93.

18. Miyake Y, Shouzu A, Nishikawa M, et al. Effect of treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on serum coenzyme Q10 in diabetic patients. Arzneimittelforschung 1999;49:324–9.

19. Caso G, Kelly P, McNurlan MA, Lawson WE. Effect of coenzyme Q10 on myopathic symptoms in patients treated with statins. Am J Cardiol 2007;99:1409–12.

20. Young JM, Florkowski CM, Molyneux SL, et al. Effect of coenzyme Q10 supplementation on simvastatin-induced myalgia. Am J Cardiol 2007;100:1400–3.

21. Garnett WR. Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am J Health Syst Pharm 1995;52:1639–45.

22. Yee HS, Fong NT. Atorvastatin in the treatment of primary hypercholesterolemia and mixed dyslipidemias. Ann Pharmacother 1998;32:1030–43.

23. Jacobson TA, Amorosa LF. Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety. Am J Cardiol 1994;73:25D–9D.

24. Jokubaitis LA. Fluvastatin in combination with other lipid-lowering agents. Br J Pract Suppl 1996;77A:28–32.

25. Davignon J, Roederer G, Montigny M, et al. Comparative efficacy and safety of pravastatin, Nicotinic acid and the two combined in patients with hypercholesterolemia. Am J Cardiol 1994;73:339–45.

26. Jacobson TA, Jokubaitis LA, Amorosa LF. Fluvastatin and niacin in hypercholesterolemia: a preliminary report on gender differences in efficacy. Am J Med 1994;96(suppl 6A):64S–8S.

27. Muggeo M, Zenti MG, Travia D, et al. Serum retinol levels throughout 2 years of cholesterol-lowering therapy. Metabolism 1995;44:398–403.

28. Neunteufl T, Kostner K, Katzenschlager R, et al. Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men. J Am Coll Cardiol 1998;32:711–6.

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