Simvastatin

Also indexed as: Zocor

About simvastatin

Simvastatin is a member of the HMG-CoA reductase inhibitor family of drugs that blocks the body��s production of cholesterol. Simvastatin is used to lower high cholesterol and to reduce the risk of heart attack and death.

Summary of Interactions with Vitamins, Herbs, and Foods
In some cases, an herb or supplement may appear in more than one category, which may seem contradictory. For clarification, read the full article for details about the summarized interactions.

May be Beneficial: Depletion or interference��The medication may deplete or interfere with the absorption or function of the nutrient. Taking these nutrients may help replenish them.	Co-Enzyme Q10
May be Beneficial: Side effect reduction/prevention��Taking these supplements may help reduce the likelihood and/or severity of a potential side effect caused by the medication.	Co-Enzyme Q10
May be Beneficial: Supportive interaction��Taking these supplements may support or otherwise help your medication work better.	Fish oil (EPA) Psyllium Sitostanol
Avoid: Adverse interaction��Avoid these supplements when taking this medication because taking them together may cause undesirable or dangerous results.	Grapefruitor grapefruit juice Pomegranate juice* Red yeast rice Vitamin A*
Check: Other��Before taking any of these supplements or eating any of these foods with your medication, read this article in full for details.	Vitamin B3 (niacin) Vitamin E*
Reduced drug absorption/bioavailability	None known

An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

Interactions with Dietary Supplements

Co-Enzyme Q10
In patients with high cholesterol, simvastatin therapy results in decreased serum co-Enzyme Q10 (CoQ10) levels.¹ ² A few trials, including double-blind trials, have confirmed this effect of simvastatin and other HMG-CoA reductase inhibitors, such as lovastatin and pravastatin.³ ⁴ ⁵ 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.⁶ ⁷ 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.⁸ 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.

Fish Oil (EPA)
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.⁹ The authors of the study concluded that the combination of simvastatin and EPA may prevent coronary heart disease better than simvastatin alone.

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.¹⁰

Vitamin B3 (niacin)
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).¹¹ ¹² Such problems appear to be uncommon.¹³ ¹⁴ Moreover, concurrent use of niacin has been reported to enhance the cholesterol-lowering effect of HMG-CoA reductase inhibitors.¹⁵ ¹⁶ 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.¹⁷ 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.

Vitamin E
In a study of seven patients with hypercholesterolaemia, eight weeks of simvastatin plus vitamin E 300 IU improved markers of blood vessel elasticity more than simvastatin alone.¹⁸

Anti-oxidants
In another study, daily supplementation with a combination of anti-oxidants (800 IU of vitamin E, 1,000 mg of vitamin C, 25 mg of beta-carotene, and 100 mcg of selenium) blocked the beneficial effect of simvastatin-plus-niacin on HDL cholesterol levels.¹⁹ Although there is evidence that some or all of these nutrients may help prevent heart disease, individuals taking simvastatin who wish to take anti-oxidants should discuss the use of these supplements with their doctor.

Interactions with Herbs

Psyllium
In one study, supplementation with 15 grams of psyllium per day for eight weeks enhanced the cholesterol-lowering effect of simvastatin.²⁰

Red yeast rice (Monascus purpureas)
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.²¹ 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.

Interactions with Foods and Other Compounds

Food
Simvastatin may be taken with or without food.²²

Grapefruit or grapefruit juice
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.²³ There is one case report of a woman developing severe muscle damage from simvastatin after she began eating one grapefruit per day.²⁴ 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.

Pomegranate juice
Pomegranate juice has been shown to inhibit the same enzyme that is inhibited by grapefruit juice.²⁵ ²⁶ 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.

References

1. 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.

2. 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.

3. 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.

4. 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.

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

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

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

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

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

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

15. 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.

16. 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.

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

18. 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.

19. 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.

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

21. 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.

22. Threlkeld DS, ed. Diuretics and Cardiovasculars, Antihyperlipidemic Agents, HMG-CoA Reductase Inhibitors. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Sep 1998, 172.

23. 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.

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

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

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

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The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or chemist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires September 2008.

2007-09-01

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About simvastatin

Interactions with Dietary Supplements

Interactions with Herbs

Interactions with Foods and Other Compounds

References