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Can I drink grapefruit juice with simvastatin?

Medically reviewed by Carmen Pope, BPharm. Last updated on Nov 4, 2022.

Official answer

by Drugs.com

You should not drink grapefruit juice with simvastatin because it can significantly increase blood levels of simvastatin and increase the risk of side effects such as liver damage and a condition called rhabdomyolysis, which is the excessive breakdown of muscle tissue. Occasionally, rhabdomyolysis can cause kidney damage and death.

Why does grapefruit interact with simvastatin?

Drugs or toxins are usually broken down (metabolized) so that they can be eliminated from the body. Grapefruit or grapefruit juice can alter enzymes in the body and affect how drugs are changed in the body before they are eliminated.

Grapefruit contains compounds called furanocoumarins that block the effects of CYP3A4 – an enzyme in the wall of your small intestine that breaks down certain substances, including simvastatin. The bioavailability of simvastatin is about 5%, which means that only 5% of a dose of simvastatin reaches the blood – the rest is metabolized before it gets there. If CYP3A4 is blocked by an inhibitor such as grapefruit juice, then a much larger amount of simvastatin reaches the blood. Increasing a drug's bioavailability from 5% to 10% will double its concentration in the body, making it more powerful than it's meant to be, resulting in a risk for new or worsened side effects.

One whole fruit or 200 milliliters of grapefruit juice (a bit less than one cup) can block the CYP3A4 enzymes and lead to toxic blood levels of the drug. Inhibition of CYP3A4 with grapefruit may last for up to 24 hours after a single dose and up to 72 hours after multiple daily dosing.

How much grapefruit interacts with simvastatin?

Many studies investigating grapefruit interactions used double-strength grapefruit juice administered multiple times daily. For example, double-strength grapefruit juice administered 3 times daily will increase the concentrations of some statins more than 10-fold, whereas single-strength grapefruit juice taken once daily results in a 2-fold increase.

Single-strength juice taken just once daily will result in a much smaller effect, especially if taken at a different time of the day to the medicine. But grapefruit is usually eaten in the morning, and the morning is the best time of day to take simvastatin. Because there are wide variations among individuals, it is best to avoid grapefruit and grapefruit products while you are taking simvastatin.

Are there any other foods or drinks I should avoid with simvastatin?

In addition to grapefruit, you should use caution when eating anything made with the Seville orange (often used in marmalades), the pomelo (a citrus fruit with a similar flavor to grapefruit but less tart), pomegranate, star fruit, and limes. These fruits also contain furanocoumarins and may cause the same interactions as grapefruit. Studies with these fruits are not as frequent, so their risk level is not fully known. Check labels closely on all drinks if you need to avoid grapefruit. For example, citrus-flavored soft drinks contain grapefruit juice or grapefruit extract. Regular orange juice does not affect the enzyme.

Green tea or green tea extracts may also increase blood levels of simvastatin in some people.

Red yeast rice is another potential problem because it contains small amounts of the medication lovastatin that can have additive effects with simvastatin, increasing the risks of side effects.

What are the symptoms of too much simvastatin?

Too much simvastatin in your blood can increase the risk of side effects of simvastatin and symptoms may include unexplained muscle pain, tenderness, or weakness; fever or dark-colored urine. Talk to your doctor if you are experiencing these side effects. Seek immediate medical attention if you develop fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark-colored urine, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage.

Do not take any other medications, including supplements or herbal medications, while you are taking simvastatin without talking to your doctor first because some of these may interact with simvastatin and increase the risk of side effects.

References
  • Chen M, Zhou SY, Fabriaga E, et al. Food-drug interactions precipitated by fruit juices other than grapefruit juice: An updated review. J Food Drug Anal. 2018 Apr;26(2S):S61-S71. doi: 10.1016/j.jfda.2018.01.009. Epub 2018 Feb 15.
  • FDA. FDA Consumer Health Articles. Grapefruit Juice and Some Drugs Don't Mix. Updated 7 January 2021. https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix
  • Bailey DG, Malcolm J, Arnold O, et al. Grapefruit juice-drug interactions. Br J Clin Pharmacol 1998;46:101-110. Accessed May 18, 2022, at https://doi.org/10.1046/j.1365-2125.1998.00764.x
  • Horn J, Hansten P. Fruit Juice Interactions. Pharmacy Times. Published Online Dec 1, 2005. Accessed May 18, 2022, at https://www.pharmacytimes.com/publications/issue/2005/2005-12/2005-12-5042
  • Mayo Clinic. Consumer Health. I like to drink grapefruit juice but hear that it can interfere with some prescription medications. Is that true? Accessed May 18, 2022, at http://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/food-and-nutrition/faq-20057918
  • Bailey DG, Dresser G, Arnold M, et al. Grapefruit-medication interactions: Forbidden fruit or avoidable consequences? CMAJ. 2012. Accessed March 30, 2019.
  • Hansten PD, Horn JR. The Top 100 Drug Interactions. A Guide to Patient Management. H&H Publications. Freeland, WA. Accessed August 31, 2019.
  • Shimomura S, Wanwimolruk S, Chen J. Drug Interactions with Grapefruit Juice: An Evidenced-Based Overview. Pharmacy Times. Accessed May 18, 2022, at http://www.direct-ms.org/wp-content/uploads/2018/01/Grapefruit-juice-drug-reactions.pdf
  • Srinivas NR. Is pomegranate juice a potential perpetrator of clinical drug-drug interactions? Review of the in vitro, preclinical and clinical evidence. Eur J Drug Metab Pharmacokinet. 2013 Dec;38(4):223-9. doi: 10.1007/s13318-013-0137-x
  • Kim H, Yoon YJ, Shon JH, et al. Inhibitory effects of fruit juices on CYP3A activity. Drug Metab Dispos. 2006 Apr;34(4):521-3. DOI: https://doi.org/10.1124/dmd.105.007930

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