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Nov 25, 2020
6 min read

Side effects of ezetimibe (brand name Zetia)

HDLs are the “good” kind that transport excess cholesterol to the liver, where it’s broken down and eliminated from the body. LDLs are the “bad” ones that, in excess, can stick around the walls of the arteries. This buildup is called arterial plaque, and too much of it can lead to a condition called atherosclerosis.

Ezetimibe, also sold under the brand name Zetia, is a cholesterol absorption inhibitor. It is prescribed to patients to reduce the amount of cholesterol in the system. Typically it is prescribed as a supplement to statins when statins alone do not bring cholesterol levels low enough. 

When combined with statins, early clinical trials showed an average 21.4% reduction in low-density lipoprotein (LDL, or “bad”) cholesterol over and above patients taking statins alone. Patients supplementing statins with ezetimibe also showed better high-density lipoprotein (HDL, or “good”) cholesterol levels (Balantyne, 2002).

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High cholesterol

Cholesterol isn’t inherently a bad thing. Our bodies need cholesterol to survive. Even if you ate a zero-cholesterol diet, you would be full of cholesterol because your body produces it. Your liver makes a great deal of the cholesterol you need and then sends it out to do its job around your body. Cholesterol is a lipid, a fatty acid that doesn’t dissolve in water (Huff, 2020).

Since it can’t dissolve in our blood, which is largely water, cholesterol needs a way to get around. For this, our body creates what are called lipoproteins. These are little microscopic packages that carry cholesterol around. There are several different lipoprotein types. LDL and HDL are the main ones we’ll discuss. 

HDLs are the “good” kind that transport excess cholesterol to the liver, where it’s broken down and eliminated from the body. LDLs are the “bad” ones that, in excess, can stick around the walls of the arteries. This buildup is called arterial plaque, and too much of it can lead to a condition called atherosclerosis.

Atherosclerosis can slow down blood flow, preventing oxygen from getting to the organs. It can also lead to clots, which can block arteries entirely, leading to a heart attack or stroke.

Heart disease is a widespread public health problem and the number one cause of death in the United States (Heron, 2019). The American Heart Association considers less than 200 mg of total cholesterol per deciliter of blood to be ideal for cardiovascular health. Studies estimate that fewer than half of adults over 20 fall below that threshold in the United States (Lloyd-Jones, 2010).

Too much cholesterol in the blood is called hypercholesterolemia. High cholesterol can be the result of many causes, often a combination of them. Bad diet, lack of exercise, smoking, and hypertension can all be contributing factors. For some patients, it’s genetic. Their bodies naturally produce too much.

Treating high cholesterol

After diet and exercise, medications called statins are the first line of treatment for high LDLs. Statins work by blocking cholesterol production in the liver (Ziaeian, 2017). They are not a replacement for diet and exercise, though.

Ezetimibe attacks the problem from a different angle than statins do. Ezetimibe blocks dietary cholesterol from getting into the circulatory system through the intestinal wall (Gagné, 2002). That doesn’t mean you can eat ice cream all day and remain healthy, of course. It provides a little extra help for patients following a proper diet and taking statins or other cholesterol-lowering medications who can’t reach their blood cholesterol goal.

If you’ve been prescribed ezetimibe in addition to another cholesterol-reducing medication, you may be wondering if there are additional side effects you might encounter.

Side effects of ezetimibe

Ezetimibe is generally well tolerated. Common side effects reported were (DailyMed, n.d.):

  • Diarrhea
  • Fatigue
  • Nasal inflammation
  • Flu-like symptoms
  • Upper respiratory infection
  • Joint pain
  • Pain in extremities (arms, legs)

The most common of these adverse effects were reported by fewer than 5% of patients in clinical trials. This number was similar to, if slightly higher than, that for patients taking a placebo (DailyMed, n.d.). 

Talk to your prescriber if any of the above symptoms are extreme or don’t go away on their own in time. Follow the medical advice of a healthcare professional before abruptly stopping any medication.

The following side effects could be signs of more severe issues, such as an allergic reaction. Contact your healthcare provider immediately if you experience any of the following (MedLine Plus, 2018):

  • Hives, skin rash, or itching
  • Trouble breathing or swallowing
  • Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
  • Hoarseness
  • Pain in the upper right part of the stomach
  • Stomach pain, abdominal pain, indigestion
  • Unusual tiredness, fatigue
  • Unusual bleeding or bruising
  • Loss of appetite
  • Yellowing of the skin or eyes
  • Flu-like symptoms
  • Unexplained muscle pain or weakness
  • Fever
  • Chills
  • Pale or fatty stools
  • Chest pain

Statins and muscle pain

Myalgia and myositis, different muscle pain types, can be side effects of statins. Statin-related myopathies are dose-dependent—the higher the dose, the higher the odds. They are rare, with an estimated 0.1% to 0.2% of patients taking statins alone experiencing them (Tomlinson, 2005).

Those experiencing it most often report pain in the shoulders, hips, and knees. Abdominal muscle and lower back pain are less common but not unheard of. These can be signs or precursors of rhabdomyolysis, a very serious condition in which muscles break down. If left untreated, rhabdomyolysis can lead to kidney failure or cardiac arrest.

The likelihood of myopathies also increases when statins are combined with certain other medications, especially fibrates (Ballantyne, 2003). Studies have suggested that supplementing statins with ezetimibe does not increase this risk above statins alone (Kashani, 2008).

If you are experiencing unexplained muscle pain when starting medication, tell your healthcare provider. A blood test can let you know if there are warning signs for this dangerous condition. If you work out regularly, you may write off muscle pain as the usual you’d experience after vigorous exercise. Some researchers suspect that many statin-related myopathies go unreported because of this (Tomlinson, 2005).

Precautions

Your prescriber will have questions about your medical history. Be sure to tell them:

  • If you are allergic to ezetimibe or any other medications.
  • If you have or have ever had liver disease or impaired liver function. Studies found higher than normal transaminase levels more frequently in patients taking ezetimibe with a statin than in those taking statins alone. A high level can be an indication of liver damage. For this reason, patients with active liver problems should not be prescribed ezetimibe (Toth, 2012).
  • If you are pregnant, plan to become pregnant, or are breastfeeding. There have been no relevant studies regarding ezetimibe in breast milk to date. Patients who are nursing should seek an alternative treatment to be safe (LactMed, 2020).

Drug interactions

Always tell your healthcare provider about all medications, prescription, and non-prescription, and any vitamins or supplements, including herbal supplements, you are taking. It’s especially important to mention any of the following (MedLine Plus, 2018):

  • Blood thinners, such as warfarin (brand name Coumadin)
  • Cyclosporine (brand names Neoral, Sandimmune)
  • Fenofibrate (brand name TriCor)
  • Gemfibrozil (brand name Lopid)

Your healthcare provider may wish to monitor you for specific side effects if you take these drugs with ezetimibe. 

Do not take bile acid sequestrants close to your ezetimibe dose. These include cholestyramine (brand name Questran), colesevelam (brand name WelChol), and colestipol (brand name Colestid). These drugs should be taken at least four hours before or two hours after taking ezetimibe.

Dosage and price

Ezetimibe is available in 10 mg tablets. If not covered by your insurance, the typical price is $10–$15 for a thirty-day supply (GoodRX, n.d.).

Ezetimibe is also prescribed in combination with other drugs: 

  • With atorvastatin under the brand name Liptruzet
  • With simvastatin under the brand name Vytorin
  • With rosuvastatin under the brand name Ridutrin
  • With bempedoic acid under the brand name Nexlizet

Storage

Store ezetimibe at room temperature in a dry area out of sight and reach of children (MedLine Plus, 2018). Do not store ezetimibe in the bathroom or anywhere that can become humid or moist. Do not store ezetimibe in the refrigerator, as condensation can develop.

References

  1. Ballantyne, C. M., Corsini, A., Davidson, M. H., Holdaas, H., Jacobson, T. A., Leitersdorf, E., et al. (2003). Risk for Myopathy With Statin Therapy in High-Risk Patients. Archives of Internal Medicine, 163(5), 553. doi: 10.1001/archinte.163.5.553. Retrieved from https://pubmed.ncbi.nlm.nih.gov/12622602/
  2. DailyMed. (n.d.). ZETIA- ezetimibe tablet. Retrieved on Nov 11, 2020 from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a773b0b2-d31c-4ff4-b9e8-1eb2d3a4d62a&audience=consumer
  3. Drugs and Lactation Database (LactMed) [Internet]. (2020, October 19). Ezetimibe. Retrieved on November 20, 2020, from https://www.ncbi.nlm.nih.gov/books/NBK501635/
  4. Gagné, C., Bays, H. E., Weiss, S. R., Mata, P., Quinto, K., Melino, M., et al. (2002). Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. The American Journal of Cardiology, 90(10), 1084–1091. doi: 10.1016/s0002-9149(02)02774-1. Retrieved from https://pubmed.ncbi.nlm.nih.gov/12423708/
  5. Heron, M. (2019). Deaths: Leading Causes for 2017 (Vol. 68, National Vital Statistics Reports, pp. 1-76) (United States, US Dept. of Health & Human Services, Centers for Disease Control and Prevention). Hyattsville, MD: National Center for Health Statistics. Retrieved from https://stacks.cdc.gov/view/cdc/79488
  6. Huff, T. (2020, August 24). Physiology, Cholesterol. Retrieved on November 19, 2020, from https://www.ncbi.nlm.nih.gov/books/NBK470561/
  7. Kashani, A., Sallam, T., Bheemreddy, S., Mann, D. L., Wang, Y., & Foody, J. M. (2008). Review of Side-Effect Profile of Combination Ezetimibe and Statin Therapy in Randomized Clinical Trials [Abstract]. The American Journal of Cardiology, 101(11), 1606-1613. doi: 10.1016/j.amjcard.2008.01.041. Retrieved from https://pubmed.ncbi.nlm.nih.gov/18489938/
  8. Lloyd-Jones, D. M., Hong, Y., Labarthe, D., Mozaffarian, D., Appel, L. J., Van Horn, L., et al. (2010). Defining and Setting National Goals for Cardiovascular Health Promotion and Disease Reduction. Circulation, 121(4), 586–613. doi: 10.1161/circulationaha.109.192703. Retrieved from https://pubmed.ncbi.nlm.nih.gov/20089546/
  9. MedlinePlus. (2018). Ezetimibe: MedlinePlus Drug Information. Retrieved on 11 November, 2020, from https://medlineplus.gov/druginfo/meds/a603015.html
  10. Tomlinson, S. S., & Mangione, K. K. (2005). Potential Adverse Effects of Statins on Muscle. Physical Therapy, 85(5), 459–465. doi: 10.1093/ptj/85.5.459. Retrieved from https://academic.oup.com/ptj/article/85/5/459/2805031
  11. Toth, P. P., Morrone, D., Weintraub, W. S., Hanson, M. E., Lowe, R. S., Lin, J., et al. (2012). Safety profile of statins alone or combined with ezetimibe: a pooled analysis of 27 studies including over 22,000 patients treated for 6-24 weeks. International Journal of Clinical Practice, 66(8), 800–812. doi: 10.1111/j.1742-1241.2012.02964.x. Retrieved from https://pubmed.ncbi.nlm.nih.gov/22805272/
  12. Ziaeian, B., & Fonarow, G. C. (2017). Statins and the Prevention of Heart Disease. JAMA Cardiology, 2(4). doi: 10.1001/jamacardio.2016.4320. Retrieved from https://pubmed.ncbi.nlm.nih.gov/28122083/