Ezetimibe side effects and how to avoid them

Common ezetimibe side effects | Serious side effects | Liver problems | Muscle damage | Side effects | Contraindications | Warnings | Interactions | How to avoid side effects | How to treat side effects

Ezetimibe is a generic prescription drug used to treat high cholesterol. For people with elevated cholesterol levels, healthcare providers may prescribe ezetimibe alone or in combination with a statin or fenofibrate, drugs that also lower cholesterol and certain fats in the blood. Ezetimibe helps lower levels of “bad” cholesterol (LDL cholesterol) and certain fats (triglycerides), while increasing levels of “good” cholesterol (HDL cholesterol). 

Ezetimibe, known by its brand-name version Zetia, is unique in the way it helps reduce cholesterol levels. Ezetimibe blocks the absorption of cholesterol from food in the small intestine. Less cholesterol reaches the liver, which leads to reduced storage of cholesterol in the liver. This action then results in the body clearing cholesterol from the blood. 

Ezetimibe may cause side effects. However, side effects are generally mild and go away as the body adjusts to the medication. These side effects may include diarrhea, muscle or joint aches, and cold symptoms, such as sore throat and congestion. In addition, if ezetimibe is taken with a statin or fenofibrate, there may be an increased risk of certain side effects. 

Continue reading to learn more about the side effects of ezetimibe. 

Common side effects of ezetimibe

Ezetimibe generally causes mild side effects, though not everyone experiences side effects from ezetimibe. One study found that about 8% of people taking ezetimibe experienced at least one mild side effect. In clinical trials, the most common side effect, upper respiratory tract infections, affected less than 1 in 20 participants. 

The most common side effects of ezetimibe include:

• Upper respiratory infections
• Sore throat and runny nose
• Swollen sinuses
• Diarrhea
• Fatigue
• Joint pain
• Muscle pain
• Pain in the extremities
• Stomach pain
• Back pain
• Nausea
• Headache
• Dizziness

Serious side effects of ezetimibe

The most serious side effects of ezetimibe include:

• Breakdown of muscle tissue (rhabdomyolysis)
• Inflammation of the gallbladder (cholecystitis)
• Inflammation of the pancreas (pancreatitis)
• Inflammation of the liver (hepatitis)
• Low platelet counts (thrombocytopenia)
• Serious allergic reactions

Ezetimibe and liver problems

By itself, ezetimibe does not significantly affect liver enzyme levels. When combined with a statin like atorvastatin or simvastatin, however, ezetimibe is more likely to affect liver function and cause increased levels of certain liver enzymes. Abnormalities in liver function affect about 1% of people who take both ezetimibe and a statin. Blood tests may be recommended to assess liver function in people who take ezetimibe with a statin. If liver enzyme levels get too high, treatment with ezetimibe or the statin may be discontinued.

Ezetimibe and muscle damage

The breakdown of muscle tissue, called rhabdomyolysis, is a rare but potentially severe side effect of ezetimibe. Muscle damage can release a protein called myoglobin, which can damage the kidneys in large quantities. Muscle problems are more commonly linked to statins and other cholesterol-lowering drugs that are sometimes prescribed with ezetimibe. However, there are also reports of muscle damage in people taking ezetimibe alone. If muscle pain and weakness develop or worsen, inform the prescribing healthcare provider, as treatment may need to be modified.

How soon do ezetimibe side effects start?

Many ezetimibe side effects are delayed side effects. The drug needs to be taken for a few weeks or months before certain side effects like infections, sore throat, and back pain may start to appear. Most of the common side effects of ezetimibe develop early, however. These include diarrhea, nausea, headache, dizziness, stomach pain, and feeling tired. Some serious side effects, such as rhabdomyolysis, pancreatitis, and hepatitis, can take weeks or months to develop and cause serious problems. Allergic reactions can develop rapidly and may include signs and symptoms such as itching, hives, and trouble breathing.

How long do ezetimibe side effects last?

Most side effects of ezetimibe tend to improve over time as the body adjusts to the medication. If side effects persist or worsen, treatment may need to be stopped. It can take about four to five days for the last dose of ezetimibe to be cleared out of the body, and side effects should subside within a few days after discontinuing treatment.

Serious side effects, such as muscle damage, gallbladder inflammation, and problems with the pancreas, can have lasting consequences that may be irreversible. Treatment with ezetimibe should be discontinued at the first sign of a serious problem. Consult a healthcare provider about any unusual side effects that arise.

As a well-tolerated drug, not many people will need to stop taking the drug due to side effects. About 3% of clinical trial participants discontinued taking the drug because of its side effects, mostly complaining about joint pain and dizziness. 

What are the long-term side effects of ezetimibe?

Ezetimibe is typically prescribed for months or years as long as it works and side effects are bearable. There are no known side effects specifically linked to the long-term use of ezetimibe. However, liver function should be monitored before and during treatment, as ezetimibe may affect liver enzyme levels. The risk of muscle damage may be increased with older age. Therefore, older adults on long-term therapy with ezetimibe should be aware of muscle aches, especially if ezetimibe is used with a statin. 

Ezetimibe contraindications

Ezetimibe should not be taken by people who are allergic to any ingredients in the drug. In addition, taking ezetimibe with a statin is contraindicated in people with active liver disease and women who are pregnant or breastfeeding.

Pregnancy

Ezetimibe is not recommended for use in pregnant women. Ezetimibe has not been studied in pregnant women and has been shown to have no clinical benefit when given during pregnancy. The combination of ezetimibe and a statin is not recommended in pregnant women, as statins are considered harmful to an unborn baby. Cholesterol is an important part of fetal growth and development; therefore, blocking cholesterol production in a fetus could lead to birth defects.

Breastfeeding

Ezetimibe is not recommended for use in women who are breastfeeding. It is not known if ezetimibe passes into human breast milk, but animal studies indicate it does. Because cholesterol synthesis is important to an infant’s development, healthcare professionals generally avoid giving a woman who is breastfeeding both ezetimibe and a statin. 

Instead of ezetimibe, a healthcare provider may consider prescribing a bile acid sequestrant, such as cholestyramine, colestipol, or colesevelam. Bile acid sequestrants help lower cholesterol, but they don’t enter the bloodstream or breast milk. However, these drugs may cause other problems that can affect a nursing infant, such as interfering with the mother’s ability to absorb fat-soluble vitamins. 

Children

The Food and Drug Administration (FDA) has approved the combination of ezetimibe and a statin for children as young as 10 to treat an inherited high cholesterol disorder called heterozygous familial hypercholesterolemia. However, it has not been studied for use in girls who have not yet had their first period or children younger than 10.

Seniors

In clinical trials, the safety and effectiveness of ezetimibe were the same in people older than 65 as in younger adults.

Ezetimibe warnings and precautions

As with most prescription drugs, serious side effects can occur with ezetimibe. Some are related to pre-existing medical conditions, while others are related to overdosing and other problems, such as drug interactions.

People with liver disease

Ezetimibe is primarily broken down by the liver. People with moderate to severe liver disease may experience high levels of the drug in the body, leading to an increased risk of side effects. For this reason, ezetimibe is not recommended for use in people with moderate to severe liver disease.

Abuse and dependence

Ezetimibe is not associated with drug abuse or physical dependence. It can be safely discontinued without withdrawal side effects.

Overdose

Seek medical attention or call a poison control center if too much ezetimibe is taken. There are no known problems caused by taking too much ezetimibe, but it is important to contact a healthcare provider to ensure no adverse effects have occurred. Avoid exceeding the maximum daily dosage of one 10 mg tablet.

Recalls

There are no current recalls of ezetimibe or Zetia. 

Ezetimibe interactions

Ezetimibe may interact with other drugs, leading to an increased risk of side effects or lower efficacy:

• Cyclosporine: Ezetimibe could increase the levels of the immune-suppressing drug cyclosporine and vice versa, raising the risk of side effects
• Fibrates: Although ezetimibe is approved for use with fenofibrate, it is not recommended for use with other fibrates because of the increased risk for gallstones. For example, healthcare providers may avoid prescribing a fibrate called gemfibrozil with ezetimibe.
• Statins: Ezetimibe is frequently prescribed with statins. However, there may be an increased risk of liver enzyme abnormalities and muscle aches when combining ezetimibe with a statin. People taking a combination of ezetimibe and a statin may require regular blood tests to monitor liver function.
• Anticoagulants: Ezetimibe may increase the effects of certain types of blood thinners like warfarin. Healthcare providers may recommend regularly monitoring blood clotting with International Normalized Ratio (INR) tests when the two drugs are taken together.

How to avoid ezetimibe side effects

Ezetimibe generally causes fewer serious side effects than other cholesterol-lowering drugs, such as statins. Still, side effects can range from unpleasant to severe. In many cases, side effects can be avoided when the drug is taken as prescribed.

1. Talk to the prescriber about current medical issues

The best way to avoid side effects is to inform the prescribing healthcare provider if you have a history of certain medical issues, particularly:

• Liver problems
• Pregnancy or pregnancy plans
• Breastfeeding or breastfeeding plans
• Unusual muscle pain or weakness

2. Follow the instructions when taking ezetimibe

The prescriber will give instructions about how to take ezetimibe and when to take it. These instructions will also be printed on the prescription label. Follow the dosage instructions as prescribed.

3. Take each day’s dose at the same time of the day

To avoid forgetting to take a dose, always take the drug at the same time each day. Not having a dosing schedule may increase the risk of accidentally taking a double dose. 

4. Do not take larger doses than prescribed

The standard dosage of ezetimibe is 10 mg per day, which is also the maximum daily dosage. Taking too much of any prescription drug can make side effects more likely to occur. 

The most common way people overdose is when they forget a dose. Never take an extra dose to make up for a missed dose. If a dose is missed, the dose can be taken on the same day it was supposed to be taken. If it’s the day after, skip the missed dose and take that day’s dose as scheduled. Only take one dose per day.

5. Ask the prescriber about when to take other drugs

It’s possible that ezetimibe is being taken with other drugs that lower blood cholesterol. Ask the prescriber about when these other drugs should be taken. It’s usually okay to take them together, but some drugs, like bile acid resins, may need to be taken several hours before or after a dose of ezetimibe is taken. 

6. Keep all follow-up appointments

Regular blood tests may be needed to make sure that ezetimibe or other cholesterol-lowering medications are not causing problems. In this way, potentially serious side effects can be spotted before they become serious.

How to treat side effects of ezetimibe

When taking ezetimibe, the odds are mostly in favor of avoiding side effects. However, side effects can and do happen, so here’s what needs to be done just in case.

Infections

Ezetimibe is associated with an increased risk of upper respiratory infections that can cause symptoms such as a stuffy nose and sore throat. Ezetimibe does not, however, make these infections worse than they normally would be. Treat these symptoms as you would normally: rest, fluids, and over-the-counter medications as needed or directed by a healthcare provider. If infections become severe or last a long time, seek medical advice from a healthcare professional.

Diarrhea

Drink plenty of fluids to avoid dehydration. Before using any over-the-counter medication or supplement to treat diarrhea, talk to a healthcare professional first. If diarrhea becomes severe or persists for a long time, get medical help.

Abdominal pain

Start by lying or sitting down and using a heating pad. Heat is often effective at easing abdominal pain. If the pain is severe or doesn’t go away, talk to a healthcare professional.

Unusual tiredness

Rest and relax. This side effect will probably get better over a few days. If it doesn’t, get medical advice from the prescribing healthcare provider.

Muscle problems

Combining ezetimibe with a statin may increase the risk of myopathy and rhabdomyolysis, which can require medical attention. Immediately talk to a healthcare professional if muscles become painful, tender, or weak. Pain that is severe and accompanied by symptoms such as dark urine, fever, or fatigue may indicate muscle damage is affecting the kidneys. If left unresolved, muscle damage can lead to kidney problems, including kidney failure. 

Sources

• Ezetimibe, Drugs and Lactation Database
• Ezetimibe, Epocrates
• Ezetimibe drug summary, Prescriber’s Digital Reference
• Ezetimibe tablet prescribing information, U.S. National Library of Medicine
• Zetia prescribing information, U.S. National Library of Medicine