Ezetimibe

Ezetimibe tablets are approved to lower cholesterol and related blood fats as an add-on to a cholesterol-lowering diet across several conditions:

• Reduces LDL ("bad") cholesterol, total cholesterol, Apo B, and non-HDL cholesterol in adults with primary hyperlipidemia (high cholesterol), alone or combined with a statin
• Zetia reduces LDL cholesterol in adults and children 10 years and older with heterozygous familial hypercholesterolemia (HeFH), an inherited high-cholesterol condition, alone or with a statin
• Reduces LDL cholesterol in adults with mixed hyperlipidemia (high cholesterol plus high triglycerides) when combined with fenofibrate
• Zetia, combined with a statin and other LDL-lowering therapies, reduces LDL cholesterol in adults and children 10 and older with homozygous familial hypercholesterolemia (HoFH), a severe inherited form
• Ezetimibe tablets combined with atorvastatin or simvastatin reduce LDL in patients with HoFH, as an adjunct to other lipid-lowering treatments or when those treatments aren't available
• Reduces elevated sitosterol and campesterol (plant sterols) in adults and children 9 and older with homozygous familial sitosterolemia, a rare inherited condition

Ezetimibe targets a protein called NPC1L1 (Niemann-Pick C1-Like 1) that sits in the wall of the small intestine and acts as a gateway for cholesterol absorption. By blocking this transporter, ezetimibe reduces how much cholesterol the intestine absorbs from food and bile and delivers to the liver. The liver then compensates by pulling more cholesterol out of the bloodstream, which lowers LDL cholesterol levels. Because this mechanism is completely different from statins (which reduce cholesterol production in the liver), ezetimibe works in a complementary way and can provide additional LDL lowering when added to a statin or fenofibrate.

Ezetimibe tablets are taken orally once a day and can be taken with or without food. If you are also taking a bile acid sequestrant (such as cholestyramine), take ezetimibe either 2 or more hours before or 4 or more hours after that medication — otherwise the sequestrant can significantly reduce ezetimibe absorption. For convenience, ezetimibe can be taken at the same time as a statin or fenofibrate.

• Take once daily at any time of day that works for you
• With or without food — no preference needed
• If you miss a dose, take it as soon as you remember; do not double up the next day
• No dose adjustment is required for kidney impairment or mild liver impairment; ezetimibe is not recommended in moderate to severe liver impairment

Most people tolerate ezetimibe well. The most commonly reported side effects include:

Rarely, ezetimibe can cause serious muscle damage (myopathy or rhabdomyolysis) or liver problems, especially when combined with a statin. Stop the medication and call your doctor right away if you develop unexplained muscle pain, weakness, yellowing of the skin, or signs of a severe allergic reaction such as swelling of the face or difficulty breathing.

• Muscle damage (myopathy/rhabdomyolysis): Muscle breakdown has been reported with ezetimibe, especially when combined with a statin or fibrate. The risk is higher in older adults, people with kidney problems or low thyroid function, and those on high statin doses. Stop ezetimibe and any statin or fibrate immediately if muscle damage is suspected.
• Liver enzyme elevations: Liver enzyme abnormalities can occur, more often when ezetimibe is combined with a statin. Liver tests should be done before and during combined therapy. Ezetimibe is not recommended in people with moderate to severe liver impairment.
• Gallbladder disease: Use with fenofibrate may increase the risk of gallstones (cholelithiasis). If gallbladder symptoms arise, your doctor may need to do gallbladder studies and consider alternative therapy.
• Severe allergic reactions: Anaphylaxis, angioedema (swelling under the skin), rash, and hives have been reported. Seek emergency care if these occur.

Ezetimibe has several important drug interactions to be aware of:

• Cyclosporine: Raises levels of both ezetimibe and cyclosporine in the blood — use together cautiously and monitor cyclosporine levels closely
• Fenofibrate: Increases ezetimibe exposure and may raise gallstone risk when taken together — watch for gallbladder symptoms
• Other fibrates (e.g., gemfibrozil): Co-use is not recommended; safety has not been adequately studied and there may be an increased risk of muscle problems
• Bile acid sequestrants (e.g., cholestyramine): Reduce ezetimibe absorption by about 55% — separate doses by at least 2 hours (before) or 4 hours (after)
• Warfarin (blood thinner): Ezetimibe may alter INR (blood-clotting level) — INR should be monitored when ezetimibe is started or changed

Not a complete list. The label covers the interactions the manufacturer studied or reported, and our own interaction database does not cover every medicine either. Bring your full medication list, including vitamins and herbal products, to your pharmacist.

• Tell your doctor if you have active liver disease or persistently elevated liver enzymes — combining ezetimibe with a statin is contraindicated in these cases
• Ezetimibe is not recommended if you have moderate to severe liver impairment (Child-Pugh B or C)
• If you are pregnant or planning to become pregnant, discuss risks carefully — ezetimibe combined with a statin may harm the fetus and should generally be avoided
• Do not take ezetimibe with a statin if you are breastfeeding — statins may pass into breast milk and pose risks to the infant; discuss with your doctor for ezetimibe alone
• Ezetimibe combined with a statin is approved in children 10 and older for HeFH and HoFH; it has not been established as safe or effective in children younger than 10 (or younger than 9 for sitosterolemia)
• Older adults (65+) may have higher ezetimibe levels in the blood, but no dose adjustment is generally needed based on age alone
• Tell your doctor about all medications you take, especially cyclosporine, fibrates, bile acid sequestrants, and warfarin
• Patients with a known allergy to any ingredient in ezetimibe should not take it

In clinical studies, higher-than-prescribed doses were generally well tolerated, and one patient who accidentally took a much higher dose for nearly a month reported no problems. There is no specific antidote for ezetimibe overdose.

If you think you or someone else has taken too much, contact Poison Control or seek medical care — treatment will focus on managing any symptoms that arise.

Ezetimibe lowers total cholesterol, LDL cholesterol, Apo B, non-HDL cholesterol, and triglycerides, while also modestly raising HDL ("good") cholesterol in people with high cholesterol. When combined with a statin, it improves all of these cholesterol markers more than either drug alone. When combined with fenofibrate, it further lowers total cholesterol, LDL, Apo B, and non-HDL cholesterol in people with mixed hyperlipidemia compared to either medication alone. Importantly, whether these cholesterol improvements from ezetimibe translate into reductions in heart attacks or cardiovascular death has not been established.

After you take an ezetimibe tablet by mouth, it is absorbed and quickly converted in the intestine and liver into an active form called ezetimibe-glucuronide. Food does not meaningfully affect the total amount absorbed, so it can be taken with or without meals — though a high-fat meal can raise the peak concentration somewhat. Both ezetimibe and its active form stay in the body for a relatively long time, with a half-life (the time it takes the body to clear half the drug) of about 22 hours, which supports once-daily dosing. The drug is mostly eliminated through the feces (about 78%) and to a lesser extent through the urine (about 11%). Older adults tend to have about twice the drug exposure of younger adults, though this has not required dose changes in clinical practice.

Store ZETIA at room temperature between 68°F to 77°F (20°C to 25°C). Protect from moisture.