Ezetimibe

• Ezetimibe, alone or combined with a statin, is used along with diet to lower total cholesterol, LDL ("bad") cholesterol, apolipoprotein B, and triglycerides, and to raise HDL ("good") cholesterol in patients with primary hypercholesterolemia.
• Ezetimibe combined with fenofibrate is used along with diet to lower total cholesterol, LDL cholesterol, apolipoprotein B, and non-HDL cholesterol in patients with mixed hyperlipidemia.
• Ezetimibe combined with a statin is used to lower total cholesterol and LDL cholesterol in patients with homozygous familial hypercholesterolemia, a severe inherited form of high cholesterol.
• Ezetimibe alone is used to lower elevated plant sterol (sitosterol and campesterol) levels in patients with homozygous familial sitosterolemia, a rare inherited lipid disorder.
• Ezetimibe is intended for use alongside an appropriate cholesterol-lowering diet, not as a substitute for it.

• There are no clinical data on ezetimibe use in pregnant women, and its effect on labour and delivery is unknown, so caution is advised if it is prescribed during pregnancy.
• When ezetimibe is combined with a statin or with fenofibrate, pregnancy is contraindicated, because statins and fenofibrate are themselves contraindicated in pregnancy.

• Ezetimibe passes into milk in animal studies, and it is not known whether it passes into human breast milk, so it should be avoided during breastfeeding unless the expected benefit clearly justifies the potential risk to the infant.
• When combined with a statin or fenofibrate, breastfeeding is contraindicated, because statins and fenofibrate are themselves contraindicated during breastfeeding.

• No dose adjustment is needed for older adults; cholesterol-lowering effect and safety are similar between elderly and younger patients, although blood levels of the drug run about twice as high in the elderly.

• Ezetimibe is not recommended in children younger than 10 years of age.
• In children 10 years of age and older, ezetimibe behaves similarly to in adults, and no dose adjustment is needed, based on limited pediatric experience mainly in sitosterolemia and homozygous familial hypercholesterolemia.

• The usual dose of ezetimibe is 10 mg once daily, taken alone, with a statin, or with fenofibrate.
• Ezetimibe can be taken at any time of day, with or without food, though taking it at the same time each day is preferred.
• When taken together with a bile acid sequestrant such as cholestyramine, ezetimibe should be taken at least 2 hours before or 4 hours after the sequestrant, since the sequestrant reduces ezetimibe absorption.
• No dose adjustment is needed for kidney impairment, mild liver impairment, or older age.
• Ezetimibe is not recommended in patients with moderate or severe liver impairment.
• If a dose is missed, the patient should simply resume their normal once-daily schedule rather than doubling the next dose.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Doses of ezetimibe well above the recommended dose, given in clinical studies, were generally well tolerated.
• Reported cases of ezetimibe overdose in practice have generally not been associated with significant adverse effects.
• There is no specific antidote; management of an overdose is symptomatic and supportive.

• Diarrhea may occur.
• Abdominal pain may occur.
• Joint pain (arthralgia) may occur.
• Back pain may occur.
• Fatigue may occur.
• Upper respiratory tract infection-type symptoms, cough, or sore throat may occur.
• Sinus congestion or sinusitis-type symptoms may occur.
• Muscle pain (myalgia) may occur.
• Gas (flatulence) may occur.
• Dizziness may occur, particularly when ezetimibe is combined with a statin.
• Mild, usually temporary increases in liver enzymes may occur on blood tests, more often when combined with a statin than when taken alone.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Liver injury, including hepatitis, may occur.
• Inflammation of the pancreas (pancreatitis) may occur.
• Muscle breakdown (rhabdomyolysis) or muscle disease (myopathy) may occur, particularly when ezetimibe is combined with a statin.
• Severe allergic reactions, including anaphylaxis and swelling of the face, lips, or throat (angioedema), may occur.
• Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), may occur.
• Gallstones or gallbladder inflammation may occur, particularly when ezetimibe is combined with fenofibrate.
• A low platelet count (thrombocytopenia) may occur.
• Seek urgent medical attention for yellowing of the skin or eyes, severe or persistent muscle pain or weakness, sudden severe abdominal pain, difficulty breathing or swelling of the face and throat, or a severe skin rash.

• Use with caution in patients with active liver disease or unexplained, persistent elevations in liver enzymes; combining ezetimibe with a statin is contraindicated in this situation.
• Use with caution in patients with a prior history of muscle pain (myalgia) on statin therapy, since they may be more prone to muscle-related side effects on ezetimibe as well.
• Use with caution in patients taking fenofibrate, monitoring for signs of gallstones such as new abdominal pain.
• Use with caution in patients with hereditary galactose intolerance, glucose-galactose malabsorption, or Lapp lactase deficiency, since the tablets contain lactose; this combination is actually contraindicated.
• Liver function tests should be checked when starting ezetimibe, whether used alone or combined with a statin or fenofibrate.

• Contraindicated in patients with known hypersensitivity to ezetimibe or to any ingredient in the formulation.
• Contraindicated in combination with a statin in patients with active liver disease or unexplained, persistent elevations in liver enzymes.
• Contraindicated in combination with a statin or fenofibrate during pregnancy, since those medications are themselves contraindicated in pregnancy.
• Contraindicated in combination with a statin or fenofibrate during breastfeeding, since those medications are themselves contraindicated during breastfeeding.
• Contraindicated in patients with hereditary galactose intolerance, glucose-galactose malabsorption, or Lapp lactase deficiency, because of the lactose content of the tablets.

• Cyclosporine can significantly raise ezetimibe blood levels, and ezetimibe can modestly raise cyclosporine levels, so cyclosporine levels should be monitored when the two are combined.
• Cholestyramine and other bile acid sequestrants reduce ezetimibe absorption and can lessen its cholesterol-lowering effect, so doses should be separated by at least 2 to 4 hours.
• Fibrates other than fenofibrate have not been studied with ezetimibe and are not recommended together, since fibrates can increase cholesterol excretion into bile and raise the risk of gallstones.
• Gemfibrozil and fenofibrate can modestly raise ezetimibe blood levels, though this is not considered clinically significant.
• No dose adjustment is needed when ezetimibe is combined with common statins, including atorvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, or rosuvastatin.
• Ezetimibe does not significantly affect the blood levels of warfarin, digoxin, oral contraceptives, glipizide, or cimetidine.
• Antacids containing aluminum and magnesium hydroxide can slow the rate of ezetimibe absorption, though this is not considered clinically significant.

• Ezetimibe can be taken with or without food, at any time of day, though taking it at the same time each day is preferred for consistency.

• Ezetimibe is taken once daily and can be taken with or without food; picking a consistent time of day helps with remembering the dose.

• Store ezetimibe tablets between 15°C and 30°C, protected from moisture.

• Ezetimibe (Ezetrol) lowers cholesterol by blocking its absorption in the gut, is usually combined with a statin or taken alone when a statin is unsuitable, and patients should report unexplained muscle pain, yellowing of the skin or eyes, or signs of a severe allergic reaction promptly.