Ezetimibe

Zetia

The recommended dose of ezetimibe is 10 mg daily. Ezetimibe can be taken with or without food and at the same time as statin drugs.

Tablets, 10 mg

Ezetimibe tablets should be stored between 15-30 C (59-86 F).

Ezetimibe is part of the drug class:

• Other lipid modifying agents

• Tell your doctor about any prescription and non-prescription medicines you are taking or plan to take, including natural or herbal remedies.
• Tell your doctor about all of your medical conditions including allergies.

Tell your doctor if you:

• have ever had liver problems
• are pregnant or breastfeeding
• experience unexplained muscle pain, tenderness, or weakness

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if ezetimibe crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using ezetimibe.

• Take ezetimibe once a day, with or without food. It may be easier to remember to take your dose if you do it at the same time every day, such as with breakfast, dinner, or at bedtime. If you also take another medicine to reduce your cholesterol, ask your doctor if you can take them at the same time.
• If you forget to take ezetimibe, take it as soon as you remember. However, do not take more than one dose of ezetimibe a day.
• Continue to follow a cholesterol-lowering diet while taking ezetimibe. 
• Keep taking ezetimibe unless your doctor tells you to stop. It is important that you keep taking ezetimibe even if you do not feel sick.
• See your doctor regularly to check your cholesterol level and to check for side effects. Your doctor may do blood tests to check your liver before you start taking ezetimibe with a statin and during treatment.

Storage

Oral

25°C (may be exposed to 15–30°C).1 Protect from moisture.1

Ezetimibe/simvastatin fixed-combination preparation: Well-closed containers at 20–25°C.20 When subdividing contents of a large-quantity container, repackage into tightly closed, light-resistant containers; entire contents must be repackaged immediately upon opening.20

• Localizes at brush border of small intestine and inhibits absorption of cholesterol,3 4 8 resulting in decreased delivery of intestinal cholesterol to liver.1 Intestinal absorption of cholesterol reduced by approximately 54% in a limited number of patients with hypercholesterolemia.1 6

• Has been shown to reduce concentrations of noncholesterol sterols,8 including sitosterol and campesterol.1 6

• Does not appear to inhibit hepatic cholesterol synthesis or increase bile acid excretion.1 Does not appear to inhibit absorption of triglycerides, fatty acids, bile acids, progesterone, or ethyl estradiol.1 No clinically relevant effects on plasma concentrations of fat-soluble vitamins A, D, and E;8 does not appear to impair adrenocortical steroid production.1

• Cholesterol-lowering effects of ezetimibe and statins or of ezetimibe and fenofibrate are additive.1

• Importance of adherence to prescribed directions for use, particularly when used concomitantly with other antilipemic agents.1 12

• Importance of adherence to a standard cholesterol-lowering diet.1 8 20

• Risk of myopathy and/or rhabdomyolysis; risk increased when used concomitantly with certain other drugs or grapefruit juice.1 20 Importance of promptly informing clinicians of unexplained muscle pain, weakness, or tenderness, particularly if accompanied by malaise or fever or if such manifestations persist after discontinuance of therapy.1 20

• Risk of adverse hepatic effects.1 20 Importance of monitoring liver function tests at initiation of ezetimibe if used in combination with a statin and thereafter in accordance with the recommendation of the statin.1 20 Importance of promptly reporting any symptoms suggestive of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice) when ezetimibe is used in combination simvastatin.20

• Importance of women informing their clinician if they are or plan to become pregnant.1 20 Importance of advising women and adolescent girls to avoid pregnancy (i.e., using effective and appropriate contraceptive methods) and informing pregnant women of risk to fetus when using ezetimibe in combination with statin therapy.1 20

• Importance of avoiding breast-feeding when using ezetimibe in combination with statin therapy.1 20 If the patient has a lipid disorder and is breast-feeding, importance of contacting a clinician to discuss other antilipemic treatment options.1 20

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1 12

• Importance of informing patients of other important precautionary information.1 12 (See Cautions.)

Before prescribing medicine for your condition, your doctor will probably try to control your condition by prescribing a personal diet for you. Such a diet may be low in fats, sugars, and/or cholesterol. Many people are able to control their condition by carefully following their doctor's orders for proper diet and exercise. Medicine is prescribed only when additional help is needed and is effective only when a schedule of diet and exercise is properly followed.

Also, ezetimibe is less effective if you are greatly overweight. It may be very important for you to go on a weight-reducing diet. However, check with your doctor before going on any diet.

Dosing

The dose of ezetimibe will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of ezetimibe. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

Follow carefully the special diet your doctor gave you. This is the most important part of controlling your condition and is necessary if the medicine is to work properly.

• For tablet dosage form:
  • For high cholesterol:
    • Adults: 10 milligrams (mg) once daily. May take with or without food.
    • Children up to 10 years of age—Use is not recommended.
    • Children 10 years of age and older—10 milligrams (mg) once daily. May take with or without food.

Missed Dose

If you miss a dose of ezetimibe, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take ezetimibe or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to ezetimibe. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate.

Primary Hyperlipidemia

Monotherapy

Ezetimibe tablets, administered alone, is indicated as adjunctive therapy to diet for the reduction of elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and non­-high-density lipoprotein cholesterol (non-HDL-C) in patients with primary (heterozygous familial and non-familial) hyperlipidemia.

Combination Therapy with HMG-CoA Reductase Inhibitors (Statins)

Ezetimibe tablets, administered in combination with a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin), is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, Apo B, and non-HDL-C in patients with primary (heterozygous familial and non-familial) hyperlipidemia.

Combination Therapy with Fenofibrate

Ezetimibe tablets, administered in combination with fenofibrate, is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, Apo B, and non-HDL-C in adult patients with mixed hyperlipidemia.

Homozygous Familial Hypercholesterolemia (HoFH)

The combination of Ezetimibe tablets and atorvastatin or simvastatin is indicated for the reduction of elevated total-C and LDL-C levels in patients with HoFH, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.

Homozygous Sitosterolemia

Ezetimibe tablets are indicated as adjunctive therapy to diet for the reduction of elevated sitosterol and campesterol levels in patients with homozygous familial sitosterolemia.

Limitations of Use

The effect of Ezetimibe tablets on cardiovascular morbidity and mortality has not been determined.

Ezetimibe tablets has not been studied in Fredrickson Type I, III, IV, and V dyslipidemias.

No dosage adjustment necessary.

May be administered without regard to meals. May be taken at the same time as a statin or fenofibrate. Administer ≥2 hours before or ≥4 hours after bile acid sequestrants.

10 years or older: 10 mg orally once a day

Uses:
-For use as monotherapy or in combination with a statin as an adjunct to diet to reduce elevated total-C, LDL-C, Apo B, and non-HDL-C in patients with primary (heterozygous familial and non-familial) hyperlipidemia
-For use as combination therapy with a fenofibrate as an adjunct to diet to reduce elevated total-C, LDL-C, Apo B, and non-HDL-C in patients with mixed hyperlipidemia
-As an adjunct to diet to reduce elevated sitosterol and campesterol levels in patients with homozygous familial sitosterolemia
-For use as combination therapy with atorvastatin or simvastatin for the reduction of elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable

Administration advice:
-Take orally once a day, with or without food
-Take at least 2 hours before or 4 hours after administration of a bile acid sequestrant
-May be taken at same time as the statin or fenofibrate, according to the dosing recommendations for the respective medications
-Consult appropriate manufacturer product information when using this drug in combination with a statin or fenofibrate.

Storage requirements:
-Protect from moisture.

General:
-Therapy with lipid-altering agents should only be a single component of multiple risk factor intervention in patients at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia.
-Drug therapy is indicated as an adjunct to diet when response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has proven inadequate.
-This drug has not been studied in Fredrickson Type I, III, IV, and V dyslipidemias.

Monitoring:
-Hepatic: When used concomitantly with a statin, liver tests should be performed prior to initiating therapy and according to the recommendations of the statin.
-Metabolic: Periodically measure fasting lipid panel.

Patient advice:
-Promptly report any unexplained muscle pain, tenderness, or weakness.
-Adhere to recommended diet, exercise program, and periodic testing of a fasting lipid panel.

Animal studies have revealed evidence of increased incidences of abnormal skeletal findings at higher doses. There are no controlled data in human pregnancy. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. AU TGA pregnancy category: B3 US FDA pregnancy category: C

Some cholesterol medications should not be taken at the same time. If you take ezetimibe with another cholesterol medicine, follow your doctor's dosing instructions very carefully.

You should not use ezetimibe if you have moderate to severe liver disease. You should not use ezetimibe with a "statin" cholesterol medicine if you have active liver disease, or if you are pregnant or breast-feeding a baby.

Call your doctor right away if you have unexplained muscle pain, tenderness, or weakness especially if you also have fever, unusual tiredness, and dark colored urine.