Ezetimibe tablets are indicated:

•

In combination with a statin, or alone when additional low-density lipoprotein cholesterol (LDL-C) lowering therapy is not possible, as an adjunct to diet to reduce elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH).

•

In combination with a statin as an adjunct to diet to reduce elevated LDL-C in pediatric patients 10 years of age and older with HeFH.

•

In combination with fenofibrate as an adjunct to diet to reduce elevated LDL-C in adults with mixed hyperlipidemia.

•

In combination with a statin, and other LDL-C lowering therapies, to reduce elevated LDL-C levels in adults and in pediatric patients 10 years of age and older with homozygous familial hypercholesterolemia (HoFH).

•

As an adjunct to diet for the reduction of elevated sitosterol and campesterol levels in adults and in pediatric patients 9 years of age and older with homozygous familial sitosterolemia.

When ezetimibe tablet is used in combination with a statin, fenofibrate, or other LDL-C lowering therapies, refer to the Prescribing Information of these products for information on the safe and effective use.

•

The recommended dose of ezetimibe tablet is 10 mg orally once daily, administered with or without food.

•

If as dose is missed, take the missed dose as soon as possible. Do not double the next dose.

•

Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating ezetimibe tablets.

•

Administer ezetimibe tablets at least 2 hours before or 4 hours after administration of a bile acid sequestrant [seeDrug Interactions (7)].

Tablets: 10-mg are white to off-white, capsule-shaped, flat, beveled edged tablets engraved with ‘G80’ on one side and plain on the other side.

 

Ezetimibe tablets are contraindicated in patients with a known hypersensitivity to ezetimibe or any of the excipients in ezetimibe tablets. Hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria have been reported [see Adverse Reactions (6.2)].

 

When used in combination with a statin, fenofibrate, or other LDL-C lowering therapy, ezetimibe tablets are contraindicated in patients for whom a statin, fenofibrate, or other LDL-C lowering therapy are contraindicated. Refer to the Prescribing Information of these products for a list of their contraindications [see Warnings and Precautions (5.1)].

The following serious adverse reactions are discussed in greater detail in other sections of the label:

•

Liver enzyme abnormalities [see Warnings and Precautions (5.2)]

•

Rhabdomyolysis and myopathy [see Warnings and Precautions (5.3)]

Table 3 includes a list of drugs with clinically important drug interactions when administered concomitantly with ezetimibe tablets and instructions for preventing or managing them.

Table 3: Clinically Important Drug Interactions with Ezetimibe

In the event of overdose, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.

Ezetimibe is in a class of lipid‑lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. The chemical name of ezetimibe, USP is 1‑(4‑fluorophenyl)‑3(R)‑[3‑(4‑fluorophenyl)‑3(S)‑ hydroxypropyl]‑4(S)‑(4‑hydroxyphenyl)‑2‑azetidinone. The empirical formula is C24H21F2NO3. Its molecular weight is 409.4 and its structural formula is:

Ezetimibe, USP is a white crystalline powder that is freely soluble in ethanol, methanol, and acetone and practically insoluble in water. Ezetimibe, USP has a melting point of about 163°C and is stable at ambient temperature. Ezetimibe Tablets, USP is available as a tablet for oral administration containing 10 mg of ezetimibe, USP and the following inactive ingredients: lactose monohydrate, magnesium stearate, povidone, sodium lauryl sulfate, and sodium starch glycolate.

FDA approved dissolution test specifications differ from USP.

Primary Hyperlipidemia in Adults

Ezetimibe reduces total-C, LDL-C, Apo B, and non-HDL-C in patients with hyperlipidemia. Maximal to near maximal response is generally achieved within 2 weeks and maintained during chronic therapy.

Monotherapy

In two multicenter, double-blind, placebo-controlled, 12-week trials in 1719 patients (age range 18 to 86 years, 52% females; 91% White, 5% Black or African American, 1% Asian, 3% other races mostly identified as Hispanic or Latino ethnicity) with primary hyperlipidemia, ezetimibe significantly lowered total-C, LDL-C, Apo B, and non-HDL-C compared to placebo (see Table 6). Reduction in LDL-C was consistent across age, sex, and baseline LDL-C.

Combination with Statins:Ezetimibe Added to On-going Statin Therapy

In a multicenter, double-blind, placebo-controlled, 8-week trial, 769 patients (age range 22 to 85 years, 42% females; 90% White, 6% Black or African American, 1% Asian, 3% other races; and 2% identified as Hispanic or Latino ethnicity) with primary hyperlipidemia, known coronary heart disease or multiple cardiovascular risk factors who were already receiving statin monotherapy, but who had not met their NCEP ATP II target LDL-C goal were randomized to receive either ezetimibe or placebo in addition to their on-going statin.

Ezetimibe, added to on-going statin therapy, significantly lowered total-C, LDL-C, Apo B, non-HDL-C compared with a statin administered alone (see Table 7). LDL-C reductions induced by ezetimibe were generally consistent across all statins.

* Patients receiving each statin: 40% atorvastatin, 31% simvastatin, 29% others (pravastatin, fluvastatin, cerivastatin, lovastatin).

† Baseline - on a statin alone.

‡ Ezetimibe + statin significantly reduced total-C, LDL-C, Apo B, non-HDL-C compared to statin alone.

Combination with Statins: Ezetimibe Initiated Concurrently with a Statin

In four multicenter, double-blind, placebo-controlled, 12-week trials, in 2,382 patients (age range 18 to 87 years, 57% female; 88% White, 5% Black or African American, 2% Asian, 5% other races mostly identified as Hispanic or Latino) with hyperlipidemia, ezetimibe or placebo was administered alone or with various doses of atorvastatin, simvastatin, pravastatin, or lovastatin.

When all patients receiving ezetimibe with a statin were compared to all those receiving the corresponding statin alone, ezetimibe significantly lowered total-C, LDL-C, Apo B, non-HDL-C compared to the statin administered alone. LDL-C reductions induced by ezetimibe were generally consistent across all statins. (See footnote †, Tables 8 to 11.)

TABLE 8: Response to Ezetimibe and Atorvastatin Initiated Concurrently in Patients with Primary Hyperlipidemia (Mean % Change from Untreated Baseline*)

TABLE 9: Response to Ezetimibe and Simvastatin Initiated Concurrently in Patients with Primary Hyperlipidemia (Mean % Change from Untreated Baseline*)

TABLE 10: Response to Ezetimibe and Pravastatin Initiated Concurrently in Patients with Primary Hyperlipidemia (Mean % Change from Untreated Baseline*)

TABLE 11: Response to Ezetimibe and Lovastatin Initiated Concurrently in Patients with Primary Hyperlipidemia (Mean % Change from Untreated Baseline*)

Combination with Fenofibrate

In a multicenter, double-blind, placebo-controlled, clinical trial in patients with mixed hyperlipidemia, 625 patients (age range 20 to 76 years, 44% female; 79% White, 1% Black or African American, 20% other races; and 11% identified as Hispanic or Latino ethnicity) were treated for up to 12 weeks and 576 for up to an additional 48 weeks. Patients were randomized to receive placebo, ezetimibe alone, 160 mg fenofibrate alone, or ezetimibe and 160 mg fenofibrate in the 12-week trial. After completing the 12-week trial, eligible patients were assigned to ezetimibe coadministered with fenofibrate or fenofibrate monotherapy for an additional 48 weeks.

Ezetimibe coadministered with fenofibrate significantly lowered total-C, LDL-C, Apo B, and non-HDL-C compared to fenofibrate administered alone (see Table 12).

TABLE 12: Response to Ezetimibe and Fenofibrate Initiated Concurrently in Patients with Mixed Hyperlipidemia (Mean % Change from Untreated Baseline*at 12 weeks)

The changes in lipid endpoints after an additional 48 weeks of treatment with ezetimibe coadministered with fenofibrate or with fenofibrate alone were consistent with the 12-week data displayed above.

HeFH in Pediatric Patients

The effects of ezetimibe coadministered with simvastatin (n=126) compared to simvastatin monotherapy (n=122) have been evaluated in males and females with HeFH. In a multicenter, double-blind, controlled trial followed by an open-label phase, 142 males and 106 postmenarchal females, 10 to 17 years of age (mean age 14.2 years, 43% females, 82% White, 4% Asian, 2% Black or African American, 13% multi-racial; 14% identified as Hispanic or Latino ethnicity) with HeFH were randomized to receive either ezetimibe coadministered with simvastatin or simvastatin monotherapy. Inclusion in the trial required 1) a baseline LDL-C level between 160 and 400 mg/dL and 2) a medical history and clinical presentation consistent with HeFH. The mean baseline LDL-C value was 225 mg/dL (range: 161 to 351 mg/dL) in the ezetimibe coadministered with simvastatin group compared to 219 mg/dL (range: 149 to 336 mg/dL) in the simvastatin monotherapy group. The patients received coadministered ezetimibe and simvastatin (10 mg, 20 mg, or 40 mg) or simvastatin monotherapy (10 mg, 20 mg, or 40 mg) for 6 weeks, coadministered ezetimibe and 40 mg simvastatin or 40-mg simvastatin monotherapy for the next 27 weeks, and open-label coadministered ezetimibe and simvastatin (10 mg, 20 mg, or 40 mg) for 20 weeks thereafter.

The results of the trial at Week 6 are summarized in Table 13. Results at Week 33 were consistent with those at Week 6.

TABLE 13: Mean Percent Difference at Week 6 Between the Pooled Ezetimibe Coadministered with Simvastatin Group and the Pooled Simvastatin Monotherapy Group in Adolescent Patients with HeFH

HoFH in Adults and Pediatric Patients

A trial was conducted to assess the efficacy of ezetimibe in the treatment of HoFH. This double-blind, randomized, 12‑week trial enrolled 50 patients (age range 11 to 74 years, 58% female; 90% White, 2% Black or African American, 8% other races identified as Hispanic or Latino) with a clinical and/or genotypic diagnosis of HoFH, with or without concomitant LDL apheresis, already receiving atorvastatin or simvastatin (40 mg). Patients were randomized to one of three treatment groups, atorvastatin or simvastatin (80 mg), ezetimibe administered with atorvastatin or simvastatin (40 mg), or ezetimibe administered with atorvastatin or simvastatin (80 mg). Due to decreased bioavailability of ezetimibe in patients concomitantly receiving cholestyramine [see Drug Interactions (7)], ezetimibe was dosed at least 4 hours before or after administration of resins. Mean baseline LDL-C was 341 mg/dL in those patients randomized to atorvastatin 80 mg or simvastatin 80 mg alone and 316 mg/dL in the group randomized to ezetimibe plus atorvastatin 40 or 80 mg or simvastatin 40 or 80 mg. ezetimibe, administered with atorvastatin or simvastatin (40 and 80 mg statin groups, pooled), significantly reduced LDL-C (21%) compared with increasing the dose of simvastatin or atorvastatin monotherapy from 40 to 80 mg (7%). In those treated with ezetimibe plus 80 mg atorvastatin or with ezetimibe plus 80 mg simvastatin, LDL‑C was reduced by 27%.

Homozygous Sitosterolemia (Phytosterolemia) in Adults and Pediatric Patients

A trial was conducted to assess the efficacy of ezetimibe in the treatment of homozygous sitosterolemia. In this multicenter, double-blind, placebo-controlled, 8-week trial, 37 patients (age range 9 to 72 years, 65% females; 89% White, 3% Asian, 8% other races identified as Hispanic or Latino) with homozygous sitosterolemia with elevated plasma sitosterol levels (>5 mg/dL) on their current therapeutic regimen (diet, bile-acid-binding resins, statins, ileal bypass surgery and/or LDL apheresis), were randomized to receive ezetimibe (n=30) or placebo (n=7). Due to decreased bioavailability of ezetimibe in patients concomitantly receiving cholestyramine [see Drug Interactions (7)], ezetimibe was dosed at least 2 hours before or 4 hours after resins were administered. Excluding the one subject receiving LDL apheresis, ezetimibe significantly lowered plasma sitosterol and campesterol, by 21% and 24% from baseline, respectively. In contrast, patients who received placebo had increases in sitosterol and campesterol of 4% and 3% from baseline, respectively. For patients treated with ezetimibe, mean plasma levels of plant sterols were reduced progressively over the course of the trial. Reductions in sitosterol and campesterol were consistent between patients taking ezetimibe concomitantly with bile acid sequestrants (n=8) and patients not on concomitant bile acid sequestrant therapy (n=21).

Ezetimibe Tablets, USP 10 mg, are white to off-white, capsule-shaped, flat, beveled edged tablets engraved with ‘G80’ on one side and plain on the other side. They are supplied as follows:

Bottles of 30, NDC 82804-211-30

Store Ezetimibe Tablets, USP at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture.

Advise the patient to read the FDA-Approved Patient Labeling (Patient Information).

Inform patients that ezetimibe may cause liver enzyme elevations [see Warnings and Precautions (5.2)].

Muscle Pain

Advise patients that ezetimibe may cause myopathy and rhabdomyolysis. Inform patients that the risk is also increased when taking certain types of medication and they should discuss all medication, both prescription and over the counter, with their healthcare provider. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever [see Warnings and Precautions (5.3), and Drug Interactions (7)].

Pregnancy

Advise patients to inform their healthcare provider of a known or suspected pregnancy to discuss if ezetimibe should be discontinued [see Use in Specific Populations (8.1)].

Breastfeeding

Advise patients who have a lipid disorder and are breastfeeding to discuss the options with their healthcare provider [see Use in Specific Populations (8.2)].

Missed Dose

Instruct patients to take ezetimibe only as prescribed. If a dose is missed, it should be taken as soon as possible. Advise patients not to double their next dose.

Manufactured by:

Glenmark Pharmaceuticals Limited

India

Manufactured for:

Glenmark Pharmaceuticals Inc., USA

Mahwah, NJ 07430

Questions? 1 (888) 721-7115

www.glenmarkpharma-us.com

Manufactured by:

Glenmark Pharmaceuticals Limited

India

Repackaged by:

Proficient Rx LP

Thousand Oaks, CA 91320

April 2024

Read this information carefully before you start taking ezetimibe tablets and each time you get more ezetimibe tablets. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. If you have any questions about ezetimibe tablets, ask your doctor. Only your doctor can determine if ezetimibe tablets are right for you.

What are ezetimibe tablets?

Ezetimibe tablet is a medicine used with a cholesterol lowering diet:

•

and with other cholesterol medicines called a statin, or alone (when additional cholesterol lowering treatments are not possible), to lower elevated low-density lipoprotein cholesterol (LDL-C) or bad cholesterol in adults with primary hyperlipidemia (too many fats in your blood), including heterozygous familial hypercholesterolemia (HeFH). HeFH is an inherited condition that causes high levels of bad cholesterol.

•

and with a statin to lower LDL-C in adults and children 10 years of age and older with HeFH.

•

and with a medicine called fenofibrate to lower elevated LDL-C in adults with mixed hyperlipidemia.

•

to lower elevated sitosterol and campesterol levels in adults and in children 9 years of age and older with homozygous familial sitosterolemia (a rare inherited condition that prevents the body from getting rid of cholesterol from plants).

Ezetimibe tablet is also used:

•

with a statin and other cholesterol lowering treatments to lower elevated LDL-C levels in adults and patients 10 years of age and older with homozygous familial hypercholesterolemia (HoFH). HoFH is an inherited condition that causes high levels of bad cholesterol.

The safety and effectiveness of ezetimibe tablets has not been established in children:

•

younger than 10 years of age with HeFH or HoFH.

•

younger than 9 years of age with homozygous familial sitosterolemia.

•

with other types of hyperlipemia.

Do not take ezetimibe tablets:

•

if you are allergic to ezetimibe or any of the ingredients in ezetimibe tablets. See the end of this Patient Information leaflet for a complete list of ingredients in ezetimibe tablets. Stop using ezetimibe tablets and get medical help right away if you have symptoms of a serious allergic reaction including:

•

swelling of the face, tongue, or throat

•

difficulty breathing or swallowing

•

fainting or feeling dizzy

•

very fast heartbeat

•

severe skin rash, hives, and itching

•

flu-like symptoms including fever, sore throat, cough, tiredness, and joint pain

•

with certain statins, fenofibrate, or other LDL-C lowering medicines if your healthcare provider has told you not to take them.

Before you take ezetimibe tablets, tell your healthcare provider about all your medical conditions, including if you:

•

have liver problems. Ezetimibe tablets may not be right for you.

•

are pregnant or plan to become pregnant. It is not known if ezetimibe tablets will harm your unborn baby. You and your healthcare provider should decide if you will take ezetimibe tablets while you are pregnant.

•

are breastfeeding. It is not known if ezetimibe tablets passes into your breast milk. You and your healthcare provider should decide the best way to feed your baby if you take ezetimibe tablets.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Talk to your healthcare provider before you start taking any new medicines.

Taking ezetimibe tablets with certain other medicines may affect each other causing side effects. Ezetimibe tablets may affect the way other medicines work, and other medicines may affect how ezetimibe tablets works.

Especially tell your healthcare provider if you take:

•

cyclosporine (a medicine for your immune system)

•

fibrates (medicine for lowering cholesterol)

•

bile acid sequestrants (medicine for lowering LDL-C)

Ask your healthcare provider or pharmacist for a list of medicines if you are not sure. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take ezetimibe tablets?

•

Take ezetimibe tablets 1-time each 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 healthcare provider if you can take them at the same time.

•

If you miss a dose, take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and go back to your regular schedule. Do not take 2 doses of ezetimibe tablets at the same time.

•

While taking ezetimibe tablets, continue to follow your cholesterol-lowering diet and to exercise as your healthcare provider told you to.

•

If you take a medicine called a bile acid sequestrant, take ezetimibe tablets at least 2 hours before or 4 hours after you take the bile acid sequestrant.

•

Your healthcare provider may do blood tests to check your LDL-C levels as early as 4 weeks after starting treatment with ezetimibe tablets.

•

In case of an overdose, get medical help or contact a live Poison Center expert right away at 1800-222-1222. Advice is also available online at poisonhelp.org.

What are the possible side effects of ezetimibe tablets?

Ezetimibe tablets may cause serious side effects including:

•

increased liver enzymes. An increase in liver enzymes can happen in people taking ezetimibe tablets alone or with statins. Your healthcare provider may do blood tests to check your liver before and during treatment. Your healthcare provider may need to change or stop your treatment with ezetimibe tablets because of an increase in liver enzymes.

•

muscle pain, tenderness, and weakness (myopathy). Muscle problems, including muscle breakdown (rhabdomyolysis) can happen. Tell your healthcare provider right away if:

•

you have unexplained muscle pain, tenderness, weakness, feel more tired than usual, or fever.

•

you have muscle problems that do not go away even after your healthcare provider has advised you to stop taking ezetimibe tablets. Your healthcare provider may do further tests to diagnose the cause of your muscle problems.

Your chances of getting muscle problems are higher if you are also taking statins or fibrates.

The most common side effects of ezetimibe tablets taken alone include:

•

upper respiratory tract infection

•

diarrhea

•

joint pain

•

inflammation of the sinuses

•

pain in arms or legs

•

feeling tired

•

flu-like symptoms

The most common side effects of ezetimibe tablets taken with a statin include:

•

runny nose, sore throat

•

muscle aches and pains

•

upper respiratory tract infection

•

joint pain

•

diarrhea

•

back pain

•

flu-like symptoms

•

pain in arms or legs

•

feeling tired

Tell your healthcare provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of ezetimibe tablets.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800FDA-1088.

How should I store ezetimibe tablets?

•

Store ezetimibe tablets at room temperature between 68ºF to 77ºF (20ºC to 25ºC).

•

Protect from moisture.

Keep ezetimibe tablets and all medicines out of the reach of children.

General information about safe and effective use of ezetimibe tablets.

Medicines are sometimes prescribed for purpose other than those listed in Patient Information leaflet. Do not use ezetimibe tablets for a condition for which it was not prescribed. Do not give ezetimibe tablets to other people, even if they have the same symptoms you have. It may harm them.

You can ask your pharmacist or healthcare provider for information about ezetimibe tablets that is written for health professionals.

What are the ingredients in ezetimibe tablets?

Active ingredient: ezetimibe.

Inactive ingredients:

Lactose monohydrate, magnesium stearate, povidone, sodium lauryl sulfate, and sodium starch glycolate.

Manufactured by:

Glenmark Pharmaceuticals Limited

India

Manufactured for:

Glenmark Pharmaceuticals Inc., USA

Mahwah, NJ 07430

Questions? 1 (888) 721-7115

www.glenmarkpharma-us.com

Repackaged by:

Proficient Rx LP

Thousand Oaks, CA 91320

April 2024

This Patient Information has been approved by the U.S. Food and Drug Administration.