Nexlizet Bempedoic Acid and Ezetimibe 180 mg; 10 mg Tablet, Film Coated, 30-count
Past resolved recalls for this product (2)
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Adenosine Triphosphate-Citrate Lyase Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Patient education
Supplement & herbal interactions
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII J9EQA3S2JM
FD&C Blue No. 1 Aluminum Lake is a blue colorant made by combining FD&C Blue No. 1 dye with aluminum salts. It is used to color tablets, capsules, and other medicines for easy identification and appearance.
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UNII 4AQJ3LG584
A synthetic blue dye combined with aluminum to create a stable colorant. It's used in medicines and supplements to add blue color or create specific shades for product identification and appearance.
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UNII G7515SW10N
A waxy liquid derived from vegetable oil and fatty acids. It works as an emulsifier and solubilizer to help blend oil and water-based ingredients together and improve how the medicine dissolves and is absorbed in the body.
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UNII 9XZ8H6N6OH
A plant-based cellulose derivative used as a binder to hold tablet ingredients together, a thickener in liquids, and a coating agent to control how fast the medicine dissolves.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII PNR0YF693Y
A plant-based powder made from purified wood cellulose. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in the stomach.
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UNII 532B59J990
Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
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UNII U725QWY32X
Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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UNII 5856J3G2A2
A starch-based powder made from potatoes and processed with sodium. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the medicine can be absorbed.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
14 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $13.814 | $414.42 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $13.59 | $407.57 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $13.91 | $417.20 / 30 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Nexlizet 180 mg/1; 10 mgthis 72426-0818-03 | Esperion | 30 tablets | $13.814 | — | Availability likely | — |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 11744816 ↗ | Method of use | U-3883 | Mar 14, 2036 |
| US 10912751 ↗ | Method of use | U-3884 | Mar 14, 2036 |
| US 11926584 ↗ | Method of use | U-3873 | Jun 19, 2040 |
| US 12404227 ↗ | Drug substance | U-4258 | Jun 19, 2040 |
| US 11744816 ↗ | Method of use | U-3692 | Mar 14, 2036 |
| US 10912751 ↗ | Method of use | U-3224 | Mar 14, 2036 |
| US 11613511 ↗ | Drug substance | — | Jun 19, 2040 |
| US 11760714 ↗ | Drug product | — | Jun 19, 2040 |
| US 7335799 ↗ | Drug substance | — | Dec 3, 2030 |
| US 12398087 ↗ | Drug substance | — | Jun 19, 2040 |
| Code | What it grants | Expires |
|---|---|---|
| I-943 | New indication (3-year) | Mar 22, 2027 |
| I-945 | New indication (3-year) | Mar 22, 2027 |
Is there a generic version of NEXLIZET 180-10 MG TABLET?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 72426-0818-03 You're viewing this | 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (72426-818-03) | $13.81 / ea | $414.42 | 2020-03-09 | Active |
| 72426-0818-09 | 90 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (72426-818-09) | — | — | 2020-03-09 | Discontinued by firm |
| 72426-0818-99 | 7 TABLET, FILM COATED in 1 BLISTER PACK (72426-818-99) | — | — | 2020-03-09 | Active |
You're viewing one of 3 pack sizes for this product.
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 72426-0818-03?
What is the difference between NDC 72426-0818-03 and NDC 72426-0818-99?
What NDC number is used to bill for this package of Nexlizet Bempedoic Acid and Ezetimibe 180 mg; 10 mg Tablet, Film Coated?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE NEXLIZET, a combination of bempedoic acid and ezetimibe, is indicated: as an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). Bempedoic acid, a component of NEXLIZET, is indicated: to reduce the risk of major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, or coronary revascularization) in adults at increased risk for these events who are unable to take recommended statin therapy (including those not taking a statin).
NEXLIZET, a combination of bempedoic acid, an adenosine triphosphate citrate lyase (ACL) inhibitor, and ezetimibe, a dietary cholesterol absorption inhibitor, is indicated: As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). ( 1 ) Bempedoic acid, a component of NEXLIZET, is indicated: To reduce the risk of major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, or coronary revascularization) in adults at increased risk for these events who are unable to take recommended statin therapy (including those not taking a statin).
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Administer one tablet (180 mg bempedoic acid and 10 mg ezetimibe) orally once daily with or without food. ( 2.1 ) Swallow the tablet whole. ( 2.1 ) Coadministration with Bile Acid Sequestrants: Administer at least 2 hours before or at least 4 hours after bile acid sequestrants. ( 2.2 )
2.1Recommended Dosage and Administration The recommended dosage of NEXLIZET is one tablet orally once daily. One tablet of NEXLIZET contains 180 mg of bempedoic acid and 10 mg of ezetimibe. Swallow the tablet whole. NEXLIZET can be taken with or without food. If a dose is missed, take the missed dose as soon as possible. Do not double the next dose. After initiation of NEXLIZET, analyze lipid levels within 8 to 12 weeks.
2.2Coadministration with Bile Acid Sequestrants Administer NEXLIZET either at least 2 hours before or at least 4 hours after administration of a bile acid sequestrant [see Drug Interactions (7) ].
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS NEXLIZET is available as: Tablets: 180 mg/10 mg, blue, oval shaped, debossed with "818" on one side and "ESP" on the other side. Tablets: 180 mg bempedoic acid/10 mg ezetimibe ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS NEXLIZET is contraindicated in patients with a prior hypersensitivity to ezetimibe or bempedoic acid or any of the excipients in NEXLIZET [see Adverse Reactions (6.2) ] . Serious hypersensitivity reactions, such as anaphylaxis, angioedema, rash and urticaria have been reported with ezetimibe or bempedoic acid. Known hypersensitivity to ezetimibe or bempedoic acid or any of the excipients in NEXLIZET. ( 4 , 6.2 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hyperuricemia: Elevations in serum uric acid have occurred. Assess uric acid levels periodically as clinically indicated. Monitor for signs and symptoms of hyperuricemia, and initiate treatment with urate-lowering drugs as appropriate.
( 5.1 ) Tendon Rupture: Tendon rupture has occurred. Discontinue NEXLIZET at the first sign of tendon rupture. Avoid NEXLIZET in patients who have a history of tendon disorders or tendon rupture.
( 5.2 )
5.1Hyperuricemia Bempedoic acid, a component of NEXLIZET, inhibits renal tubular OAT2 and may increase blood uric acid levels [see Clinical Pharmacology (12.3) ] . In the primary hypercholesterolemia trials [see Clinical Studies (14.1) ] , 26% of bempedoic acid-treated patients with normal baseline uric acid values (versus 9.5% placebo) experienced hyperuricemia one or more times, and 3.5% of patients experienced clinically significant hyperuricemia reported as an adverse reaction (versus 1.1% placebo). Increases in uric acid levels usually occurred within the first 4 weeks of treatment initiation, persisted throughout treatment, and returned to baseline following discontinuation of treatment.
After 12 weeks of treatment, the mean placebo-adjusted increase in uric acid compared to baseline was 0.8 mg/dL for patients treated with bempedoic acid. In the cardiovascular outcomes trial [see Clinical Studies (14.2) ] , 16.4% of bempedoic acid-treated patients experienced clinically significant hyperuricemia reported as an adverse reaction (versus 8.2% placebo). Elevated blood uric acid may lead to the development of gout.
In the primary hypercholesterolemia trials, gout was reported in 1.5% of patients treated with bempedoic acid versus 0.4% of patients treated with placebo. In the cardiovascular outcomes trial, gout was reported in 3.2% of patients treated with bempedoic acid and 2.2% treated with placebo. Advise patients to contact their healthcare provider if symptoms of hyperuricemia occur.
Assess serum uric acid when clinically indicated. Monitor patients for signs and symptoms of hyperuricemia, and initiate treatment with urate-lowering drugs as appropriate.
5.2Tendon Rupture Bempedoic acid, a component of NEXLIZET, is associated with an increased risk of tendon rupture or injury. In the primary hypercholesterolemia trials [see Clinical Studies (14.1) ] , tendon rupture occurred in 0.5% of patients treated with bempedoic acid versus 0% of placebo-treated patients and involved the rotator cuff (the shoulder), biceps tendon, or Achilles tendon. Tendon rupture occurred within weeks to months of starting bempedoic acid.
In the cardiovascular outcomes trial [see Clinical Studies (14.2) ] , tendon rupture events occurred in 1.2% of bempedoic acid-treated patients versus 0.9% of placebo-treated patients. Tendon rupture may occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders. Discontinue NEXLIZET immediately if the patient experiences rupture of a tendon.
Consider discontinuing NEXLIZET if the patient experiences joint pain, swelling, or inflammation. Advise patients to rest at the first sign of tendinitis or tendon rupture and to contact their healthcare provider if tendinitis or tendon rupture symptoms occur. Consider alternative therapy in patients with a history of tendon disorders or tendon rupture.
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hyperuricemia [see Warnings and Precautions (5.1) ] Tendon Rupture [see Warnings and Precautions (5.2) ] Common adverse reactions with NEXLIZET in the primary hypercholesterolemia trials (incidence ≥ 2% and more frequently than placebo) were upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, elevated liver enzymes, diarrhea, arthralgia, sinusitis, fatigue, and influenza.
( 6.1 ) The common adverse reaction associated with bempedoic acid in the cardiovascular outcomes trial (incidence ≥ 2% and more frequently than placebo) were hyperuricemia, renal impairment, anemia, elevated liver enzymes, muscle spasms, gout, and cholelithiasis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Esperion at 833-377-7633 (833 ESPRMED) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Bempedoic acid The data in Table 1 reflect exposure to bempedoic acid in two placebo-controlled primary hypercholesterolemia trials that included 2,009 patients treated with bempedoic acid for 52 weeks (median treatment duration of 52 weeks) [see Clinical Studies (14.1) ] .
The mean age for bempedoic acid-treated patients was 65 years, 29% were female, 95% were White, 3% were Black or African American, 1% were Asian, and 1% were other races; 3% identified as Hispanic or Latino ethnicity. All patients received bempedoic acid 180 mg orally once daily plus maximally tolerated statin therapy alone or in combination with other lipid-lowering therapies. At baseline, 97% of patients had CVD and about 4% had a diagnosis of HeFH.
Patients on simvastatin 40 mg/day or higher were excluded from the trials. In the primary hypercholesterolemia trials, adverse reactions led to discontinuation of treatment in 11% of bempedoic acid-treated patients and 8% of placebo-treated patients. The most common reasons for bempedoic acid treatment discontinuation were muscle spasms (0.5% versus 0.3% placebo), diarrhea (0.4% versus 0.1% placebo), and pain in extremity (0.3% versus 0.0% placebo).
Adverse reactions reported in at least 2% of bempedoic acid-treated patients and more frequently than in placebo-treated patients are shown in Table 1. Table 1. Adverse Reactions (≥ 2% and greater than placebo) in Bempedoic Acid-Treated Patients with Primary Hypercholesterolemia and CVD or HeFH (Trials 2 and 3) Adverse Reaction Placebo Background therapy included statin ± other lipid-lowering therapies (N = 999) % Bempedoic acid (N = 2,009) % Upper respiratory tract infection 4.0
4.5Muscle spasms 2.3
3.6Hyperuricemia Grouped term that includes other related terms 1.1
3.5Back pain 2.2
3.3Abdominal pain or discomfort 2.2
3.1Bronchitis 2.5
3.0Pain in extremity 1.7
3.0Anemia 1.9
2.8Elevated liver enzymes 0.8
2.1In the cardiovascular outcomes trial in which 7,001 patients were exposed to bempedoic acid and 6,964 patients were exposed to placebo for a median of 3.1 years [see Clinical Studies (14.2) ] , adverse reactions led to discontinuation of treatment in 11% of bempedoic acid-treated patients and 10% of placebo-treated patients. Adverse reactions reported in at least 2% of bempedoic acid-treated patients and more frequently than placebo are shown in Table 2. Table 2.
Adverse Reactions (≥ 2% and 0.5% greater than placebo) in Bempedoic Acid-Treated Patients with CVD or at High Risk for CVD (Trial 4) Adverse Reaction Placebo (N=6,964) % Bempedoic Acid (N=7,001) % Hyperuricemia Grouped term that includes other related terms 8 16 Renal impairment Renal impairment includes laboratory related…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS No specific pharmacokinetic drug interaction studies with NEXLIZET have been conducted. Table 4 lists drug interactions with NEXLIZET that have been identified in studies with bempedoic acid or ezetimibe. Table 4.
Clinically Important Drug Interactions with NEXLIZET Simvastatin Clinical Impact: Concomitant use of NEXLIZET with simvastatin causes an increase in simvastatin concentration and may increase the risk of simvastatin-related myopathy [see Clinical Pharmacology (12.3) ] . Intervention: Avoid concomitant use of NEXLIZET with simvastatin greater than 20 mg. Pravastatin Clinical Impact: Concomitant use of NEXLIZET with pravastatin causes an increase in pravastatin concentration and may increase the risk of pravastatin-related myopathy [see Clinical Pharmacology (12.3) ] .
Intervention: Avoid concomitant use of NEXLIZET with pravastatin greater than 40 mg. Cyclosporine Clinical Impact: Concomitant use of NEXLIZET and cyclosporine increases ezetimibe and cyclosporine concentrations. The degree of increase in ezetimibe exposure may be greater in patients with severe renal insufficiency [see Clinical Pharmacology (12.3) ] .
Intervention: Monitor cyclosporine concentrations in patients receiving NEXLIZET and cyclosporine. In patients treated with cyclosporine, weigh the potential effects of the increased exposure to ezetimibe from concomitant use against the benefits of alterations in lipid levels provided by NEXLIZET. Fibrates Clinical Impact: Both fenofibrate and ezetimibe (a component of NEXLIZET) may increase cholesterol excretion into the bile, leading to cholelithiasis.
Coadministration of NEXLIZET with fibrates other than fenofibrate is not recommended [see Adverse Reactions (6.1) ] . Intervention: If cholelithiasis is suspected in a patient receiving NEXLIZET and fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered. Clinical Impact: Concomitant administration of fibrates with bempedoic acid (a component of NEXLIZET) resulted in increased triglycerides and decreased high-density lipoprotein cholesterol (HDL-C) in some patients in clinical studies and post-marketing reports.
Reversibility of both increased triglycerides and decreased HDL-C levels was observed when either bempedoic acid or fibrate therapy was discontinued. Intervention: Monitor triglycerides and HDL-C four weeks after initial concomitant use of NEXLIZET and a fibrate and periodically thereafter. If increased triglycerides or decreased HDL-C levels are detected, discontinue NEXLIZET or fibrate therapy based on clinical judgment.
Monitor triglycerides and HDL-C levels until levels return to baseline. Cholestyramine Clinical Impact: Concomitant use of NEXLIZET and cholestyramine decreases ezetimibe concentration. This may result in a reduction of efficacy [see Clinical Pharmacology (12.3) ].
Intervention: Administer NEXLIZET either at least 2 hours before or at least 4 hours after bile acid sequestrants [see Dosage and Administration (2.2) ] . Simvastatin: Avoid concomitant use of NEXLIZET with simvastatin greater than 20 mg. ( 7 ) Pravastatin: Avoid concomitant use of NEXLIZET with pravastatin greater than 40 mg.
( 7 ) Cyclosporine: Monitor cyclosporine concentrations. ( 7 ) Fibrates: If cholelithiasis is suspected in a patient receiving NEXLIZET and fenofibrate, consider alternative lipid-lowering therapy. ( 6.2 , 7 ) Concomitant use of NEXLIZET with fibrates may increase triglycerides and decrease high-density lipoprotein cholesterol.
( 7 )
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on mechanism of action, may cause fetal harm. ( 8.1 )
8.1Pregnancy Risk Summary Discontinue NEXLIZET when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus. There are insufficient data on bempedoic acid use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are insufficient data on ezetimibe use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
In animal reproduction studies, bempedoic acid was not teratogenic in rats and rabbits when administered at doses resulting in exposures up to 11 and 12 times, respectively, the human exposures at the maximum clinical dose, based on AUC. In oral (gavage) embryo-fetal development studies of ezetimibe conducted in rats and rabbits during organogenesis, there was no evidence of maternal toxicity or embryo-fetal teratogenic or toxicologic effects at exposures up to 10 and 150 times the human exposure, respectively, based on AUC (see Data ) .
NEXLIZET decreases cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol; therefore, NEXLIZET may cause fetal harm when administered to pregnant women based on the mechanism of action [see Clinical Pharmacology (12.1) ] . In addition, treatment of hypercholesterolemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia for most patients.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Report pregnancies to the Esperion Therapeutics, Inc.
Adverse Event reporting line at 1-833-377-7633. Data Animal Data Bempedoic acid Bempedoic acid was not teratogenic when given orally at doses of 60 and 80 mg/kg/day, resulting in 11 and 12 times the systemic exposure in humans at the maximum recommended human dose (MRHD) of 180 mg to pregnant rats and rabbits, respectively. In an embryofetal development study in rats, bempedoic acid was given orally to pregnant rats at 10, 30, and 60 mg/kg/day during the period of organogenesis from gestation day 6 to 17.
There were increases in the incidence of non-adverse fetal skeletal variations (bent long bones and bent scapula and incomplete ossification) at doses ≥ 10 mg/kg/day (less than the clinical exposure) in the absence of maternal toxicity. At maternally toxic doses, bempedoic acid caused decreases in the numbers of viable fetuses, increases in post-implantation loss, and increased total resorptions at 60 mg/kg/day (11 times MRHD) and reduced fetal body weight at ≥ 30 mg/kg/day (4 times the MRHD). No adverse development effects were observed when bempedoic acid was given to pregnant rabbits during the period of organogenesis (gestation day 6 to 18) at doses up to 80 mg/kg/day (12 times MRHD).
In a pre- and post-natal development study in pregnant rats given oral doses of bempedoic acid at 5, 10, 20, 30 and 60 mg/kg/day throughout pregnancy and lactation (gestation day 6 to lactation day 20), there were adverse effects on delivery in the presence of maternal toxicity, including: increases in stillborn pups, reductions in numbers of live pups, pup survival, pup growth and slight delays in learning and memory at ≥ 10 mg/kg/day (at exposures equivalent to the MRHD). Ezetimibe In oral (gavage) embryo-fetal development studies of ezetimibe conducted in rats (gestation days 6-15) and rabbits (gestation days 7-19), there was no evidence of maternal toxicity or embryolethal effects at the doses te…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Discontinue NEXLIZET when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus. There are insufficient data on bempedoic acid use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are insufficient data on ezetimibe use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
In animal reproduction studies, bempedoic acid was not teratogenic in rats and rabbits when administered at doses resulting in exposures up to 11 and 12 times, respectively, the human exposures at the maximum clinical dose, based on AUC. In oral (gavage) embryo-fetal development studies of ezetimibe conducted in rats and rabbits during organogenesis, there was no evidence of maternal toxicity or embryo-fetal teratogenic or toxicologic effects at exposures up to 10 and 150 times the human exposure, respectively, based on AUC (see Data ) .
NEXLIZET decreases cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol; therefore, NEXLIZET may cause fetal harm when administered to pregnant women based on the mechanism of action [see Clinical Pharmacology (12.1) ] . In addition, treatment of hypercholesterolemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia for most patients.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Report pregnancies to the Esperion Therapeutics, Inc.
Adverse Event reporting line at 1-833-377-7633. Data Animal Data Bempedoic acid Bempedoic acid was not teratogenic when given orally at doses of 60 and 80 mg/kg/day, resulting in 11 and 12 times the systemic exposure in humans at the maximum recommended human dose (MRHD) of 180 mg to pregnant rats and rabbits, respectively. In an embryofetal development study in rats, bempedoic acid was given orally to pregnant rats at 10, 30, and 60 mg/kg/day during the period of organogenesis from gestation day 6 to 17.
There were increases in the incidence of non-adverse fetal skeletal variations (bent long bones and bent scapula and incomplete ossification) at doses ≥ 10 mg/kg/day (less than the clinical exposure) in the absence of maternal toxicity. At maternally toxic doses, bempedoic acid caused decreases in the numbers of viable fetuses, increases in post-implantation loss, and increased total resorptions at 60 mg/kg/day (11 times MRHD) and reduced fetal body weight at ≥ 30 mg/kg/day (4 times the MRHD). No adverse development effects were observed when bempedoic acid was given to pregnant rabbits during the period of organogenesis (gestation day 6 to 18) at doses up to 80 mg/kg/day (12 times MRHD).
In a pre- and post-natal development study in pregnant rats given oral doses of bempedoic acid at 5, 10, 20, 30 and 60 mg/kg/day throughout pregnancy and lactation (gestation day 6 to lactation day 20), there were adverse effects on delivery in the presence of maternal toxicity, including: increases in stillborn pups, reductions in numbers of live pups, pup survival, pup growth and slight delays in learning and memory at ≥ 10 mg/kg/day (at exposures equivalent to the MRHD). Ezetimibe In oral (gavage) embryo-fetal development studies of ezetimibe conducted in rats (gestation days 6-15) and rabbits (gestation days 7-19), there was no evidence of maternal toxicity or embryolethal effects at the doses tested (250, 500, 1,000 mg/kg/day).
In rats, increased incidences of common fetal skeletal findings (ex…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of NEXLIZET have not been established in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 301 patients in the clinical trial of NEXLIZET, 149 (50%) were 65 years of age and older, while 49 (16%) were 75 years of age and over. No overall differences in safety or effectiveness of NEXLIZET have been observed between patients 65 years of age and older and younger adult patients.
🆘 Overdosage ▾
10 OVERDOSAGE There is no clinical experience with NEXLIZET overdosage. In the event of an overdosage, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action NEXLIZET contains bempedoic acid and ezetimibe. NEXLIZET reduces elevated LDL-C through inhibition of cholesterol synthesis in the liver and absorption in the intestine. Bempedoic acid Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers LDL-C by inhibition of cholesterol synthesis in the liver.
ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway. Bempedoic acid and its active metabolite, ESP15228, require coenzyme A (CoA) activation by very long-chain acyl-CoA synthetase 1 (ACSVL1) to ETC-1002-CoA and ESP15228-CoA, respectively. ACSVL1 is expressed primarily in the liver.
Inhibition of ACL by ETC-1002-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of low-density lipoprotein receptors. Ezetimibe Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols.
Ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in LDL receptors, resulting in clearance of cholesterol from the blood.
12.2Pharmacodynamics Administration of bempedoic acid and ezetimibe in combination with other lipid modifying agents, decreases LDL-C, non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apo B), and total cholesterol (TC) in patients with hypercholesterolemia. Cardiac Electrophysiology At a dose of 240 mg (1.3 times the approved recommended dose), bempedoic acid does not prolong the QT interval to any clinically relevant extent. The effect of ezetimibe or NEXLIZET on QT interval has not been evaluated.
12.3Pharmacokinetics Absorption NEXLIZET The bioavailability of NEXLIZET tablets was similar relative to that from the individual tablets, coadministered. Maximum plasma concentration (C max ) values for bempedoic acid and its active metabolite (ESP15228) were similar between formulations, but ezetimibe glucuronide and ezetimibe C max values were approximately 22% and 13% lower, respectively, for NEXLIZET relative to the individual tablets, coadministered. Given a similar overall extent of ezetimibe glucuronide and ezetimibe exposure (as measured by AUC), a 22% lower C max is unlikely to be clinically significant.
Bempedoic acid Following single oral administration of NEXLIZET (180 mg of bempedoic acid and 10 mg of ezetimibe), mean (± SD) C max and AUC of bempedoic acid were 12.6 (± 2.80) µg/mL and 202 (± 43.4) µg.hr/mL, respectively; the median time to maximum concentration (T max ) was 3.0 hours. Following multiple-dose administration of bempedoic acid monotherapy, the steady-state maximum plasma concentration (C max ) and AUC at 180 mg/day were 20.6 ± 6.1 µg/mL and 289.0 ± 96.4 µg∙h/mL, respectively. Bempedoic acid steady-state pharmacokinetics were generally linear over a range of >60 mg to 220 mg (approximately 33% to 122% of the recommended dosage of 180 mg daily).
There were no time-dependent changes in bempedoic acid pharmacokinetics following repeat administration at the recommended dosage, and bempedoic acid steady-state was achieved after 7 days. The mean accumulation ratio was approximately 2.3-fold. The steady-state C max and AUC of the active metabolite (ESP15228) of bempedoic acid were 2.8 ± 0.9 µg/mL and 51.2 ± 17.2 µg∙h/mL, respectively.
ESP15228 likely made a minor contribution to the overall clinical activity of bempedoic acid based on systemic exposure, relative potency, and pharmacokinetic properties. Ezetimibe After a single dose of NEXLIZET to fasted adults, mean ± SD ezetimi…
🧬 Mechanism of Action ▾
12.1Mechanism of Action NEXLIZET contains bempedoic acid and ezetimibe. NEXLIZET reduces elevated LDL-C through inhibition of cholesterol synthesis in the liver and absorption in the intestine. Bempedoic acid Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers LDL-C by inhibition of cholesterol synthesis in the liver.
ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway. Bempedoic acid and its active metabolite, ESP15228, require coenzyme A (CoA) activation by very long-chain acyl-CoA synthetase 1 (ACSVL1) to ETC-1002-CoA and ESP15228-CoA, respectively. ACSVL1 is expressed primarily in the liver.
Inhibition of ACL by ETC-1002-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of low-density lipoprotein receptors. Ezetimibe Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols.
Ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in LDL receptors, resulting in clearance of cholesterol from the blood.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied NEXLIZET tablets are supplied as follows: Tablet Strength Description Package Configuration NDC No. 180 mg of bempedoic acid and 10 mg of ezetimibe blue, oval shaped, debossed with "818" on one side and "ESP" on the other side Bottle of 30 tablets with child-resistant cap 72426-818-03 Storage and Handling Store at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to 86°F (15°C to 30°C) [see USP Controlled Room Temperature] . Store and dispense in the original package protected from extreme heat and humidity.
Do not discard desiccant.
How Supplied NEXLIZET tablets are supplied as follows: Tablet Strength Description Package Configuration NDC No. 180 mg of bempedoic acid and 10 mg of ezetimibe blue, oval shaped, debossed with "818" on one side and "ESP" on the other side Bottle of 30 tablets with child-resistant cap 72426-818-03
📦 Storage and Handling ▾
Storage and Handling Store at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to 86°F (15°C to 30°C) [see USP Controlled Room Temperature] . Store and dispense in the original package protected from extreme heat and humidity. Do not discard desiccant.
📋 Description ▾
11 DESCRIPTION NEXLIZET tablets, for oral use, contain bempedoic acid, an adenosine triphosphate-citrate lyase (ACL) inhibitor, and ezetimibe, a dietary cholesterol absorption inhibitor. The chemical name for bempedoic acid is 8-hydroxy-2,2,14,14-tetramethyl-pentadecanedioic acid. The molecular formula is C 19 H 36 O 5 , and the molecular weight is 344.5 grams per mole.
Bempedoic acid is a white to off-white crystalline powder that is highly soluble in ethanol, isopropanol and pH 8.0 phosphate buffer, and insoluble in water and aqueous solutions below pH 5. Structural formula: The chemical name for ezetimibe is 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)- hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone. The molecular formula is C 24 H 21 F 2 NO 3 and the molecular weight is 409.4 grams per mole.
Ezetimibe is a white, crystalline powder that is freely to very soluble in ethanol, methanol, and acetone and practically insoluble in water. Structural formula: Each film-coated tablet of NEXLIZET contains 180 mg of bempedoic acid and 10 mg of ezetimibe, and the following inactive ingredients: colloidal silicon dioxide, hydroxy propyl cellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K30, sodium lauryl sulfate, sodium starch glycolate. The film coating comprises of FD&C Blue #1/Brilliant Blue FCF Aluminum Lake, FD&C Blue #2/Indigo Carmine Aluminum Lake, glyceryl monocaprylocaprate, partially hydrolyzed polyvinyl alcohol, sodium lauryl sulfate, talc, and titanium dioxide.
Chemical Structure Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling (Patient Information). Risk of Hyperuricemia Advise patients of the risk of elevated serum uric acid levels, including development of gout. Inform patients that serum uric acid levels may be monitored during treatment with NEXLIZET.
Patients with signs or symptoms of hyperuricemia should contact their healthcare provider if symptoms occur [see Warnings and Precautions (5.1) ]. Risk of Tendon Rupture Inform patients of the risk of tendon rupture. Advise patients to rest at the first sign of tendinitis or tendon rupture and to immediately contact their healthcare provider if tendinitis or tendon rupture symptoms occur [see Warnings and Precautions (5.2) ] .
Risk of Myopathy with Concomitant Use of Simvastatin or Pravastatin Advise patients to notify their healthcare provider(s) if they are taking, or plan to take simvastatin or pravastatin. The risk of myopathy occurring with the use of simvastatin or pravastatin may be increased when taken with NEXLIZET [see Drug Interactions (7) ]. Pregnancy Advise pregnant women of the potential risk to a fetus based on NEXLIZET's mechanism of action.
Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise patients that there is a pregnancy safety study that monitors pregnancy outcomes in patients exposed to NEXLIZET during pregnancy. Encourage these patients to report their pregnancy to Esperion at 1-833-377-7633 [see Use in Specific Populations (8.1) ].