These Highlights Do Not Include All The Information Needed To Use Nexlizet®

How Supplied

NEXLIZET tablets are supplied as follows:

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.

In 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.

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.

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.

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 C₁₉H₃₆O₅, 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 C₂₄H₂₁F₂NO₃ 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.

Simvastatin: Administration of simvastatin 20 mg with 240 mg of bempedoic acid or 40 mg with 180 mg of bempedoic acid in healthy subjects at steady-state resulted in approximately 2-fold (91% for 20 mg and 96% for 40 mg) and 1.5-fold (54% for 20 mg and 52% for 40 mg) increases in simvastatin acid AUC and C_max, respectively [see Drug Interactions (7)].

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.

The safety and effectiveness of NEXLIZET have not been established in pediatric patients.

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.

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.

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.

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)]

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.

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.

No dosage adjustment is necessary in patients with mild hepatic impairment (Child-Pugh A) [see Clinical Pharmacology (12.3)]. NEXLIZET is not recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C) due to the unknown effects of the increased exposure to ezetimibe [see Clinical Pharmacology (12.3)].

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 contains bempedoic acid and ezetimibe. NEXLIZET reduces elevated LDL-C through inhibition of cholesterol synthesis in the liver and absorption in the intestine.

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)

• 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)

NEXLIZET is available as:

• Tablets: 180 mg/10 mg, blue, oval shaped, debossed with "818" on one side and "ESP" on the other side.

The following adverse reactions have been identified during post approval use of ezetimibe and/or bempedoic acid. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood Disorders: thrombocytopenia

Gastrointestinal Disorders: abdominal pain; pancreatitis; nausea

Hepatobiliary Disorders: elevations in liver transaminases, including elevations more than 5× ULN; hepatitis; cholelithiasis; cholecystitis

Immune System Disorders: Hypersensitivity reactions including: anaphylaxis, angioedema, wheezing, rash, and urticaria

Musculoskeletal Disorders: elevated creatine phosphokinase; myopathy/rhabdomyolysis

Nervous System Disorders: dizziness; paresthesia; depression; headache

Skin and Subcutaneous Tissue Disorders: erythema multiforme

• Pregnancy: Based on mechanism of action, may cause fetal harm. (8.1)

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.

Advise patients to read the FDA-approved patient labeling (Patient Information).

• 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.

Administer NEXLIZET either at least 2 hours before or at least 4 hours after administration of a bile acid sequestrant [see Drug Interactions (7)].

The efficacy of NEXLIZET was investigated in a single, multi-center, randomized, double-blind, placebo-controlled, parallel group trial that enrolled 301 patients with HeFH, established CVD, or multiple risk factors for CVD on maximally tolerated statin therapy.

Trial 1 (NCT03337308) was a 4-arm, 12-week trial that assessed the efficacy of NEXLIZET in 301 patients randomized 2:2:2:1 to receive either oral NEXLIZET (180 mg of bempedoic acid and 10 mg of ezetimibe) (n = 86), bempedoic acid 180 mg (n = 88), ezetimibe 10 mg (n = 86), or placebo (n = 41) once daily as add-on to maximally tolerated statin therapy. Patients were stratified by cardiovascular risk and baseline statin intensity. Patients on simvastatin 40 mg per day or higher and patients taking non-statin lipid-lowering therapy (including fibrates, niacin, bile acid sequestrants, ezetimibe, and PCSK9 inhibitors) were excluded from the trial.

NDC 72426-818-03

Rx only

NEXLIZET^®

(bempedoic acid

and ezetimibe) tablets

Contains

30 Tablets

180 mg/10 mg

Trial 4 (NCT02993406) was a randomized, double-blind, placebo-controlled, event-driven trial in 13,970 adult patients with established CVD (70%) or at high risk for a CVD event but without CVD (30%) who were not receiving recommended statin dosages. Patients with established CVD had documented history of coronary artery disease, symptomatic peripheral arterial disease, and/or cerebrovascular atherosclerotic disease. Patients without established CVD were considered at high risk for CVD based on meeting at least one of the following criteria:

•  
  (1) Diabetes mellitus (type 1 or type 2) in females over 65 years of age or males over 60 years of age;
  
  (2) A Reynolds Risk score > 30% or a SCORE Risk score > 7.5% over 10 years. Reynolds risk score and SCORE risk score evaluate a 10-year risk of having a cardiovascular (CV) event. The Reynolds risk score is based on the following risk factors: sex, age, smoking status, systolic blood pressure, total cholesterol, HDL cholesterol, high sensitivity C-reactive protein (hsCRP), and familial history of CVD events. LDL-C is an additional risk factor considered in SCORE risk score; or
  
  (3) A coronary artery calcium score >400 Agatston units at any time in the past.

Patients were randomized 1:1 to receive either oral bempedoic acid 180 mg per day (n = 6,992) or placebo (n = 6,978), alone or as an add on to other background lipid-lowering therapies. Background therapy could include less than low-intensity statin dosages. Overall, 95.3% of adult patients were followed until the end of the trial or death. The median follow-up duration was 3.4 years.

How Supplied

NEXLIZET tablets are supplied as follows:

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.

In 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.

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.

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.

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 C₁₉H₃₆O₅, 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 C₂₄H₂₁F₂NO₃ 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.

Simvastatin: Administration of simvastatin 20 mg with 240 mg of bempedoic acid or 40 mg with 180 mg of bempedoic acid in healthy subjects at steady-state resulted in approximately 2-fold (91% for 20 mg and 96% for 40 mg) and 1.5-fold (54% for 20 mg and 52% for 40 mg) increases in simvastatin acid AUC and C_max, respectively [see Drug Interactions (7)].

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.

The safety and effectiveness of NEXLIZET have not been established in pediatric patients.

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.

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.

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.

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)]

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.

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.

No dosage adjustment is necessary in patients with mild hepatic impairment (Child-Pugh A) [see Clinical Pharmacology (12.3)]. NEXLIZET is not recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C) due to the unknown effects of the increased exposure to ezetimibe [see Clinical Pharmacology (12.3)].

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 contains bempedoic acid and ezetimibe. NEXLIZET reduces elevated LDL-C through inhibition of cholesterol synthesis in the liver and absorption in the intestine.

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)

• 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)

NEXLIZET is available as:

• Tablets: 180 mg/10 mg, blue, oval shaped, debossed with "818" on one side and "ESP" on the other side.

The following adverse reactions have been identified during post approval use of ezetimibe and/or bempedoic acid. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood Disorders: thrombocytopenia

Gastrointestinal Disorders: abdominal pain; pancreatitis; nausea

Hepatobiliary Disorders: elevations in liver transaminases, including elevations more than 5× ULN; hepatitis; cholelithiasis; cholecystitis

Immune System Disorders: Hypersensitivity reactions including: anaphylaxis, angioedema, wheezing, rash, and urticaria

Musculoskeletal Disorders: elevated creatine phosphokinase; myopathy/rhabdomyolysis

Nervous System Disorders: dizziness; paresthesia; depression; headache

Skin and Subcutaneous Tissue Disorders: erythema multiforme

• Pregnancy: Based on mechanism of action, may cause fetal harm. (8.1)

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.

Advise patients to read the FDA-approved patient labeling (Patient Information).

• 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.

Administer NEXLIZET either at least 2 hours before or at least 4 hours after administration of a bile acid sequestrant [see Drug Interactions (7)].

The efficacy of NEXLIZET was investigated in a single, multi-center, randomized, double-blind, placebo-controlled, parallel group trial that enrolled 301 patients with HeFH, established CVD, or multiple risk factors for CVD on maximally tolerated statin therapy.

Trial 1 (NCT03337308) was a 4-arm, 12-week trial that assessed the efficacy of NEXLIZET in 301 patients randomized 2:2:2:1 to receive either oral NEXLIZET (180 mg of bempedoic acid and 10 mg of ezetimibe) (n = 86), bempedoic acid 180 mg (n = 88), ezetimibe 10 mg (n = 86), or placebo (n = 41) once daily as add-on to maximally tolerated statin therapy. Patients were stratified by cardiovascular risk and baseline statin intensity. Patients on simvastatin 40 mg per day or higher and patients taking non-statin lipid-lowering therapy (including fibrates, niacin, bile acid sequestrants, ezetimibe, and PCSK9 inhibitors) were excluded from the trial.

NDC 72426-818-03

Rx only

NEXLIZET^®

(bempedoic acid

and ezetimibe) tablets

Contains

30 Tablets

180 mg/10 mg

Trial 4 (NCT02993406) was a randomized, double-blind, placebo-controlled, event-driven trial in 13,970 adult patients with established CVD (70%) or at high risk for a CVD event but without CVD (30%) who were not receiving recommended statin dosages. Patients with established CVD had documented history of coronary artery disease, symptomatic peripheral arterial disease, and/or cerebrovascular atherosclerotic disease. Patients without established CVD were considered at high risk for CVD based on meeting at least one of the following criteria:

•  
  (1) Diabetes mellitus (type 1 or type 2) in females over 65 years of age or males over 60 years of age;
  
  (2) A Reynolds Risk score > 30% or a SCORE Risk score > 7.5% over 10 years. Reynolds risk score and SCORE risk score evaluate a 10-year risk of having a cardiovascular (CV) event. The Reynolds risk score is based on the following risk factors: sex, age, smoking status, systolic blood pressure, total cholesterol, HDL cholesterol, high sensitivity C-reactive protein (hsCRP), and familial history of CVD events. LDL-C is an additional risk factor considered in SCORE risk score; or
  
  (3) A coronary artery calcium score >400 Agatston units at any time in the past.

Patients were randomized 1:1 to receive either oral bempedoic acid 180 mg per day (n = 6,992) or placebo (n = 6,978), alone or as an add on to other background lipid-lowering therapies. Background therapy could include less than low-intensity statin dosages. Overall, 95.3% of adult patients were followed until the end of the trial or death. The median follow-up duration was 3.4 years.