Skip to Content

Bempedoic Acid

Class: Antilipemic Agents, Miscellaneous
- Adenosine Triphosphate-citrate Lyase (ACL) Inhibitors
Chemical Name: 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
Molecular Formula: C19H36O5
CAS Number: 738606-46-7
Brands: Nexletol

Medically reviewed by Drugs.com on May 10, 2021. Written by ASHP.

Introduction

Bempedoic acid, an adenosine triphosphate-citrate lyase (ACL) inhibitor, is an antilipemic agent.

Uses for Bempedoic Acid

Dyslipidemias

Used alone or in combination with ezetimibe as an adjunct to diet and maximally tolerated hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (i.e., statin) therapy in patients with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease (ASCVD) who require additional reduction in low-density lipoprotein (LDL)-cholesterol concentrations.

When added to maximally tolerated statin therapy, further reduces LDL-cholesterol concentrations by approximately 17% or 38% (if used in addition to ezetimibe); however, effects on cardiovascular morbidity and mortality not established.

AHA/ACC cholesterol management guidelines state that lifestyle modification is the foundation of ASCVD risk reduction. If pharmacologic therapy is needed, statins are first-line drugs of choice because of their demonstrated benefits in reducing risk of ASCVD. The addition of a nonstatin drug may be considered in certain high-risk patients who require further reduction in LDL-cholesterol concentrations.

Bempedoic Acid Dosage and Administration

General

  • Periodically reinforce adherence to lifestyle modifications. Antilipemic therapy is an adjunct to, not a substitute for, lifestyle modifications that reduce the risk of ASCVD.

  • Monitor serum LDL-cholesterol concentrations within 8–12 weeks of initiating therapy.

Administration

Oral Administration

Administer orally without regard to meals.

Administer bempedoic acid/ezetimibe fixed-combination tablets whole; do not cut, crush, or chew.

Dosage

Adults

Dyslipidemias
Bempedoic Acid Therapy
Oral

180 mg once daily as an adjunct to maximally tolerated statin therapy. Do not use concomitantly with simvastatin dosages >20 mg daily or with pravastatin dosages >40 mg daily. (See Interactions.)

Bempedoic Acid/Ezetimibe Fixed Combination
Oral

Bempedoic acid 180 mg/ezetimibe 10 mg once daily as an adjunct to maximally tolerated statin therapy. Do not use concomitantly with simvastatin dosages >20 mg daily or with pravastatin dosages >40 mg daily. (See Interactions.)

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe hepatic impairment (Child-Pugh class C): Not studied.

Renal Impairment

Mild or moderate renal impairment: No dosage adjustment necessary.

Severe renal impairment (eGFR <30 mL/minute per 1.73 m2): Data lacking.

End-stage renal disease undergoing dialysis: Not studied.

Geriatric Patients

No specific dosage recommendations.

Cautions for Bempedoic Acid

Contraindications

  • No known contraindications.

Warnings/Precautions

Hyperuricemia

Inhibits renal tubular organic anion transporter (OAT) 2 and may increase blood uric acid concentrations. Hyperuricemia and gout reported. Increases in uric acid concentrations generally occurred within 4 weeks after initiating therapy and persisted throughout therapy.

Assess serum uric acid concentrations as clinically indicated during therapy. Monitor patients for signs and symptoms of hyperuricemia and initiate urate-lowering therapy as appropriate.

Tendon Rupture

Bempedoic acid is associated with an increased risk of tendon rupture involving the rotator cuff (shoulder), biceps, or Achilles tendon. Reported within weeks to months after initiating therapy. Risk may be increased with older age (usually >60 years), concomitant use of corticosteroids or fluoroquinolone drugs, renal failure, and history of tendon disorders.

Discontinue bempedoic acid immediately if tendon rupture occurs. Consider discontinuance of therapy in patients who develop joint pain, swelling, or inflammation. Advise patients to rest at first sign of tendinitis or tendon rupture and to contact a clinician if symptoms of tendinitis or tendon rupture occur.

Avoid use in patients with a history of tendon disorders or tendon rupture; consider alternative therapy.

Combination Therapy

When bempedoic acid is used in combination with other drugs (e.g., statins, ezetimibe), consider the usual cautions, precautions, and contraindications associated with the other drug.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm based on mechanism of action. No data available on use in pregnant women. Teratogenicity not demonstrated in animal reproduction studies; however, bempedoic acid decreases cholesterol synthesis and also may decrease synthesis of other biologically active cholesterol-derived substances.

Specific Populations

Pregnancy

May cause fetal harm. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

If pregnancy occurs, discontinue drug unless benefits outweigh potential risks to fetus. Treatment of hyperlipidemia generally not necessary during pregnancy; atherosclerosis is a chronic process, and discontinuance of antilipemic drugs during pregnancy should have little impact on long-term outcomes.

Lactation

Not known whether bempedoic acid is distributed into human milk. Effects of drug on breast-fed infants and human milk production also unknown. Breast-feeding not recommended during treatment.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No overall differences in efficacy or safety relative to younger adults; however, possibility of increased sensitivity cannot be ruled out.

Hepatic Impairment

Decreased exposure in patients with mild or moderate hepatic impairment (Child-Pugh class A or B). (See Special Populations under Pharmacokinetics.) Not studied in patients with severe hepatic impairment (Child-Pugh class C).

Renal Impairment

Increased exposure in patients with mild, moderate, and severe renal impairment. (See Special Populations under Pharmacokinetics.)

Data are lacking in patients with severe renal impairment (eGFR <30 mL/minute per 1.73 m2). Not studied in patients with end-stage renal disease undergoing dialysis.

Common Adverse Effects

Bempedoic acid: Upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, extremity pain, anemia, increased hepatic enzymes.

Bempedoic acid in fixed combination with ezetimibe: Upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, extremity pain, anemia, increased hepatic enzymes, diarrhea, arthralgia, sinusitis, fatigue, influenza.

Interactions for Bempedoic Acid

Bempedoic acid, its active metabolite, and its glucuronide conjugates are not substrates, inhibitors, or inducers of CYP isoenzymes.

Bempedoic acid, its active metabolite, and its glucuronide conjugates are not substrates of commonly characterized drug transporters; exception is bempedoic acid glucuronide, which is an organic anion transporter (OAT) 3 substrate. Bempedoic acid is a weak inhibitor of OAT2. Bempedoic acid is a weak inhibitor of OAT3 at concentrations exceeding clinically relevant concentrations. Bempedoic acid and its glucuronide conjugate are weak inhibitors of organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 at clinically relevant concentrations.

The following drug interactions are based on studies using bempedoic acid. When bempedoic acid is used in fixed combination with ezetimibe, consider interactions associated with both drugs.

Specific Drugs

Drug

Interaction

Comments

Ezetimibe

Increases in exposure and peak plasma concentrations of ezetimibe by <20% observed

Not considered clinically important; dosing recommendations not affected

HMG-CoA reductase inhibitors (statins)

Pravastatin: Substantial increases in pravastatin acid peak plasma concentrations and exposure; may increase risk of statin-related myopathy

Simvastatin: Substantial increases in simvastatin acid peak plasma concentrations and exposure; may increase risk of statin-related myopathy

Atorvastatin, rosuvastatin: Increased exposure to the statin and/or major metabolites observed, but to a lesser extent than simvastatin and pravastatin

Pravastatin: Avoid concomitant use with pravastatin dosages >40 mg daily

Simvastatin: Avoid concomitant use with simvastatin dosages >20 mg daily

Atorvastatin, rosuvastatin: Interaction not considered clinically important and no dosage adjustments necessary

Hormonal contraceptives

No effect on pharmacokinetics of an oral contraceptive (containing ethinyl estradiol and norethindrone)

Metformin

No effect on pharmacokinetics of metformin

Probenecid

Increased peak plasma concentrations and AUC of bempedoic acid and its active metabolite

Not considered clinically important; dosing recommendations not affected

Warfarin

Not expected to affect pharmacokinetics of warfarin

Bempedoic Acid Pharmacokinetics

Pharmacokinetics do not appear to be affected by age, gender, race, or weight.

Absorption

Bioavailability

Pharmacokinetics generally linear over dose range of >60 mg to 220 mg; no time-dependent changes observed following repeated administration at recommended dosage.

Median time to peak plasma concentrations is 3.5 hours.

Steady-state concentrations achieved after 7 days with approximately 2.3-fold mean accumulation.

Onset

Maximum LDL-cholesterol reductions occurred at 4 weeks.

Food

Administration with food has no effect on oral bioavailability.

Special Populations

Mild hepatic impairment (Child-Pugh class A): Peak plasma concentrations and AUC of bempedoic acid were 11 and 22% lower, respectively; peak plasma concentrations and AUC of the active metabolite (ESP15228) were 13 and 23% lower, respectively.

Moderate hepatic impairment (Child-Pugh class B): Peak plasma concentrations and AUC of bempedoic acid were 14 and 16% lower, respectively; peak plasma concentrations and AUC of the active metabolite (ESP15228) were 24 and 36% lower, respectively.

Mild renal impairment: AUC of bempedoic acid was approximately 1.4–1.5 times higher.

Moderate renal impairment: AUC of bempedoic acid was approximately 1.9–2.3 times higher.

Severe renal impairment: AUC of bempedoic acid was 2.4 times higher.

Distribution

Extent

Not known whether bempedoic acid is distributed into milk.

Plasma Protein Binding

Highly bound (>99%) to plasma proteins.

Elimination

Metabolism

Primary route of elimination is through metabolism of acyl glucuronide.

Elimination Route

Renal clearance of unchanged bempedoic acid accounts for <2% of total clearance.

Following oral administration of a single 240-mg dose, approximately 70% of total dose (parent drug and metabolites) recovered in urine (principally as the acyl glucuronide conjugate) and approximately 30% recovered in feces; <5% of dose excreted as unchanged drug in urine and feces combined.

Half-life

Mean elimination half-life is 21 hours.

Stability

Storage

Oral

Tablets

20–25ºC (may be exposed to 15–30ºC). Store and dispense in original container. Do not discard desiccant.

Bempedoic acid/ezetimibe fixed-combination preparation: 20–25ºC (may be exposed to 15–30ºC). Store and dispense in original container. Protect from extreme heat and humidity. Do not discard desiccant.

Actions

  • Antilipemic agent with a distinct mechanism of action. A prodrug that requires activation by very long-chain acyl-CoA synthetase 1 (ACSVL1) in the liver.

  • The active form of bempedoic acid inhibits ACL, a key enzyme in the cholesterol biosynthesis pathway that acts upstream of HMG-CoA reductase.

  • Inhibition of ACL reduces hepatic cholesterol synthesis, which leads to upregulation of LDL-cholesterol receptors and increased clearance of circulating LDL cholesterol.

  • Selectively activated in the liver and not in skeletal muscle, potentially avoiding myotoxicity associated with statin therapy.

Advice to Patients

  • Importance of advising patients to read the manufacturer’s patient information.

  • Risk of hyperuricemia, including the development of gout. Importance of informing patients that serum uric acid concentrations may require monitoring during therapy with bempedoic acid. Importance of informing clinician if signs or symptoms associated with hyperuricemia occur.

  • Risk of tendinitis or tendon rupture. Advise patients to rest at the first sign of tendinitis or tendon rupture and to immediately contact their clinician if any symptoms of tendinitis or tendon rupture occur.

  • Risk of myopathy with concomitant simvastatin or pravastatin therapy. Advise patients to notify their clinician if they are taking or plan to take simvastatin or pravastatin.

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

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

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

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Bempedoic Acid

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

180 mg

Nexletol

Esperion

Bempedoic Acid Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

180 mg with Ezetimibe 10 mg

Nexlizet

Esperion

AHFS DI Essentials™. © Copyright 2021, Selected Revisions May 10, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

Show article references