Dosing & Uses
Dosage Forms & Strengths
bempedoic acid/ezetimibe
tablet
- 180mg/10mg
Hypercholesterolemia
Indicated as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of low-density lipoprotein cholesterol (LDL-C)
1 tablet (bempedoic acid 180 mg/ezetimibe 10 mg) PO qDay
Dosage Modifications
Renal impairment
Mild or moderate (eGFR ≥30 mL/min/1.73 m2): No dosage adjustment required
Severe (eGFR <30 mL/min/1.73 m2): Data are limited
End-stage renal disease with dialysis: Not studied
Hepatic impairment
Mild (Child-Pugh A): No dosage adjustment required
Moderate or severe (Child-Pugh B or C): Not recommended owing to unknown effects of increased ezetimibe exposure
Dosing Considerations
Limitations of use: Effect on cardiovascular morbidity and mortality not determined
Monitoring: After initiating, analyze lipid levels within 8-12 weeks
Safety and efficacy not established
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
>10%
Bempedoic acid plus statin
- Upper respiratory tract infection (4.5%)
- Muscle spasms (3.6%)
- Hyperuricemia (3.5%)
- Back pain (3.3%)
- Abdominal pain or discomfort (3.1%)
- Bronchitis (3%)
- Pain in extremity (3%)
- Anemia (2.8%)
- Elevated liver enzymes (2.1%)
- Gout (1.5%)
- Benign prostatic hyperplasia (1.3%)
- Atrial fibrillation (1.7%)
Ezetimibe
- Upper respiratory tract infection (4.3%)
- Diarrhea (4.1%)
- Arthralgia (3%)
- Sinusitis (2.8%)
- Pain in extremity (2.7%)
- Fatigue (2.4%)
- Influenza (2%)
<1%
Bempedoic acid
- Tendon rupture (0.5%)
Postmarketing Reports
Ezetimibe
- Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria
- Erythema multiforme
- Myalgia
- Elevated creatinine phosphokinase
- Myopathy/rhabdomyolysis
- Elevated liver transaminases
- Hepatitis
- Abdominal pain
- Thrombocytopenia
- Pancreatitis
- Nausea
- Dizziness
- Paresthesia
- Depression
- Headache
- Cholelithiasis
- Cholecystitis
Warnings
Contraindications
Known hypersensitivity to ezetimibe, including anaphylaxis, angioedema, rash, and urticaria
Cautions
Hyperuricemia
- Bempedoic acid inhibits renal tubular OAT2 and may increase blood uric acid levels
- Elevated uric acid levels usually occurred within the first 4 weeks of treatment initiation and persisted throughout treatment; elevated blood uric acid may lead to gout
Tendon rupture
- Bempedoic acid associated with increased risk of tendon rupture or injury
- Tendon rupture occurred within weeks to months of initiating
- May occur more frequently in patients aged ≥60 yr
- Discontinue immediately if tendon rupture occurs
- Consider discontinuing with joint pain, swelling, or inflammation
Drug interaction overview
-
Simvastatin or pravastatin
- Bempedoic acid increases simvastatin or pravastatin serum concentrations which, may increase simvastatin/pravastatin-related myopathy
- Avoid use with simvastatin doses >20 mg
- Avoid use with pravastatin doses >40 mg
- Atorvastatin and rosuvastatin: Elevations of 1.7-fold in AUC of atorvastatin, rosuvastatin, and/or their major metabolites were observed with bempedoic acid coadministration, suggesting a weak interaction; these elevations were generally within the individual statin exposures and do not affect dosing recommendations
-
Cyclosporine
- Coadministration of cyclosporine and ezetimibe increases both cyclosporine and ezetimibe concentrations
- If coadministered, monitor cyclosporine concentrations
-
Fibrates
- Both fenofibrate and ezetimibe may increase cholesterol excretion into the bile, leading to cholelithiasis
- Coadministration of ezetimibe with fibrates other than fenofibrate is not recommended
- If cholelithiasis suspected, gallbladder studies are indicated
- Consider alternant lipid-lowering therapies
-
Cholestyramine
- Coadministration of cholestyramine and ezetimibe decreases ezetimibe concentration, which may lead to reduced efficacy
- Administer ezetimibe-containing products at least 2 hr before or 4 hr after bile acid sequestrants
Pharmacology
Mechanism of Action
Bempedoic acid
- Adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers LDL-C by inhibiting 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, but absent in most peripheral tissues
Ezetimibe
- Blocks GI cholesterol absorption via NPC1L1 (Niemann-Pick C1-Like 1) inhibition, reducing cholesterol deliver to the liver
- This action reduces hepatic cholesterol stores and increases LDL receptors, resulting in clearance of cholesterol from the blood
- NPC1L1 is a sterol transporter that mediates intestinal cholesterol absorption
Absorption
Peak plasma time
- Bempedoic acid: 3 hr
- Ezetimibe: 1 hr
- Ezetimibe glucuronide: 5 hr
Peak plasma concentration
- Bempedoic acid: 12.6 mcg/mL
- Active metabolite, ESP15228: 2.8 mcg/mL
- Ezetimibe: 3.56 ng/mL
- Ezetimibe glucuronide: 107 ng/mL
AUC
- Bempedoic acid: 202 mcgh/mL
- Active metabolite, ESP15228: 51.2 mcgh/mL
Distribution
Vd
- Bempedoic acid: 18 L
Protein bound
- Bempedoic acid: 99.3%
- Bempedoic acid glucuronide metabolite: 99.8%
- Active metabolite, ESP15228: 99.2%
- Ezetimibe: >90%
Metabolism
Bempedoic acid
- Primarily through metabolism of the acyl glucuronide
- Also reversibly converted to an active metabolite (ESP15228) based on aldo-keto reductase activity observed in vitro from human liver
Ezetimibe
- Primarily metabolized in small intestine and liver via glucuronide conjugation with subsequent biliary and renal excretion
- Rapidly metabolized to ezetimibe-glucuronide
Elimination
Half-life
- Bempedoic acid: 21 hr
- Ezetimibe and ezetimibe glucuronide: ~22 hr
Excretion
- Bempedoic acid: 70% urine (primarily as the acyl glucuronide conjugate); 30% feces
- Ezetimibe and ezetimibe glucuronide: 11% urine; 78% feces; ezetimibe was the major component in feces (69%), while ezetimibe-glucuronide was the major component in urine (9%)
Administration
Oral Administration
May take with or without food
Swallow tablet whole
Storage
Store at 68-77ºF (20-25ºC); excursions permitted to 59-86ºF (15-30ºC)
Store and dispense in the original package
Do not discard desiccant
Images
Patient Handout
Formulary
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