Bempedoic acid was developed to help lower cholesterol in patients who cannot tolerate statins. Approved by the FDA in 2020, it works by inhibiting an enzyme in the liver involved in cholesterol production, reducing LDL cholesterol. The drug is taken orally and can be used alone or with other cholesterol-lowering medications to help prevent heart attacks and strokes.
BRAND NAMES
Nexletol – oral tablet for lowering LDL cholesterol
Nexlizet – oral tablet combining bempedoic acid with ezetimibe
MECHANISM OF ACTION
Bempedoic acid lowers LDL cholesterol by inhibiting the liver enzyme ATP citrate lyase, which is involved in cholesterol production. This reduces the liver’s cholesterol synthesis, helping to prevent cardiovascular events, while avoiding muscle-related side effects common with statins.
PHARMACOKINETICS
Absorption
Bempedoic acid is well absorbed orally, with peak blood levels occurring about 3–5 hours after ingestion. Its absorption is not significantly affected by food, so it can be taken with or without meals.
Distribution
Bempedoic acid is highly protein-bound in the blood (about 99%), which limits its free circulation. It is primarily distributed in the plasma and liver, the main site of its action, with minimal penetration into other tissues.
Metabolism
Bempedoic acid is primarily metabolized in the liver through glucuronidation by the enzyme UGT2B7, forming inactive metabolites. It is not significantly metabolized by the cytochrome P450 system, which reduces the potential for drug–drug interactions.
Excretion
Bempedoic acid is mainly excreted in the urine as glucuronide metabolites, with a smaller portion eliminated in the feces. Its half-life is approximately 21 hours, allowing for once-daily oral dosing.
PHARMACODYNAMICS
Bempedoic acid lowers LDL cholesterol by blocking ATP citrate lyase in the liver, which reduces cholesterol production and increases LDL clearance from the blood, helping to prevent cardiovascular events
ADMINISTRATION
Bempedoic acid is administered orally as a once-daily tablet, with or without food.
DOSAGE AND STRENGTH
Bempedoic acid is available as 180 mg oral tablets, typically taken once daily. The dose may be used alone or in combination with other lipid-lowering agents, depending on the patient’s LDL cholesterol levels and treatment goals.
FOOD INTERACTIONS
Bempedoic acid can be taken with or without food, as its absorption is not significantly affected by meals. There are no major food interactions reported, making it convenient for daily use.
DRUG INTERACTIONS
Statins – May slightly increase the risk of tendon or muscle-related side effects when combined with certain statins, especially simvastatin ≥40 mg.
Cholesterol-lowering drugs – Can be safely combined with ezetimibe for additive LDL-C reduction.
UGT2B7 substrates – Bempedoic acid is metabolized via UGT2B7, so drugs relying heavily on this pathway may have minor interactions.
CONTRAINDICATIONS
Known hypersensitivity to bempedoic acid or any component of the tablet.
Active liver disease or unexplained persistent elevations of liver enzymes (ALT/AST).
Pregnancy and breastfeeding unless clearly needed, as safety has not been established.
SIDE EFFECTS
Muscle-related symptoms (pain, spasms, rarely tendon rupture)
Elevated liver enzymes
Gout or increased uric acid levels
Mild gastrointestinal symptoms (constipation, abdominal pain)
Upper respiratory tract infections
TOXICITY
Bempedoic acid is generally well tolerated, with low toxicity. Overdose may cause elevated liver enzymes, muscle symptoms, or increased uric acid, but serious toxicity is rare, and management is mainly supportive.
