Bempedoic Acid

Products

Bempedoic acid was approved in the EU, the United States, and many countries in 2020 in the form of film-coated tablets (Nilemdo). The active ingredient is also combined fixed with ezetimibe (Nustendi film-coated tablets).

Structure and properties

Bempedoic acid (C19H36O5, Mr = 344.5 g/mol) exists as a white crystalline powder that is practically insoluble in water. It is a hydroxylated, long-chain dicarboxylic acid and a fatty acid derivative. Bempedoic acid is a prodrug that requires CoA activation by the enzyme ACSVL1 to ETC-1002-CoA.

Effects

Bempedoic acid (ATC C10AX15) has lipid-lowering properties. The effects are due to inhibition of the enzyme ATP citrate lyase (ACL), which is important for the synthesis of cholesterol. This enzyme is upstream of HMG-CoA reductase, the drug target of statins. Inhibition results in inhibition of cholesterol synthesis. Bempedoic acid reduces LDL-C, non-HDL-C, apo B, and total cholesterol. Furthermore, it decreases fatty acid synthesis in the liver.

Indications

For the treatment of adults with primary hypercholesterolemia (heterozygous familial and nonfamilial) or mixed dyslipidemia. Official indication in many countries: In addition to diet and in combination with a statin, at the maximum tolerated dose, with or without other lipid-lowering therapies for treatment in adults with clinically manifest atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who require additional LDL-C lowering.

Dosage

According to the SmPC. Tablets are taken once daily, independent of meals.

Contraindications

  • Hypersensitivity
  • Pregnancy
  • Lactation
  • Concurrent use with simvastatin at a daily dose of > 40 mg.

For complete precautions, see the drug label.

Interactions

Neither bempedoic acid nor its metabolites interact with CYP450. The drug is a weak inhibitor of OATP1B1 and OATP1B3 and an inhibitor of OAT2. Drug-drug interactions have been described with statins and others.

Adverse effects

The most common potential adverse effects include hyperuricemia (gout), pain in an extremity, and anemia.