bempedoic acid (Rx)

1-10%

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%)

<1%

Tendon rupture (0.5%)

Contraindications

None

Cautions

Hyperuricemia

• 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

• 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

  • Coadministration increases simvastatin or pravastatin serum concentrations and 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

Pregnancy

Discontinue bempedoic acid when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus

No available data regarding use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Note: Statins are contraindicated in pregnant women

Clinical considerations

• Treatment of hyperlipidemia is not generally necessary during pregnancy
• Cholesterol and cholesterol derivatives are needed for normal fetal development

Animal studies

• Bempedoic acid was not teratogenic in rats and rabbits when administered at doses resulting in exposures up to 11 and 12 times, respectively, the human exposures at the maximum clinical dose, based on AUC

Lactation

Data are not available regarding drug presence in human or animal milk, effects on breastfed infants, or effects on milk production

Since bempedoic acid decreases cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, these actions may cause harm to the breastfed infant

Based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

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

Absorption

Peak plasma time: 3.5 hr

Peak plasma concentration

• Bempedoic acid: 20.6 mcg/mL
• Active metabolite, ESP15228: 2.8 mcg/mL

AUC

• Bempedoic acid: 289 mcgh/mL
• Active metabolite, ESP15228: 51.2 mcgh/mL

Distribution

Vd: 18 L

Protein bound

• Bempedoic acid: 99.3%
• Glucuronide metabolite: 99.8%
• Active metabolite, ESP15228: 99.2%

Metabolism

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

Elimination

Half-life: 21 hr

Excretion: 70% urine (primarily as the acyl glucuronide conjugate); 30% feces

Oral Administration

May take with or without food

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