Bempedoic
Indications
Bempedoic is used for:
Hypercholesterolemia
Adult Dose
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)
180 mg PO qDay in combination with maximally tolerated statin therapy
Hepatic impairment
Mild or moderate (Child-Pugh A or B): No dosage adjustment required
Severe (Child-Pugh C): Not studied
Child Dose
Renal Dose
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
Administration
May take with or without food
Contra Indications
Precautions
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
Pregnancy-Lactation
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
Interactions
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
Adverse Effects
Side effects of Bempedoic :
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%)
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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