Bempedoic Acid

Bempedoic acid is a first-in-class oral lipid-lowering agent that inhibits ATP-citrate lyase (ACL), an enzyme upstream of HMG-CoA reductase in the cholesterol biosynthesis pathway. Bempedoic acid is a prodrug that is converted in hepatocytes by very-long-chain acyl-CoA synthetase-1 (ACSVL1) to its active coenzyme-A derivative (bempedoyl-CoA). Inhibition of ACL reduces hepatic cholesterol synthesis and upregulates LDL receptor expression, lowering LDL-C in the blood.

Bempedoic acid is an effective option for statin-intolerant patients, reducing LDL-C by approximately 25-30% in clinical trials. It can be used as monotherapy or in combination with ezetimibe.

• Heterozygous familial hypercholesterolemia
• Atherosclerotic cardiovascular disease
• Patients requiring additional LDL-C lowering despite maximally tolerated statin therapy

Bempedoic acid is a first-in-class ATP-citrate lyase (ACL) inhibitor. It works by inhibiting ACL, an enzyme upstream of HMG-CoA reductase in the cholesterol biosynthesis pathway. Bempedoic acid is a prodrug that is converted in hepatocytes by very-long-chain acyl-CoA synthetase-1 (ACSVL1) to its active coenzyme-A derivative (bempedoyl-CoA).

Inhibition of ACL reduces hepatic cholesterol synthesis and upregulates LDL receptor expression, leading to enhanced LDL-C clearance. Unlike statins, it is not activated in muscle tissue, resulting in a lower risk of myalgia and muscle damage.

Bempedoic acid inhibits ACL enzyme in the liver, reducing cholesterol synthesis and increasing LDL receptor numbers, which accelerates the removal of LDL-C from the blood. By targeting an enzyme upstream of HMG-CoA reductase, it provides an important alternative for statin-intolerant patients.

Recommended Dose: 180 mg orally once daily.

May be taken with or without food. Should be used in combination with maximally tolerated statin therapy. Lipid profile should be checked within 8-12 weeks of treatment initiation.

With Simvastatin: Avoid concomitant use with simvastatin greater than 20 mg.

With Pravastatin: Avoid concomitant use with pravastatin greater than 40 mg.

Take 180 mg once daily with or without food. Swallow the tablet whole; do not chew or crush. If used with bile acid sequestrants, take 2 hours before or 4 hours after.

If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not double the dose.

• Upper respiratory tract infection (4.5%)
• Muscle spasms (3.6%)
• Hyperuricemia/increased blood uric acid (3.5%)
• Back pain (3.3%)
• Abdominal pain or discomfort (3.1%)
• Bronchitis (3.0%)
• Pain in extremity (3.0%)
• Anemia (2.8%)
• Elevated liver enzymes (2.1%)

Serious (rare): Allergic reactions (rash, flushing, hives, itching, swelling of eyes/face/lips/tongue/throat), tendon rupture.

• Hyperuricemia: Bempedoic acid may increase serum uric acid levels. Inform your doctor if you have a history of gout or experience symptoms of uric acid elevation. Monitor uric acid levels periodically.
• Tendon Rupture: Tendon rupture has been reported. Discontinue at the first sign of tendon pain, swelling, or inflammation. Avoid use in patients with a history of tendon disorders or tendon rupture.
• Discontinue when pregnancy is recognized unless benefits outweigh risks.
• Not recommended during breastfeeding.

• Serious hypersensitivity to bempedoic acid or any excipient
• Pregnancy
• Breastfeeding
• Concomitant use with simvastatin >20 mg
• Concomitant use with pravastatin >40 mg

• Simvastatin: Bempedoic acid increases plasma concentrations of simvastatin; avoid co-administration with doses >20 mg.
• Pravastatin: Bempedoic acid increases plasma concentrations of pravastatin; avoid co-administration with doses >40 mg.
• Bile acid sequestrants: May reduce absorption; take 2 hours before or 4 hours after.

Can be taken with or without food.

[CONSULT YOUR DOCTOR] There are no adequate data on bempedoic acid use in pregnant women. Discontinue when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

[CONSULT YOUR DOCTOR] There is no information regarding the presence of bempedoic acid in human or animal milk. Breastfeeding is not recommended during treatment with bempedoic acid.

Safety and efficacy in pediatric patients have not been established.

No dose adjustment needed for elderly patients. However, the risk of tendon rupture is higher in patients over 60 years of age.

Caution in severe renal impairment. Monitor uric acid levels.

Caution in hepatic impairment. Monitor liver enzymes.

No specific antidote for overdose. Provide symptomatic and supportive treatment.

Store below 30°C, away from light and moisture. Keep out of reach of children.

Bempedoic acid (C₁₉H₃₆O₅)