Bempedoic acid is a new drug approved to treat high cholesterol. It works by inhibiting cholesterol production in the liver. Common side effects include muscle spasms and back or joint pain. It can also increase the risk of tendon rupture. Bempedoic acid increases levels of some statins like simvastatin and pravastatin, so doses of those statins may need to be lowered. It is removed from the body through urine and feces after being converted to inactive metabolites.

1. Bempedoic Acid

2. Indication
• In the US, bempedoic acid is indicated for the treatment of hypercholesterolemia in combination
with diet and the highest tolerated statin therapy in adults with heterozygous familial
hypercholesterolemia, or with established atherosclerotic cardiovascular disease, who need
additional lowering of LDL cholesterol.
• In the EU, bempedoic acid is indicated in adults with primary hypercholesterolaemia
(heterozygous familial and non familial) or mixed dyslipidaemia, as an adjunct to diet in
combination with a statin or statin with other lipid-lowering therapies in patients unable to
reach LDL C goals with the maximum tolerated dose of a statin; or alone or in combination with
other lipid-lowering therapies in patients who are statin intolerant, or for whom a statin is
contraindicated.

3. Side Effects
• Common adverse effects in clinical trials were muscle spasms (3.6% of treated patients, as
compared to 2.3% under placebo), pain in the back (3.3% versus 2.2%) or in a limb (3.0% versus
1.7%), gout (1.5% versus 0.4%), and gastrointestinal problems such as diarrhea.
• A less common but more serious adverse effect was tendon rupture in the rotator cuff of the
shoulder, the biceps tendon or the Achilles tendon (0.5% versus 0.0%).

4. Interactions
• Bempedoic acid does not interact with the cytochrome P450 enzyme system in the liver and only
weakly inhibits the transporter proteins SLCO1B1, SLCO1B3 and SLC22A7 (the latter possibly
being responsible for the increase of uric acid in the blood, and therefore the adverse effect
gout).
• Despite this, the drug increases blood levels of statins.
• The effect is most pronounced with simvastatin and pravastatin, whose AUC is increased about
twofold. No other clinically relevant interactions have been found in studies.

5. Mechanism of action
• Bempedoyl-CoA, the active metabolite. Coenzyme A is shown in blue.
• Bempedoic acid is a prodrug. It is activated to the thioester with coenzyme A by the enzyme
SLC27A2 in the liver.
• The activated substance inhibits ATP citrate lyase, which is involved in the liver's biosynthesis of
cholesterol upstream of HMG-CoA reductase, the enzyme that is blocked by statins.
• The substance also activates AMP-activated protein kinase, but this effect is likely not relevant in
humans.

7. Pharmacokinetics
• ESP15228, the (also) active metabolite
• Following oral intake, bempedoic acid reaches highest blood plasma concentrations after 3.5
hours.
• Food does not affect its absorption. When in the bloodstream, 99.3% of the substance are
bound to plasma proteins.
• About a fifth of the substance is reversibly converted by an aldo-keto reductase enzyme to a
metabolite (called ESP15228) that is also pharmacologically active in form of its coenzyme A–
thioester.
• Of ESP15228, 99.2% are bound to plasma proteins.
• Both bempedoic acid and the metabolite are inactivated by glucuronidation of their carboxylic
acid groups.
• Bempedoic acid has a biological half-life of 21±11 hours.Over 95% of the substance are excreted
in form of metabolites; about 70% with the urine and 30% with the feces.

8. Label DeatilsFDA
• ----------------------------INDICATIONS AND USAGE--------------------------
• NEXLIZET, which contains an adenosine triphosphate-citrate lyase (ACL) inhibitor and a cholesterol
absorption inhibitor, is indicated as an adjunct to diet and maximally tolerated statin therapy for
the treatment of adults with heterozygous familial hypercholesterolemia or established
atherosclerotic cardiovascular disease who require additional lowering of LDL-C.
• -----------------------DOSAGE AND ADMINISTRATION----------------------
• Administer one tablet (180 mg bempedoic acid and 10 mg ezetimibe)
• orally once daily with or without food. (2.1)
• Swallow the tablet whole. (2.1)
• Coadministration with Bile Acid Sequestrants: Administer at least
• 2 hours before or at least 4 hours after bile acid sequestrants. (2.2, 7)

9. • -----------------------DOSAGE AND ADMINISTRATION----------------------
• Administer one tablet (180 mg bempedoic acid and 10 mg ezetimibe)
• orally once daily with or without food. (2.1)
• Swallow the tablet whole. (2.1)
• Coadministration with Bile Acid Sequestrants: Administer at least
• 2 hours before or at least 4 hours after bile acid sequestrants. (2.2, 7)
---------------------DOSAGE FORMS AND STRENGTHS---------------------
Tablets: 180 mg bempedoic acid/10 mg ezetimibe (3)
--------------------------------CONTRAINDICATIONS----------------------------
• Known hypersensitivity to ezetimibe tablets. (4, 6.2)

10. -----------------------WARNINGS AND PRECAUTIONS-----------------------
• Hyperuricemia: Elevations in serum uric acid have occurred. Assess uric acid levels periodically as
clinically indicated. Monitor for signs and symptoms of hyperuricemia, and initiate treatment with
urate_x0002_lowering drugs as appropriate. (5.1)
• Tendon Rupture: Tendon rupture has occurred. Discontinue NEXLIZET at the first sign of tendon rupture.
Avoid NEXLIZET in patients who have a history of tendon disorders or tendon rupture. (5.2)
--------------------------------ADVERSE REACTIONS----------------------------
• Most common (incidence ≥2% and greater than placebo) adverse reactions are upper respiratory tract
infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in
extremity, anemia, elevated liver enzymes, diarrhea, arthralgia, sinusitis, fatigue, and influenza. (6.1)

11. ------------------------------DRUG INTERACTIONS------------------------------
• Simvastatin: Avoid concomitant use of NEXLIZET with simvastatin great than 20 mg. (7)
• Pravastatin: Avoid concomitant use of NEXLIZET with pravastatin greater than 40 mg. (7)
• Cyclosporine: Monitor cyclosporine concentrations. (7)
• Fibrates: If cholelithiasis is suspected in a patient receiving NEXLIZET and fenofibrate, consider alternative
lipid-lowering therapy. (6.2, 7)
----------------------USE IN SPECIFIC POPULATIONS------------------------
• Pregnancy: Based on mechanism of action, may cause fetal harm. (8.1)
• Lactation: Breastfeeding is not recommended with NEXLIZET. (8.2)
IMS Data not avaliable have to check the lastest data of Q1.