Nexletol

Nexletol Uses, Dosage, Side Effects, Food Interaction and all others data.

High levels of LDL cholesterol (LDL-C) are a major risk factor for cardiovascular events. Caused by genetic mutations or lifestyle factors, hypercholesterolemia can significantly reduce quality of life and increase the risk of mortality from cardiovascular disease. About 1 in 4 patients, or 15 million Americans with elevated LDL-C, are insufficiently managed with maximally tolerated statin therapy alone, requiring additional treatment for hypercholesterolemia.

Nexletol is first-in-class adenosine triphosphate-citrate lyase (ACL) inhibitor used once a day for reducing LDL cholesterol levels in statin-refractory patients. It was developed by Esperion Therapeutics Inc. and approved by the FDA on February 21, 2020. A combination product of bempedoic acid and ezetimibe was approved on February 26, 2020 for increased control of LDL cholesterol levels in patients experiencing refractory elevations despite previous statin treatment.

Nexletol inhibits the synthesis of cholesterol in the liver, reducing LDL-C levels. This reduces the development of atherosclerotic plaques that may increase the risk of cardiovascular events. Earlier clinical trials studying the effects of bempedoic acid showed a dose‐dependent reduction of LDL‐C levels in addition to decreased LDL particle number, and reduced levels of apolipoprotein B, non–HDL cholesterol, and high‐sensitivity C‐reactive protein.

Nexletol
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Nexletol
Generic	Bempedoic acid
Bempedoic acid Other Names	Bempedoic acid
Weight	180mg,
Type	Oral tablet
Formula	C₁₉H₃₆O₅
Weight	Average: 344.492 Monoisotopic: 344.256274259
Protein binding	The plasma protein binding of bempedoic acid and its metabolites is about 99%.
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country	United States,
Last Updated:	September 19, 2023 at 7:00 am

Uses

Nexletol is a drug used in conjunction with lifestyle modification and/or other agents for the treatment of refractory hypercholesterolemia.

Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia or existing atherosclerotic cardiovascular disease that warrants additional lowering of LDL-C.

The combination of bempedoic and ezetimibe is also indicated with diet management and maximally tolerated statin therapy to treat elevated LDL-C levels in adults with heterozygous familial hypercholesterolemia or existing atherosclerotic cardiovascular disease who require further lowering of LDL-C.

Nexletol is also used to associated treatment for these conditions: Atherosclerotic Cardiovascular Diseases, Heterozygous Familial Hypercholesterolemia

How Nexletol works

Normally, LDL cholesterol is produced in the liver and circulates in the blood. When the blood becomes saturated, excess LDL deposits in blood vessels including the coronary arteries, increasing the risk of cardiovascular events.

Nexletol is a prodrug that requires activation in the liver. The very-long-chain acyl-CoA synthetase-1 (ACSVL1) enzyme is responsible for its activation to ETC-1002-CoA, the pharmacologically active metabolite. ATP lyase (also known as ATP synthase) plays an important part of cholesterol synthesis. BETC-1002-CoA directly inhibits this enzyme after the parent drug is activated in the liver by coenzyme A (CoA).

This inhibition leads to upregulation of the LDL cholesterol receptor, reducing serum LDL-C via increased uptake and LDL clearance in the liver. By the above mechanisms, bempedoic acid causes a total decrease of circulating LDL-C that normally damages blood vessels and leads to atherosclerosis. Lastly, ETC-1002 activates AMP-activated protein kinase (AMPK) in rodents, which inhibits the synthesis of cholesterol via the inhibition of HMG-CoA reductase. The relevance of this to humans is unknown.

Toxicity

LD50 information for bempedoic acid is not readily available in the literature. In the case of an overdose with bempedoic acid, contact the local poison control center. To this date, there is no experience with bempedoic acid overdoses. Employ general supportive measures.

Food Interaction

Take with or without food.

Volume of Distribution

The apparent volume of distribution of bempedoic acid is about 18L.

Elimination Route

Nexletol is rapidly absorbed in the small intestine. The Tmax of the 180mg tablet is estimated at 3.5 hours.

Half Life

The half-life of bempedoic acid ranges between 15 and 24 hours. Prescribing information indicates a clearance of 21 hours +/- 11 hours.

Clearance

The clearance (CL/F) of bempedoic acid at steady state was estimated at 11.2 mL/min during clinical trials.

Elimination Route

Nexletol's conjugates are primarily eliminated via the urine (70%) and the feces (30%). A total of 5% of the unchanged drug is excreted in the urine and feces, combined.