Bempedoic Acid

FDA Drug Information • Also known as: Nexletol

Brand Names: Nexletol
Dosage Form: TABLET, FILM COATED
Product Type: DRUG FOR FURTHER PROCESSING

Description

11 DESCRIPTION NEXLETOL tablets, for oral use, contain bempedoic acid, an adenosine triphosphate-citrate lyase (ACL) inhibitor. The chemical name for bempedoic acid is 8-hydroxy-2,2,14,14-tetramethyl-pentadecanedioic acid. The molecular formula is C 19 H 36 O 5 , and the molecular weight is 344.5 grams per mole. Bempedoic acid is a white to off-white crystalline powder that is highly soluble in ethanol, isopropanol and pH 8 phosphate buffer, and insoluble in water and aqueous solutions below pH 5. Structural formula: Each film-coated tablet of NEXLETOL contains 180 mg of bempedoic acid and the following inactive ingredients: colloidal silicon dioxide, hydroxyl propyl cellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The film coating comprises of partially hydrolyzed polyvinyl alcohol, polyethylene glycol, talc, and titanium dioxide. Chemical Structure

What Is Bempedoic Acid Used For?

1 INDICATIONS AND USAGE NEXLETOL is indicated: to reduce the risk of major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, or coronary revascularization) in adults at increased risk for these events who are unable to take recommended statin therapy (including those not taking a statin). as an adjunct to diet and exercise, in combination with other low-density lipoprotein cholesterol (LDL-C) lowering therapies, or alone when concomitant LDL-C lowering therapy is not possible, to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). NEXLETOL, an adenosine triphosphate-citrate lyase (ACL) inhibitor, is indicated: to reduce the risk of major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, or coronary revascularization) in adults at increased risk for these events who are unable to take recommended statin therapy (including those not taking a statin). ( 1 ) as an adjunct to diet and exercise, in combination with other low-density lipoprotein cholesterol (LDL-C) lowering therapies, or alone when concomitant LDL-C lowering therapy is not possible, to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Administer 180 mg orally once daily with or without food. ( 2.1 ) 2.1 Recommended Dosage The recommended dosage of NEXLETOL is 180 mg administered orally once daily. NEXLETOL can be taken with or without food. After initiation of NEXLETOL, analyze lipid levels within 8 to 12 weeks.

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hyperuricemia [see Warnings and Precautions (5.1) ] Tendon Rupture [see Warnings and Precautions (5.2) ] Common adverse reactions in the ( 6.1 ): Primary hypercholesterolemia trials (incidence ≥ 2% and more frequent than placebo) were upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, and elevated liver enzymes. Cardiovascular outcomes trial (incidence ≥ 2% and 0.5% greater than placebo) were hyperuricemia, renal impairment, anemia, elevated liver enzymes, muscle spasms, gout, and cholelithiasis. To report SUSPECTED ADVERSE REACTIONS, contact Esperion at 833-377-7633 (833 ESPRMED) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The data in Table 1 reflect exposure to NEXLETOL in two placebo-controlled primary hypercholesterolemia trials that included 2,009 patients treated with NEXLETOL for 52 weeks (median treatment duration of 52 weeks) [see Clinical Studies (14.2) ] . The mean age for NEXLETOL-treated patients was 65 years, 29% were female, 95% were White, 3% were Black or African American, 1% were Asian, and 1% were other races; 3% identified as Hispanic or Latino ethnicity. All patients received NEXLETOL 180 mg orally once daily plus maximally tolerated statin therapy alone or in combination with other lipid-lowering therapies. At baseline, 97% of patients had CVD and about 4% had a diagnosis of HeFH. Patients on simvastatin 40 mg/day or higher were excluded from the trials. In the primary hypercholesterolemia trials, adverse reactions led to discontinuation of treatment in 11% of NEXLETOL-treated patients and 8% of placebo-treated patients. The most common reasons for NEXLETOL treatment discontinuation were muscle spasms (0.5% versus 0.3% placebo), diarrhea (0.4% versus 0.1% placebo), and pain in extremity (0.3% versus 0.0% placebo). Adverse reactions reported in at least 2% of NEXLETOL-treated patients and more frequently than in placebo-treated patients are shown in Table 1. Table 1. Adverse Reactions (≥ 2% and greater than placebo) in NEXLETOL-Treated Patients with Primary Hypercholesterolemia and CVD or HeFH (Trials 2 and 3) Adverse Reaction Placebo Background therapy included statin and ± other lipid-lowering therapies (N = 999) % NEXLETOL (N = 2,009) % Upper respiratory tract infection 4.0 4.5 Muscle spasms 2.3 3.6 Hyperuricemia Grouped term that includes other related terms 1.1 3.5 Back pain 2.2 3.3 Abdominal pain or discomfort 2.2 3.1 Bronchitis 2.5 3.0 Pain in extremity 1.7 3.0 Anemia 1.9 2.8 Elevated liver enzymes 0.8 2.1 In the cardiovascular outcomes trial, in which 7,001 patients were exposed to NEXLETOL and 6,964 patients were exposed to placebo for a median of 3.1 years [see Clinical Studies, (14.1) ] , adverse reactions led to discontinuation of treatment in 11% of NEXLETOL-treated patients and 10% of placebo-treated patients. Adverse reactions reported in at least 2% of NEXLETOL-treated patients and 0.5% greater than placebo are shown in Table 2. Table 2. Adverse Reactions (≥ 2% and 0.5% greater than placebo) in NEXLETOL-Treated Patients with CVD or at High Risk for CVD (Trial 1) Adverse Reaction Placebo (N=6,964) % NEXLETOL (N=7,001) % Hyperuricemia Grouped term that includes other related terms 8 16 Renal impairment Renal impairment includes laboratory related terms including glomerular filtration rate decreased, blood creatinine increased and hematuria 9 11 Anemia 4 5 Elevated liver enzymes 3 4 Muscle spasms 3 4 Gout 2 3 Cholelithiasis 1 2 Other Adverse Reactions Tendon Rupture In the...

Drug Interactions

7 DRUG INTERACTIONS Table 3 includes a list of drugs with clinically important drug interactions when administered concomitantly with NEXLETOL and instructions for preventing or managing them. Table 3. Clinically Important Drug Interactions with NEXLETOL Simvastatin Clinical Impact: Concomitant use of NEXLETOL with simvastatin causes an increase in simvastatin concentration and may increase the risk of simvastatin-related myopathy [see Clinical Pharmacology (12.3) ] . Intervention : Avoid concomitant use of NEXLETOL with simvastatin greater than 20 mg. Pravastatin Clinical Impact: Concomitant use of NEXLETOL with pravastatin causes an increase in pravastatin concentration and may increase the risk of pravastatin-related myopathy [see Clinical Pharmacology (12.3) ] . Intervention: Avoid concomitant use of NEXLETOL with pravastatin greater than 40 mg. Fibrates Clinical Impact: Concomitant administration of fibrates with NEXLETOL resulted in increased triglycerides and decreased high-density lipoprotein cholesterol (HDL-C) in some patients in clinical studies and post-marketing reports. Reversibility of both increased triglycerides and decreased HDL-C levels was observed when either NEXLETOL or fibrate therapy was discontinued. Intervention: Monitor triglycerides and HDL-C four weeks after initial concomitant use of NEXLETOL and a fibrate and periodically thereafter. If increased triglycerides or decreased HDL-C levels are detected, discontinue NEXLETOL or fibrate therapy based on clinical judgment. Monitor triglycerides and HDL-C levels until levels return to baseline. Simvastatin: Avoid concomitant use of NEXLETOL with simvastatin greater than 20 mg. ( 7 ) Pravastatin: Avoid concomitant use of NEXLETOL with pravastatin greater than 40 mg. ( 7 ) Fibrates: Concomitant use of NEXLETOL with fibrates may increase triglycerides and decrease high-density lipoprotein cholesterol. ( 7 )

Contraindications

4 CONTRAINDICATIONS NEXLETOL is contraindicated in patients with a prior serious hypersensitivity reaction to bempedoic acid or any of the excipients in NEXLETOL. Serious hypersensitivity reactions, such as angioedema, have occurred [see Adverse Reactions (6.2) ]. History of a serious hypersensitivity reaction to bempedoic acid or any of the excipients in NEXLETOL. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Discontinue NEXLETOL when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus. There are insufficient data on NEXLETOL use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction 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 (see Data ) . NEXLETOL decreases cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol; therefore, NEXLETOL may cause fetal harm when administered to pregnant women based on the mechanism of action [see Clinical Pharmacology (12.1) ] . In addition, treatment of hypercholesterolemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia for most patients. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Report pregnancies to the Esperion Therapeutics, Inc. Adverse Event reporting line at 1-833-377-7633. Data Animal Data Bempedoic acid was not teratogenic when given orally at doses of 60 and 80 mg/kg/day, resulting in 11 and 12 times the systemic exposure in humans at the maximum recommended human dose (MRHD) of 180 mg to pregnant rats and rabbits, respectively. In an embryofetal development study in rats, bempedoic acid was given orally to pregnant rats at 10, 30, and 60 mg/kg/day during the period of organogenesis from gestation day 6 to 17....

Overdosage

10 OVERDOSAGE There is no clinical experience with NEXLETOL overdose. In the event of an overdosage, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied NEXLETOL tablets are supplied as follows: Tablet Strength Description Package Configuration NDC No. 180 mg White to off white and oval, debossed with "180" on one side and "ESP" on the other side Bottle of 30 tablets with child-resistant cap 72426-118-03 Storage and Handling Store at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to 86°F (15°C to 30°C) [see USP Controlled Room Temperature] . Store and dispense in the original package.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.