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

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). 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 is available as: Tablets: 180 mg, white to off-white, oval shaped, debossed with "180" on one side and "ESP" on the other side. Tablets: 180 mg

Administer 180 mg orally once daily with or without food

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.

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-lowering drugs as appropriate. Tendon Rupture: Tendon rupture has occurred. Discontinue NEXLETOL at the first sign of tendon rupture. Avoid NEXLETOL in patients who have a history of tendon disorders or tendon rupture. 5.1 Hyperuricemia NEXLETOL inhibits renal tubular OAT2 and may increase blood uric acid levels . In the primary hypercholesterolemia trials , 26% of NEXLETOL-treated patients with normal baseline uric acid values (versus 9.5% placebo) experienced hyperuricemia one or more times, and 3.5% of patients experienced clinically significant hyperuricemia reported as an adverse reaction (versus 1.1% placebo). Increases in uric acid levels usually occurred within the first 4 weeks of treatment initiation, persisted throughout treatment, and returned to baseline following discontinuation of treatment. After 12 weeks of treatment, the mean placebo-adjusted increase in uric acid compared to baseline was 0.8 mg/dL for patients treated with NEXLETOL. In the cardiovascular outcomes trial , 16.4% of NEXLETOL-treated patients experienced clinically significant hyperuricemia reported as an adverse reaction (versus 8.2% placebo). Elevated blood uric acid may lead to the development of gout. In the primary hypercholesterolemia trials, gout was reported in 1.5% of patients treated with NEXLETOL and 0.4% of patients treated with placebo. In the cardiovascular outcomes trial, gout was reported in 3.2% of patients treated with NEXLETOL and 2.2% treated with placebo. Advise patients to contact their healthcare provider if symptoms of hyperuricemia occur. Assess serum uric acid when clinically indicated. Monitor patients for signs and symptoms of hyperuricemia, and initiate treatment with urate-lowering drugs as appropriate

Tendon Rupture NEXLETOL is associated with an increased risk of tendon rupture or injury. In the primary hypercholesterolemia trials , tendon rupture occurred in 0.5% of patients treated with NEXLETOL versus 0% of placebo-treated patients and involved the rotator cuff (the shoulder), biceps tendon, or Achilles tendon. Tendon rupture occurred within weeks to months of starting NEXLETOL. In the cardiovascular outcomes trial , tendon rupture events occurred in 1.2% of NEXLETOL-treated patients versus 0.9% of placebo-treated patients. Tendon rupture may occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders. Discontinue NEXLETOL immediately if the patient experiences rupture of a tendon. Consider discontinuing NEXLETOL if the patient experiences joint pain, swelling, or inflammation. Advise patients to rest at the first sign of tendinitis or tendon rupture and to contact their healthcare provider if tendinitis or tendon rupture symptoms occur. Consider alternative therapy in patients with a history of tendon disorders or tendon rupture.

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 . 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 . 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. Pravastatin: Avoid concomitant use of NEXLETOL with pravastatin greater than 40 mg. Fibrates: Concomitant use of NEXLETOL with fibrates may increase triglycerides and decrease high-density lipoprotein cholesterol.