Nexletol

— THERAPEUTIC CATEGORIES —
  • Hyperlipoproteinemias
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Nexletol Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Bempedoic acid 180mg; tabs.

    Pharmacological Class

    Adenosine triphosphate-citrate lyase (ACL) inhibitor.

    How Supplied

    Tabs—30, 90

    How Supplied

    Nexletol tablets are supplied as 180 mg strength tablets in 30- and 90-count bottles. Each tablet is white to off white and oval, debossed with “180” on one side and “ESP” on the other side.

    Storage

    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. 

    Manufacturer

    Esperion Therapeutics, Inc.

    Generic Availability

    NO

    Mechanism of Action

    Bempedoic acid is an ACL inhibitor that lowers LDL-C by inhibition of cholesterol synthesis in the liver.

    Nexletol Indications

    Indications

    To reduce the risk of myocardial infarction (MI) and coronary revascularization in adults who are unable to take recommended statin therapy (including those not taking a statin) with: established cardiovascular disease (CVD), or a high risk for a CVD event but without established CVD. An adjunct to diet, in combination with other low-density lipoprotein cholesterol (LDL-C) lowering therapies, or along when concomitant LDL-C lowering therapy is not possible, to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH).

    Nexletol Dosage and Administration

    Adult

    180mg once daily.

    Children

    Not established.

    Nexletol Contraindications

    Not Applicable

    Nexletol Boxed Warnings

    Not Applicable

    Nexletol Warnings/Precautions

    Warnings/Precautions

    Hyperuricemia. Assess serum uric acid as clinically indicated. History of gout. Increased risk for tendon rupture/injury (esp. >60yrs, renal failure); discontinue immediately if occurs. Consider discontinuing if joint pain, swelling, or inflammation develop. History of tendon disorders/rupture: consider alternative therapy. Assess lipid levels within 8–12 weeks after initiation. Elderly. Severe hepatic (Child-Pugh C) or renal impairment (eGFR <30mL/min/1.73 m2). ESRD on dialysis. Pregnancy: discontinue if occurs. Nursing mothers: not recommended.

    Warnings/Precautions

    Hyperuricemia

    • Nexletol may increase blood uric acid levels, which typically occurred within the first 4 weeks of initiating treatment and persisted during treatment.

    • Elevated blood uric acid may result in gout. Patients with a history of gout have an increased risk for gout events.

    • Assess serum uric acid as clinically indicated. Monitor for signs/symptoms of hyperuricemia, and initiate treatment appropriately.

    Tendon Rupture

    • Increased risk for tendon rupture or injury especially in patients >60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in those with renal failure, and in those with previous tendon disorders. 

    • Discontinue immediately if tendon rupture occurs. Consider discontinuing if joint pain, swelling, or inflammation develop. 

    • Advise patients to rest at the first sign of tendinitis or tendon rupture. Consider alternative therapy if history of tendon disorders or tendon rupture.

    Pregnancy Considerations

    Discontinue Nexletol if pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

    If Nexletol is administered during pregnancy, healthcare providers should report Nexletol exposure by contacting Esperion at 1-833-377-7633.

    Nursing Mother Considerations

    Advise patients that breastfeeding is not recommended during treatment.

    Pediatric Considerations

    The safety and efficacy of Nexletol have not been established in pediatric patients.

    Renal Impairment Considerations

    There is limited experience with Nexletol in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2), and Nexletol has not been studied in patients with end-stage renal disease (ESRD) receiving dialysis.

    Hepatic Impairment Considerations

    Patients with severe hepatic impairment (Child-Pugh C) have not been studied.

    Nexletol Pharmacokinetics

    Absorption

    Median time to maximum concentration: 3.5 hours.

    Distribution

    Apparent volume of distribution: 18 L. Plasma protein bound: 99.3%.

    Metabolism

    The primary route of elimination for bempedoic acid is through metabolism of the acyl glucuronide. 

    Elimination

    Renal (~70%), fecal (~30%). Steady-state clearance: 11.2 mL/min. Half-life: 21 ± 11 hours.

    Nexletol Interactions

    Interactions

    Avoid concomitant simvastatin >20mg or pravastatin >40mg. Increased risk for tendon rupture with corticosteroid or fluoroquinolone drugs.

    Nexletol Adverse Reactions

    Adverse Reactions

    Upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, elevated liver enzymes, renal impairment, gout, cholelithiasis; BPH.

    Nexletol Clinical Trials

    Clinical Trials

    Cardiovascular Outcomes Trial in Adults With CVD or at High Risk for CVD

    The approval was based on data from the randomized, double-blind, placebo-controlled phase 3 CLEAR Outcomes study (ClinicalTrials.gov Identifier: NCT02993406), which assessed the effects of bempedoic acid, an adenosine triphosphate-citrate lyase (ACL) inhibitor, on the occurrence of major cardiovascular events in 13,970 adults with established CVD or at high risk for a CVD event but without CVD who were not receiving recommended statin dosages.

    Study participants were randomly assigned 1:1 to receive either bempedoic acid 180mg orally once daily or placebo, alone or as an add on to other lipid-lowering therapies. The primary endpoint was the number of participants with first occurrence of a 4-component composite adjudicated major adverse cardiovascular events (MACE-4), defined as death from CV causes, nonfatal MI or stroke, or coronary revascularization. The key secondary composite endpoint was MACE-3, defined as time to first occurrence of CV death, nonfatal MI or stroke.

    After a median follow-up of 3.4 years, results showed treatment with bempedoic acid met the primary endpoint demonstrating a significant reduction in MACE-4 compared with placebo (11.7% vs 13.3%, respectively; hazard ratio [HR], 0.87; [95% CI, 0.79-0.96]; P =.0037). Moreover, patients who received bempedoic acid had a significant reduction in MACE-3 compared with placebo patients (8.2% vs 9.5%, respectively; HR, 0.85; [95% CI, 0.76-0.96]; P =.0058). The difference between the bempedoic acid and placebo groups in mean percent change in LDL-C from baseline to month 6 was -20% (95% CI, -21%, -19%).

     

    Primary Hyperlipidemia Trials in Adults

    The approval was based on data from two phase 3, multicenter, double-blind, placebo-controlled studies (CLEAR Harmony [NCT02666664] and CLEAR Wisdom [NCT02991118]) that evaluated the efficacy and safety of Nexletol in 3009 adult patients with HeFH and/or ASCVD as an add on to a maximally tolerated statin therapy for 52 weeks. 

    Results demonstrated that Nexletol provided a statistically significant lowering of LDL-C from baseline with a placebo-adjusted difference of -18% (95% CI, -20 to -16; P <.001) in CLEAR Harmony and -17% (95% CI, -21 to -14; P <.001) in CLEAR Wisdom; in both trials, the maximum LDL-C lowering effects occurred at week 4.  

    Nexletol Note

    Not Applicable

    Nexletol Patient Counseling

    Patient Counseling

    Risk of Hyperuricemia

    • Advise patients of the risk of elevated serum uric acid levels, including development of gout. Inform patients that serum uric acid levels may be monitored during treatment with Nexletol. Contact your healthcare provider if signs or symptoms of hyperuricemia occur. 

    Risk of Tendon Rupture 

    • Inform patients of the risk of tendon rupture. Advise patients to rest at the first sign of tendinitis or tendon rupture and to immediately contact their healthcare provider if tendinitis or tendon rupture symptoms occur. 

    Risk of Myopathy with Concomitant Use of Simvastatin or Pravastatin 

    • Advise patients to notify their healthcare provider(s) if they are taking, or plan to take simvastatin or pravastatin. The risk of myopathy occurring with the use of simvastatin or pravastatin may be increased when taken with Nexletol.

    Pregnancy 

    • Advise pregnant women of the potential risk to a fetus based on Nexletol’s mechanism of action. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women who are exposed to Nexletol during pregnancy that there is a pregnancy surveillance study. Encourage these patients to report their pregnancy to Esperion at 1-833-377- 7633.

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    NEXSTEP Patient Support

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