Nexletol

NEXLETOL- bempedoic acid tablet, film coated
Esperion Therapeutics, Inc.

1 INDICATIONS AND USAGE

NEXLETOL 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.

Limitations of Use

The effect of NEXLETOL on cardiovascular morbidity and mortality has not been determined.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

The recommended dosage of NEXLETOL, in combination with maximally tolerated statin therapy, 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.

3 DOSAGE FORMS AND STRENGTHS

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.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Hyperuricemia

NEXLETOL inhibits renal tubular OAT2 and may increase blood uric acid levels [see Clinical Pharmacology (12.3)]. In clinical 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 and persisted throughout 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.

Elevated blood uric acid may lead to the development of gout. Gout was reported in 1.5% of patients treated with NEXLETOL and 0.4% of patients treated with placebo. The risk for gout events was higher in patients with a prior history of gout (11.2% NEXLETOL versus 1.7% placebo), although gout also occurred more frequently than placebo in patients treated with NEXLETOL who had no prior gout history (1.0% NEXLETOL versus 0.3% 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.

5.2 Tendon Rupture

NEXLETOL is associated with an increased risk of tendon rupture or injury. In clinical 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. 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.

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

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 described below reflect exposure to NEXLETOL in two placebo-controlled trials that included 2009 patients treated with NEXLETOL for 52 weeks (median treatment duration of 52 weeks) [see Clinical Studies (14)]. The mean age for NEXLETOL-treated patients was 65.4 years, 29% were women, 3% were Hispanic, 95% White, 3% Black, 1% Asian, and 1% other races. 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 clinical atherosclerotic cardiovascular disease (ASCVD) and about 4% had a diagnosis of heterozygous familial hypercholesterolemia (HeFH). Patients on simvastatin 40 mg/day or higher were excluded from the 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 ASCVD and HeFH (Studies 1 and 2)
Adverse Reaction NEXLETOL + Statin and ± Other Lipid Lowering Therapies (N = 2009) % Placebo (N = 999) %
*
Hyperuricemia includes hyperuricemia and blood uric acid increased.
Abdominal pain or discomfort includes abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort.
Elevated liver enzymes includes AST increased, ALT increased, hepatic enzyme increased, and liver function test increased.
Upper respiratory tract infection 4.5 4.0
Muscle spasms 3.6 2.3
Hyperuricemia * 3.5 1.1
Back pain 3.3 2.2
Abdominal pain or discomfort 3.1 2.2
Bronchitis 3.0 2.5
Pain in extremity 3.0 1.7
Anemia 2.8 1.9
Elevated liver enzymes 2.1 0.8

Tendon Rupture

NEXLETOL was associated with an increased risk of tendon rupture, occurring in 0.5% of NEXLETOL-treated patients versus 0% of placebo-treated patients.

Gout

NEXLETOL was associated with an increased risk of gout, occurring in 1.5% of NEXLETOL-treated patients versus 0.4% of placebo-treated patients.

Benign Prostatic Hyperplasia

NEXLETOL was associated with an increased risk of benign prostatic hyperplasia (BPH) or prostatomegaly in men with no reported history of BPH, occurring in 1.3% of NEXLETOL-treated patients versus 0.1% of placebo-treated patients. The clinical significance is unknown.

Atrial Fibrillation

NEXLETOL was associated with an imbalance in atrial fibrillation, occurring in 1.7% of NEXLETOL-treated patients versus 1.1% of placebo-treated patients.

Laboratory Tests

NEXLETOL was associated with persistent changes in multiple laboratory tests within the first 4 weeks of treatment. Laboratory test values returned to baseline following discontinuation of treatment.

Increase in Creatinine and Blood Urea Nitrogen: Overall, there was a mean increase in serum creatinine of 0.05 mg/dL compared to baseline with NEXLETOL at Week 12. Approximately 3.8% of patients treated with NEXLETOL had blood urea nitrogen values that doubled (versus 1.5% placebo), and about 2.2% of patients had creatinine values that increased by 0.5 mg/dL (versus 1.1% placebo).

Decrease in Hemoglobin and Leukocytes: Approximately 5.1% of patients (versus 2.3% placebo) had decreases in hemoglobin levels of 2 or more g/dL and below the lower limit of normal on one or more occasion. Anemia was reported in 2.8% of patients treated with NEXLETOL and 1.9% of patients treated with placebo. Hemoglobin decrease was generally asymptomatic and did not require medical intervention. Decreased leukocyte count was also observed. Approximately 9.0% of NEXLETOL-treated patients with normal baseline leukocyte count had a decrease to less than the lower limit of normal on one or more occasion (versus 6.7% placebo). Leukocyte decrease was generally asymptomatic and did not require medical intervention. In clinical trials, there was a small imbalance in skin or soft tissue infections, including cellulitis (0.8% versus 0.4%), but there was no imbalance in other infections.

Increase in Platelet Count: Approximately 10.1% of patients (versus 4.7% placebo) had increases in platelet counts of 100× 109 /L or more on one or more occasion. Platelet count increase was asymptomatic, did not result in increased risk for thromboembolic events, and did not require medical intervention.

Increase in Liver Enzymes: Increases in hepatic transaminases (AST and/or ALT) were observed with NEXLETOL. In most cases, the elevations were transient and resolved or improved with continued therapy or after discontinuation of therapy. Increases to more than 3× the upper limit of normal (ULN) in AST occurred in 1.4% of patients treated with NEXLETOL versus 0.4% of placebo patients, and increases to more than 5× ULN occurred in 0.4% of NEXLETOL-treated versus 0.2% of placebo-treated patients. Increases in ALT occurred with similar incidence between NEXLETOL- and placebo-treated patients. Elevations in transaminases were generally asymptomatic and not associated with elevations ≥2× ULN in bilirubin or with cholestasis.

Increase in Creatine Kinase: Approximately 1.0% of patients (versus 0.6% placebo) had elevations of CK levels of 5 or more times the normal value on one or more occasions, and 0.4% of patients (versus 0.2% placebo) had elevations of CK levels of 10 or more times.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2021. All Rights Reserved.