Nextletol
(bempedoic acid)Dosage & Administration
Administer 180 mg orally once daily with or without food.
By using PrescriberAI, you agree to the AI Terms of Use.
Nextletol Prescribing Information
NEXLETOL is indicated:
- To reduce the risk of myocardial infarction 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.
- As an adjunct to diet, 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 primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH).
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.
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.
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 hyperlipidemia 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 hyperlipidemia 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. There were increases in the incidence of non-adverse fetal skeletal variations (bent long bones and bent scapula and incomplete ossification) at doses ≥ 10 mg/kg/day (less than the clinical exposure) in the absence of maternal toxicity. At maternally toxic doses, bempedoic acid caused decreases in the numbers of viable fetuses, increases in post-implantation loss, and increased total resorptions at 60 mg/kg/day (11 times MRHD) and reduced fetal body weight at ≥ 30 mg/kg/day (4 times the MRHD). No adverse development effects were observed when bempedoic acid was given to pregnant rabbits during the period of organogenesis (gestation day 6 to 18) at doses up to 80 mg/kg/day (12 times MRHD).
In a pre- and post-natal development study in pregnant rats given oral doses of bempedoic acid at 5, 10, 20, 30 and 60 mg/kg/day throughout pregnancy and lactation (gestation day 6 to lactation day 20), there were adverse effects on delivery in the presence of maternal toxicity, including: increases in stillborn pups, reductions in numbers of live pups, pup survival, pup growth and slight delays in learning and memory at ≥ 10 mg/kg/day (at exposures equivalent to the MRHD).
Lactation
Risk Summary
There is no information regarding the presence of NEXLETOL in human or animal milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. NEXLETOL decreases cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant. Because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with NEXLETOL [see Use in Specific Populations (8.1), Clinical Pharmacology (12.1)].
Pediatric Use
The safety and effectiveness of NEXLETOL have not been established in pediatric patients.
Geriatric Use
Of the 3,009 adult patients in the primary hyperlipidemia trials of NEXLETOL, 1,753 (58%) were 65 years of age and older, while 478 (16%) were 75 years of age and older.
Of the 13,970 adult patients in the cardiovascular outcomes trial [see Clinical Studies (14.2)], 8,204 (59%) were 65 years of age and older, while 2,107 (15%) were 75 years of age and older.
No overall differences in safety or effectiveness of NEXLETOL have been observed between patients 65 years of age and older and younger adult patients.
Renal Impairment
No dosage adjustment is necessary in patients with mild or moderate renal impairment. 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 [see Clinical Pharmacology (12.3)].
Hepatic Impairment
No dosage adjustment is necessary in patients with mild or moderate hepatic impairment (Child-Pugh A or B) [see Clinical Pharmacology (12.3)]. Patients with severe hepatic impairment (Child-Pugh C) have not been studied.
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)].
Hyperuricemia
NEXLETOL inhibits renal tubular OAT2 and may increase blood uric acid levels [see Clinical Pharmacology (12.3)]. In the primary hyperlipidemia trials [see Clinical Studies (14.2)], 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 [see Clinical Studies (14.1)], 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 hyperlipidemia 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 hyperlipidemia trials [see Clinical Studies (14.2)], 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 [see Clinical Studies (14.1)], 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.