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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
NEXLETOL (NDA-211616)
(BEMPEDOIC ACID)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
01/09/2026 (SUPPL-26)
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
Additions and/or revisions to Table 3 underlined:
…
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.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONAdditions and/or revisions underlined:
…
NEXLETOL may affect the way other medicines work, and other medicines may affect how NEXLETOL works. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
…
fibrates (triglyceride-lowering medicines). Taking a fibrate medicine with NEXLETOL may lead to increases in triglycerides (fat in the blood) and decreases in high-density lipoprotein (HDL, good cholesterol).
…
11/21/2025 (SUPPL-24)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
Additions and/or revisions underlined:
What is NEXLETOL?
NEXLETOL is a prescription medicine used:
- to lower the risk of major adverse cardiovascular (CV) events, such as death from cardiovascular disease, heart attack, stroke, or heart procedures like stent placement or bypass surgery in adults at increased risk for these events who are unable to take recommended statin treatment (a cholesterol- lowering medicine), or are not taking a statin.
- along with diet and exercise and other cholesterol-lowering medicines, or alone when use with other cholesterol-lowering medicines is not possible, to reduce low-density lipoprotein (LDL, or bad cholesterol) in adults with high blood cholesterol levels called hypercholesterolemia, including a type of high blood cholesterol called heterozygous familial hypercholesterolemia (HeFH).
It is not known if NEXLETOL is safe and effective in children.
. . .
What are possible side effects of NEXLETOL? NEXLETOL may cause serious side effects, including:
. . .
The most common side effects of NEXLETOL in people with primary hypercholesterolemia include:
- symptoms of the common cold, flu, or flu-like symptoms
- bronchitis
- muscle spasms
- pain in shoulder, legs, or arms
- back pain
- anemia
- stomach pain
- increased liver enzymes
. . .
Other
Revised ‘hyperlipidemia’ to ‘hypercholesterolemia’ throughout label; please refer to label for complete information.
07/21/2025 (SUPPL-23)
8 Use in Specific Populations
8.2 Lactation
Additions and/or revisions underlined:
Risk Summary
Bempedoic acid was detected in breast milk of lactating women who received six consecutive daily doses of 180 mg bempedoic acid. The mean daily infant dose of bempedoic acid through breast milk was approximately 0.03 mg/day (95% CI: 0.02; 0.05) with a mean calculated daily infant oral dosage of 0.012 mg/kg/day based on a standard infant milk intake of 150 mL/kg/day. The mean (SD) relative infant dose (RID) was approximately 0.5 (0.2)% of the maternal weight- adjusted dosage (see Data). Concentrations of ESP15228, the active metabolite, in breast milk were below the limit of quantitation (20 ng/mL) in 7 of 8 subjects studied. There is no information regarding the effects of NEXLETOL on the breastfed infant, or the effects 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. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for NEXLETOL and any potential adverse effects on the breastfed infant from NEXLETOL or from the underlying maternal condition [see Use in Specific Populations (8.1), Clinical Pharmacology (12.1)].
Data
A lactation study in 8 healthy lactating women evaluated the concentrations of bempedoic acid in mature breast milk. NEXLETOL 180 mg oral tablet was given once daily for six consecutive days. The geometric mean estimate of bempedoic acid Cmax in breast milk was 118 ng/mL (range: 79.6 to 251 ng/mL) with a median Tmax of about 3 hours.
03/22/2024 (SUPPL-12)
4 Contraindications
Additions
and/or revisions underlined:
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)].
5 Warnings and Precautions
5.1 Hyperuricemia
Additions and/or revisions underlined:
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.
…
5.2Tendon Rupture
Additions and/or revisions underlined:
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.
6 Adverse Reactions
6.1 Clinical Trials Experience
Extensive changes; please refer to label for complete information.
6.2 Postmarketing Experience
Additions and/or revisions underlined:
Immune System Disorders: Hypersensitivity reactions including: angioedema, wheezing, rash, and urticaria.
7 Drug Interactions
Addition of title to table 3; please refer to label for complete information
Additions and/or revisions underlined:
Table 3 includes a list of drugs with clinically important drug interactions when administered concomitantly with NEXLETOL and instructions for preventing or managing them.
8 Use in Specific Populations
8.1 Pregnancy
Additions and/or revisions underlined:
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.
…
8.5 Geriatric Use
Additions and/or revisions underlined:
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.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION03/22/2024 (SUPPL-13)
4 Contraindications
Additions
and/or revisions underlined:
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)].
5 Warnings and Precautions
5.1 Hyperuricemia
Additions and/or revisions underlined:
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.
…
5.2Tendon Rupture
Additions and/or revisions underlined:
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.
6 Adverse Reactions
6.1 Clinical Trials Experience
Extensive changes; please refer to label for complete information.
6.2 Postmarketing Experience
Additions and/or revisions underlined:
Immune System Disorders: Hypersensitivity reactions including: angioedema, wheezing, rash, and urticaria.
7 Drug Interactions
Addition of title to table 3; please refer to label for complete information
Additions and/or revisions underlined:
Table 3 includes a list of drugs with clinically important drug interactions when administered concomitantly with NEXLETOL and instructions for preventing or managing them.
8 Use in Specific Populations
8.1 Pregnancy
Additions and/or revisions underlined:
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.
…
8.5 Geriatric Use
Additions and/or revisions underlined:
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.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATIONExtensive changes, please refer to label for complete information
09/20/2023 (SUPPL-14)
6 Adverse Reactions
6.2 Postmarketing ExperienceNewly added subsection:
The following adverse reactions have been identified during postapproval use of NEXLETOL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypersensitivity: angioedema, wheezing, rash, and urticaria.
8 Use in Specific Populations
8.1 PregnancyAdditions and/or revisions underlined:
…
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.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONAdditions and/or revisions underlined:
…
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 patients that there is a pregnancy safety study that monitors pregnancy outcomes in patients exposed to NEXLETOL during pregnancy. Encourage these patients to report their pregnancy to Esperion at 1-833-377-7633 [see Use in Specific Populations (8.1)].
…
Additions and/or revisions underlined:
…
Before you start taking NEXLETOL, tell your healthcare provider about all your medical conditions, including if you:
have or had gout.
have or had tendon problems.
are pregnant. Tell your healthcare provider right away if you become pregnant while taking NEXLETOL. You and your healthcare provider will decide if you should take NEXLETOL while you are pregnant. If you are pregnant during NEXLETOL treatment, you are encouraged to call Esperion at 1-833-377-7633 to share information about the health of you and your baby.
are breastfeeding or plan to breastfeed. It is not known if NEXLETOL passes into your breast milk. You and your healthcare provider should decide if you will take NEXLETOL or breastfeed. You should not do both.
have severe kidney problems.
have severe liver problems.
…
What are possible side effects of NEXLETOL? NEXLETOL may cause serious side effects, including:
…
tendon rupture or injury. Tendon problems can happen in people who take NEXLETOL. Tendons are tough cords of tissue that connect muscles to bones. Symptoms of tendon problems may include pain, swelling, tears, and inflammation of tendons including the arm, shoulder, and back of the ankle (Achilles).
Tendon rupture can happen while you are taking NEXLETOL. Tendon ruptures can happen within weeks or months of starting NEXLETOL.
…