NEXLETOL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NEXLETOL (NEXLETOL).

How it works

Inhibits microsomal triglyceride transfer protein (MTP), thereby reducing the hepatic secretion of apolipoprotein B-containing lipoproteins including LDL and VLDL.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 with contribution from CYP2C8.
Excretion	Primarily hepatic metabolism followed by biliary excretion into feces. <2% excreted unchanged in urine.
Half-life	Terminal elimination half-life is approximately 15 to 20 hours. Steady-state reached within 2 to 4 weeks.
Protein binding	>99% bound to plasma proteins, primarily albumin.
Volume of Distribution	Approximately 18 L (0.21 L/kg for 70 kg individual), indicating limited extravascular distribution.
Bioavailability	Oral bioavailability is approximately 20% due to extensive first-pass metabolism.
Onset of Action	LDL-C reduction observed as early as 2 weeks; maximal effect at 4 to 6 weeks with oral administration.
Duration of Action	LDL-C lowering persists for at least 24 hours; sustained effect with daily dosing. Reversal of effect upon discontinuation within 2 to 4 weeks.

Classification & Brands

Dosing & administration

240 mg orally once daily (two 120 mg tablets) with or without food. Do not break, crush, or chew tablets.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m2). Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m2) or end-stage renal disease; use not recommended.
Liver impairment	No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment; avoid use.
Pediatric use	Safety and efficacy not established in pediatric patients; no recommended dose.
Geriatric use	No dose adjustment required; no specific elderly considerations beyond general monitoring for renal function and potential interactions.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for NEXLETOL (NEXLETOL).

Breastfeeding	Unknown if bempedoic acid excreted in human milk. M/P ratio not established. Because of potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during therapy and for 5 days after last dose.
Teratogenic Risk	NEXLETOL (bempedoic acid) is contraindicated in pregnancy. Animal studies show fetal harm at exposures below human exposure. There are no adequate human data. Risk cannot be ruled out in any trimester.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Risk of hepatotoxicity, including liver injury and hepatic steatosis, and risk of gastrointestinal adverse events. Requires monitoring of liver function tests and dietary fat restriction.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Patients with moderate to severe hepatic impairment (Child-Pugh class B or C).","Concurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin).","History of hypersensitivity to lomitapide or any excipient.","Due to risk of hepatotoxicity, contraindicated in patients with active liver disease or unexplained persistent elevations of transaminases."]

Clinical Precautions

Precautions

["Hepatotoxicity: Monitor ALT, AST, alkaline phosphatase, and bilirubin before and during therapy. Discontinue if clinically significant liver injury occurs.","Gastrointestinal adverse events: Diarrhea, nausea, vomiting, abdominal pain, dyspepsia. May require dosage adjustment or discontinuation.","Potential for increased transaminases and hepatic steatosis (seen in clinical trials).","May decrease absorption of fat-soluble vitamins; monitor vitamin E, A, D, K levels."]

Clinical Tips & Counseling

Drug interactions

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NEXLETOL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NEXLETOL (NEXLETOL).

How it works

Inhibits microsomal triglyceride transfer protein (MTP), thereby reducing the hepatic secretion of apolipoprotein B-containing lipoproteins including LDL and VLDL.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 with contribution from CYP2C8.
Excretion	Primarily hepatic metabolism followed by biliary excretion into feces. <2% excreted unchanged in urine.
Half-life	Terminal elimination half-life is approximately 15 to 20 hours. Steady-state reached within 2 to 4 weeks.
Protein binding	>99% bound to plasma proteins, primarily albumin.
Volume of Distribution	Approximately 18 L (0.21 L/kg for 70 kg individual), indicating limited extravascular distribution.
Bioavailability	Oral bioavailability is approximately 20% due to extensive first-pass metabolism.
Onset of Action	LDL-C reduction observed as early as 2 weeks; maximal effect at 4 to 6 weeks with oral administration.
Duration of Action	LDL-C lowering persists for at least 24 hours; sustained effect with daily dosing. Reversal of effect upon discontinuation within 2 to 4 weeks.

Classification & Brands

Dosing & administration

240 mg orally once daily (two 120 mg tablets) with or without food. Do not break, crush, or chew tablets.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m2). Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m2) or end-stage renal disease; use not recommended.
Liver impairment	No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment; avoid use.
Pediatric use	Safety and efficacy not established in pediatric patients; no recommended dose.
Geriatric use	No dose adjustment required; no specific elderly considerations beyond general monitoring for renal function and potential interactions.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for NEXLETOL (NEXLETOL).

Breastfeeding	Unknown if bempedoic acid excreted in human milk. M/P ratio not established. Because of potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during therapy and for 5 days after last dose.
Teratogenic Risk	NEXLETOL (bempedoic acid) is contraindicated in pregnancy. Animal studies show fetal harm at exposures below human exposure. There are no adequate human data. Risk cannot be ruled out in any trimester.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Risk of hepatotoxicity, including liver injury and hepatic steatosis, and risk of gastrointestinal adverse events. Requires monitoring of liver function tests and dietary fat restriction.