NEXLIZET
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NEXLIZET (NEXLIZET).
Bempedoic acid inhibits ATP-citrate lyase, reducing cholesterol synthesis; ezetimibe inhibits intestinal cholesterol absorption via NPC1L1 blockade.
| Metabolism | Bempedoic acid: primarily glucuronidation (UGT2B7) and oxidation (CYP3A4/5); ezetimibe: glucuronidation (UGT1A1, UGT1A3, UGT2B15). |
| Excretion | Bempedoic acid: ~70% renal (unchanged and as glucuronide conjugate), ~30% fecal; ezetimibe: primarily fecal (78%) and renal (11%) after enterohepatic recycling. |
| Half-life | Bempedoic acid: 15–24 hours (terminal); ezetimibe: 22 hours (terminal) for ezetimibe-glucuronide, with clinical steady-state achieved within 3–5 days. |
| Protein binding | Bempedoic acid: >99% (albumin); ezetimibe: >90% (albumin). |
| Volume of Distribution | Bempedoic acid: ~0.8 L/kg (suggests distribution into tissues); ezetimibe: ~10 L/kg (extensive extravascular distribution). |
| Bioavailability | Bempedoic acid: ~80% (oral); ezetimibe: highly variable (35–65%) due to rapid glucuronidation in the gut wall and liver. |
| Onset of Action | Bempedoic acid: 4 weeks (LDL-C reduction); ezetimibe: 2 weeks (LDL-C reduction); both oral. |
| Duration of Action | Bempedoic acid: sustained effect with once-daily dosing; ezetimibe: effect persists beyond 24 hours due to enterohepatic recycling. |
Bempedoic acid 180 mg and ezetimibe 10 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m²) or dialysis. |
| Liver impairment | Contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases (ALT or AST >3x ULN). No specific adjustment for Child-Pugh A; not studied in Child-Pugh B or C. |
| Pediatric use | Not established; safety and efficacy in pediatric patients have not been studied. |
| Geriatric use | No specific dose adjustment required; monitor renal function in elderly due to age-related decline. Consider risk of myopathy in patients >65 years with concomitant statin use. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEXLIZET (NEXLIZET).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Bempedoic acid and ezetimibe are present in rat milk. M/P ratio: Unknown. Because of potential for adverse reactions, breastfeeding is not recommended during treatment and for 2 weeks after last dose. |
| Teratogenic Risk | NEXLIZET (bempedoic acid and ezetimibe) is contraindicated in pregnancy. Bempedoic acid: Animal studies show fetal toxicity and malformations at clinically relevant exposures. There are no adequate human data. Ezetimibe: Limited human data; animal studies show no teratogenicity at systemic exposures. Based on bempedoic acid component, risk cannot be excluded. First trimester: Potential teratogenic effects. Second and third trimesters: Fetal toxicity including reduced fetal weight and skeletal variations. Use only if maternal benefit justifies risk. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant use with simvastatin >20 mg or pravastatin >40 mg due to increased risk of myopathy","Known hypersensitivity to bempedoic acid or ezetimibe"]
| Precautions | ["Increased risk of myalgia and tendon rupture","Elevations in uric acid and risk of gout","Increased blood glucose","Hepatic enzyme elevations","Increased risk of nephrolithiasis"] |
Loading safety data…
| Fetal Monitoring | Monitor hepatic function (ALT, AST) at baseline and as clinically indicated. Monitor lipid profiles (LDL-C, total cholesterol). In pregnancy, assess fetal growth and well-being via ultrasound if exposure occurs. Monitor for adverse effects including myalgia, elevated creatine kinase, and gout. |
| Fertility Effects | No human data. Animal studies: Bempedoic acid did not impair fertility in male or female rats at exposures up to 7 and 11 times MRHD, respectively. Ezetimibe had no effects on fertility at doses up to 1000 mg/kg/day in rats. Combined effects unknown. Clinical significance in humans is uncertain. |