Nexletol (bempedoic acid)

Bempedoic acid should not be used concomitantly with simvastatin dosages greater than 20 mg daily or with pravastatin dosages greater than 40 mg daily.

Bempedoic acid is administered orally without regard to meals.

Bempedoic acid is also available in fixed combination with ezetimibe. The fixed-combination preparation is administered orally without regard to meals; the fixed-combination tablets should be swallowed whole and not cut, chewed, or crushed.

No dosing information is available for this tab.

In vitro studies suggest that bempedoic acid, its active metabolite, and its glucuronide conjugates are not substrates, inhibitors, or inducers of cytochrome P-450 (CYP) isoenzymes.

In vitro studies suggest that bempedoic acid, its active metabolite, and its glucuronide conjugates are not substrates of commonly characterized drug transporters, with the exception of bempedoic acid glucuronide, which is an organic anion transporter (OAT) 3 substrate. Bempedoic acid is a weak inhibitor of OAT2 in vitro. Bempedoic acid is a weak inhibitor of OAT3 at concentrations higher than those used clinically. Bempedoic acid and its glucuronide conjugate are weak inhibitors of organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 at clinically relevant concentrations.

When bempedoic acid is used in fixed combination with ezetimibe, interactions associated with ezetimibe must be considered in addition to those associated with bempedoic acid.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Bempedoic Acid/Pravastatin (> 40 Mg); Simvastatin (> 20 Mg)

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Bempedoic acid weakly inhibits OATP1B1.(1) Pravastatin and simvastatin are substrates for OATP1B1 transport.(2,3) OATP transport inhibition may decrease influx of substrates from the blood into hepatocytes and decrease hepatic elimination.

CLINICAL EFFECTS: Transport inhibition may lead to higher plasma concentrations of pravastatin or simvastatin, increasing the risk for statin-induced myopathy or rhabdomyolysis.(1)

PREDISPOSING FACTORS: The risk for myopathy or rhabdomyolysis may be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis.

PATIENT MANAGEMENT: The manufacturer of bempedoic acid recommends avoiding concomitant use of pravastatin doses greater than 40 mg and simvastatin doses greater than 20 mg.(1) Instruct patients to report unexplained muscle pain, tenderness, weakness, or dark, cola-colored urine.

DISCUSSION: In healthy volunteers, bempedoic acid (240 mg daily) increased the area-under-curve (AUC) and maximum concentration (Cmax) of pravastatin 40 mg both by 2-fold. Bempedoic acid 240 mg daily given with simvastatin 20 mg and bempedoic acid 180 mg daily given with simvastatin 40 mg both increased the AUC and Cmax of simvastatin by 2-fold and 1.5-fold, respectively.(1)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Bempedoic Acid/Fibrates

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism for this interaction is unknown.

CLINICAL EFFECTS: Concomitant use of bempedoic acid with fibrates may increase triglycerides and decrease high-density lipoprotein cholesterol (HDL-C).(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of bempedoic acid states monitor triglycerides and HDL-C four weeks after initial concomitant use of bempedoic acid and a fibrate and periodically thereafter. If increased triglycerides or decreased HDL-C levels are detected, discontinue bempedoic acid or fibrate therapy based on clinical judgment. Monitor triglycerides and HDL-C levels until levels return to baseline.(1,2)

DISCUSSION: In some patients in clinical studies and post-marketing reports, concomitant administration of fibrates with bempedoic acid resulted in increased triglycerides and decreased HDL-C. Reversibility of both increased triglycerides and decreased HDL-C levels was observed when either bempedoic acid or fibrate therapy was discontinued.(1,2)

Bempedoic Acid/Pravastatin (<= 40 Mg); Simvastatin (<=20 Mg)

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Bempedoic acid weakly inhibits OATP1B1.(1) Pravastatin and simvastatin are substrates for OATP1B1 transport.(2,3) OATP transport inhibition may decrease influx of substrates from the blood into hepatocytes and decrease hepatic elimination.

CLINICAL EFFECTS: Transport inhibition may lead to higher plasma concentrations of pravastatin or simvastatin, increasing the risk for statin-induced myopathy or rhabdomyolysis.(1)

PREDISPOSING FACTORS: The risk for myopathy or rhabdomyolysis may be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis.

PATIENT MANAGEMENT: The manufacturer of bempedoic acid recommends avoiding concomitant use of pravastatin doses greater than 40 mg and simvastatin doses greater than 20 mg.(1) Instruct patients to report unexplained muscle pain, tenderness, weakness, or dark, cola-colored urine.

DISCUSSION: In healthy volunteers, bempedoic acid (240 mg daily) increased the area-under-curve (AUC) and maximum concentration (Cmax) of pravastatin 40 mg both by 2-fold. Bempedoic acid 240 mg daily given with simvastatin 20 mg and bempedoic acid 180 mg daily given with simvastatin 40 mg both increased the AUC and Cmax of simvastatin by 2-fold and 1.5-fold, respectively.(1)

*Bempedoic acid: None.

*Bempedoic acid and ezetimibe: Known hypersensitivity to ezetimibe.

• Lactation
• Tendon rupture

• Pregnancy

• Hyperuricemia

Adverse effects reported in >=2% of patients receiving bempedoic acid in clinical studies include upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, extremity pain, anemia, and increased hepatic enzymes.

Adverse effects reported in >=2% of patients receiving bempedoic acid in fixed combination with ezetimibe in clinical studies include upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, extremity pain, anemia, elevated liver enzymes, diarrhea, arthralgia, sinusitis, fatigue, and influenza.

More Frequent

• Abnormal hepatic function tests
• Atrial fibrillation
• Hyperuricemia
• Tendon rupture

Less Frequent

• Biliary calculus
• Increased alanine transaminase
• Increased aspartate transaminase
• Leukopenia

Rare or Very Rare

• Angioedema

More Frequent

• Acute abdominal pain
• Anemia
• Back pain
• Bronchitis
• Muscle spasm
• Pain
• Upper respiratory infection

Less Frequent

• Benign prostatic hyperplasia
• Gout
• Thrombocytosis

Rare or Very Rare

• Increased creatine kinase level
• Skin rash
• Urticaria
• Wheezing

No enhanced messaging available.

Safety and efficacy of bempedoic acid have not been established in pediatric patients.

Bempedoic acid may cause fetal harm if used during pregnancy.

If pregnancy occurs during therapy, bempedoic acid should be discontinued unless the benefits of the drug outweigh the potential risks to the fetus. Treatment of hyperlipidemia generally is not necessary during pregnancy; atherosclerosis is a chronic process, and discontinuance of antilipemic drugs during pregnancy should have little impact on long-term outcomes of antilipemic therapy.

There is a pregnancy surveillance study for bempedoic acid. If bempedoic acid is administered during pregnancy, healthcare providers should report such exposure to Esperion at 1-833-377-7633.

It is not known whether bempedoic acid is distributed into human milk. The effects of the drug on breast-fed infants and on milk production also are unknown. Because of the potential for serious adverse reactions from bempedoic acid in nursing infants, breast-feeding is not recommended during treatment with the drug.

The manufacturer makes no specific dosage recommendations for geriatric patients.

In clinical studies, 58% of patients who received bempedoic acid were >=65 years of age and 16% were >=75 years of age. Although no overall differences in safety or efficacy have been observed between geriatric patients and younger adults in controlled studies or in other clinical experience, the possibility of increased sensitivity to bempedoic acid in some geriatric patients cannot be ruled out.