Version May 2024
Atherosclerotic cardiovascular disease, primary or secondary prevention (primary prevention is off-label use) (adjunctive agent):
Note: May use as an additional agent in patients who do not meet cholesterol treatment goals with dietary modification plus maximally tolerated lipid-lowering therapies (eg, a high-intensity statin plus ezetimibe and/or a PCSK9 monoclonal antibody) or as an alternative agent in patients intolerant of such therapies (Ref).
Oral: 180 mg once daily.
Heterozygous familial hypercholesterolemia (adjunctive agent):
Note: May use as an additional agent in patients who do not meet cholesterol treatment goals with dietary modification plus maximally tolerated lipid-lowering therapies (eg, a high-intensity statin plus ezetimibe and/or a PCSK9 monoclonal antibody) or as an alternative agent in patients intolerant of such therapies (Ref).
Oral: 180 mg once daily.
eGFR ≥30 mL/minute/1.73 m2 : No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (limited experience).
End stage renal disease receiving dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild to moderate impairment (Child-Pugh class A and B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing. Pharmacokinetics were not affected by weight.
Refer to adult dosing.
Hyperuricemia and gout have occurred.
Mechanism: Dose-related; related to the pharmacologic action; inhibition of tubular OAT2 may increase blood uric acid levels.
Onset: Intermediate; usually within the first 4 weeks of treatment initiation and persisted throughout treatment.
Risk factors:
• Prior history of gout
Rupture of tendon or injury has rarely occurred; involved the rotator cuff, biceps tendon, or Achilles tendon in clinical trials.
Onset: Varied; occurrence is typically within weeks to months of treatment initiation.
Risk factors:
• Patients >60 years of age
• Concomitant use of corticosteroids or fluoroquinolones
• Kidney failure
• Prior tendon disorders
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Endocrine & metabolic: Hyperuricemia (26%; severe hyperuricemia: 4%) (table 1)
|
Drug (Bempedoic Acid) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Bempedoic Acid) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
26% |
10% |
180 mg once daily plus maximally tolerated statin therapy alone or in combination with other lipid-lowering therapies |
Tablet |
Heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease |
N/A |
N/A |
N/A |
|
4% |
1% |
180 mg once daily plus maximally tolerated statin therapy alone or in combination with other lipid-lowering therapies |
Tablet |
Heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease |
2,009 |
999 |
Severe |
Neuromuscular & skeletal: Gout (2%; with prior gout history: 11%) (table 2)
|
Drug (Bempedoic Acid) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Bempedoic Acid) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
2% |
0.4% |
180 mg once daily plus maximally tolerated statin therapy alone or in combination with other lipid-lowering therapies |
Tablet |
Heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease |
2,009 |
999 |
N/A |
|
11% |
2% |
N/A |
Tablet |
N/A |
N/A |
N/A |
In patients with a prior history of gout |
1% to 10%:
Cardiovascular: Atrial fibrillation (2%), increased serum creatine kinase (1%)
Gastrointestinal: Abdominal distress (≤3%), abdominal pain (≤3%)
Genitourinary: Benign prostatic hyperplasia (1%)
Hematologic & oncologic: Anemia (3%), leukopenia (9%), thrombocytosis (10%)
Hepatic: Increased liver enzymes (2%), increased serum aspartate aminotransferase (1%)
Neuromuscular & skeletal: Back pain (3%), limb pain (3%), muscle spasm (4%)
Renal: Increased blood urea nitrogen (4%), increased serum creatinine (2%)
Respiratory: Upper respiratory tract infection (5%)
<1%: Neuromuscular & skeletal: Rupture of tendon (table 3)
|
Drug (Bempedoic Acid) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Bempedoic Acid) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
0.5% |
0% |
180 mg once daily plus maximally tolerated statin therapy alone or in combination with other lipid-lowering therapies |
Tablet |
Heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease |
2,009 |
999 |
Postmarketing: Hypersensitivity: Hypersensitivity reaction (including angioedema)
There are no contraindications listed in the manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Nexletol: 180 mg
No
Tablets (Nexletol Oral)
180 mg (per each): $16.31
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: May be administered without regard to food.
Atherosclerotic cardiovascular disease, secondary prevention: Treatment of atherosclerotic cardiovascular disease, as an adjunct to diet and statin therapy, in adult patients who require additional lowering of low-density lipoprotein cholesterol (LDL-C).
Heterozygous familial hypercholesterolemia: Treatment of heterozygous familial hypercholesterolemia, as an adjunct to diet and statin therapy, in adult patients who require additional lowering of LDL-C.
Atherosclerotic cardiovascular disease, primary prevention
Substrate of OAT1/3; Inhibits OATP1B1/1B3 (SLCO1B1/1B3)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Atogepant. Management: For episodic migraine, the recommended atogepant dose is 10 mg or 30 mg once daily if given with OATP1B1/1B3 inhibitors. For chronic migraine, the recommended atogepant dose is 30 mg once daily with OATP1B1/1B3 inhibitors. Risk D: Consider therapy modification
Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider therapy modification
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Risk X: Avoid combination
Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid combination
Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Risk D: Consider therapy modification
Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Momelotinib. Risk C: Monitor therapy
Pravastatin: Bempedoic Acid may increase the serum concentration of Pravastatin. Management: Avoid coadministration of bempedoic acid with pravastatin doses greater than 40 mg due to the potential for increased pravastatin concentrations and pravastatin-related myopathy. Risk D: Consider therapy modification
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Risk X: Avoid combination
Simvastatin: Bempedoic Acid may increase the serum concentration of Simvastatin. Management: Avoid coadministration of bempedoic acid with simvastatin doses greater than 20 mg due to the potential for increased simvastatin concentrations and simvastatin-related myopathy. Risk D: Consider therapy modification
Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Taurursodiol. Risk X: Avoid combination
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Risk X: Avoid combination
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Zavegepant. Risk X: Avoid combination
Based on the mechanism of action, in utero exposure to bempedoic acid may cause fetal harm. In general, bempedoic acid should be discontinued if pregnancy occurs.
Other agents may be preferred if treatment is needed during pregnancy (AACE [Jellinger 2017]; NLA [Jacobson 2015]).
Data collection to monitor pregnancy and infant outcomes following exposure to bempedoic acid is ongoing. Health care providers are encouraged to contact Esperion to report patients exposed to bempedoic acid during pregnancy (1-833-377-7633).
It is not known if bempedoic acid is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer. Other agents may be preferred when treatment is needed in a breastfeeding patient (NLA [Jacobson 2015]).
Monitor lipid levels within 8 to 12 weeks of therapy initiation; signs/symptoms of hyperuricemia, assess uric acid levels as clinically indicated; signs/symptoms of tendinopathy or tendon rupture (eg, joint pain, swelling, inflammation).
Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) by inhibiting cholesterol synthesis in the liver. ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase in the cholesterol biosynthesis pathway. Bempedoic acid and its active metabolite, ESP15228, require coenzyme A (CoA) activation by very long-chain acyl-CoA synthetase 1 (ACSVL1) to ETC-1002-CoA and ESP15228-CoA, respectively. ACSVL1 is expressed primarily in the liver. Inhibition of ACL by ETC-1002-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of LDL receptors.
Distribution: Vd: 18 L.
Protein binding: 99.3% to plasma proteins.
Metabolism: Hepatic; primarily through metabolism of the acyl glucuronide; reversibly converted by aldo-keto reductase enzyme to an active metabolite (ESP15228), which is also converted to a glucuronide conjugate.
Half-life elimination: 21 ± 11 hours.
Time to peak: 3.5 hours.
Excretion: Feces (30%; <5% as unchanged drug); urine (<5% as unchanged drug; ~70% of total dose as bempedoic acid and metabolites).
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