adenosine triphosphate citrate lyase inhibitors
cholesterol absorption inhibitors
Heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease in patients who require additional lowering of low-density lipoprotein cholesterol (LDL-C) levels (as adjunct to diet and maximally tolerated statin therapy).
Bempedoic acid– Inhibits adenosine triphosphate-citrate lyase, which inhibits cholesterol synthesis in the liver and subsequently lowers LDL-C. Ezetimibe– Inhibits absorption of cholesterol in the small intestine.
Reduction in LDL-C levels.
Distribution: Some distribution to extravascular tissues.
Metabolism and Excretion: Metabolized in liver to active metabolite (ESP15228); both parent drug and ESP15228 are also metabolized via glucuronidation to inactive metabolites. 70% excreted in urine and 30% excreted in feces primarily as metabolites (<5% excreted as unchanged drug in urine and feces).
Half-life: 21 hr.
Absorption: Following absorption, rapidly converted to ezetimibe-glucuronide, which is active. Bioavailability is variable.
Metabolism and Excretion: Undergoes enterohepatic recycling, mostly eliminated in feces, minimal renal excretion.
Half-life: 22 hr.
TIME/ACTION PROFILE (plasma concentrations)
|Bempedoic acid||unknown||3.5 hr||24 hr|
|Ezetimibe||unknown||1 hr||24 hr|
- Moderate or severe hepatic impairment
- OB: Pregnancy (may cause fetal harm);
- Lactation: Lactation.
Use Cautiously in:
- History of gout
- Concurrent use of corticosteroids or fluoroquinolones, renal failure, or previous tendon disorders (↑ risk of tendon rupture/injury)
- Severe renal impairment or end-stage renal disease
- Pedi: Safety and effectiveness in children not established;
- Geri: ↑ risk of tendon rupture/injury in patients >60 yr.
Adverse Reactions/Side Effects
CV: atrial fibrillation
GI: abdominal pain, cholecystitis, cholelithiasis, ↑ liver enzymes, nausea, pancreatitis
GU: benign prostatic hyperplasia, ↑ blood urea nitrogen, ↑ serum creatinine
Metabolic: hyperuricemia, gout
MS: back pain, ↑ creatine kinase, muscle spasm, tendon rupture/injury
Resp: upper respiratory tract infection
Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis and angioedema)
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Concurrent therapy with corticosteroids or fluoroquinolones may ↑ the risk of tendon rupture/injury associated with bempedoic acid.
- Bempedoic acid may ↑ levels of and risk of myopathy with pravastatin and simvastatin ; do not exceed 40 mg/day of pravastatin or 20 mg/day of simvastatin.
- Effects of ezetimibe may be ↓ by cholestyramine or other bile acid sequestrants.
- Concurrent use of fibrates may ↑ levels and the risk of cholelithiasis associated with ezetimibe.
- Cyclosporine may ↑ ezetimibe levels.
- Ezetimibe may ↑ risk of rhabdomyolysis when used with HMG CoA-reductase inhibitors.
PO (Adults): One tablet once daily.
Tablets: bempedoic acid 180 mg/ezetimibe 10 mg
- Obtain a diet history, especially with regard to fat consumption.
- Monitor for signs and symptoms of hyperuricemia (gout) periodically during therapy. May occur within 4 wks of therapy. Initiate treatment with urate-lowering drugs as appropriate.
- Monitor for signs and symptoms of tendon rupture (joint pain, swelling, inflammation) periodically during therapy. May occur within days to months of starting therapy and more frequently in patients >60 years of age, taking corticosteroid or fluoroquinolones, with renal failure, and with previous tendon disorders. Consider discontinuing therapy if symptoms occur and discontinue therapy if tendon rupture occurs.
- Monitor for signs and symptoms of allergic reactions (anaphylaxis, angioedema, rash, urticaria) during therapy.
Lab Test Considerations:
Evaluate serum cholesterol levels before initiating, after 8–12 wk of therapy, and periodically thereafter.
- Monitor serum uric acid levels periodically if symptoms of hyperuricemia occur.
- May cause ↑ BUN and serum creatinine.
- May cause ↓ hemoglobin and leukocytes and ↑ platelet count.
- May cause ↑ AST, ALT, and creatine kinase.
- Noncompliance (Patient/Family/Teaching)
- PO Administer once daily without regard to food. Swallow tablet whole; do not break, crush, or chew.
- Administer bempedoic acid/ezetimibe either at least 2 hrs before or at least 4 hrs after bile acid sequestrants.
- Instruct patient to take medication as directed. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
- Advise patient that this medication should be used in conjunction with diet restrictions (fat, cholesterol, carbohydrates, alcohol), exercise, and cessation of smoking.
- Advise patient to notify health care professional if signs and symptoms of hyperuricemia (severe foot pain especially in the toe joint, tender joints, warm joints, joint redness, swelling) occur.
- Advise patient to rest at the first sign of tendinitis (pain, swelling, tears, inflammation of tendons including arm, shoulder, back of the ankle) or tendon rupture (hear or feel a snap or pop in a tendon area, bruising right after an injury in a tendon area, unable to move affected area or put weight on affected area) and stop medication and contact health care professional if tendinitis or tendon rupture symptoms occur.
- Advise patient to notify health care professional immediately if signs and symptoms of allergic reactions (swelling of face, lips, mouth or tongue; trouble breathing; wheezing; skin rashes, redness, or swelling; severe itching; dizziness or fainting; fast heart beat or pounding in chest) occur.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
- Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breast feeding. Bempedoic acid/ezetimibe should be discontinued during pregnancy and lactation.
Reduction in LDL-C levels. Evaluate in 8–12 wks.