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.