bempedoic acid/ezetimibe
General
Pronunciation:
bem-pe-doe-ik as-id/e-zet-i-mibe
Trade Name(s)
- Nexlizet
Ther. Class.
lipid-lowering agents
none assigned
Pharm. Class.
adenosine triphosphate citrate lyase inhibitors
cholesterol absorption inhibitors
Indications
- Primary hyperlipidemia, including heterozygous familial hypercholesterolemia (as adjunct to diet, alone or in combination with other LDL-C-lowering therapies).
- To reduce the risk of MI and coronary revascularization in patients who are unable to take recommended statin therapy (including those not taking a statin) and have established cardiovascular disease (CVD) or are at high risk for a CVD event but without established CVD.
Action
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.
Therapeutic Effect(s):
- Reduction in LDL-C levels.
- Reduction in risk of MI or coronary revascularization.
Pharmacokinetics
Bempedoic acid
Absorption: Unknown.
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; 30% excreted in feces primarily as metabolites (<5% excreted as unchanged drug in urine and feces).
Half-life: 21 hr.
Ezetimibe
Absorption: Following absorption, rapidly converted to ezetimibe-glucuronide, which is active. Bioavailability is variable.
Distribution: Unknown.
Metabolism and Excretion: Undergoes enterohepatic recycling, mostly eliminated in feces; minimal renal excretion.
Half-life: 22 hr.
TIME/ACTION PROFILE (plasma concentrations)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
Bempedoic acid | unknown | 3.5 hr | 24 hr |
Ezetimibe | unknown | 1 hr | 24 hr |
Contraindication/Precautions
Contraindicated in:
- Hypersensitivity;
- Moderate or severe hepatic impairment;
- OB: Pregnancy;
- 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
Derm: rash
GI: ↑ liver enzymes, abdominal pain, cholecystitis, cholelithiasis, nausea, pancreatitis
GU: ↑ blood urea nitrogen, ↑ serum creatinine, benign prostatic hyperplasia
Hemat: anemia
Metabolic: hyperuricemia, gout
MS: ↑ creatine kinase, back pain, 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.
Interactions
Drug-Drug
- 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.
Route/Dosage
PO (Adults): One tablet once daily.
Availability
Tablets: bempedoic acid 180 mg/ezetimibe 10 mg
Assessment
- 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 wk 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 mos of starting therapy and more frequently in patients >60 yr of age, taking corticosteroids 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.
Implementation
- 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 hr before or at least 4 hr after bile acid sequestrants.
Patient/Family Teaching
- 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 or 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), 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 heartbeat 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 breastfeeding. Bempedoic acid/ezetimibe should be discontinued during pregnancy and lactation.
Evaluation/Desired Outcomes
- Reduction in LDL-C levels. Evaluate in 8–12 wk.
- Reduction in risk of MI or coronary revascularization.