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.
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.
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.
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.
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.
Obtain an exercise and diet (saturated fats) history.
Monitor for signs/symptoms of hyperuricemia (gout). May occur within 4 wk of therapy. Initiate therapy with urate-lowering drugs as indicated.
Monitor for signs/symptoms of allergic reaction (anaphylaxis, angioedema) during therapy.
Monitor for signs/symptoms of tendon rupture periodically during therapy. May occur within days to months of starting therapy. If joint pain, swelling, or inflammation occur, consider discontinuing bempedoic acid/ezetimibe. If tendon rupture occurs, immediately discontinue bempedoic acid/ezetimibe.
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 signs/symptoms of hyperuricemia occur.
Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications.
Advise patient that this medication should be used in conjunction with diet restrictions (fat, cholesterol, carbohydrates, alcohol), exercise, and smoking cessation.
Advise patient to notify health care provider if signs/symptoms of hyperuricemia (severe foot pain especially in the toe joint, tender joints, warm joints, joint redness, swelling) occur.
Advise patient to stop therapy, rest, and notify health care provider 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).
Advise patient to notify health care provider immediately if signs/symptoms of allergic reaction (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.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.