BEM-pe-DOE-ik AS-id/e-ZET-i-mibe

Therapeutic Classification: lipid-lowering agents, n/a

Pharmacologic Classification: 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.

Bempedoic acid

Absorption: Unknown.

Distribution: Some distribution to extravascular tissues.

Metabolism/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.

Ezetimibe

Absorption: Following absorption, rapidly converted to ezetimibe-glucuronide, which is active. Bioavailability is variable.

Distribution: Unknown.

Metabolism/Excretion: Undergoes enterohepatic recycling, mostly eliminated in feces, minimal renal excretion.

Half-life: 22 hr.

(plasma concentrations)

Contraindicated in:

• Hypersensitivity
• 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.

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.

Metab: hyperuricemia, gout.

MS: ↑creatine kinase, back pain, muscle spasm, tendon rupture/injury.

Resp: upper respiratory tract infection.

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA).

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 andsimvastatin; 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.

• 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.

• 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.

Nexlizet