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)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Moderate or severe hepatic impairment
• OB:   Pregnancy.

Use Cautiously in:

• History of gout;
• Concurrent use of corticosteroids or fluoroquinolones, renal failure, or previous tendon disorders (↑ risk of tendon rupture/injury)
• Lactation:  Use during breastfeeding only if potential maternal benefit justifies potential risk to infant;
• Pedi:  Safety and effectiveness not established in children;
• 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: ↑ CK, 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

•   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.

Route/Dosage

PO (Adults): One tablet once daily.

Availability

Tablets: bempedoic acid 180 mg/ezetimibe 10 mg

Assessment

• 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.
• May ↑ BUN, serum creatinine, AST, ALT, and CK.
• May ↓ hemoglobin and leukocytes and ↑ platelets.

Implementation

• PO Administer without regard to food.  DNC: Swallow whole; do not break, crush, or chew tablet .
  • Administer ≥2 hr before or ≥4 hr after bile acid sequestrants.

Patient/Family Teaching

• 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.

Evaluation/Desired Outcomes

• Reduction in LDL-C levels. Evaluate in 8–12 wk.
• Reduction in risk of MI or coronary revascularization.