Bempedoic acid and ezetimibe
Regulatory sources consulted
Approved indications
- In adults with primary hypercholesterolemia or mixed dyslipidemia as an adjunct to diet, with or without a statin according to tolerance and control, and in established atherosclerotic cardiovascular disease or high risk to reduce cardiovascular risk by lowering LDL-C.
Contraindications
Absolute
- Hypersensitivity to bempedoic acid, ezetimibe or excipients.
- Pregnancy (CIMA contraindication).
- Simvastatin >40 mg/day (CIMA contraindication).
- With a statin: active liver disease or unexplained persistent transaminase elevations.
Clinical warnings
- Major warning · With statins, the risk of myopathy and rhabdomyolysis increases; report muscle pain, tenderness or weakness and discontinue Nustendi and the statin if CPK is >10 times normal. — https://cima.aemps.es/cima/dochtml/ft/1201424002/FT_1201424002.html
- Major warning · It may increase uric acid and precipitate or worsen gout; discontinue if hyperuricemia with gout symptoms occurs. — https://cima.aemps.es/cima/dochtml/ft/1201424002/FT_1201424002.html
- Major warning · Check liver function at initiation and discontinue if transaminases persist above 3 times normal. Additional monitoring may be needed in severe renal impairment or dialysis. — https://cima.aemps.es/cima/dochtml/ft/1201424002/FT_1201424002.html
- Major warning · The FDA label warns of tendinitis and tendon rupture. Discontinue at the first sign of rupture; consider an alternative if joint pain or swelling occurs, and avoid treatment in patients with a history of tendon disorder or rupture. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3fa2108c-0300-47b8-9d34-f762af7c93c6
Drug interactions
- ModerateSimvastatin
Mechanism: Bempedoic acid increases exposure and the risk of myopathy.
Recommendation: FDA: do not exceed 20 mg/day. CIMA: limit to 20 mg/day, with 40 mg/day only exceptionally in severe hypercholesterolemia and high cardiovascular risk; >40 mg/day is contraindicated.
https://cima.aemps.es/cima/dochtml/ft/1201424002/FT_1201424002.htmlhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3fa2108c-0300-47b8-9d34-f762af7c93c6
- ModeratePravastatin
Mechanism: Bempedoic acid increases pravastatin exposure and may increase the risk of myopathy.
Recommendation: According to the FDA label, avoid pravastatin doses above 40 mg/day.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3fa2108c-0300-47b8-9d34-f762af7c93c6
- ModerateFenofibrate and other fibrates
Mechanism: Fibrates with bempedoic acid may increase triglycerides and reduce HDL-C. Fenofibrate and ezetimibe may increase cholesterol excretion into bile and promote cholelithiasis; CIMA states that a lithogenic risk with Nustendi cannot be excluded.
Recommendation: The FDA label does not recommend combining NEXLIZET with fibrates other than fenofibrate. With fenofibrate, if cholelithiasis is suspected, perform gallbladder studies and consider alternative lipid-lowering therapy; CIMA also indicates gallbladder studies. Check triglycerides and HDL-C at 4 weeks and periodically thereafter.
https://cima.aemps.es/cima/dochtml/ft/1201424002/FT_1201424002.htmlhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3fa2108c-0300-47b8-9d34-f762af7c93c6
- ModerateCyclosporine
Mechanism: It may markedly increase ezetimibe exposure and alter cyclosporine levels.
Recommendation: Use caution and monitor cyclosporine concentrations.
https://cima.aemps.es/cima/dochtml/ft/1201424002/FT_1201424002.html
Adverse events
Common (≥1%)
Hyperuricemia · Constipation · Anemia or decreased hemoglobin · Headache or dizziness · Hypertension · Abdominal pain, diarrhea or nausea · Myalgia or muscle spasms · Increased creatinine · Fatigue
Rare but serious
Myopathy or rhabdomyolysis · Anaphylaxis or angioedema · Hepatitis or pancreatitis · Thrombocytopenia
Pregnancy and lactation
CIMA contraindicates it during pregnancy and requires discontinuation before conception or when pregnancy is planned or recognized, with effective contraception. The FDA label directs discontinuation when pregnancy is recognized unless the benefits of treatment outweigh fetal risks. During breastfeeding, CIMA allows the benefit to the child and to the woman to be weighed.