Ezetimibe
Regulatory sources consulted
- openfda-label-697ae8a7-2359-455f-9c21-e266f1c31288
- aemps-ft-65382
- ansm-rcp-69988728
- PubMed PMID:35863366 ↗
- PubMed PMID:39111840 ↗
- PubMed PMID:37956957 ↗
- PubMed PMID:38599725 ↗
- PubMed PMID:36770634 ↗
- professional-knowledge
- OpenFDA · C10AX09
- RxNorm rxcui 341248 ↗
Approved indications
- Adjunctive therapy to diet for patients with primary (heterozygous familial and non-familial) hypercholesterolemia or mixed hyperlipidemia, when a statin is considered inappropriate or is not tolerated. As monotherapy or in combination with a statin.
- In combination with a statin, as adjunctive therapy to diet for patients with Homozygous Familial Hypercholesterolemia (HoFH).
- Adjunct to statin therapy or administered concomitantly with a statin, to reduce the risk of cardiovascular events in patients with coronary heart disease (CHD) and a history of acute coronary syndrome (ACS).
Contraindications
Absolute
- Hypersensitivity to the active substance or to any of the excipients.
- When combined with a statin: active liver disease or unexplained persistent elevations in serum transaminases.
- When combined with a statin: pregnancy and lactation.
Clinical warnings
- Major warning · Risk of myopathy/rhabdomyolysis, especially when used in combination with a statin. Very rare cases have been reported with ezetimibe monotherapy. Patients should be advised to promptly report any unexplained muscle pain, tenderness, or weakness. — EMA SPC
- Elevations in serum transaminases. Liver function tests are recommended at initiation of combination therapy with a statin and thereafter when clinically indicated. — EMA SPC
Drug interactions
- HighCyclosporineL04AD01
Mechanism: Significant increase in exposure to both ezetimibe (AUC ↑3.4x to 12x) and cyclosporine. Complex mechanism, possibly involving inhibition of transporters like OATP1B1.
Recommendation: Concomitant use requires caution and close monitoring. Some SPCs for statin combinations contraindicate it. Evaluate risk/benefit in monotherapy.
EMA SPCOpenFDA label
- ModerateFibratesC10AB
Mechanism: Fibrates increase cholesterol excretion into the bile, increasing the risk of cholelithiasis. Ezetimibe may also increase cholesterol in gallbladder bile. Modest increase in ezetimibe exposure.
Recommendation: Coadministration with gemfibrozil is not recommended. With fenofibrate, monitor for signs of cholelithiasis. If suspected, gallbladder studies are indicated and alternative therapy should be considered.
EMA SPCOpenFDA label
- ModerateCholestyramineC10AC01
Mechanism: Cholestyramine (a bile acid sequestrant) decreases the AUC of total ezetimibe by ~55% by binding to it in the intestine, reducing its absorption.
Recommendation: Administer ezetimibe at least 2 hours before or 4 hours after cholestyramine to avoid the interaction.
OpenFDA labelEMA SPC
Adverse events
Common (≥1%)
diarrhea · abdominal pain · fatigue · myalgia · headache · increased ALT
Rare but serious
rhabdomyolysis · myopathy · hepatitis · pancreatitis · thrombocytopenia · hypersensitivity reactions (including angioedema and anaphylaxis)
Pregnancy and lactation
Contraindicated in combination with a statin. As monotherapy, it should be avoided during pregnancy and lactation unless strictly necessary, due to lack of safety data.
Recent literature (PubMed)
El ensayo RACING demostró que la terapia combinada de estatina de intensidad moderada (rosuvastatina 10 mg) con ezetimiba 10 mg no fue inferior a la monoterapia con estatinas de alta intensidad (rosuvastatina 20 mg) para resultados cardiovasculares a 3 años en pacientes con ECVA. La terapia combinada logró un mayor porcentaje de pacientes con C-LDL <70 mg/dL y tuvo una menor tasa de intolerancia.
Revisión que resume la evidencia sobre la regresión de la placa coronaria con terapia hipolipemiante. Destaca que la reducción del C-LDL mediante estatinas combinadas con ezetimiba y/o inhibidores de PCSK9 muestra consistentemente mejoras en la carga de placa y cambios morfológicos favorables.
Artículo de revisión sobre la dislipidemia diabética. Posiciona a las estatinas como pilar del tratamiento y a la ezetimiba como la terapia de combinación de elección para pacientes que no alcanzan los objetivos de C-LDL solo con estatinas.
Revisión sobre la hipercolesterolemia familiar (HF). Subraya la importancia del diagnóstico y tratamiento tempranos. Menciona que si no se alcanzan los objetivos de C-LDL con la dosis máxima de estatina, se puede añadir ezetimiba antes de considerar terapias más nuevas como los inhibidores de PCSK9.
Revisión narrativa sobre la lipoproteína(a) (Lp(a)). Señala que las terapias hipolipemiantes estándar como las estatinas y la ezetimiba tienen un efecto mediocre en la reducción de los niveles de Lp(a), un factor de riesgo cardiovascular causal.