ezetimibe + simvastatin: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
ezetimibe + simvastatin: clinical details
Prescribing considerations
- Review prescribed, over-the-counter and herbal products for CYP3A4, OATP1B1 and BCRP interactions and additive myotoxicity.
- Myopathy risk is greater with higher simvastatin exposure, renal impairment, uncontrolled hypothyroidism, previous statin or fibrate muscle toxicity, hereditary muscle disorders or substantial alcohol use.
- Paediatric initiation requires specialist review; evidence is limited to selected adolescents with heterozygous familial hypercholesterolaemia.
- Moderate or severe hepatic impairment is not a recommended setting for this combination.
Contraindications and cautions
- Hypersensitivity to either active ingredient or an excipient
- Pregnancy or lactation
- Active liver disease or unexplained persistent transaminase elevation
- Concomitant potent CYP3A4 inhibitors
- Concomitant gemfibrozil, ciclosporin or danazol
- Certain combinations with lomitapide in homozygous familial hypercholesterolaemia
Monitoring
- Check liver function before treatment and subsequently when clinically indicated.
- Measure baseline CK when important rhabdomyolysis risk factors are present; investigate CK promptly if unexplained muscle symptoms develop.
- Repeat and follow rising transaminases; interrupt treatment for clinically significant liver injury.
- Monitor INR appropriately with coumarin anticoagulants or fluindione.
- Monitor glucose clinically and biochemically in people at increased diabetes risk.
Clinical pharmacology
Ezetimibe and its active glucuronide undergo enterohepatic recycling and inhibit intestinal NPC1L1. Simvastatin is an inactive lactone converted mainly in the liver to an HMG-CoA reductase inhibitor; CYP3A4, OATP1B1 and BCRP affect exposure and interactions.
Formulation and product differences
- The fixed-dose, white to off-white capsule-shaped tablet is available in several simvastatin strengths.
- Tablets are unscored and should not be divided.
- The formulation contains lactose monohydrate and is essentially sodium-free.
- Pack sizes and container types vary, and not all may be marketed.
ezetimibe + simvastatin interactions
Important interactions include medicines and foods that increase simvastatin exposure, muscle toxicity or anticoagulant effects.
Potent CYP3A4 inhibitors, including clarithromycin, erythromycin, azole antifungals, HIV protease inhibitors and cobicistat-containing products
These combinations are contraindicated because they can markedly increase simvastatin exposure and the risk of myopathy or rhabdomyolysis.
Gemfibrozil, ciclosporin or danazol
Concomitant use is contraindicated because muscle-toxicity risk is increased.
Systemic fusidic acid
Concurrent treatment is not recommended because severe rhabdomyolysis has occurred; clinician review is required.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.