💊 Ezetimibe
Drug Class & Overview
Ezetimibe is a selective cholesterol absorption inhibitor, often used as an adjunct to statin therapy or as monotherapy in patients intolerant to statins. It is a lipid-lowering agent that reduces the absorption of cholesterol from the gut.
Mechanism of Action
Ezetimibe selectively inhibits the Niemann-Pick C1-Like 1 (NPC1L1) protein, which is responsible for cholesterol absorption in the brush border of the small intestine. This reduces the delivery of dietary and biliary cholesterol to the liver, leading to a compensatory increase in hepatic LDL receptor expression and subsequent reduction in circulating LDL cholesterol.
Key Indications
Ezetimibe is indicated for primary hypercholesterolaemia, either as monotherapy in patients intolerant to statins or as an adjunct to statins when the LDL cholesterol target is not met with statin monotherapy. It is also used in homozygous familial hypercholesterolaemia and homozygous sitosterolaemia.
Contraindications
Absolute contraindications include active liver disease or persistent unexplained elevations of serum transaminases when co-administered with a statin. It should be used with caution in patients with moderate to severe hepatic impairment. Pregnancy and breastfeeding are also contraindications.
Adverse Effects
Common adverse effects include gastrointestinal disturbances (e.g., abdominal pain, diarrhoea), headache, and fatigue. When used with a statin, the adverse effect profile may resemble that of the statin, including a small increased risk of myalgia and elevated liver enzymes. Hypersensitivity reactions are rare.
Monitoring
When used in combination with a statin, liver function tests (LFTs) should be monitored according to statin guidelines. If used as monotherapy, routine LFT monitoring is generally not required unless clinically indicated. Lipid profiles should be monitored to assess treatment efficacy.
Prescribing Safety (OSCE)
When prescribing, check for active liver disease, especially if co-prescribing with a statin. Counsel patients on the importance of adherence to therapy and to report any unusual muscle pain or abdominal discomfort. Be aware of interactions with ciclosporin (increased ezetimibe levels) and fibrates (increased risk of cholelithiasis).
MLA High-Yield Notes
High-yield facts include its mechanism of action (inhibiting intestinal cholesterol absorption via NPC1L1) and its role as a second-line agent for LDL-C reduction, either as an add-on to statins or for statin-intolerant patients. Remember it does not cause the same degree of muscle-related side effects as statins when used alone, making it an option for intolerance.
Common SBA Themes
SBAs often focus on ezetimibe's role as an add-on therapy to statins or as an alternative for statin-intolerant patients. Questions might present a patient whose LDL-C remains high despite maximal statin therapy and ask about the next step, or a patient with statin-induced myalgia requiring an alternative lipid-lowering agent. Its unique mechanism of action is also a common theme.
References
- BNF (British National Formulary)
- NICE (National Institute for Health and Care Excellence)
- Joint Formulary Committee. British National Formulary (online)