Ezetimibe

Ezetimibe is a cholesterol-lowering medication that works by reducing the absorption of dietary and biliary cholesterol from the small intestine.

It is prescribed for the treatment of primary hypercholesterolaemia, either alone or in combination with a statin, and for homozygous familial hypercholesterolaemia as an adjunct to other lipid-lowering treatments.

Unlike statins, which reduce cholesterol production in the liver, ezetimibe targets a different step in cholesterol metabolism.

It selectively inhibits the Niemann-Pick C1-Like 1 (NPC1L1) protein on the intestinal brush border, blocking cholesterol uptake into enterocytes.

This leads to a compensatory increase in hepatic LDL receptor expression, further lowering circulating LDL cholesterol.

When combined with a statin, ezetimibe provides additional LDL reduction of approximately 15 to 20 per cent beyond what the statin achieves alone.

The IMPROVE-IT trial demonstrated that the combination of ezetimibe and simvastatin reduced cardiovascular events compared with simvastatin alone in patients with recent acute coronary syndrome.

Take one ezetimibe tablet daily by mouth, with or without food. It may be taken at any time of day, though taking it at a consistent time helps with adherence.

If you are also taking a statin, both medications may be taken at the same time. Swallow the tablet whole with water.

Continue taking ezetimibe even if you feel well, as high cholesterol typically causes no symptoms.

Dietary modification, regular exercise, and weight management should be maintained alongside the medication. Do not stop or change your dose without consulting your prescriber.

The standard adult dose is 10 mg once daily. No dose adjustment is required for elderly patients or those with mild to moderate hepatic or renal impairment.

Ezetimibe is not recommended in patients with moderate to severe hepatic impairment when used in combination with a statin.

In children aged 6 years and over with familial hypercholesterolaemia, the dose is also 10 mg once daily under specialist supervision.

Common side effects (affecting 1 in 10 to 1 in 100 patients) include headache, abdominal pain, diarrhoea, and flatulence.

When used with a statin, the side-effect profile largely reflects that of the statin component.

Uncommon effects include elevated liver transaminases, particularly when co-administered with a statin.

Myalgia (muscle pain) may occur, though the risk of clinically significant myopathy is low with ezetimibe monotherapy.

Rare adverse effects include hypersensitivity reactions (rash, urticaria, anaphylaxis), pancreatitis, hepatitis, thrombocytopenia, and rhabdomyolysis (almost exclusively reported in combination with a statin).

If you develop unexplained muscle pain, tenderness, or weakness, particularly if accompanied by fever or dark urine, contact your doctor immediately.

If ezetimibe is prescribed with a statin, liver function tests should be checked before starting and periodically thereafter.

Report any signs of liver injury such as unexplained fatigue, loss of appetite, right upper abdominal pain, dark urine, or yellowing of the skin.

Patients taking fibrates concurrently should be monitored for gallstone formation. Ezetimibe should not be combined with a statin during pregnancy or breastfeeding.

Ezetimibe is contraindicated in patients with known hypersensitivity to the active substance or any excipient.

When given in combination with a statin, it is contraindicated in active liver disease, persistently elevated transaminases of unexplained cause, pregnancy, and breastfeeding.

Ezetimibe with a statin is not recommended in moderate to severe hepatic impairment.