What is in Zetia? The Active Ingredient and Mechanism
Zetia is a brand-name prescription drug containing the active ingredient ezetimibe. Ezetimibe is classified as a cholesterol absorption inhibitor and is also available as a generic medication.
Ezetimibe primarily functions by selectively inhibiting the absorption of cholesterol and related plant sterols in the small intestine. It targets the Niemann-Pick C1-Like 1 (NPC1L1) protein on the intestinal wall, which is responsible for transporting cholesterol. By blocking NPC1L1, ezetimibe prevents dietary and biliary cholesterol from being absorbed and delivered to the liver. This process reduces the cholesterol content in the liver, leading to an increase in LDL receptors. These receptors then enhance the clearance of LDL ('bad') cholesterol from the bloodstream, ultimately lowering blood cholesterol levels.
Unlike statins, which reduce cholesterol production in the liver, ezetimibe's action on absorption makes it a complementary therapy often used with statins for greater cholesterol reduction.
Inactive Ingredients and Formulation
Beyond ezetimibe, Zetia tablets include inactive ingredients that contribute to the tablet's structure and function. The medication is a white to off-white, capsule-shaped oral tablet marked with '414' on one side. It is typically taken once daily, with or without food.
How Zetia Compares with Statins
Zetia and statins both lower cholesterol but use different mechanisms. Combining them often yields better results than either alone.
| Feature | Ezetimibe (Zetia) | Statins (e.g., Lipitor, Crestor) |
|---|---|---|
| Mechanism of Action | Inhibits intestinal absorption of cholesterol. | Inhibits the HMG-CoA reductase enzyme, preventing the liver from making new cholesterol. |
| Primary Effect | Reduces LDL-C and other lipoproteins by decreasing cholesterol delivered to the liver. | Reduces cholesterol production in the liver, also helping to raise HDL and lower triglycerides. |
| Cardiovascular Outcomes | Shown to reduce major cardiovascular events, especially in combination with statins (IMPROVE-IT trial). | Proven to reduce cardiovascular events and mortality. |
| Common Side Effects | Generally mild; may include diarrhea, abdominal pain, and joint pain. | Potential for more severe side effects, including muscle pain, liver problems, and, in rare cases, myopathy or rhabdomyolysis. |
Common Uses and Combination Therapies
Zetia is FDA-approved for managing high cholesterol in specific patient groups, usually with diet changes. This includes use alone or with a statin for primary hyperlipidemia in adults and children 10+, with fenofibrate for mixed hyperlipidemia in adults, with a statin and other treatments for homozygous familial hypercholesterolemia in adults and children 10+, and alone for homozygous sitosterolemia in adults and children 9+. Zetia can be an option for patients who cannot tolerate statins or can be added to statin therapy to lower the statin dose while still reducing LDL-C significantly.
Potential Side Effects and Drug Interactions
Zetia is typically well-tolerated, but side effects can occur. Common ones include diarrhea, joint pain, upper respiratory tract infections, fatigue, back pain, sinusitis, limb pain, and headache.
Less common but more serious side effects include allergic reactions, liver problems, muscle pain (myopathy), and severe muscle breakdown (rhabdomyolysis). The risk of muscle issues increases when Zetia is combined with a statin, especially at high doses.
Zetia can interact with other medications. Bile acid sequestrants can decrease Zetia's effectiveness if taken too close together; it's recommended to take Zetia at least 2 hours before or 4 hours after a sequestrant. Cyclosporine taken with Zetia can increase levels of both drugs, requiring monitoring. Combining Zetia with most fibrates is not advised due to a higher risk of gallstones, though fenofibrate is an exception. An interaction with warfarin is possible, which may necessitate adjusting the warfarin dose.
Conclusion
Zetia contains the active ingredient ezetimibe, a cholesterol absorption inhibitor. Its unique mechanism of blocking intestinal cholesterol absorption offers a valuable approach to managing high cholesterol, either alone or in combination with statins for enhanced lipid-lowering effects. This is particularly useful for patients with statin intolerance or those requiring further LDL-C reduction. While generally safe with mild common side effects, serious reactions like myopathy are possible, especially in combination therapy. Clinical evidence, including the IMPROVE-IT trial, supports ezetimibe's role in reducing cardiovascular risk by effectively lowering LDL-C levels.
