Zetia

Zetia (ezetimibe) represents a significant advancement in the management of hypercholesterolemia, offering a unique, targeted mechanism of action distinct from statin therapy. As a selective cholesterol absorption inhibitor, Zetia works directly within the intestine to reduce the amount of dietary and biliary cholesterol entering the bloodstream. This monograph provides a comprehensive, evidence-based overview for healthcare professionals seeking to optimize lipid-lowering regimens for their patients, particularly those who require additional LDL-C reduction beyond what statins alone can achieve or for whom statins are not tolerated.

Features

• Active ingredient: Ezetimibe 10mg
• Pharmacologic class: Selective cholesterol absorption inhibitor
• Administration: Oral tablet
• Bioavailability: Not significantly affected by food
• Protein binding: >90% to human plasma proteins
• Metabolism: Primarily in the small intestine and liver via glucuronide conjugation
• Elimination: Half-life approximately 22 hours; primarily excreted in feces
• FDA-approved for: Primary hyperlipidemia, homozygous familial hypercholesterolemia, homozygous sitosterolemia

Benefits

• Provides significant additional LDL-C reduction when added to statin therapy (typically 15-20% further reduction)
• Offers an alternative lipid-lowering approach for statin-intolerant patients
• Works through a complementary mechanism to statins, targeting intestinal cholesterol absorption rather than hepatic synthesis
• Demonstrated cardiovascular outcomes benefit when combined with simvastatin in the IMPROVE-IT trial
• May be particularly effective for patients with sitosterolemia or those who are poor responders to statin monotherapy
• Does not significantly affect the absorption of fat-soluble vitamins

Common use

Zetia is primarily indicated as adjunctive therapy to diet for the reduction of elevated total cholesterol, LDL cholesterol, and apolipoprotein B in patients with primary hyperlipidemia, either alone or in combination with an HMG-CoA reductase inhibitor (statin). It is also approved for the reduction of elevated sitosterol and campesterol levels in patients with homozygous familial sitosterolemia. In clinical practice, it is most commonly prescribed when maximally tolerated statin therapy fails to achieve LDL-C goals, or when patients cannot tolerate adequate statin doses due to muscle-related symptoms.

Dosage and direction

The recommended dosage of Zetia is 10mg once daily, with or without food. It may be administered at the same time as statins or other lipid-lowering agents. For patients with mild hepatic impairment (Child-Pugh score 5-6), no dosage adjustment is necessary. In moderate to severe hepatic impairment, the effects of Zetia are not known, and caution should be exercised. No dosage adjustment is required for renal impairment or in elderly patients. The tablet should be swallowed whole and not crushed or chewed.

Precautions

Liver function tests should be performed at initiation and during therapy according to clinical judgment. When used with statins, follow the statin labeling for liver enzyme monitoring. Zetia is not recommended in patients with moderate to severe hepatic impairment. Caution should be exercised when administering to patients with a history of gallstones, as cholesterol is excreted in bile and may contribute to stone formation. Patients should be advised to continue following a cholesterol-lowering diet during treatment. Monitor for muscle pain, tenderness, or weakness, particularly when used in combination with statins.

Contraindications

Zetia is contraindicated in patients with a known hypersensitivity to any component of the medication. The combination of Zetia with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations in hepatic transaminases. Concomitant use with fibrates is generally not recommended unless the potential benefit outweighs the increased risk of cholelithiasis. The combination of Zetia with a statin is contraindicated in pregnant and breastfeeding women.

Possible side effects

Most common adverse reactions (incidence >2% and greater than placebo) include: upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremity. Less common but potentially serious side effects may include: elevated hepatic transaminases (particularly when combined with statins), myopathy/rhabdomyolysis (rare, but risk increased with statin combination), hypersensitivity reactions including angioedema and rash, pancreatitis, and cholelithiasis. Hepatic enzyme elevations generally return to baseline after discontinuation or with continued therapy.

Drug interaction

Ciclosporin: Concomitant use increases ezetimibe concentrations approximately 12-fold; monitor for adverse effects. Fibrates: May increase cholesterol excretion into bile, potentially increasing risk of cholelithiasis; combination generally not recommended. Cholestyramine: Reduces ezetimibe AUC by approximately 55%; administer Zetia at least 2 hours before or 4 hours after bile acid sequestrants. Fenofibrate: Increases total ezetimibe concentrations approximately 1.5-fold; monitor for adverse effects. Warfarin: Small effect on INR reported; monitor INR when initiating or discontinuing Zetia. Other fibrates and lipid-lowering agents: Use with caution due to potential additive effects.

Missed dose

If a dose is missed, patients should take it as soon as they remember, unless it is almost time for the next dose. In that case, they should skip the missed dose and resume the usual dosing schedule. Patients should not take two doses at the same time to make up for a missed dose. Healthcare providers should educate patients about the importance of adherence to achieve optimal lipid-lowering effects.

Overdose

Experience with Zetia overdose is limited. In clinical studies, administration of 50mg daily for 14 days was generally well tolerated. In the event of overdose, symptomatic and supportive measures should be taken. Ezetimibe is not dialyzable due to extensive protein binding. Liver function should be monitored, and appropriate treatment instituted if necessary. There is no specific antidote for ezetimibe overdose.

Storage

Store at room temperature, 20-25°C (68-77°F), with excursions permitted to 15-30°C (59-86°F). Keep in the original container to protect from moisture and light. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging. Properly discard any unused medication that is no longer needed.

Disclaimer

This information is intended for healthcare professionals and should not replace professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read in this product information. Individual patient responses may vary, and therapeutic decisions should be based on the clinician’s judgment and knowledge of the patient’s comprehensive medical history.

Reviews

Clinical trials and post-marketing experience demonstrate that Zetia provides consistent LDL-C reduction with generally favorable tolerability. The IMPROVE-IT trial showed that adding ezetimibe to simvastatin therapy resulted in significant additional reduction in major cardiovascular events compared to simvastatin alone in patients with acute coronary syndrome. Real-world evidence supports its utility in statin-intolerant patients and those requiring additional LDL-C lowering. Most prescribers report satisfactory efficacy with a favorable side effect profile, particularly noting its value as an add-on therapy when statin monotherapy is insufficient. Patient satisfaction surveys indicate good adherence rates due to once-daily dosing and generally minimal side effects.