Ezetim10 mg

Ezetim is indicated, as an adjunct to diet, for the management of elevated cholesterol. Indications are classified below by strength of evidence.

Established / FDA-approved uses

• Primary hyperlipidemia: Ezetim, alone or in combination with a statin, reduces total cholesterol, LDL-cholesterol, and apolipoprotein B in patients with primary (heterozygous familial or non-familial) hyperlipidemia.
• Homozygous familial hypercholesterolemia (HoFH): Ezetim, in combination with atorvastatin or simvastatin, is used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or when such treatments are unavailable.
• Homozygous sitosterolemia (phytosterolemia): Ezetim reduces elevated sitosterol and campesterol levels.
• Mixed hyperlipidemia: Ezetim in combination with fenofibrate is used to reduce total cholesterol, LDL-C, apolipoprotein B, and triglycerides, and to increase HDL-C.

Guideline-supported / combination-therapy use

• Cardiovascular risk reduction: when added to a statin in patients with established atherosclerotic cardiovascular disease (e.g., after acute coronary syndrome), Ezetim combination therapy has been shown in outcome trials to further reduce the risk of major cardiovascular events compared with statin therapy alone. This requires combination therapy with a statin and is not an effect of Ezetim monotherapy.

Note: Ezetim monotherapy has a modest LDL-lowering effect (roughly 15–20%); combination with a statin is more common in practice and produces substantially greater lipid lowering.

Each tablet contains Ezetimibe INN 10 mg as the active ingredient, along with standard pharmaceutical excipients. Ezetimibe is also available as a fixed-dose combination tablet with a statin (e.g., simvastatin) in some markets.

Ezetim is a selective cholesterol absorption inhibitor belonging to the azetidinone class of lipid-lowering agents. Unlike statins, which reduce hepatic cholesterol synthesis, Ezetim acts at the brush border of the small intestine to block absorption of dietary and biliary cholesterol, lowering the delivery of cholesterol to the liver and increasing clearance of cholesterol from the blood.

Ezetim is used alone as an adjunct to diet, or together with a statin or fenofibrate, for the management of elevated cholesterol. It does not affect absorption of triglycerides or fat-soluble vitamins.

Antihyperlipidemic agent – selective cholesterol absorption inhibitor

Mechanism of action

Ezetimibe localizes at the brush border of the small intestine and inhibits the Niemann-Pick C1-Like 1 (NPC1L1) transporter, which mediates intestinal uptake of cholesterol and related phytosterols. By blocking NPC1L1, Ezetimibe reduces delivery of dietary and biliary cholesterol to the liver. This lowers hepatic cholesterol stores and increases clearance of cholesterol from the blood, distinct from statins (which inhibit HMG-CoA reductase) and bile acid sequestrants.

Pharmacokinetics

• Absorption: Ezetimibe is absorbed and extensively conjugated to an active glucuronide metabolite (ezetimibe-glucuronide).
• Distribution: Both Ezetimibe and its glucuronide are more than 90% bound to plasma proteins.
• Metabolism: Primarily via glucuronidation in the small intestine and liver (minimal oxidative CYP metabolism); undergoes enterohepatic recirculation.
• Elimination half-life: Approximately 22 hours for both Ezetimibe and its active metabolite, supporting once-daily dosing.
• Excretion: Roughly 78% in feces and 11% in urine, mainly as the glucuronide conjugate.

Take Ezetim orally, with or without food, at approximately the same time each day. If taken with a bile acid sequestrant, separate dosing by at least 2 hours before or 4 hours after the sequestrant. See Dosage and Administration for details.

Clinically significant interactions with Ezetim include:

• Cyclosporine: Coadministration can substantially increase plasma concentrations of both Ezetim and cyclosporine; cyclosporine levels should be monitored when used together with Ezetim.
• Bile acid sequestrants (e.g., cholestyramine): Reduce absorption of Ezetim; separate administration times as described in Dosage and Administration.
• Fibrates (fenofibrate, gemfibrozil): Fenofibrate combined with Ezetim increases the risk of cholelithiasis (gallstones); gemfibrozil increases Ezetim exposure and concurrent use should generally be avoided.
• Statins: When Ezetim is combined with a statin, there is an increased (though still low) risk of myopathy/rhabdomyolysis compared with statin monotherapy; liver enzymes should be monitored.
• Coumarin anticoagulants (e.g., warfarin): Cases of increased INR have been reported when Ezetim is added to warfarin therapy; INR should be monitored.

Ezetim is generally well tolerated. Reported adverse effects include:

Common

• Upper respiratory tract infection
• Diarrhea
• Arthralgia (joint pain)
• Sinusitis
• Pain in extremity
• Fatigue

When combined with a statin

• Myalgia (muscle pain)
• Elevated liver transaminases
• Increased creatine kinase

Uncommon / rare

• Hypersensitivity reactions (rash, urticaria, angioedema)
• Myopathy and rare rhabdomyolysis (chiefly with concomitant statin)
• Hepatitis
• Thrombocytopenia
• Pancreatitis

Ezetim monotherapy should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus; a physician should be consulted before use in pregnancy. When Ezetim is used together with a statin, the combination is contraindicated in pregnancy because of the statin component.

It is not known whether Ezetim passes into human breast milk. Because many drugs are excreted in breast milk, a decision should be made whether to discontinue nursing or to discontinue Ezetim, taking into account the importance of the drug to the mother; Ezetim combined with a statin should not be used during breastfeeding. Consult a physician before use while breastfeeding.

Liver enzymes: When Ezetim is coadministered with a statin, liver function tests should be performed as recommended for the statin, since combination therapy can increase the risk of transaminase elevation. See Contraindications for use in active liver disease.

Muscle effects: Patients on Ezetim combined with a statin should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by fever or malaise, as this may indicate myopathy or rhabdomyolysis.

Gallbladder disease: Ezetim combined with fenofibrate increases the risk of cholelithiasis; use with caution in patients with pre-existing gallbladder disease.

Severe renal or hepatic impairment: Use Ezetim with caution in severe renal impairment, and avoid in moderate-to-severe hepatic impairment (see Dosage and Administration).

Clinical experience with Ezetim overdose is limited; doses up to 50 mg/day in normal volunteers and up to 40 mg/day in patients with a pre-existing condition have generally been well tolerated in studies. In case of a suspected overdose of Ezetim, seek immediate medical attention or contact a poison control center. Treatment should be symptomatic and supportive; there is no specific antidote.

Store Ezetim at room temperature (below 30°C), protected from light and moisture. Keep out of the reach of children.

Renal impairment: No dose adjustment of Ezetim is needed in mild-to-moderate renal impairment; use with caution and limited data exist in severe renal impairment.

Hepatic impairment: No adjustment is needed in mild hepatic impairment; Ezetim is not recommended in moderate-to-severe hepatic impairment (see Dosage and Administration).

Elderly: No dose adjustment of Ezetim is required based on age alone, though age-related decline in renal/hepatic function should be considered.

Pediatric use: See Pediatric Uses.

Ezetim is generally used long-term as part of chronic management of hyperlipidemia, alongside diet and lifestyle modification. Duration is determined by the treating physician based on lipid response and cardiovascular risk, with periodic monitoring of lipid profile (and liver enzymes if combined with a statin).

Antihyperlipidemic agents; cholesterol absorption inhibitors

Ezetimibe selectively inhibits the NPC1L1 transporter at the intestinal brush border, blocking absorption of dietary and biliary cholesterol. This reduces cholesterol delivery to the liver and lowers circulating LDL-cholesterol, complementing statins (which reduce hepatic cholesterol synthesis) rather than duplicating their mechanism.

C

Safety and efficacy of Ezetim have been established in select pediatric populations:

• Heterozygous familial hypercholesterolemia: Ezetim may be used in children 10 years of age and older, generally in combination with a statin, under specialist supervision.
• Homozygous sitosterolemia: Ezetim may be used in children 6 years of age and older.

Safety and efficacy of Ezetim have not been established in children below these age thresholds or for other indications.