Winolip EZ180 mg + 10 mg

Winolip EZ is a fixed-dose combination lipid-lowering medicine indicated as an adjunct to diet, either alone or together with maximally tolerated statin therapy, in adults with the following conditions:

• Established/FDA-approved use: Treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein cholesterol (LDL-C).
• Guideline/label-supported use: In patients with, or at high risk for, cardiovascular disease who are statin-intolerant or unable to take an adequate dose of a statin, to reduce the risk of myocardial infarction and coronary revascularization, based on the bempedoic acid component's outcomes data.
• Adjunct use: Used together with a statin when statin therapy alone does not achieve adequate LDL-C reduction.
• Not indicated for: Primary prevention in the general population without elevated cardiovascular risk, and not intended as monotherapy for severe/homozygous familial hypercholesterolemia (specialist-directed therapy is required in that setting).

Winolip EZ is not a substitute for lifestyle measures such as diet, exercise, and weight management, which should continue during treatment.

Each film-coated tablet of Bempedoic acid + Ezetimibe contains two active ingredients:

• Bempedoic acid 180 mg - an ATP citrate lyase (ACL) inhibitor that reduces cholesterol synthesis in the liver.
• Ezetimibe 10 mg - a cholesterol-absorption inhibitor that blocks intestinal absorption of dietary and biliary cholesterol.

Together, the two components of Bempedoic acid + Ezetimibe lower LDL-C through complementary, non-overlapping mechanisms.

Winolip EZ is an oral fixed-dose combination therapy that brings together two distinct classes of lipid-lowering agents in a single tablet. It combines the ATP citrate lyase inhibitor bempedoic acid with the cholesterol-absorption inhibitor ezetimibe.

Winolip EZ is used, as an adjunct to diet and (in most patients) statin therapy, to further reduce elevated LDL cholesterol in adults with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia, including patients who cannot tolerate an adequate dose of a statin.

Winolip EZ belongs to the therapeutic class of antihyperlipidemic (lipid-lowering) agents, specifically the combination of an ATP citrate lyase inhibitor with a cholesterol-absorption inhibitor, used in the management of dyslipidemia and reduction of cardiovascular risk.

Bempedoic acid + Ezetimibe lowers LDL cholesterol through two complementary, non-overlapping mechanisms acting on cholesterol synthesis and absorption.

Bempedoic acid component

Bempedoic acid is a prodrug that is activated in the liver, where it inhibits ATP citrate lyase (ACL), an enzyme upstream of HMG-CoA reductase in the cholesterol biosynthesis pathway. This inhibition reduces hepatic cholesterol synthesis and upregulates low-density lipoprotein (LDL) receptor expression, increasing clearance of LDL-C from the blood. Because the activating enzyme is not present in skeletal muscle, bempedoic acid carries a lower risk of muscle-related adverse effects than statins.

Ezetimibe component

Ezetimibe acts at the brush border of the small intestine, where it inhibits the Niemann-Pick C1-Like 1 (NPC1L1) protein responsible for cholesterol uptake. This reduces delivery of intestinal cholesterol to the liver, decreasing hepatic cholesterol stores and increasing clearance of LDL-C from the blood.

The combined effect of Bempedoic acid + Ezetimibe produces a greater reduction in LDL-C than either component alone.

Winolip EZ tablets should be swallowed whole with water. They may be taken with or without food and at any time of day, but should be taken consistently at the same time each day. Tablets should not be split, crushed, or chewed unless specifically directed by a physician or pharmacist.

Winolip EZ has the following well-established, clinically significant drug interactions:

• Simvastatin: The bempedoic acid component increases simvastatin plasma concentrations, raising the risk of myopathy. When Winolip EZ is used with simvastatin, the simvastatin dose should not exceed 20 mg/day (or 40 mg/day if the patient has previously tolerated simvastatin 80 mg/day without muscle toxicity).
• Pravastatin: The bempedoic acid component increases pravastatin plasma concentrations. When Winolip EZ is used with pravastatin, the pravastatin dose should not exceed 40 mg/day.
• Cyclosporine: Concomitant use increases exposure to both the bempedoic acid and ezetimibe components; monitor for adverse effects, and cyclosporine levels should also be monitored.
• Fibrates (especially gemfibrozil): May increase the risk of cholelithiasis (gallstones) and myopathy when combined with the ezetimibe component; concomitant use should generally be avoided.
• Bile acid sequestrants (e.g., cholestyramine): Reduce absorption of the ezetimibe component; Winolip EZ should be taken at least 2 hours before or 4 hours after a bile acid sequestrant.
• Warfarin and other vitamin K antagonists: Rare reports of increased INR; monitor INR when Winolip EZ is started or the dose is changed in patients on anticoagulants.

The most commonly reported side effects of Winolip EZ include:

• Upper respiratory tract infection
• Muscle spasms
• Hyperuricemia (elevated uric acid levels)
• Back pain
• Abdominal pain, diarrhea, or constipation
• Extremity pain
• Anemia
• Mild elevation of liver enzymes

Less common but clinically important effects include gout flares, tendon rupture or tendinitis, and, rarely, gallstones (cholelithiasis). See Precautions and Warnings for details on monitoring for these effects.

Pregnancy: Winolip EZ is contraindicated in pregnancy. Cholesterol and other products of cholesterol biosynthesis are essential for fetal development, and reducing maternal cholesterol synthesis may cause fetal harm. If a patient becomes pregnant while taking Winolip EZ, the medicine should be discontinued immediately and the patient referred to a physician promptly. Winolip EZ should be used only if clearly needed and only under direct physician supervision if pregnancy occurs, and generally should not be used at all during pregnancy given the availability of contraindication-level guidance.

Lactation: It is not known whether the components of Winolip EZ pass into human breast milk. Because of the potential for serious adverse effects in a nursing infant, breastfeeding is not recommended during treatment with Winolip EZ; a physician should advise on either discontinuing breastfeeding or discontinuing the medicine, considering the importance of therapy to the mother.

The following precautions apply to patients using Winolip EZ:

• Hyperuricemia and gout: The bempedoic acid component may increase serum uric acid levels and has been associated with new onset or worsening of gout, particularly in patients with a prior history of gout. Uric acid levels may be monitored, and patients should report joint pain or swelling.
• Tendon rupture: Tendon rupture or tendon injury has been reported with the bempedoic acid component, particularly involving the rotator cuff, biceps tendon, or Achilles tendon, and may occur within weeks to months of starting treatment. Winolip EZ should be discontinued promptly and the patient evaluated if tendon pain, swelling, or inflammation occurs; risk may be increased in patients with a history of tendon disorders, renal failure, or concomitant corticosteroid or fluoroquinolone use.
• Liver enzyme elevations: Periodic monitoring of liver function is reasonable, particularly when Winolip EZ is used together with a statin, as elevated transaminases have been reported.
• Myopathy/rhabdomyolysis: This risk is primarily associated with concomitant statin therapy rather than with Winolip EZ itself; patients on combined regimens should be counseled to report unexplained muscle pain, tenderness, or weakness.
• Gastrointestinal effects: Mild diarrhea and abdominal discomfort have been reported with the ezetimibe component and are usually self-limited.
• Renal function: Dosing should be individualized with consideration of renal function, as efficacy may be reduced in significant renal impairment (see Dosage and Administration).

There is limited clinical experience with overdose of Winolip EZ. In the event of a suspected overdose, the patient should seek immediate medical attention or contact a poison control center/emergency services. Management is supportive and symptomatic, guided by the patient's clinical status; there is no specific antidote. Do not attempt home treatment for a suspected overdose.

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

Elderly: No overall differences in safety or effectiveness of Winolip EZ have been observed between elderly and younger patients, though greater sensitivity in some older individuals cannot be ruled out.

Renal impairment: Use with caution in patients with eGFR below 30 mL/min/1.73m²; such patients were not well represented in clinical trials and may have reduced efficacy (see Dosage and Administration).

Hepatic impairment: Use with caution in moderate to severe hepatic impairment; not well studied.

Pediatric patients: Safety and efficacy of Winolip EZ have not been established in patients under 18 years of age (see Pediatric Uses).

Pregnant or breastfeeding women: See Pregnancy and Lactation.

Winolip EZ is intended for long-term, ongoing use as part of chronic management of elevated LDL cholesterol and cardiovascular risk reduction. Treatment duration is determined by the prescribing physician based on lipid response, tolerability, and overall cardiovascular risk, and is typically continued indefinitely alongside diet and lifestyle measures unless a physician advises stopping.

Bempedoic acid + Ezetimibe combines two drug classes: an ATP citrate lyase (ACL) inhibitor (bempedoic acid) and a cholesterol-absorption inhibitor (ezetimibe), both within the broader category of antihyperlipidemic agents.

Bempedoic acid + Ezetimibe lowers LDL cholesterol via two complementary pathways: the bempedoic acid component inhibits ATP citrate lyase in the liver to reduce cholesterol synthesis and upregulate LDL receptors, while the ezetimibe component blocks the NPC1L1 transporter in the intestine to reduce cholesterol absorption. Together these mechanisms increase clearance of LDL-C from the bloodstream more effectively than either agent alone.

The safety and efficacy of Winolip EZ have not been established in pediatric patients under 18 years of age. Winolip EZ is not recommended for use in children or adolescents, and use in this population should be avoided outside of specialist-directed care for rare inherited lipid disorders where a physician determines the potential benefit justifies the unknown risk.