Zenon Rosuvastatin Calcium and Ezetimibe Tablets (Ⅰ)

1. Indications and Usage
Hypercholesterolemia:
Indicated as an adjunct to diet in adult patients with primary hypercholesterolemia (heterozygous familial or non-familial) or mixed dyslipidemia, whose LDL-C levels have not been adequately controlled on statin monotherapy.
Homozygous Familial Hypercholesterolemia (HoFH):
Indicated as an adjunct to other lipid-lowering therapies (e.g., LDL apheresis) or as an alternative when such therapies are unavailable, to reduce elevated total cholesterol (TC) and LDL-C levels in patients with HoFH.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY. Can be taken at any time of day, with or without food, and swallowed whole with water.
Recommended Dosage:
The recommended dose is one tablet once daily. Patients should continue a low-fat diet during treatment.
Dosing with Bile Acid Sequestrants:
If co-administered with bile acid sequestrants, this product must be taken at least 2 hours before or at least 4 hours after the bile acid sequestrant.
Special Populations:
Hepatic Impairment: No dosage adjustment is required for mild hepatic impairment (Child-Pugh score 5-6). Not recommended for moderate to severe hepatic impairment (Child-Pugh score >6).
Renal Impairment: No dosage adjustment is required for mild to moderate renal impairment. Contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min).
Asian Patients: Due to increased systemic exposure, Asian patients may require a lower starting dose (e.g., rosuvastatin 5 mg/ezetimibe 10 mg), depending on regional availability and clinical judgment.
3. Mechanism of Action
Dual Complementary Action:
This product combines two lipid-lowering agents with complementary mechanisms:
Rosuvastatin: A selective, competitive HMG-CoA reductase inhibitor that reduces endogenous cholesterol synthesis in the liver. It increases hepatic LDL receptor expression, enhancing LDL-C uptake and catabolism.
Ezetimibe: Selectively inhibits the intestinal absorption of dietary and biliary cholesterol by targeting the Niemann-Pick C1-like 1 (NPC1L1) protein at the brush border of the small intestine.
Pharmacodynamic Effect:
The combination significantly lowers LDL-C, total cholesterol, apolipoprotein B, and triglycerides, while raising HDL-C. Maximal therapeutic response is typically achieved within 4 weeks.
4. Safety and Warnings
Contraindications:
Active liver disease, unexplained persistent elevations in serum transaminases (>3x ULN), severe renal impairment, myopathy, pregnancy, lactation, and concomitant use of cyclosporine.
Skeletal Muscle Effects:
Dose-related myalgia, myopathy, and rare rhabdomyolysis with acute renal failure have been reported. Risk is higher in elderly patients (≥65 years) and those with renal impairment. Discontinue if CK levels exceed 5x ULN or if severe muscle symptoms occur.
Hepatic Effects:
Transient, asymptomatic, dose-related elevations in liver enzymes may occur. Monitor liver function tests periodically.
Renal Effects:
Proteinuria has been observed, mostly tubular in origin, usually transient and resolving spontaneously.
5. Adverse Reactions
Most Common:
Headache, dizziness, constipation, nausea, abdominal pain, diarrhea, flatulence, and diabetes mellitus.
Musculoskeletal:
Myalgia, arthralgia, and back pain. Rare cases of immune-mediated necrotizing myopathy.
Metabolic & Endocrine:
Increased blood glucose/HbA1c, leading to new-onset diabetes (especially in patients with risk factors like BMI >30 or impaired fasting glucose).
Immune System:
Rare hypersensitivity reactions, including angioedema.
6. Drug Interactions
Cyclosporine:
Concomitant use is contraindicated due to significantly increased rosuvastatin exposure and heightened risk of myopathy/rhabdomyolysis.
Bile Acid Sequestrants:
May decrease ezetimibe absorption; requires staggered dosing (2 hours before or 4 hours after).
Genetic Polymorphisms:
Patients with SLCO1B1 (OATP1B1) c.521CC or ABCG2 (BCRP) c.421AA genotypes exhibit increased rosuvastatin exposure. Lower doses are recommended for these individuals.
7. Pharmaceutical Information
Chemical Composition:
Each film-coated tablet contains Rosuvastatin calcium 10 mg (equivalent to rosuvastatin 10 mg) and Ezetimibe 10 mg.
Excipients:
Lactose, croscarmellose sodium, sodium lauryl sulfate, povidone, magnesium stearate, microcrystalline cellulose, colloidal silicon dioxide, hypromellose, macrogol 6000, titanium dioxide, and talc.
Appearance:
White to off-white, round, biconvex, film-coated tablets with a white to pale yellow core upon removal of the coating.
Storage:
Store in a tightly closed container, protected from moisture and light, at temperatures below 30°C (86°F).