HANHUI HAISHUYAN Rosuvastatin Calcium Tablets For Hypercholesterolemia 5mg*28

[Drug Name]
Generic Name: Rosuvastatin Calcium Tablets
Trade Name: Haishuyan Rosuvastatin Calcium Tablets 5mg x 28 Tablets

[Main Ingredient]
The active ingredient of this product is rosuvastatin calcium.

[Properties]
This product is a pink film-coated tablet.

[Indications/Main Functions]
This product is indicated for primary hypercholesterolemia (type Ila, including heterozygous familial hypercholesterolemia) or mixed dyslipidemia (type b), whose dyslipidemia is not adequately controlled with diet and other non-drug therapies (e.g., exercise therapy, weight loss). This product is also indicated for patients with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering measures (e.g., LDL-density lipoprotein depletion therapy), or when these measures are inadequate.

[Specifications]
5mg x 28 tablets

[Dosage and Administration]
Before starting treatment, patients should be placed on a standard cholesterol-lowering diet and maintain this diet during treatment. The use of this product should be individualized, taking into account the patient's individual cholesterol level, anticipated cardiovascular risk, and potential risk of adverse reactions. Oral administration. The usual starting dose of this product is 5 mg once daily. The selection of the starting dose should take into account the patient's individual cholesterol level, anticipated cardiovascular risk, and potential risk of adverse reactions. For patients requiring more intensive low-density lipoprotein cholesterol (LDL-C) lowering, a starting dose of 10 mg once daily can be considered; this dose controls lipid levels in most patients. If necessary, the dose can be adjusted to the next higher dose level after four weeks of treatment. The maximum daily dose of this product is 20 mg. This product can be taken at any time of day, with or without food. Patients with Renal Impairment: No dose adjustment is required for patients with mild and moderate renal impairment. All doses of this product are contraindicated in patients with severe renal impairment. In patients with hepatic impairment, systemic exposure to rosuvastatin was not increased in subjects with a Child-Pugh score of 7 or less. Elevated systemic exposure was observed in subjects with Child-Pugh scores of 8 and 9. In these patients, renal function should be evaluated. There is no experience with this drug in patients with Child-Pugh scores exceeding 9. This drug is contraindicated in patients with active liver disease. Ethnicity: Increased systemic exposure has been observed in Asian subjects. This factor should be considered when determining the dosage for patients of Asian descent.

[Adverse Reactions]
Adverse reactions observed with this drug were generally mild and transient. In controlled international clinical trials, less than 4% of patients withdrew due to adverse events. The frequency of adverse events is as follows: common (incidence >1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10,000, <1/100); and very rare (<1/10,000). Immune system disorders: Rare: Hypersensitivity reactions, including angioedema. Neurological disorders: Common: Headache, dizziness. Gastrointestinal disorders: Common: Constipation, nausea, abdominal pain. Skin and subcutaneous tissue disorders: Rare: Itching, rash, and urticaria.
Skeletal muscle, joint, and bone disorders: Common: Myalgia. Rare: Myopathy and rhabdomyolysis. Systemic disorders: Common: Asthenia. As with other HMG-CoA reductase inhibitors, the incidence of adverse reactions with this drug tends to increase with increasing dose. Renal effects: Proteinuria (as determined by dipstick) has been observed in patients receiving this drug, with the majority of the protein originating from the renal tubules. Approximately 1% of patients experienced an increase in proteinuria from absent or trace levels to ++ or greater at some point during treatment with the 10 mg and 20 mg doses, and approximately 3% of patients receiving the 40 mg dose experienced this increase. With the 20 mg dose, a slight increase in proteinuria from absent or trace levels to ++ was observed. In most cases, proteinuria spontaneously decreased or resolved with continued treatment. See the package insert for details.

[Contraindications]
This product is contraindicated in the following: 1. Patients with hypersensitivity to rosuvastatin or any of its ingredients. 2. Patients with active liver disease, including patients with unexplained persistent elevations in serum transaminases and any elevations in serum transaminases exceeding three times the upper limit of normal (ULN). 3. Patients with severe renal impairment (creatinine clearance <30 ml/min). 4. Patients with myopathy. 5. Patients taking cyclosporine concomitantly. 6. Pregnant or lactating women, as well as women who may become pregnant and are not using adequate contraceptive measures.

[Drug Interactions]
1. Cyclosporine: When rosuvastatin is coadministered with cyclosporine, the AUC of rosuvastatin is, on average, seven times higher than that observed in healthy volunteers (compared to the same dose of rosuvastatin). Coadministration does not affect cyclosporine plasma concentrations. 2. Vitamin K antagonists: As with other HMG-CoA reductase inhibitors, initiating or increasing the dose of rosuvastatin may result in an increase in the INR in patients taking vitamin K antagonists (e.g., warfarin). Discontinuation of this product or gradual dose reduction may result in a decrease in the INR. In such cases, appropriate INR monitoring is necessary. 3. Gemfibrozil and Other Lipid-Lowering Products: Concomitant use of this product with gemfibrozil may increase the Cmax and AUC of rosuvastatin by 2-fold. 4. Based on data from dedicated interaction studies, no pharmacokinetic interaction is expected between this product and fenofibrate, but a pharmacodynamic interaction may occur. 5. Concomitant use of gemfibrozil, fenofibrate, other fibrates, and lipid-lowering doses (>1 g/day) of niacin with HMG-CoA reductase inhibitors increases the risk of myopathy, possibly due to their ability to cause myopathy when administered alone. 6. Antacids: Concomitant administration of this product with an antacid suspension containing aluminum magnesium hydroxide may reduce rosuvastatin plasma concentrations by approximately 50%. This effect may be mitigated if the antacid is administered 2 hours after taking this product. The clinical significance of this drug interaction has not been studied. 7. Erythromycin: Coadministration of this product with erythromycin resulted in a 20% decrease in the AUC (O-t) and a 30% decrease in the Cmax of rosuvastatin. This interaction may be due to the increased gastrointestinal motility caused by erythromycin. 8. Oral Contraceptives/Hormone Replacement Therapy (HRT): Concomitant use of this product with oral contraceptives increased the AUCs of ethinyl estradiol and norgestrel by 26% and 34%, respectively. These increased plasma concentrations should be considered when selecting oral contraceptive dosages. Pharmacokinetic data are not available in subjects taking this product with HRT, so the possibility of a similar interaction cannot be ruled out. However, in clinical trials, this combination was widely used and well tolerated by patients. 9. Other Medications: Based on data from dedicated drug interaction studies, no clinically relevant interactions are expected between this product and digoxin. 10. Cytochrome P450 Enzymes: Both in vitro and in vivo data indicate that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. Additionally, rosuvastatin is a weak substrate for these enzymes. No clinically relevant interactions were observed between rosuvastatin and fluconazole (an inhibitor of CYP2CP and CYP3A4) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4). Coadministration with itraconazole (a CYP3A4 inhibitor) increased the AUC of rosuvastatin by 28%, an increase not considered clinically significant. Therefore, drug interactions due to cytochrome P450-mediated metabolism are not expected.

[Precautions]
Renal Effects: Proteinuria (as determined by dipstick) was observed in patients treated with high doses, particularly 40 mg. The protein was primarily derived from the renal tubules and, in most cases, was transient or intermittent. Proteinuria is not considered a precursor to acute or progressive renal disease (see "Adverse Reactions"). Effects on Skeletal Muscle: Skeletal muscle effects, such as myalgia, myopathy, and, rarely, rhabdomyolysis, have been reported in patients treated with this drug at all doses, particularly at doses greater than 20 mg. Very rare cases of rhabdomyolysis have been reported with the concomitant use of ezetimibe and HMG-CoA reductase inhibitors. Drug interactions cannot be ruled out, and caution should be exercised when these drugs are used together. Creatine kinase (CK) testing should not be performed after strenuous exercise or in the presence of plausible factors causing CK elevation, as this can confound interpretation of the results. If baseline CK values ​​are significantly elevated (5×ULN), retesting should be performed within 5–7 days. If repeat testing confirms a baseline CK value >5×ULN, treatment should not be initiated. As with other HMG-CoA reductase inhibitors, caution should be exercised when using this drug in patients with predisposing factors for myopathy/rhabdomyolysis. See the package insert for details. Please read this package insert carefully and use as directed by your healthcare provider.

[Pediatric Use]
The safety and efficacy of this drug in children have not been established. Pediatric use experience is limited to a small number of children (aged >8 years) with homozygous familial hypercholesterolemia. Therefore, this drug is not recommended for pediatric use.

[Elderly Use]
No dose adjustment is required.

[Overdose]
There is no specific treatment for overdose with this drug. In the event of an overdose, symptomatic treatment should be initiated, with supportive measures as needed. Liver function and CK levels should be monitored. Hemodialysis may not be significantly effective.

[Pharmacology and Toxicology]
Central Nervous System Toxicity: Several similar drugs have been shown in canine studies to damage CNS blood vessels, including perivascular hemorrhage, edema, and perivascular mononuclear cell infiltration. A drug with a similar structure to this class of drugs has also been shown to cause dose-dependent optic nerve degeneration (Wallrian degeneration of the retinal-geniculate fibers) in dogs at plasma concentrations 30 times higher than the average human concentration at the maximum recommended dose. A female dog given oral rosuvastatin at 90 mg/kg/day (systemic exposure equivalent to 100 times the human exposure at 40 mg/day, based on AUC) was euthanized on day 24 due to moribundity. Choroid plexus interstitial edema, hemorrhage, and partial necrosis were observed. A dog given oral rosuvastatin at 6 mg/kg/day (systemic exposure equivalent to 20 times the human exposure at 40 mg/day, based on AUC) for 52 weeks developed corneal opacity. A dog given oral rosuvastatin at 30 mg/kg/day (systemic exposure equivalent to 60 times the human exposure at 40 mg/day, based on AUC) for 12 weeks developed cataracts. A dog given oral rosuvastatin at 90 mg/kg/day (systemic exposure equivalent to 100 times the human exposure at 40 mg/day, based on AUC) for 4 weeks developed retinal dysplasia and retinal detachment. In dogs, no retinal effects were observed at doses ≤30 mg/kg/day (systemic exposure equivalent to 60 times the human exposure at 40 mg/day, based on AUC) administered continuously for one year. Genotoxicity: Rosuvastatin was negative in the Ames test, mouse lymphoma assay, CHL cell chromosome aberration assay, and mouse micronucleus assay. In a rat fertility study, oral administration of 5, 15, and 50 mg/kg/day was performed in male rats from 9 weeks before mating to mating, and in female rats from 2 weeks before mating to day 7 of gestation. No adverse effects on fertility were observed at the highest dose (systemic exposure equivalent to 10 times the human exposure at 40 mg/day, based on AUC). In dogs, oral administration of 30 mg/kg/day of rosuvastatin for one month resulted in the presence of giant spermatocytes in the testes. Monkeys given rosuvastatin at 30 mg/kg/day orally for six months showed vacuolation of giant spermatocytes and vas deferens epithelium. The above doses in dogs and monkeys, calculated based on body surface area, are equivalent to 20 and 10 times the human equivalent of 40 mg/day, respectively. Similar phenomena have been observed with similar drugs. Female rats given oral doses of 5, 15, and 50 mg/kg/day from before mating to 7 days after mating (systemic exposure equivalent to 10 times the human exposure at 40 mg/day, calculated based on AUC) showed reduced fetal weight and delayed ossification in the high-dose group (systemic exposure equivalent to 10 times the human exposure at 40 mg/day, calculated based on AUC). Rats given oral doses of 2, 10, and 50 mg/kg/day from gestational day 7 to lactation day 21 (weaning) showed decreased pup survival in the high-dose group (12 times or more the human equivalent of 40 mg/day, calculated based on body surface area). Oral administration of 0.3, 1, and 3 mg/kg/day (equivalent to a human exposure of 40 mg/day, based on body surface area) to domestic rabbits from gestational day 6 to lactation day 18 (weaning) resulted in decreased fetal survival and maternal mortality. Rosuvastatin was not teratogenic at doses ≤ 25 mg/kg/day in rats and ≤ 3 mg/kg/day in rabbits (equivalent to a human exposure of 40 mg/day, based on AUC and body surface area, respectively). Carcinogenicity: In a 104-week carcinogenicity study in rats, oral doses of 2, 20, 60, and 80 mg/kg/day were administered. A significant increase in the incidence of uterine polyps was observed in females at 80 mg/kg/day (systemic exposure equivalent to 20 times the human exposure of 40 mg/day, based on AUC), although no increase was observed at lower doses. In a 107-week carcinogenicity study in mice, oral doses of 10, 60, and 200 mg/kg/day were administered. An increased incidence of hepatocellular adenomas/carcinomas was observed in animals in the 200 mg/kg/day dose group (based on AUC, systemic exposure is 20 times the human exposure at 40 mg/day), while no increased incidence was observed at lower doses.