LEPU YOULIPIN Atorvastatin Calcium Tablets For Hypercholesterolemia 20mg*14

[Drug Name]
Generic Name: Atorvastatin Calcium Tablets
Trade Name: Ulipin Atorvastatin Calcium Tablets, 20mg x 7 tablets

[Main Ingredients]
Atorvastatin Calcium

[Properties]
This product is a white film-coated tablet that appears white after removal of the film coating.

[Indications/Main Functions]
For the treatment of hypercholesterolemia and combined hyperlipidemia; prevention and treatment of coronary heart disease and stroke

[Specifications]
20mg x 7 tablets

[Dosage and Administration]
This product can be swallowed orally orally. It can also be dissolved in an appropriate amount of boiled water and allowed to disperse evenly before oral administration. The usual starting dose is 10mg once daily. Dosage adjustments should be made every 4 weeks or longer. The maximum dose is 80mg once daily. Atorvastatin can be taken at any time of day, regardless of meals.

[Adverse Reactions]
1. General: malaise, fever;
2. Digestive System: abdominal discomfort, belching, flatulence, hepatitis, cholestasis;
3. Musculoskeletal System: myalgia, muscle fatigue, neck pain, joint swelling;
4. Nutritional and Metabolic System: elevated transaminases, abnormal liver function tests, elevated blood alkaline phosphatase, elevated creatine phosphokinase, hyperglycemia;
5. Nervous System: nightmares;
6. Respiratory System: epistaxis;
7. Skin and Appendages: urticaria;
8. Special Senses: blurred vision, tinnitus;
9. Genitourinary System: positive urine leukocytes.

[Contraindications]
1. Active liver disease, including persistently elevated liver transaminases of unexplained origin.
2. Known hypersensitivity to any ingredient in this product.
3. Pregnancy. This product is contraindicated in pregnant women or women of childbearing age who may become pregnant. This product may cause fetal harm if taken by pregnant women. Serum cholesterol and triglyceride levels are elevated during normal pregnancy, and
4. Cholesterol or cholesterol derivatives are essential for fetal development. Atherosclerosis is a chronic disease process, so discontinuing lipid-lowering medication during pregnancy in patients with primary hypercholesterolemia has minimal impact on the long-term outcomes of atherosclerotic disease. Adequately controlled studies of atorvastatin use in pregnant women are lacking; however, there have been occasional reports of fetal congenital anomalies associated with intrauterine exposure to statins. Rat and rabbit reproduction studies have not observed evidence of teratogenicity with atorvastatin. Lipitor should be prescribed to women of childbearing potential only if conception is extremely unlikely and who have been informed of the potential risk. If a patient becomes pregnant while taking Lipitor, the drug should be discontinued immediately, and the potential hazard to the fetus should be considered (see [Use in Pregnant and Lactating Women]).
5. Lactating Women: It is unknown whether atorvastatin is excreted in human breast milk; however, other drugs in this class are excreted in breast milk in small amounts. Because statins may have potentially serious adverse reactions in nursing newborns, women taking this drug should not breastfeed.

[Drug Interactions]
During statin therapy, coadministration of the following drugs may increase the risk of myopathy, such as fibrates, lipid-modifying doses of niacin, cyclosporine, or strong CYP3A4 inhibitors (such as clarithromycin, HIV protease inhibitors, and itraconazole) (see [Precautions], "Skeletal Muscle" and [Pharmacology and Toxicology]). 1. Strong CYP3A4 Inhibitors: Lipitor is metabolized by cytochrome P450 3A4. Coadministration of Lipitor with strong CYP3A4 inhibitors may increase atorvastatin plasma concentrations. The extent of the drug interaction and the potential for potentiation depend on the degree to which the drug affects CYP3A4. 2. Clarithromycin: Coadministration of 80 mg of Lipitor with clarithromycin (500 mg twice daily) significantly increased the atorvastatin AUC compared to Lipitor alone (see [Pharmacology and Toxicology]). Therefore, caution should be exercised when Lipitor is used at a dose of 20 mg in patients taking clarithromycin (see "Skeletal Muscle" and "Dosage and Administration" in the "Precautions" section). 3. Co-administration with protease inhibitors: Compared with Lipitor alone, the AUC of atorvastatin was significantly increased when Lipitor 40 mg was co-administered with ritonavir + saquinavir (400 mg twice daily) or when Lipitor 20 mg was co-administered with lopinavir + ritonavir (400 mg + 100 mg twice daily) (see "Pharmacology and Toxicology"). Therefore, caution should be exercised when Lipitor is used at a dose of 20 mg in patients taking HIV protease inhibitors (see "Skeletal Muscle" and "Dosage and Administration" in the "Precautions" section). 4. Itraconazole: The AUC of atorvastatin was significantly increased when Lipitor 40 mg was co-administered with itraconazole 200 mg (see "Pharmacology and Toxicology"). Therefore, caution should be exercised when Lipitor is used at a dose of 20 mg in patients taking itraconazole (see "Skeletal Muscle" and "Dosage and Administration" in the "Precautions" section). 5. Grapefruit juice: Contains one or more components that inhibit cytochrome P450 3A4 and can increase atorvastatin plasma concentrations, especially when large amounts of grapefruit juice are consumed (more than 1.2 liters per day). 6. Cyclosporin: Atorvastatin and its metabolites are substrates for the OATP1B1 transporter. OATP1B1 inhibitors (such as cyclosporin) can increase the bioavailability of atorvastatin. Compared with atorvastatin alone, the combined use of Lipitor 10 mg and cyclosporin 5.2 mg/g/day significantly increased the AUC of atorvastatin (see "Pharmacology and Toxicology"). If coadministration of Lipitor and cyclosporin is necessary, the Lipitor dose should not exceed 10 mg (see "Skeletal Muscle" in the "Precautions" section). 7. Rifampicin and Other Cytochrome P450 3A4 Inducers: Coadministration of Lipitor with cytochrome P450 3A4 inducers (e.g., efavirenz, rifampicin) can result in varying degrees of decreases in atorvastatin plasma concentrations. Due to the dual interaction mechanism of rifampicin, delayed administration of Lipitor after rifampicin is associated with a significant decrease in atorvastatin plasma concentrations. Therefore, coadministration of Lipitor and rifampicin is recommended. 8. Digoxin: When multiple doses of Lipitor are coadministered with digoxin, steady-state plasma concentrations of digoxin increase by approximately 20%. Patients taking digoxin should be appropriately monitored. 9. Oral Contraceptives: Coadministration of Lipitor with oral contraceptives increases the area under the concentration-time curve (AUC) of norethindrone and ethinyl estradiol (see [Pharmacology and Toxicology]) by approximately 30% and 20%, respectively. Women taking this medication should consider this increase in AUC when choosing an oral contraceptive. 10. Warfarin: Lipitor had no clinically significant effect on prothrombin time in patients receiving long-term warfarin therapy.

[Precautions]
1. Skeletal Muscle: Rare case reports of acute renal failure secondary to myoglobinuria caused by rhabdomyolysis have been reported with atorvastatin and other statins. A history of renal impairment may be a risk factor for rhabdomyolysis, and such patients require close monitoring for drug effects on skeletal muscle. Like other statins, atorvastatin may occasionally cause myopathy (defined as muscle pain or weakness accompanied by creatine phosphokinase (CPK) levels exceeding 10 times the upper limit of normal). Concomitant use of high-dose atorvastatin with certain medications, such as cyclosporine or strong CYP3A4 inhibitors (such as clarithromycin, itraconazole, and HIV protease inhibitors), may increase the risk of myopathy or rhabdomyolysis. Myopathy should be considered in any patient with diffuse muscle pain, tenderness, or weakness, and/or significant creatine phosphokinase elevations. Patients should be advised to immediately report unexplained muscle pain, tenderness, or weakness, especially if accompanied by malaise or fever. If a significant elevation in creatine phosphokinase levels occurs or myopathy is confirmed or suspected, atorvastatin therapy should be interrupted. The risk of myopathy is increased during treatment with these medications if cyclosporine A, fibric acid derivatives (fibrates), erythromycin, clarithromycin, ritonavir plus saquinavir or lopinavir plus ritonavir, niacin, or imidazole antifungals are used concurrently. Physicians should carefully weigh the potential benefits and risks when considering the combined use of atorvastatin with fibric acid derivatives (fibrates), erythromycin, clarithromycin, ritonavir plus saquinavir or lopinavir plus ritonavir, immunosuppressive drugs, imidazole antifungals, or lipid-lowering doses of niacin. Patients should be carefully monitored for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of treatment and during dose increases of either medication. When atorvastatin is used concomitantly with the aforementioned medications (see [Drug Interactions]), a reduction in the initial and maintenance dose of atorvastatin should be considered. In this setting, regular creatine phosphokinase testing should be considered, but such monitoring cannot guarantee the prevention of severe myopathy. 2. Liver Function Abnormalities: Like other lipid-lowering therapies, statins can cause abnormalities in liver biochemical parameters. Clinical trial results showed that 0.7% of patients treated with Lipitor experienced persistent elevations in serum transaminases (two or more episodes exceeding three times the upper limit of normal). The incidence of transaminase abnormalities was 0.2%, 0.2%, 0.6%, and 2.3% in patients receiving doses of 10, 20, 40, and 80 mg, respectively. The following findings were observed in patients taking Lipitor in clinical trials: One patient developed jaundice; in the other patients, elevated liver function test (LFT) levels were not associated with jaundice or other clinical signs or symptoms. Following dose reduction, drug interruption, or discontinuation, transaminase levels returned to or near pre-treatment levels without sequelae. Eighteen of the 30 patients with persistent elevations in liver function test levels continued treatment at a reduced Lipitor dose. Liver function tests should be performed before treatment, 12 weeks after starting treatment, and 12 weeks after a dose increase, and periodically thereafter (e.g., every six months). Liver enzyme abnormalities typically occur within the first three months of Lipitor treatment, and patients with elevated transaminases should be monitored until normalization occurs. If ALT or AST levels persist and exceed three times the upper limit of normal, a dose reduction or discontinuation of Lipitor is recommended. Lipitor should be used with caution in patients who consume alcohol excessively and/or have a history of liver disease. It is contraindicated in patients with active liver disease or persistently elevated transaminases. 3. Endocrine Function Statins can interfere with cholesterol synthesis and, theoretically, inhibit adrenal and/or gonadal steroid synthesis. Clinical studies have shown that Lipitor does not reduce basal plasma cortisol concentrations or impair adrenal reserve. The effects of statins on male fertility are insufficiently studied, and their effects on the pituitary-gonadal axis in premenopausal women are currently unknown. Caution should be exercised when statins are coadministered with drugs that reduce the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone, and cimetidine. Central nervous system toxicity has been reported in a female dog given atorvastatin at 120 mg/kg/day for 3 months, resulting in cerebral hemorrhage. Another female dog, treated with atorvastatin at an escalating dose of 280 mg/kg/day for 11 weeks, was sacrificed in a moribund state and also exhibited cerebral hemorrhage and optic nerve vacuolation. A dose of 120 mg/kg body weight, calculated at the maximum human dose of 80 mg per day, results in systemic exposure approximately 16 times the area under the curve (AUC, 0-24 hours) in human plasma. In a 2-year study, one tonic seizure was observed in two male dogs (one receiving 10 mg/kg/day and the other 120 mg/kg/day). No central nervous system damage was observed in mice and rats following long-term dosing for 2 years at doses up to 400 mg/kg/day and 100 mg/kg/day. Based on the recommended maximum human dose of 80 mg daily, these doses represent 6-11 times (mice) and 8-16 times (rats) the area under the curve (AUC) in humans (0-24). Other statins have been associated with central nervous system vascular damage in dogs, characterized by perivascular hemorrhage, edema, and mononuclear cell infiltration into the perivascular space. In clinically normal dogs, another drug of the same chemical structure produced optic nerve degeneration (Wallerian degeneration of the retinal-geniculate fibers) in a dose-dependent manner at plasma levels approximately 30 times higher than the recommended maximum human dose. The SPARCL study (Stroke Prevention with Intensive Cholesterol Lowering) in patients with recent stroke or transient ischemic attack enrolled 4731 patients without coronary artery disease who had a stroke or transient ischemic attack within the previous 6 months and received either 80 mg of Lipitor or placebo. A post-hoc analysis of the study showed that the incidence of hemorrhagic stroke was higher in the 80 mg Lipitor group than in the placebo group (55 patients [2.3%] vs. 33 patients [1.4%], respectively; HR = 1.68; 95% CI: 1.09-2.59; p = 0.0168). The incidence of fatal hemorrhagic stroke was similar in the two groups (17 patients in the atorvastatin and 18 patients in the placebo group). The incidence of nonfatal hemorrhagic stroke was higher in the atorvastatin group (38 patients, 1.6%) than in the placebo group (16 patients, 0.7%). The higher incidence of hemorrhagic stroke in the atorvastatin group was associated with certain baseline characteristics at study entry, including hemorrhagic and lacunar strokes.

[Pediatric Use]
This drug should only be used in children by specialists. Pediatric experience with this drug is limited to a small number of patients (aged 4 to 17 years) with severe lipid disorders, such as homozygous familial hypercholesterolemia.

[Use in Elderly Patients]
Use with caution

[Overdose]
There is no specific treatment for overdose with this drug. In the event of an overdose, patients should receive symptomatic and supportive care as needed. Because atorvastatin is extensively bound to plasma proteins, hemodialysis does not significantly increase its clearance.

[Pharmacology and Toxicology]
Carcinogenic, teratogenic, and reproductive harm.