Atorvastatin Calcium Tablets

1. Mechanism of Action Lipitor is a selective, competitive inhibitor of HMG-CoA reductase. The role of HMG-CoA is to convert hydroxymethylglutaryl coenzyme A into mevalonate, a precursor of sterols including cholesterol. Clinical, pathological and epidemiological studies have shown that elevated plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) promote the formation of atherosclerosis in humans and are risk factors for cardiovascular disease, while elevated levels of high-density lipoprotein cholesterol are associated with a reduced risk of cardiovascular disease. In animal models, Lipitor reduces plasma cholesterol and lipoprotein levels by inhibiting the synthesis of HMG-CoA reductase and cholesterol in the liver, and increases the number of LDL receptors on the surface of liver cells to enhance the uptake and catabolism of low-density lipoproteins; Lipitor also reduces low-density lipoprotein production and the number of low-density lipoprotein particles. Lipitor can reduce the level of low-density lipoprotein cholesterol in some patients with homozygous familial hypercholesterolemia (FH), for whom other lipid-lowering drugs usually have little clinical efficacy. Lipitor reduces total cholesterol, LDL cholesterol, and apolipoprotein B levels in patients with homozygous and heterozygous familial hypercholesterolemia, non-familial hypercholesterolemia, and mixed dyslipidemia. Lipitor also reduces very low-density lipoprotein cholesterol and triglyceride levels, and can increase high-density lipoprotein cholesterol and apolipoprotein A-1 levels. Lipitor reduces total cholesterol, LDL cholesterol, very low-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and non-high-density lipoprotein cholesterol in patients with simple hypertriglyceridemia, and increases high-density lipoprotein cholesterol levels. Lipitor can reduce intermediate-density lipoprotein cholesterol in patients with dyslipoprotein B. 2. Pharmacodynamics Lipitor and some of its metabolites are pharmacologically active in the human body. The liver is the basic site of action and the main site of cholesterol synthesis and LDL clearance. The dosage rather than the systemic drug concentration is more related to the reduction of LDL cholesterol. Individualized dosage should be determined based on the efficacy of treatment (see [Dosage and Administration]).

The main ingredient of this product is atorvastatin calcium.

This product is a white oval film-coated tablet.

1. Hypercholesterolemia Patients with primary hypercholesterolemia, including familial hypercholesterolemia (heterozygous type) or mixed hyperlipidemia (equivalent to type IIa and IIb of Fredrickson classification), can use this product to treat elevated total cholesterol, elevated low-density lipoprotein cholesterol, elevated apolipoprotein B and elevated triglycerides if dietary therapy and other non-drug treatments are unsatisfactory. In patients with homozygous familial hypercholesterolemia, atorvastatin calcium can be used in combination with other lipid-lowering therapies (such as LDL plasma dialysis) or alone (when no other treatment is available) to lower total cholesterol and low-density lipoprotein cholesterol. 2. Coronary heart disease Coronary heart disease or coronary heart disease-related critical illnesses (such as diabetes, symptomatic atherosclerotic disease, etc.)

Before starting treatment with this product, patients should follow a standard low-cholesterol diet and maintain a reasonable diet throughout the treatment period. The dose should be adjusted individually based on the baseline level of low-density lipoprotein cholesterol, treatment goals, and the patient's treatment effect. 1. The commonly used starting dose is 10 mg once a day. The dose adjustment interval should be 4 weeks or longer. The maximum dose of this product is 80 mg once a day. The daily dose of atorvastatin can be taken once at any time of the day and is not affected by meals. For patients at low risk of cardiovascular events, the treatment goal is LDL-C <4.14mmol/L (or <160mg/dL) and total cholesterol <6.22mmol/L (or <240mg/dL); for patients at intermediate risk, the treatment goal is LDL-C <3.37mmol/L (or <130mg/dL) and total cholesterol <5.18mmol/L (or <200mg/dL); for patients at high risk, the treatment goal is LDL-C <2.59mmol/L (or <100mg/dL) and total cholesterol <4.14mmol/L (or <160mg/dL); for patients at very high risk, the treatment goal is LDL-C <2.07mmol/L (or <80mg/dL) and total cholesterol <3.11mmol/L (or <120mg/dL). From the "Guidelines for the Prevention and Treatment of Dyslipidemia in Adults in China" in the Chinese Journal of Cardiovascular Diseases, Vol. 35, No. 5, pp. 390-413, 2007. 2. Treatment of primary hypercholesterolemia and mixed hyperlipidemia Most patients can control their blood lipid levels by taking atorvastatin calcium 10 mg once a day. Significant therapeutic effects can be seen within 2 weeks of treatment, and the maximum therapeutic effect can be seen within 4 weeks of treatment. Long-term treatment can maintain the therapeutic effect. 3. Treatment of heterozygous familial hypercholesterolemia The initial dose for patients should be 10 mg/day. The dose should be gradually adjusted to 40 mg/day every 4 weeks in accordance with the principle of individualized dose. If satisfactory therapeutic effect is still not achieved, the dose can be adjusted to the maximum dose of 80 mg/day or 40 mg once a day can be used in combination with bile acid chelators. 4. Treatment of homozygous familial hypercholesterolemia In a charity drug study involving 64 patients, 46 patients had confirmed LDL receptor information. The LDL-C of these 46 patients decreased by an average of 21%. The dose of this product can be increased to 80 mg/day. For patients with homozygous familial hypercholesterolemia, the recommended dose of this product is 10-80 mg/day. Atorvastatin calcium should be used as an adjunct to other lipid-lowering treatments (such as LDL plasma dialysis). Or when these treatment conditions are not available, this product can be used alone. 5. Dosage for patients with renal insufficiency Kidney disease will neither affect the plasma concentration of this product nor its lipid-lowering effect, so there is no need to adjust the dose.

Clinical Adverse Reactions During the implementation of clinical trials, the conditions of the subjects are complicated; therefore, the incidence rates of adverse reactions obtained from two different drugs in clinical studies cannot be directly compared, and may not reflect the incidence rates of adverse reactions in clinical practice. A total of 16,066 patients were enrolled in the placebo-controlled clinical trials of Lipitor (Lipitor n=8755, placebo n=7311, aged 10 to 93 years, 39% female; 91% Caucasian, 3% black, 2% Asian, 4% other races, with a median treatment period of 53 weeks; 9.7% and 9.5% of patients in the Lipitor and placebo groups, respectively, discontinued the drug due to adverse reactions, regardless of causality. The five most common adverse reactions that led to patient discontinuation and occurred more frequently in the Lipitor group than in the placebo group were: 1. Myalgia (0.7%), 2. Diarrhea (0.5%), 3. Nausea (0.4%), 4. Elevated ALT (0.4%) and elevated liver enzymes (0.4%). Regardless of causality, the most common adverse reactions in the placebo-controlled trials of Lipitor (n=8755) (2%) ) and the incidence rate was higher than that of placebo, in order: 1. Nasopharyngitis (8.3%), 2. Arthralgia (6.9%), 3. Diarrhea (6.8%), 4. Pain in the limbs (6.0%), 5. Urinary tract infection (5.7%). Other adverse reactions reported in placebo-controlled studies include: 1. General: malaise, fever. 2. Digestive system: abdominal discomfort, heating, flatulence, hepatitis, cholestasis. 3. Musculoskeletal system: skeletal myocardial pain, muscle fatigue, neck pain, joint swelling. 4. Nutritional and metabolic system: increased transaminase, abnormal liver function test, increased blood alkaline phosphatase, increased creatine phosphokinase, hyperglycemia. 5. Nervous system: nightmare. 6. Respiratory system: epistaxis. 7. Skin and appendages: urticaria. 8. Special senses: blurred vision, tinnitus. 9. Urogenital system: positive urine leukocytes.

1. Active liver disease, which may include unexplained persistent elevation of liver transaminases. 2. Known allergy to any ingredient in this product. 3. Pregnancy. This product is prohibited for pregnant women or women of childbearing age who may become pregnant. Pregnant women may cause harm to the fetus when taking this product. In normal pregnancy, serum cholesterol and triglyceride levels in the body are elevated, and cholesterol or cholesterol derivatives are essential substances for fetal development. Atherosclerosis is a chronic disease process, so the discontinuation of lipid-lowering drug treatment during pregnancy in patients with primary hypercholesterolemia has little effect on the long-term outcome of atherosclerotic disease. There is currently a lack of sufficient controlled studies on pregnant women taking atorvastatin; however, occasional reports have observed that congenital abnormalities of the fetus may occur when exposed to statins in utero. Rat and rabbit reproduction studies have not observed evidence that atorvastatin is teratogenic. For women of childbearing age, only those who are extremely unlikely to become pregnant and have been informed of the potential hazards can be prescribed Lipitor. If a patient becomes pregnant during medication, the drug should be discontinued immediately, and the potential harm of the drug to the fetus should be considered (see [Use of drugs in pregnant and lactating women]). 4. It is not known whether atorvastatin can be secreted from human breast milk during lactation; however, other drugs of this type can be secreted into breast milk in small amounts. Because statins may have potentially serious adverse reactions on breastfed newborns, women taking this product are prohibited from breastfeeding (see [Use of atorvastatin in pregnant and lactating women]).

Precautions for children: This product should only be used in children by specialists. The experience of treating children with this product is limited to a small number of patients (4 to 17 years old) with severe lipid disorders such as homozygous familial hypercholesterolemia. The recommended starting dose of this product in this patient population is 10 mg/day. There is no safety data on the growth and development of this population. Precautions during pregnancy and lactation: 1. Pregnant women or women of childbearing age who may become pregnant are prohibited from taking Lipitor. 1) Serum cholesterol and triglyceride levels in the body are elevated during normal pregnancy, and cholesterol or cholesterol derivatives are essential substances for fetal development. Atherosclerosis is a chronic disease process, so the discontinuation of lipid-lowering drug treatment during pregnancy in patients with primary hypercholesterolemia has little effect on the long-term outcome of atherosclerotic disease. 2) There is currently a lack of adequate controlled studies on the use of Lipitor during pregnancy. There are rare reports of congenital abnormalities caused by intrauterine exposure to statins. A follow-up study involving approximately 100 pregnant women exposed to other statins found that the incidence of congenital anomalies, spontaneous abortion, and fetal death/stillbirth did not exceed the expected values for the general population, but this study could only exclude a risk of 3-4 times the basic incidence of congenital anomalies. At the same time, 89% of the patients started taking the drug before pregnancy, but stopped taking the drug within 3 months after being informed of pregnancy. 3) Atorvastatin crosses the placenta of rats and reaches the same drug level in the fetal liver as in maternal plasma. Atorvastatin did not produce teratogenic effects when the dose was up to 300 mg/kg/day in rats and 100 mg/kg/day in rabbits. Based on body surface area (mg/m2), these doses are approximately 30 times (rats) or 20 times (rabbits) the human exposure dose (see [Contraindications], Pregnancy). In one study, rats were dosed with 20, 100, or 225 mg/kg/day from gestation day 7 to lactation day 21 (weaning), and pups had reduced survival at birth, neonatal, weaning, and maturity when the mothers were dosed with 225 mg/kg/day. Pups with 100 mg/kg/day had reduced body weights at 4 and 21 days; pups with 225 mg/kg/day had reduced body weights at birth, 4 days, 21 days, and 91 days; and pups had developmental delays (Rothel syndrome at 100 mg/kg/day and auditory startle response at 225 mg/kg/day; auricular separation and palpebral fissures at 225 mg/kg/day). These doses are equivalent to 6 times (100 mg/kg/day) and 22 times (225 mg/kg/day) the area under the curve for humans taking 80 mg daily. 4) Statins may harm the fetus when given to pregnant women. Women of childbearing age should only take this product when the possibility of pregnancy is extremely small and they have been informed of the potential risks of the drug to pregnant women. Once a woman taking this product becomes pregnant, the drug should be stopped immediately and informed of the potential risks to the fetus. There is a lack of known clinical benefits to continuing the drug during pregnancy. 2. It is not clear whether atorvastatin is secreted through human milk in lactating women, but another similar drug can be secreted into breast milk in small amounts. The atorvastatin drug concentrations in the plasma and liver of lactating rat pups are 50% and 40% of the drug concentrations in breast milk, respectively. Animal milk drug concentration levels may not accurately reflect human milk drug concentration levels because another similar drug can be secreted through human milk. At the same time, statins may cause serious adverse reactions to newborns receiving breastfeeding. Therefore, mothers taking this product should not breastfeed (see [Contraindications]). Elderly precautions: Among the 39,828 patients taking Lipitor in clinical studies, 15,813 (40%) were ≥65 years old and 2,800 (7%) were ≥75 years old. There was no difference in the overall safety and effectiveness of these two populations compared with young subjects. Other clinical experience reports also show that there is no difference between the elderly and the younger population. However, it cannot be ruled out that some elderly patients are more sensitive to drugs, and advanced age (≥65 years old) is a susceptibility factor for myopathy, so Lipitor should be used with caution in the elderly.

During statin therapy, co-administration with the following drugs may increase the risk of myopathy, such as: fibric acid derivatives, lipid-lowering 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 P4503A4. Co-administration of Lipitor with strong CYP3A4 inhibitors may cause an increase in atorvastatin plasma concentrations. The extent of drug interactions and the degree of effect enhancement depend on the extent to which different products affect CYP3A4. Clarithromycin: Compared with Lipitor alone, the AUC of atorvastatin was significantly increased when Lipitor 80 mg was co-administered with clarithromycin (500 mg, twice daily) (see [Pharmacology and Toxicology]). Therefore, patients who are taking clarithromycin should use Lipitor at a dose of 20 mg with caution (see "Skeletal muscle" and "Dosage and Administration" in the "Precautions" section). 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, patients who are taking HIV protease inhibitors should use Lipitor at a dose of 20 mg with caution (see "Skeletal muscle" and "Dosage and Administration" in the "Precautions" section). Itraconazole: The AUC of atorvastatin was significantly increased when Lipitor 40 mg was co-administered with itraconazole 200 mg (see "Pharmacology and Toxicology"). Therefore, patients taking itraconazole should be cautious when using Lipitor at a dose of 20 mg (see "Skeletal muscle" and "Usage and Dosage" in the "Precautions" section). 2. Grapefruit juice: Contains one or more ingredients that inhibit cytochrome P4503A4, which can increase the plasma concentration of atorvastatin, especially when a large amount of grapefruit juice is consumed (more than 1.2 liters per day). 3. Cyclosporine: Atorvastatin and its metabolites are substrates of the OATP1B1 carrier. OATP1B1 inhibitors (such as cyclosporine) can increase the bioavailability of atorvastatin. Compared with atorvastatin alone, the combined use of Lipitor 10 mg and cyclosporine 5.2 mg/kg/day significantly increased the AUC of atorvastatin (see "Pharmacology and Toxicology"). In cases where Lipitor and cyclosporine must be used together, the dose of Lipitor should not exceed 10 mg (see "Skeletal muscle" in the "Precautions" section). 4. Rifampicin and other cytochrome P4503A4 inducers: The combined use of Lipitor and cytochrome P4503A4 inducers (such as efavirenz, rifampicin) can reduce the plasma concentration of atorvastatin to varying degrees. Due to the dual interaction mechanism of rifampicin, delayed administration of Lipitor after rifampicin administration is associated with a significant decrease in atorvastatin plasma concentrations, so it is recommended that Lipitor and rifampicin be administered simultaneously. 5. Digoxin: When multiple doses of Lipitor are co-administered with digoxin, the steady-state plasma concentration of digoxin increases by approximately 20%, and patients should be appropriately monitored when taking digoxin. 6. Oral contraceptives: When Lipitor is co-administered with oral contraceptives, the area under the concentration-time curve (AUC) of norethindrone and ethinyl estradiol (see [Pharmacology and Toxicology]) is increased by approximately 30% and 20%, respectively. The increase in AUC should be considered when women taking this product choose oral contraceptives. 7. Warfarin: Lipitor has no clinically significant effect on prothrombin time when patients are receiving long-term warfarin treatment.

Keep tightly closed.

10 mg

36 months.

Viatris Pharmaceuticals (DALIAN) Co., Ltd.

• Founded in:

  1989-10-07

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  No. 22 Daqing Road, Dalian Economic and Technological Development Zone, Liaoning Province

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  912102006048147187

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  $80.4 million

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