Atorvastatin Calcium Tablets

Clinical Pharmacology 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 enhances the uptake and catabolism of low-density lipoprotein by increasing the number of LDL receptors on the surface of liver cells; Lipitor also reduces low-density lipoprotein production and the number of low-density lipoprotein particles. Lipitor can reduce LDL cholesterol levels in some patients with homozygous familial hypercholesterolemia (FH), for whom other lipid-lowering drugs are generally ineffective. Lipitor reduces total cholesterol, LDL cholesterol, and apolipoprotein B levels in patients with homozygous and heterozygous FH, non-familial hypercholesterolemia, and mixed dyslipidemia. Lipitor also reduces VLDL cholesterol and triglyceride levels, and can increase HDL cholesterol and apolipoprotein A-1 levels. Lipitor reduces total cholesterol, LDL cholesterol, VLDL cholesterol, apolipoprotein B, triglycerides, and non-HDL cholesterol in patients with isolated hypertriglyceridemia, and increases HDL cholesterol levels. Lipitor reduces intermediate-density lipoprotein cholesterol in patients with dyslipidemia of beta. 2. Pharmacodynamics Lipitor and some of its metabolites are pharmacologically active in humans. The liver is the primary site of action and major site for cholesterol synthesis and LDL clearance. The dose rather than the systemic drug concentration is more related to the reduction of LDL cholesterol. Individualized dose should be determined based on the efficacy of the treatment (see [Dosage and Administration]).

The main ingredient of this product is atorvastatin calcium.

1. Primary hypercholesterolemia and mixed hyperlipidemia, to reduce elevated TC, LDL-C, ApoB and TG levels. 2. Patients with hypercholesterolemia and risk of atherosclerosis.

1. Oral administration, once a day, 1 tablet each time or as directed by a physician. 2. Patients should follow a standard low-cholesterol diet before and during treatment with atorvastatin calcium. The recommended starting dose of atorvastatin calcium is 10 mg/day, with a dose range of 10 to 60 mg/day. Blood lipid levels should be monitored within 2-4 weeks of use, and the dose should be adjusted accordingly based on the treatment goals and efficacy response.

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, median treatment period was 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%), ALT increase (0.4%), and liver enzyme increase (0.4%). Regardless of causality, the most common adverse reactions in the placebo-controlled trials of Lipitor (n=8755) were (2%) and the adverse reactions with a higher incidence than placebo were: nasopharyngitis (8.3%), arthralgia (6.9%), diarrhea (6.8%), pain in the limbs (6.0%) and 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. Nutrition 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 this product in children 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 for pregnancy and lactation: Pregnancy classification X1. Pregnant women or women of childbearing age who may become pregnant are prohibited from taking Lipitor. 1.1 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. 1.2 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 of 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 baseline incidence of congenital anomalies. At the same time, 89% of the patients started taking the drug before pregnancy but stopped taking it within 3 months after being informed of pregnancy. 1.3 Atorvastatin crosses the placenta of rats and reaches drug levels in the fetal liver that are equivalent to maternal plasma. Atorvastatin did not produce teratogenic effects when dosed 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 (see [Contraindications], Pregnancy). 1.4 In one study, rats were dosed with 20, 100, or 225 mg/kg/day from gestation day 7 to lactation day 21 (weaning). The survival of pups at birth, neonatal, weaning, and maturity was reduced when the mothers were dosed with 225 mg/kg/day. The weight of pups on days 4 and 21 was reduced when the mothers were dosed with 100 mg/kg/day; the weight of pups at birth, days 4, 21, and 91 was reduced when the mothers were dosed with 225 mg/kg/day; the development of pups was delayed (Rothel's syndrome occurred at 100 mg/kg/day, while auditory startle response occurred at 225 mg/kg/day; auricular separation and palpebral fissures occurred 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 of humans taking 80 mg daily. 1.5 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, she should stop taking it immediately and be 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. The drug concentration level in animal milk may not accurately reflect the drug concentration level in human milk, because another similar drug can be secreted through human milk. At the same time, statins may cause serious adverse reactions to newborns receiving breastfeeding, so 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 is no difference in overall safety and efficacy between these two populations and younger subjects. Other clinical experience reports also show no difference between the elderly and younger populations. However, it cannot be ruled out that some elderly patients are more sensitive to drugs, and advanced age (ge; 65 years old) is a susceptibility factor for myopathy, so Lipitor should be used with caution in the elderly.

During statin therapy, the risk of myopathy may be increased when used in combination with the following drugs, 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. The combined use of Lipitor and strong CYP3A4 inhibitors may increase the plasma concentration of atorvastatin. The degree of drug interaction and the degree of effect enhancement depend on the degree of effect of different products on CYP3A4. 2. Clarithromycin: Compared with Lipitor alone, the AUC of atorvastatin was significantly increased when Lipitor 80 mg was combined with clarithromycin (500 mg, twice daily) (see [Pharmacology and Toxicology]). Therefore, patients using clarithromycin should use Lipitor with caution at a dose of 20 mg (see skeletal muscle and [Dosage and Administration] in the [Precautions]). 3. Combined use with protease inhibitors: Compared with Lipitor alone, the AUC of atorvastatin increased significantly when Lipitor 40 mg was combined with ritonavir-saquinavir (400 mg, twice daily) or Lipitor 20 mg was combined with lopinavir-ritonavir (400 mg 100 mg, twice daily) (see [Pharmacology and Toxicology]). Therefore, patients using 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). 4. Itraconazole: The AUC of atorvastatin increased significantly when Lipitor 40 mg was combined with itraconazole 200 mg (see [Pharmacology and Toxicology]). Therefore, patients using itraconazole should use Lipitor at a dose of 20 mg with caution (see skeletal muscle and [Dosage and Administration] in the [Precautions] section). 5. 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). 6. 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 the case where Lipitor and cyclosporine must be used together, the dose of Lipitor should not exceed 10 mg (see [Precautions], skeletal muscle). 7. 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 is associated with a significant decrease in atorvastatin plasma concentrations, so it is recommended that Lipitor be administered simultaneously with rifampicin. 8. 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. 9. 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. 10. 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.