What Is the Connection Between Statins and Muscle Pain?

Atorvastatin calcium tablets, indications for patients with primary hypercholesterolemia. Including patients with familial hypercholesterolemia (heterozygous type) or mixed hyperlipidemia (equivalent to type IIa and IIb of the Fredrickson classification). If diet therapy and other non-drug treatments are not satisfactory, this product can be used to treat Its total cholesterol (TC) increased, low density lipoprotein cholesterol (LDL-C) increased, apolipoprotein B (Apo B) increased, and triglycerides (TG) increased. In patients with homozygous familial hypercholesterolemia, atorvastatin can be used in combination with other lipid-lowering therapies (such as LDL plasma dialysis) or alone (when no other treatment is available) to reduce TC and LDL-C. Coronary heart disease, coronary heart disease or coronary heart disease and other critical diseases (such as: diabetes, symptomatic atherosclerosis, etc.) patients with hypercholesterolemia or mixed dyslipidemia, this product is suitable for: reduce the risk of non-fatal myocardial infarction , Reduce the risk of fatal and non-fatal stroke, reduce the risk of revascularization, reduce the risk of hospitalization due to congestive heart failure, and reduce the risk of angina pectoris.

Atorvastatin calcium tablets, indications for patients with primary hypercholesterolemia. Including patients with familial hypercholesterolemia (heterozygous type) or mixed hyperlipidemia (equivalent to type IIa and IIb of the Fredrickson classification). If diet therapy and other non-drug treatments are not satisfactory, this product can be used to treat Its total cholesterol (TC) increased, low density lipoprotein cholesterol (LDL-C) increased, apolipoprotein B (Apo B) increased, and triglycerides (TG) increased. In patients with homozygous familial hypercholesterolemia, atorvastatin can be used in combination with other lipid-lowering therapies (such as LDL plasma dialysis) or alone (when no other treatment is available) to reduce TC and LDL-C. Coronary heart disease, coronary heart disease or coronary heart disease and other critical diseases (such as: diabetes, symptomatic atherosclerosis, etc.) patients with hypercholesterolemia or mixed dyslipidemia, this product is suitable for: reduce the risk of non-fatal myocardial infarction , Reduce the risk of fatal and non-fatal stroke, reduce the risk of revascularization, reduce the risk of hospitalization due to congestive heart failure, and reduce the risk of angina pectoris.

Drug Name

Atorvastatin calcium tablets

Drug type

Prescription drugs, medicines for medical workers' injuries

Use classification

Lipid-lowering drugs

Atorvastatin calcium tablets ingredients

The main ingredient of this product is atorvastatin calcium.
Chemical name: [R- (R ', R')]-2- (4-fluorophenyl) -, -dihydroxy-5- (1-methylethyl)-3-phenyl-4- [(Aniline) carbonyl] -1 Hydrogen-pyrrole-1-heptanoic acid calcium trihydrate.
Chemical Structure:

Molecular formula: (C ₃₃ H ₃₄ FN ₂ O ₅ ) ₂ Ca · 3H ₂ O
Molecular weight: 1209.42

Atorvastatin calcium tablet traits

This product is a white film-coated tablet. It appears white when the film coating is removed.

Atorvastatin calcium tablets indications

Hypercholesterolemia in patients with primary hypercholesterolemia. Including patients with familial hypercholesterolemia (heterozygous type) or mixed hyperlipidemia (equivalent to type IIa and IIb of the Fredrickson classification). If diet therapy and other non-drug treatments are not satisfactory, this product can be used to treat Its total cholesterol (TC) increased, low density lipoprotein cholesterol (LDL-C) increased, apolipoprotein B (Apo B) increased, and triglycerides (TG) increased.
In patients with homozygous familial hypercholesterolemia, atorvastatin can be used in combination with other lipid-lowering therapies (such as LDL plasma dialysis) or alone (when no other treatment is available) to reduce TC and LDL-C.
Coronary heart disease, coronary heart disease or coronary heart disease and other critical diseases (such as: diabetes, symptomatic atherosclerosis, etc.) patients with hypercholesterolemia or mixed dyslipidemia, this product is suitable for: reduce the risk of non-fatal myocardial infarction , Reduce the risk of fatal and non-fatal stroke, reduce the risk of revascularization, reduce the risk of hospitalization due to congestive heart failure, and reduce the risk of angina pectoris.

Atorvastatin calcium tablets specifications

(1) 10 mg, (2) 20 mg. Based on atorvastatin (C ₃₃ H ₃₅ FN ₂ O ₅ ).

Atorvastatin calcium tablets dosage

Patients should undergo standard low-cholesterol diet control before starting treatment with this product, and they should maintain a reasonable diet throughout the treatment period. Dosage adjustments should be made based on baseline LDL cholesterol levels, treatment goals, and patient outcomes.
The usual starting dose is 10 mg once daily. Dosage adjustment intervals should be 4 weeks or longer. The maximum dose of this product is 80mg once a day. Can be taken at any time of the day and is not affected by meals.
The treatment goals for low-risk patients with cardiovascular events are LDL-C <4.14mmol / L (or <160mg / dL) and total cholesterol <6.62mmol / L (or <240mg / dL). The treatment goals of intermediate-risk patients are LDL-C <3.37mmol / L (or <130mg / dL) and total cholesterol <5.18mmol / L (or <220mg / dL). The treatment goals for high-risk patients are LDL-C <2.59mmol / L (or <100mg / dL) and total cholesterol <4.14mmol / L (or <160mg / dL). The treatment goals of extremely high-risk patients are LDL-C <2.07mmol / L (or <80mg / dL) and total cholesterol <3.11mmol / L (or <120mg / dL).
Excerpted from Chinese Journal of Cardiovascular Diseases, Vol. 35, No. 5, 2007, pp. 390-431, "Guidelines for Prevention and Treatment of Dyslipidemia in Chinese Adults"
Treatment of primary hypercholesterolemia and mixed hyperlipidemia Most patients take atorvastatin calcium 10 mg once daily, and their blood lipid levels can be controlled. Significant results were seen within 2 weeks of treatment, and significant results were seen within 4 weeks of treatment. Long-term treatment can maintain the effect.
The initial dose for treating heterozygous familial hypercholesterolemia is 10 mg daily. The principle of dose individualization should be followed and the dose should be gradually adjusted to 40 mg per day at intervals of 4 weeks. If you still do not achieve satisfactory results, you can choose to adjust the dose to the maximum dose of 80 mg daily or 40 mg of this product with cholic acid chelator treatment. Homozygous familial hypercholesterolemia In a charity drug study involving 64 patients, 46 patients had corresponding LDL receptor information. These 46 patients had an average 21% decrease in LDL-C. The dose of this product can be increased to 80 mg per day.
Treatment of homozygous familial hypercholesterolemia In a charity drug study involving 64 patients, 46 patients had confirmed LDL receptor information. These 46 patients had an average 21% decrease in LDL-C. The dose of this product can be increased to 80mg / day.
For patients with homozygous familial hypercholesterolemia, the recommended dose of this product is 10-80 mg per day. Atorvastatin calcium should be used as an adjunct to other lipid-lowering treatments, such as LDL plasma dialysis. Or in the absence of these treatment conditions, this product can be used alone.
The dosage of medication for patients with renal insufficiency kidney disease will not affect the plasma concentration of this product, nor will it affect its lipid-lowering effect, so there is no need to adjust the dose.

Atorvastatin calcium tablets adverse reactions

The following serious adverse reactions are described in detail elsewhere in this specification;
Rhabdomyolysis and myopathy (see [Precautions])
Liver enzyme abnormalities (see [Precautions])
Clinical adverse reactions During the implementation of clinical trials, the subject's condition is complex, so the incidence of adverse reactions obtained in clinical studies of two different drugs cannot be directly compared, and it may not reflect the incidence of adverse reactions in clinical practice.
Atorvastatin placebo-controlled clinical trials included a total of 16,066 patients (lipitor n = 8755, placebo n = 7311, aged 10 to 93 years, 39% were women; 91% were Caucasian whites, and 3% were Black, 2% Asian, 4% other race), with a median treatment period of 53 weeks; without causality, 9.7% and 9.5% of patients in the atorvastatin group and placebo Withdrawal due to adverse reactions. The five most common adverse reactions that led to discontinuation of the drug and a higher incidence in the Lipitor group than in the placebo group were myalgia (0.7%), diarrhea (0.5%), nausea (0.4%), and increased ALT (0.4 %) And elevated liver enzymes (0.4%).
Regardless of causality, the most common adverse reactions in Lipitor placebo-controlled trials (n = 8755) (2%) with a higher incidence than placebo are: Pain (6.9%), diarrhea (6.8%), limb pain (6.0%), and urinary tract infections (5.7%). Table 1 summarizes the incidence of adverse reactions in 2% of 8755 patients treated with Lipitor in 17 placebo-controlled trials, which are higher than those in the placebo group (causality is not considered).

Other adverse reactions reported in placebo-controlled studies include:
Whole body: discomfort, fever;
Digestive system: abdominal discomfort, belching, flatulence, hepatitis, cholestasis;
Musculoskeletal system: skeletal muscle pain, muscle fatigue, neck pain, joint swelling;
Nutrition and metabolic systems: elevated transaminase, abnormal liver function tests, elevated blood alkaline phosphatase, elevated creatine phosphokinase, hyperglycemia;
Nervous system: nightmare;
Respiratory system: epistaxis;
Skin and appendages: urticaria;
Special sensation: blurred vision, tinnitus, urogenital system: urinary white blood cell positive.
Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)
The ASCOT study (see [Clinical Trials]) included 10305 participants (age range 40-80 years, 19% women; 94.6% Caucasian Caucasian, 2.6% African, 1.5% South Asian, 1.3% mixed race or others Species), were given atorvastatin 10 mg (N = 5168) or placebo (N = 5137) daily. During a median follow-up of 3.3 years, the safety and tolerability of the atorvastatin-treated group was comparable to that of the placebo group.
Atorvastatin Collaborative Study on Diabetes (CARDS)
In the CARDS study (see [Clinical Trials]), a total of 2838 subjects with type 2 diabetes were selected (age range 39-77 years, 32% females; 94.3% Caucasian whites, 2.4% South Asians, 2.3% Black Caribbean, 1.0% of other races) who were treated with atorvastatin 10 mg (n = 1428) or placebo (n = 1410) per day, with a median follow-up of 3.9 years across the treatment groups overall There were no differences in the frequency of adverse events or serious adverse events, and there were no reports of rhabdomyolysis.
New Target Therapy Study (TNT)
The TNT study (see [Clinical Trials]) involved 1,0001 patients with coronary heart disease with clinical evidence (age range 29-78 years, 19% females; 94.1% Caucasian whites, 2.9% blacks, 1.0% Asians, 2.0% others Species), receiving Lipitor 10 mg (n = 5006) or 80 mg (n = 4995) daily, with a median follow-up period of 4.9 years, compared with the low-dose group, severe adverse events in the high-dose group There were more patients who discontinued treatment due to adverse events (92,1.8%; 497,9.9% in the high-dose group and 69,1.4%; 404,8.1% in the low-dose group). In the atorvastatin 80 mg treatment group, 62 patients (1.3%) experienced continuous elevation of transaminases (more than three times the upper limit of normal twice in 4-10 days), compared with 9 cases (0.2%) in the atorvastatin 10 mg group. ). Creatine kinase elevations (more than 10 times above the upper limit of normal) were generally lower, but compared with the low-dose atorvastatin group, the high-dose group had a higher incidence of 6,0.1% and 13,0.3%, respectively.
Intensive lipid-lowering study to further reduce clinical endpoint events (IDEAL)
The IDEAL study (see [Clinical Trials]) involved 8,888 patients (age range 26-80 years, 19% females; 99.3% Caucasian whites, 0.4% Asians, 0.3% blacks, 0.04% other races), receiving daily Total occurrence of adverse events or serious adverse events in the two treatment groups during atorvastatin 80 mg (n = 4439) or simvastatin 20-40 mg (n = 4449) with a median follow-up of 4.8 years There is no difference in rates.
Intensive Cholesterol-lowering Therapy Study (SPARCL)
The SPARCL study included 4,731 subjects without clinical evidence of coronary heart disease but with a history of stroke or transient ischemic attack (TIA) within the past 6 months (ages 21-92, 40% females; 93.3% Caucasian whites, 3.0% black, 0.6% Asian, 3.1% other races), received Lipitor 80mg (N = 2365) or placebo (N = 2366), and the median follow-up period was 4.9 years. Patients in the atorvastatin group had a higher rate of transaminase (more than three times the upper limit of normal twice in 4-10 days). The incidence (0.9%) was higher than that in the placebo group (0.1%). Creatine kinase elevations (more than 10 times the upper limit of normal) are rare, but the incidence of atorvastatin (0.1%) is higher than that of placebo (0.0%). Diabetes as an adverse reaction was reported in 144 (6.1%) and 89 (3.8%) cases in the atorvastatin and placebo groups, respectively (see [Precautions]).
Post hoc analysis showed that compared with the placebo group, the incidence of ischemic stroke was reduced in the atorvastatin 80 mg group (218/2365 [9.2%] vs. 274/2366 [11.6%]), and the incidence of hemorrhagic stroke increased. High (55/2365 [2.3%] vs. 33/2366 [1.4%]). The incidence of fatal hemorrhagic stroke was similar in the atorvastatin and placebo groups, at 17 and 18, respectively. The incidence of non-fatal hemorrhagic stroke was significantly higher in the atorvastatin group than in the placebo group, with 38 and 16 patients, respectively. Patients with a previous history of hemorrhagic stroke may have an increased risk of hemorrhagic stroke during the study (7 in the atorvastatin group [16%] vs. 2 in the placebo group [4%]). All-cause mortality was not significantly different between the two groups: atorvastatin 80 mg daily group 216 (9.1%) and placebo group 211 (8.9%). The proportion of cardiovascular deaths in the Lipitor 80mg group (3.3%) was numerically lower than in the placebo group (4.1%). The proportion of non-cardiovascular deaths (5.0%) in the Lipitor 80mg group was higher than that in the placebo group (4.0%).
Post-Marketing Reports The following adverse reactions were reported after atorvastatin approved the marketing application. Post-marketing adverse reaction reports are actively reported by patients, and the number of people who actually use the drug is uncertain. Therefore, the exact incidence of these adverse reactions cannot be calculated, and the causal relationship between these adverse reactions and the drug cannot be determined.
Regardless of causality, related adverse reactions not listed above after Lipitor is listed include: allergic reactions, angioedema, herpes (including erythema polymorphic, Stevens-Johnson syndrome, and toxicity Epidermal necrolysis), rhabdomyolysis, fatigue, tendon rupture, liver failure, dizziness, memory loss, depression and peripheral neuropathy. Pediatric Patients (Age 10-17)
In a 26-week controlled study involving boys and girls after menarche, atorvastatin 10 mg-20 mg / day (n = 140, 31% were girls; 92% Caucasian, 1.6% black, 1.6% Asian, 4.8 % Other races) are similar in safety and tolerability to placebo (see [Pharmacology and Toxicology], [Clinical Trials], [Precautions], and [Children's Medication]).

Atorvastatin calcium taboo

1. Active liver disease, which may include persistently elevated liver aminotransferases of unknown cause 2. Known allergies to any of the ingredients in this product.
3. Pregnancy This product is prohibited to be used by pregnant women or women of childbearing age who may become pregnant. Pregnant women may cause damage to the fetus when taking this product. In normal pregnancy, serum cholesterol and triglyceride levels rise, and cholesterol or cholesterol derivatives are essential for fetal development. Atherosclerosis is a chronic disease process, so the discontinuation of lipid-lowering medication during pregnancy in patients with primary hypercholesterolemia has little effect on the long-term outcome of atherosclerotic disease. There are currently insufficient controlled studies on atorvastatin administration in pregnant women; occasionally, fetal congenital abnormalities have been reported with intrauterine exposure to statins. Rat and rabbit reproduction studies have not observed evidence of teratogenicity of atorvastatin. For women of childbearing age, only those who are extremely unlikely to conceive and who have been informed of the potential harm can be prescribed Lipitor. Patients should be discontinued immediately during pregnancy while taking the drug, and consider the potential harm of the drug to the fetus (see [Medication for pregnant and lactating women]).
4. Whether atorvastatin can be secreted from human milk by lactating women is unknown; but other drugs of this type can be secreted into milk in small amounts. Because statins may have potentially serious adverse effects on breast-feeding newborns, women taking this product are prohibited from breast-feeding (see [Medications for pregnant and lactating women]).

Atorvastatin calcium tablets precautions

1. A few cases of atorvastatin and other statins caused by myoglobinuria secondary to acute renal failure due to rhabdomyolysis. A history of kidney damage may be a risk factor for rhabdomyolysis, and these patients need to be closely monitored for the effects of the drug on skeletal muscle.
Like other statins, atorvastatin can cause myopathy (myopathy is defined as muscle pain or muscle weakness, accompanied by creatine phosphokinase CPK more than 10 times the upper limit of normal). High-dose atorvastatin in combination with specific drugs such as cyclosporine or strong CYP3A4 inhibitors (such as clarithromycin, itraconazole, and HIV protease inhibitors) can increase the risk of myopathy or rhabdomyolysis.
Any patient with diffuse myalgia, muscle tenderness or weakness, and / or significant elevation of creatine phosphokinase should be considered myopathy. Patients should be advised to immediately report unexplained muscle pain, muscle tenderness, or muscle weakness, especially if accompanied by discomfort or fever. Atorvastatin treatment should be discontinued if there is a significant increase in creatine phosphokinase levels or if a diagnosis / suspected myopathy is present.
If cyclosporine A, fibric acid derivatives (fibrates), erythromycin, clarithromycin, ritonavir plus saquinavir or lopinavir plus are used during the treatment of such drugs The combination of navir, nicotinic acid, or imidazole antifungals increases the risk of myopathy. Doctors are considering a combination of atorvastatin and fibric acid derivatives (fibrates), erythromycin, clarithromycin, ritonavir plus saquinavir or lopinavir plus ritonavir, Potential benefits and risks should be carefully weighed in the treatment of immunosuppressive drugs, imidazole antifungals or lipid-lowering niacin, and patients should be carefully monitored for any signs and symptoms of muscle pain, muscle tenderness or muscle weakness, especially During the first few months of treatment and during any dose increase. When atorvastatin is used concurrently with the previously mentioned drugs (see [Drug Interactions]), consideration should be given to reducing the initial and maintenance doses of atorvastatin. In this case, periodic measurements of creatine phosphokinase should be considered, but such monitoring does not ensure that severe myopathy can be prevented.
A summary of recommended prescription dosages and interacting drugs is shown in Table 2 (see [Usage and Dosage], [Drug Interactions], and [Pharmacology and Toxicology] for details).
Table 2 Interacting drugs causing increased risk of atorvastatin myopathy / striated muscle lysis

Any patient with acute or severe conditions that indicates myopathy or risk factors (e.g., severe acute infection, hypotension, major surgery, trauma, severe metabolism, endocrine and electrolyte disorders, uncontrolled seizures) is likely to induce secondary For renal failure with rhabdomyolysis, Lipitor should be suspended or discontinued.
2. Abnormal liver function Like other lipid-lowering treatments, statins can cause abnormal liver function biochemical indicators. The results of clinical trials showed that 0.7% of patients receiving Lipitor had persistently elevated serum transaminase levels (two or more times exceeding the upper limit of normal by three times). The prevalence of transaminase abnormalities was 0.2%, 0.2%, 0.6%, and 2.3% in patients at 10, 20, 40, and 80 mg. The following results were observed in patients taking Lipitor in clinical trials. One patient developed jaundice, and the elevation of liver function tests (LFT) in other patients was not associated with jaundice and other clinical signs or symptoms. After reducing the dosage, discontinuing or stopping the medication, the transaminase level returned to or near the pre-treatment level without sequelae. Of the 30 patients whose liver function indicators continued to increase, 18 patients continued treatment with a reduced dose of Lipitor.
Liver function should be checked before treatment, 12 weeks after the start of treatment, and 12 weeks after the dose is increased, and thereafter (eg every six months) should be checked regularly. Hepatic enzyme abnormalities usually occur within 3 months before Lipitor treatment, and patients with elevated transaminase should be monitored until normal. If ALT or AST continues to rise more than three times the upper limit of normal, it is recommended to reduce the dose of this product or stop using it. Lipitor should be used with caution in patients with excessive alcohol consumption and / or history of liver disease. Active liver disease or unexplained transaminase continues to rise, this product is contraindicated (see [taboo] for details).
3. Endocrine function Statins can interfere with cholesterol synthesis and theoretically inhibit the synthesis of adrenal and / or gonadal steroids. Clinical studies have shown that Lipitor does not reduce basal plasma cortisol concentrations or damage adrenal reserve. There are no sufficient case studies on the effects of statins on male fertility, and the effect on the pituitary-gonadal axis of premenopausal women is unclear. Statins should be used with caution when used in combination with drugs that reduce the level or activity of endogenous steroid hormones, such as ketoconazole, spironolactone, and cimetidine.
4. Central nervous system toxicity Cerebral hemorrhage occurred in a female dog given atorvastatin 120 mg / kg / day for 3 months. After increasing the dose to another female dog, atorvastatin at 280 mg / kg / day for 11 weeks, she was sacrificed in a near-death state, and cerebral hemorrhage and optic nerve vacuole formation were also found. A dose of 120 mg per kilogram of body weight, calculated at the maximum human dose of 80 mg per day, would result in a systemic exposure approximately 16 times the area under the human plasma curve (AUC, 0-24 hours). In a two-year study, two male dogs (one administered at 10 mg / kg / day and the other at 120 mg / kg / day) were observed to have one tonic convulsion. No central nervous system damage was observed in mice dosed up to 400 mg / kg / day and rats dosed up to 100 mg / kg / day for 2 years of long-term administration. Based on the recommended maximum human dose of 80 mg per day, these doses are 6-11 times (mouse) and 8-16 times (rat) the area under the human curve (0-24). In the administration of other statins, canine central nervous system vascular damage was observed, characterized by perivascular bleeding, edema, and monocyte perivascular infiltration. In clinically normal dogs, when the plasma drug level of another class of drugs with similar chemical structure is about 30 times higher than the recommended maximum human dose, optic nerve degeneration (retinal-knee-shaped fiber Wallerian degeneration) occurs in a dose-dependent manner.
5. Application of the SPARCL study (strengthening cholesterol-lowering therapy to prevent stroke) in patients with recent stroke or transient ischemic attack A total of 4,731 patients had a stroke or transient ischemic attack but no coronary heart disease in the last 6 months Of patients received Lipitor 80mg or placebo. Post hoc analysis of this study showed that the incidence of hemorrhagic stroke was higher in the Lipitor 80mg group than in the placebo group (55 [2.3%] and 33 [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 and 18 in the atorvastatin and placebo groups, respectively), and the incidence of non-fatal hemorrhagic stroke in the atorvastatin group (38 (1.6%) were higher than those in the placebo group (16, 0.7%). The higher incidence of hemorrhagic stroke in the atorvastatin group was related to certain baseline characteristics of the patient at the beginning of the study, including hemorrhagic stroke and lacunar stroke (see [Adverse Reactions]).
Lipitor is contraindicated in patients with active liver disease, including persistently elevated liver aminotransferase levels of unknown origin [see [Contraindications] and [Pharmacokinetics]].

Atorvastatin calcium tablets for pregnant and lactating women

Pregnancy Pregnancy Classification X Serum cholesterol and triglyceride levels are elevated in the body during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Atherosclerosis is a chronic disease process, so the discontinuation of lipid-lowering medication during pregnancy in patients with primary hypercholesterolemia has little effect on the long-term outcome of atherosclerotic disease.
There are currently insufficient controlled studies of Lipitor in pregnancy. Rare reports of congenital anomalies due to intrauterine exposure to statins. A follow-up study of approximately 100 pregnant women exposed to other statins found that the incidence of congenital abnormalities, spontaneous abortion and fetal death / stillbirth did not exceed the general population's expectations, but this study could only rule out congenital abnormalities The basic incidence is 3-4 times the risk. At the same time, 89% of patients start medication before pregnancy, but stop using it within 3 months of becoming aware of it.
Atorvastatin reaches the same drug level in the fetal rat liver as the maternal plasma through the rat's placenta. When rat doses were as high as 300 mg / kg / day and rabbit doses were as high as 100 mg / kg / day, atorvastatin did not cause teratogenic effects. According to body surface area (mg / m ² )
By calculation, these doses are approximately 30 times (rat) or 20 times (rabbit) the human exposure (see [Contraindications], pregnancy).
In one study, rats were administered a dose of 20, 100, or 225 mg / kg / day, from day 7 of pregnancy to day 21 of lactation (weaning), and the mother was administered a dose of 225 mg / kg / day The survival rate of young animals is reduced at birth, newborn, weaning and maturity. The mother's dose was 100 mg / kg / day, and the body weight of the young animals decreased on the 4th and 21st days; the mother's dose was 225mg / kg / day at birth, and the body weight of the young animals was on the 4th, 21st and 91th days Decreased; delayed development of young animals (Routel syndrome at a dose of 100 mg / kg / day, and auditory startle response at 225 mg / kg / day; auricle separation and cracked eyes at a dose of 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 when a person takes a daily dose of 80 mg.
Statins may harm the fetus when administered to a pregnant woman. Women of childbearing age should only take this product when they are extremely unlikely to become pregnant and have been informed of the potential dangers of the drug to pregnant women. As soon as a woman taking this product becomes pregnant, she should discontinue her medication and inform her of the potential danger to her fetus. Continued medication during pregnancy lacks known clinical benefits.
Whether atorvastatin is secreted by human milk from lactating women is unknown, but another similar drug can be secreted into milk in small amounts. The atorvastatin drug concentration in plasma and liver of breast-fed pups was 50% and 40% of the drug concentration in breast milk, respectively. Animal milk drug concentration levels may not accurately reflect human milk drug concentration levels, because another drug of the same type can be secreted through human milk, and statins may cause serious adverse reactions to breast-feeding newborns. Therefore, mothers taking this product do not Should breastfeed (see [taboo]).

Atorvastatin calcium tablets for children

This product should only be used in children by specialists. The treatment experience of this product in children is limited to a few (4 to 17 years old) patients 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 data on the safety of this product for the growth and development of this population.

Atorvastatin calcium tablets for elderly

In the clinical study of 39828 patients taking Lipitor, 15813 (40%) were 65 years old and 2800 (7%) were 75 years old. There was no difference in overall safety and effectiveness between these two populations and young 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. Older age (65 years) is a susceptible factor for myopathy, so Lipitor should be used with caution in the elderly.

Atorvastatin calcium tablets drug interactions

During treatment with statins, the risk of myopathy is increased in combination with the following drugs, such as: fibric acid derivatives, lipid-adjusted doses of niacin, cyclosporine or strong CYP3A4 inhibitors (such as HIV protease inhibitor and itraconazole) (see [Precautions], "Skeletal Muscle" and [Pharmacology and Toxicology]).
1. CYP3A4 strong inhibitor: Lipitor is metabolized by cytochrome P4503A4. Lipitor and CYP3A4 strong inhibitors can increase the plasma concentration of atorvastatin. The degree of drug interactions and the enhancement of effects depend on the degree of influence of different products on CYP3A4.
2. Clarithromycin: Compared with Lipitor alone, Lipoxal 80mg and clarithromycin (500mg, twice daily) in combination with atorvastatin AUC significantly increased (see [Pharmacology and Toxicology]). Therefore, patients using clarithromycin should be used with caution when the dosage of Lipitor is> 20 mg (see "skeletal muscle" and [usage and dosage] in the [Precautions]).
3. Combination with protease inhibitors: Compared with Lipitor alone, Lipitor 40mg is combined with ritonavir + saquinavir (400mg, twice daily) or Lipitor 20mg and lopinavir When combined with ritonavir (400mg + 100mg, twice daily), the AUC of atorvastatin increased significantly (see [Pharmacology and Toxicology]). Therefore, patients with HIV protease inhibitors should be used with caution when using Lipitor 20mg (see "skeletal muscle" and "Dosage and Administration" in the [Cautions] section).
4. Itraconazole: Atorvastatin AUC significantly increased when Lipitor 40mg and itraconazole 200mg were combined (see [Pharmacology and Toxicology]). Therefore, patients who use itraconazole should be used cautiously when the dosage of Lipitor is> 20 mg (see "skeletal muscle" and [usage and dosage] in the [Precautions]).
5. Grapefruit juice: Contains one or more ingredients that inhibit cytochrome P4503A4, which can increase the plasma concentration of atorvastatin, especially when ingesting a large amount of grapefruit juice (drinking more than 1.2 liters per day).
6. Cyclosporine: Atorvastatin and its metabolites are substrates of the OATP1B1 vector. OATP1B1 inhibitors (such as cyclosporine) can increase the bioavailability of atorvastatin. Compared with atorvastatin alone, the combined application of Lipitor 10mg and cyclosporine 5.2mg / kg / day significantly increased the AUC of atorvastatin (see [Pharmacology and Toxicology]). In the case that Lipitor and cyclosporin must be used in combination, the dose of Lipitor should not exceed 10mg (see [Caution], "Skeletal Muscle").
7. Rifampicin and other cytochrome P4503A4 inducers: Lipitor and cytochrome P4503A4 inducers (such as efavirenz and rifampicin) can cause different levels of atorvastatin plasma reduction. Due to the dual interaction mechanism of rifampicin, the delayed administration of Lipitor after rifampicin administration is associated with a significant decrease in atorvastatin plasma concentration, so it is recommended that Lipitor be administered concurrently with rifampin.
8. Digoxin: When multiple doses of Lipitor and digoxin are combined, the steady-state plasma concentration of digoxin increases by about 20%. Patients should be properly monitored when taking digoxin.
9. Oral contraceptives: When Lipitor is used in combination with oral contraceptives, the AUCs of norethindrone and ethinyl estradiol (see [Pharmacology and Toxicology]) are increased by about 30% and 20%, respectively. Increased 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 receive long-term warfarin treatment.

Atorvastatin calcium tablets overdose

There is no special treatment for this product overdose. Once overdose occurs, patients should take symptomatic and supportive measures as needed. Due to the extensive binding of atorvastatin to plasma proteins, hemodialysis cannot significantly increase the clearance of atorvastatin.

Atorvastatin calcium tablets pharmacology and toxicology

Clinical pharmacological action mechanism Atorvastatin is a selective and competitive inhibitor of HMG-CoA reductase. The role of HMG-CoA is to convert methylolglutarate coenzyme A to mevalonate, a sterol precursor including cholesterol. Clinical, pathological, and epidemiological studies have shown that elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apo B) promote human atherosclerosis. Risk factors for cardiovascular disease, and elevated HDL cholesterol levels are associated with a reduced risk of cardiovascular disease.
In animal models, atorvastatin reduces plasma cholesterol and lipoprotein levels by inhibiting the synthesis of HMG-CoA reductase and cholesterol in the liver, and enhances LDL uptake by increasing the number of LDL receptors on the surface of liver cells And catabolism; Lipitor also reduces LDL production and the number of LDL particles. Lipitor can reduce the level of low-density lipoprotein cholesterol in some homozygous familial hypercholesterolemia (FH) patients. Generally, other lipid-lowering drugs have little clinical effect on such patients.
Atorvastatin reduces total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels in patients with homozygous and heterozygous familial hypercholesterolemia, nonfamilial hypercholesterolemia, and mixed dyslipidemia. Atorvastatin also reduces very low-density lipoprotein cholesterol and triglyceride levels, and can increase high-density lipoprotein cholesterol and apolipoprotein A-1 levels. Atorvastatin lowers total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and non-high-density lipoprotein cholesterol in patients with pure hypertriglyceridemia, and increases high LDL cholesterol levels. Atorvastatin can reduce intermediate density lipoprotein cholesterol in patients with B lipoproteinemia.
Pharmacodynamics Atorvastatin and some of its metabolites have pharmacological activity in the human body. The liver is the basic site and main site of cholesterol synthesis and low-density lipoprotein clearance. The dose administered rather than the systemic drug concentration was more related to the lowering of LDL cholesterol. The individualized dose should be determined according to the efficacy of the treatment (see [Dosage and Administration]).
Nonclinical toxicology carcinogenic, teratogenic, and reproductive damage In a 2-year study in rats, doses of 10, 30, and 100 mg / kg / day were given to rats and found in high doses of female rat muscle Two rare tumors: one is rhabdomyosarcoma and the other is fibrosarcoma. This dose shows an area under the plasma curve (0-24) that is approximately 16 times the average human plasma drug exposure after a maximum oral dose of 80 mg.
In a 2-year carcinogenicity study in mice, the doses administered were 100, 200, or 400 mg / kg / day, which resulted in a significant increase in high-dose liver adenomas in male mice and high-dose female mice. These findings occurred when the area under the plasma curve (0-24) was approximately 6 times the average plasma drug concentration after human exposure to an oral dose of 80 mg.
In vitro studies, atorvastatin was not mutagenic or teratogenic in the following experiments with or without metabolic activity: Ames experiments with Salmonella typhimurium and Escherichia coli in Chinese hamster lung cells HGPRT mutagenicity assay and chromosome aberration assay in Chinese hamster lung cells. Atorvastatin was negative in micronucleus experiments in mice.
In studies conducted in rats at doses as high as 175 mg / kg / day (15 times the human exposure), atorvastatin did not have any effect on animal fertility. 10 rats were given atorvastatin 100 mg / kg / day (16 times the area under the curve when the 80 mg dose was administered to humans) for 3 months, of which 2 rats had epididymal hypoplasia and azoospermia; 30 And the testicular weight of the 100 mg / kg / day dose group decreased significantly, and the epididymal weight of the 100 mg dose group decreased. Atorvastatin was given to male rats at 100 mg / kg / day before mating for a total of 11 weeks. Sperm motility and sperm cell head concentration decreased, while abnormal sperm increased. Administration of 10, 40, or 120 mg / kg / day atorvastatin to dogs for two years did not adversely affect semen parameters or histopathology of reproductive organs.

Atorvastatin calcium tablets pharmacokinetics

Pharmacokinetics and drug metabolism absorption: Atorvastatin is absorbed rapidly after oral administration; the plasma concentration reaches a peak within 1-2 hours. The degree of absorption increases in proportion to the dose of atorvastatin. Compared with the solution, the bioavailability of atorvastatin tablets is 95% -99%. The absolute bioavailability is about 12%. The systemic availability of HMG-CoA reductase inhibitory activity is about 30%. The lower systemic availability is due to gastric mucosal clearance and / or liver first-pass effects before entering the human circulation. Compared with breakfast, plasma concentration at night is slightly lower (Cmax and AUC about 30%). However, no matter what time of day it is administered, the reduction in LDL cholesterol is the same (see [Dosage and Administration]).
Distribution: The average distribution volume of atorvastatin is about 381L. More than 98% of atorvastatin binds to plasma proteins. A blood / plasma ratio of about 0.25 indicates that only a small amount of drug penetrates into the red blood cells. Based on observations in rats. Atorvastatin may be secreted into human milk ([taboo], [pregnant and lactating women] and [notes], "lactating women").
Metabolism: Atorvastatin is metabolized by cytochrome P450 3A4 into ortho and para hydroxyl derivatives and other beta oxidation products. In vitro tests, the ortho- and para-hydroxylated metabolites inhibited HMG-CoA reductase on an equivalent basis with atorvastatin. About 70% of HMG-CoA reductase inhibitory activity is produced by active metabolism. In vitro studies have shown the importance of cytochrome P450 3A4 in the metabolism of atorvastatin, while taking the known isoenzyme inhibitor erythromycin is consistent with the increase of atorvastatin plasma concentration in humans (see [Cautions ], [Drug interaction]) In animals, the ortho-hydroxy metabolite undergoes a further glucouronic acid process.
Excretion: Atorvastatin is mainly cleared by the bile after hepatic and / or extrahepatic metabolism. However, atorvastatin does not appear to have significant enterohepatic recirculation. Atorvastatin has an average plasma elimination half-life of approximately 14 hours. Due to the effect of its active metabolite, the half-life of atorvastatin on HMG-CoA reductase is about 20-30 hours. After oral administration of atorvastatin, the urine recovery was less than 2% of the dose.
Special population:
Elderly: Atorvastatin has a higher blood concentration in healthy older adults (aged 65 years) than younger adults (Cmax is about 40% and AUC is about 30%). Clinical data show that atorvastatin at any dose can significantly reduce LDL-C in younger people than young people (see [Notes], "Geriatric Drugs")
Children: Pharmacokinetic data in children are not sufficient.
Gender: There is a gender difference in the plasma concentration of atorvastatin (women are about 20% higher than men in terms of Cmax, and women are 10% lower than men in terms of AUC). However, in clinical applications, there is no significant gender difference in the effect of atorvastatin on LDL-C.
Patients with renal insufficiency: Kidney disease has no effect on the plasma concentration and lipid-lowering effect of atorvastatin and its active metabolites. Therefore, patients with renal insufficiency do not need to adjust the dose (see [Dosage and Administration]).
Patients with hepatic insufficiency: In patients with chronic alcoholic liver disease, the plasma concentration of atorvastatin is significantly increased; in Childs-Pugh A patients, Cmax and AUC are increased by 4 times, while in Childs-Pugh B patients, Cmax And AUC increased by 16 times and 11 times, respectively (see [Contraindications]).

Atorvastatin calcium tablets storage

Shaded and sealed.

Atorvastatin calcium tablets packaging

1. Packed in aluminum-plastic blister, composite film bag, 7 pcs / board / bag, 10 pcs / board / bag.
2. Double aluminum blister packaging, 7 pcs / board, 10 pcs / board.

Atorvastatin Calcium

36 months

Atorvastatin calcium tablets

YBH07002009 ^[1]