What Is the Connection between Lipitor and Liver Enzymes?

Atorvastatin is a chemical. Chemical name (3 R , 5 R ) -7- [2- (4-fluorophenyl) -3-phenyl-4- (phenylcarbamoyl) -5-isopropyl-pyrrole-1-yl] -3,5-dihydroxyheptanoic acid, with a molecular formula of C ₆₆ H ₆₈ CaF ₂ N ₄ O ₁₀ and a molecular weight of 1155.34000.

Lipitor (English trade name Lipitor, generic name atorvastatin calcium tablets) is a lipid-lowering drug developed by Pfizer. Indications: 1. Hypercholesterolemia 2. Patients with coronary heart disease or coronary heart disease (such as diabetes, symptomatic atherosclerotic disease, etc.) with hypercholesterolemia or mixed dyslipidemia, this product Applicable to: 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.

Lipitor has nearly 20 years of real-world experience and is being used in 137 countries. Its efficacy and safety have been proven in more than 400 clinical trials and 230 million patient-years of clinical medication experience. Numerous evidence-based evidence and clinical practice have consistently confirmed that Lipitor 10-80mg can effectively reduce low-density lipoprotein cholesterol (LDL-C). It is high-risk for patients with coronary heart disease, ischemic stroke, diabetes, and hypertension. In patients, Lipitor has been shown to reduce major cardiovascular events and has been shown to be safe.

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 daily. Atorvastatin can be taken once daily at any time of the day and is not affected by meals.

Drug Name: Lipitor

Drug type: Prescription drugs, medicines for medical workers' injuries
Use classification: Lipid-lowering drugs

Lipitor ingredients

The main ingredient of this product is atorvastatin calcium.
Chemical name: [R- (R ^^, R ^^)]-2- (4-fluorophenyl) -, -dihydroxy-5- (1-methylethyl) -3-phenyl- Chemical structure of 4-[(aniline) carbonyl] -1H-pyrrole-1-heptanoic acid calcium salt (2: 1) trihydrate:

Molecular formula: (C ₃₃ H ₃₄ FN ₂ O ₅ ) ₂ Ca · 3H ₂ O
Molecular weight: 1209.42 ^[1]

Lipitor traits

This product is a white oval film-coated tablet.

Lipitor indications

Hypercholesterolemia:

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 and other non-pharmacological treatments The curative effect is unsatisfactory. The application of this product can treat the increase of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and triglyceride.

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 reduce total cholesterol and low-density lipids. Protein cholesterol ^[2] .

Coronary heart disease:

For patients with coronary heart disease or coronary heart disease (such as diabetes, symptomatic atherosclerotic disease, etc.) combined with hypercholesterolemia or mixed dyslipidemia, this product is suitable for: reducing the risk of non-fatal myocardial infarction, Reduce the risk of fatal and non-fatal strokes, reduce the risk of revascularization, reduce the risk of hospitalization due to congestive heart failure, and reduce the risk of angina pectoris ^[2] .

Lipitor specifications

(1) 10mg; (2) 20mg; (3) 40mg

Lipitor 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.
A common 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 daily. Atorvastatin can be taken once daily at any time of the day and is not affected by meals.
For low-risk patients with cardiovascular events, the treatment target is LDL-C <4.14mmol / L (or <160mg / dL) and total cholesterol <6.22mmol / L (or <240 mg / dL). The treatment target for intermediate-risk patients is LDL -C <3.37mmol / L (or <130mg / dL) and total cholesterol <5.18mmol / L (or <200 mg / dL). The treatment target for high-risk patients is LDL-C <2.59mmol / L (or <100mg / dL) ) And total cholesterol <4.14mmol / L (or <160 mg / dL), the treatment target for very high-risk patients is LDL-C <2.07mmol / L (or <80mg / dL) and total cholesterol <3.11mmol / L (or < 120 mg / dL) ^[3] .
Treatment of primary hypercholesterolemia and mixed hyperlipidemia < br Most patients take atorvastatin calcium 10mg once daily, and their blood lipid levels can be controlled. The obvious effect can be seen within 2 weeks of treatment, and the maximum effect can be seen within 4 weeks of treatment. Long-term treatment can maintain the effect ^[3] .
Treatment of heterozygous familial hypercholesterolemia The initial dose of patients is 10mg / day. The principle of dose individualization should be followed and the dose should be gradually adjusted to 40 mg / day at intervals of 4 weeks. If you still have not achieved satisfactory results, you can choose to adjust the dose to a maximum dose of 80mg / day or 40mg once daily with bile acid sequestrants ^[3] .
Treatment of homozygous familial hypercholesterolemia In a charity drug study involving 64 patients, 46 patients had corresponding LDL receptor information. The average of LDL-C in these 46 patients decreased by 21%. The dose of this product can be increased to 80mg / day.
For patients with homozygous familial hypercholesterolemia, the recommended dose of this product is 10-80mg / 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.
Dosage for patients with renal insufficiency < br 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.

Lipitor adverse reactions

The following serious adverse reactions are described in detail elsewhere in this specification:
Rhabdomyolysis myopathy (see [Precautions])
Liver enzyme abnormalities (see [Precautions])
Clinical adverse reactions < br The clinical conditions of the subjects during the implementation of clinical trials are complicated, 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. .
Lipitor's placebo-controlled clinical trials enrolled 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% are Asians, 4% are other races), the median treatment period is 53 weeks, and regardless of causality, the Lipitor group and the placebo group had 9.7% and 9.5% of patients, respectively. Withdrawal of 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 were: nasopharyngitis (8.3%), joints Pain (6.9%), diarrhea (6.8%), limb pain (6.0%), and urinary tract infections (5.7%) ^[2] .

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 system: Transaminase is elevated, liver function tests are abnormal, and blood alkaline phosphatase is elevated. Elevated creatine phosphokinase, hyperglycemia;
Nervous system: nightmare;
Respiratory system: epistaxis;
Skin and appendages: Urticaria Special sensation: blurred vision, tinnitus;
Genitourinary 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% female, 94 6% Caucasian Caucasian, 2.6% African, 1.5% South Asian, 1.3% mixed race Or other races), Lipitor 10mg (N = 5168) or placebo (N = 5137) were given. During a median follow-up of 3.3 years, the safety and tolerability of the Lipitor 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% women: 94.3% Caucasian Caucasian, 2.4% South Asian, 2.3% Black Caribbean, 1.0% of other races) who were treated with Lipitor 10mg (n = 1428) or placebo (n = 1410) per day, with a median follow-up of 3.9 years. There were no differences in the overall frequency of adverse events or serious adverse events between treatment groups, and there were no reports of rhabdomyolysis ^[3] .
Therapeutic New Targets Study (TNT)
The TNT study (see [Clinical Trials]) involved 1,001 patients with coronary heart disease with clinical evidence (age range 29-78 years, 19% women, 94.1% Caucasian whites. 2.9% blacks, 1.0% Asians, 2.0% others Species), receiving 10 mg (n = 5006) or 80 mg (n = 4995) of Lipitor daily with a median duration of 4.9 years during the follow-up visit, compared with the low-dose group, the severe adverse events in the high-dose group There were more patients who discontinued treatment due to adverse events (high doses were 92, 1.8%: 497, 9.9%, and low dose groups were 69, 1.4%; 404, 8.1%). In the Lipitor 80mg treatment group, 62 patients (1.3%) experienced continuous elevation of transaminase (more than 3 times over the upper limit of normal twice in 4-10 days), while 9 patients (0.2%) in the atorvastatin 10mg group. Creatine kinase elevations (more than 10 times above the upper limit of normal) were generally less, but compared to 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), daily During the treatment of Lipitor 80mg (n = 443.9) or Simvastatin 20-40mg (n = 4449), there was no difference in the overall incidence of adverse events or serious adverse events between the two treatment groups during a median follow-up of 4.8 years .
Intensive Cholesterol-lowering Therapy Study (SPARCL)
The SPARCL study included 4,731 subjects who had no clinical evidence of coronary heart disease but had a history of stroke or transient ischemic attack (TIA) within the past 6 months (aged 21-92 years old, 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 continued to have elevated transaminases (more than three times the upper limit of normal twice in 4-10 days), and 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 group and the placebo group, respectively (see [Precautions]) ^[2] .
Post hoc analysis shows. Compared with the placebo group, the incidence of ischemic stroke was lower in the Lipitor 80mg group (218/2365 [9.2%] vs. 274/2366 [11.6%]), and the incidence of hemorrhagic stroke was increased (55/2365 [2.3%] vs. 33/2366 [1.4%]). The rates of fatal hemorrhagic stroke in the Lipitor and placebo groups were similar, 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 Lipitor group [16%] vs. 2 in the placebo group [4%]).
There was no significant difference in all-cause mortality between the two groups: Lipitor 216 (9.1%) in the 80 mg daily group and 211 (8.9%) in the placebo group. The proportion of cardiovascular deaths in the Lipitor 80mg group (3.3%) was lower than that in the placebo group (4.1%). The proportion of patients worried about vascular death (50%) in the Lipitor 80mg group was higher than that in the placebo group (4.0%).

Post-market reports < br The following adverse reactions came from reports of Lipitor after approval for market application. Post-marketing adverse reaction reports are actively reported by patients, and the number of actual drug users 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.
Without considering the cause and effect, related adverse reactions not listed above after Li Jintuo's listing include: allergic reactions. Angioedema, herpes (including polymorphous erythema, Stevens-Johnson syndrome and toxic epidermal necrolysis), rhabdomyolysis, fatigue, tendon rupture, liver failure, dizziness, memory loss, depression, and peripheral nerves Lesions.
Pediatric Patients (Age 10-17)
In a 26-week controlled study involving boys and girls after menarche, atorvastatin 10mg-20mg / day (n = 140, 31% were girls: 92% Caucasian 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 Drugs] ^[2] .

Lipitor taboo

1. Active liver disease, which can 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 for 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 substances 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. At present, there are insufficient controlled studies on atorvastatin in pregnant women: occasionally, fetal congenital abnormalities have been reported during 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. Lactating women: Whether atorvastatin can be secreted from human milk 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]) ^[3] ^[2]

Lipitor precautions

1. Skeletal muscle Several cases of myoglobinuria secondary to acute renal failure due to rhabdomyolysis have been reported by lipitor and other statins. Renal impairment may be a risk factor for rhabdomyolysis, and these patients need to be closely monitored for the effects of drugs 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 Statins in combination with certain 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. Lipitor therapy should be discontinued if there is a significant increase in creatine phosphokinase levels or a diagnosis / suspected myopathy.
During the treatment of such drugs, if cyclosporine A, fibric acid derivatives (fibrates) are used at the same time. Erythromycin, clarithromycin, ritonavir plus saquinavir or lopinavir plus ritonavir. Nicotinic acid or imidazole antifungals increase the risk of myopathy. Physicians are considering a combination of atorvastatin and fibric acid derivatives (fibrates), erythromycin, clarithromycin, ritonavir plus saquinavir or lopinavir plus ritonavir 2. Immunosuppressive drugs, imidazole antifungals or lipid-adjusting doses of niacin should be carefully weighed for potential benefits and risks, and patients should be carefully monitored for any signs and symptoms of muscle pain, muscle tenderness or muscle weakness, especially It is 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 the recommended dosage and interacting drugs is shown in Table 2 (see [Usage and Dosage], [Drug Interactions], [Pharmacology and Toxicology] for details).

Any patient with acute or severe conditions indicating myopathy or risk factors (eg, 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 < br <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 aminotransferases (two or more times exceeding the upper limit of normal values by three times). The occurrence of transaminase abnormalities in shore-drainers at doses of 10, 20, 40, and 80 mg was 0.2%, 0.2%, 0.6%, and 2.3%, respectively.
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 related to jaundice and other clinical signs or symptoms. After reducing the dosage, the level of aminotransferase returned to or close to the level before treatment without sequelae after the drug was discontinued or stopped. Of the 30 patients whose liver function tests 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, it should be checked regularly (such as every six months). 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 can 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 < br <Cerebral hemorrhage occurred in a male 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 the dying state, and cerebral hemorrhage and formation of optic nerve vacuoles 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 of approximately 16 times the area under the human plasma curve (AUC, 0-24 hours). In a 2-year study, two male dogs (one administered at 10 mg / kg / day and the other at 120 mg / kg / day) were observed to each have an tonic convulsion. In the long-term administration for 2 years, no central nervous system damage was observed in mice with a dose of up to 4 mmg / kg / day and rats with a dose of 100 mg / kg / 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 infiltration of monocyte perivascular space. 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 maximum recommended human dose, optic neurodegeneration (retinal-knee-shaped fiber Wallerian degeneration) occurs in a dose-dependent manner.
5. The application of the SPARCL study (strengthening cholesterol-lowering therapy to prevent stroke) in patients with recent stroke or transient cerebral hemorrhage attack included a total of 4,731 patients with stroke or transient ischemic attack but no coronary heart disease in the past 6 months. After receiving Lipitor 80mg or placebo, post hoc analysis of the study showed. The incidence of hemorrhagic stroke was higher in the Lipitor 80mg group than in the placebo group (55 [2.3% and 33 [1.4%], HR = 1.68, 95% CI: 1.09-2.59, p = 0.0168), respectively. The incidence of fatal hemorrhagic stroke was similar in the group (17 and 18 in the atorvastatin and placebo groups, respectively). The incidence of non-fatal hemorrhagic stroke (38, 1.6%) in the atorvastatin group was higher than that in the atorvastatin group. Placebo group (16 persons, 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 medication for pregnant and lactating women

Pregnancy < br Pregnancy classification x
Lipitor is not allowed to be taken by pregnant women or women of childbearing age who may become pregnant. 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. Therefore, 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 taking medication within 3 months of being aware of pregnancy.
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. Based on body surface area (mg / m2), these doses are approximately 30 times (rats) or 20 times (rabbit) human exposure (see [Contraindications], pregnancy).
In one study, rats were administered a dose of 20, 100, or 225 mg / kg / day from the 7th day of pregnancy to the 21st day of lactation (weaning). When the mother administered a dose of 225 mg / kg / day, the young animals were born, and the survival rate of newborns, weaning, and maturation was reduced. The mother's dose was 100 mg / kg / day, and the weight of the young animals was reduced at 4 and 21 days: the mother's dose was 225 mg / kg / day at birth, and the body weight of the young animals at day 4, 21, and 91 Decreased, delayed development of young animals (Routel syndrome occurred at a dose of 100 mg / kg / day, and auditory startle response occurred at 225 mg / kg / day, and auricle separation and cracking occurred 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 the likelihood of pregnancy is extremely low and the potential danger of the drug to pregnant women has been informed. As soon as a woman taking this product becomes pregnant, she should discontinue the drug immediately and inform her of the potential danger to the fetus. Continued medication during pregnancy lacks known clinical benefits ^[2] .
Breastfeeding women Whether atorvastatin is secreted by human milk 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 similar drug can be secreted through human milk, and statins may cause serious adverse reactions in neonates who are breastfeeding, mothers taking this product should not breastfeed (see [Contraindications]).

Lipitor for children

This product should only be used in children by specialists. The treatment experience of this product in children is limited to a small number (4-17 years) of 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 ^[3] .

Lipitor for the 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 cause of myopathy, so Lipitor should be used with caution in the elderly.

Lipitor drug interactions

During the 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 clarithromycin, HIV protease inhibitor and itraconazole) (see [Precautions], "Skeletal Muscle" and [Pharmacology and Toxicology]).
1. CYP 3A4 strong inhibitor: Lipitor is metabolized by cytochrome P450 3A4. 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.
Clarithromycin: Compared with Lipitor alone, Atorvastatin AUC significantly increased when combined with Lipitor 80mg and Clarithromycin (500mg. Twice daily) (see [Pharmacology and Toxicology]). Therefore, patients who use clarithromycin should be used with caution when using Lipitor 20mg (see "skeletal muscle" and "Dosage and Administration" in the [Precautions]).
Combination with protease inhibitors: Compared with Lipitor alone, Lipitor 40mg is combined with ritonavir + saquinavir (400mg, twice daily) or Lipitor 20mg with lopinavir + lip Atorvastatin AUC increased significantly when combined with tonavir (400 mg + 100 mg, twice daily) (see [Pharmacology and Toxicology]). Therefore, patients with HIV protease inhibitors should be used cautiously when using Lipitor 20mg (see "skeletal muscle" and [usage and dosage] in the [Cautions] section).
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 with caution when using Lipitor 20mg (see "skeletal muscle" and "dosage 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 ingesting a large amount of grapefruit juice (drinking more than 1.2 liters per day)
3. Cyclosporine: Atorvastatin and its metabolites are substrates of the OATPIB1 vector. OATPIB1 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 of Lipitor combined with cyclosporin, the dose of Lipitor should not exceed 10mg (see [Caution], "Skeletal Muscle").
4 Rifampicin other cytochrome P450 3A4 inducers: Lipitor and cytochrome P450 3A4 inducers (such as efavirenz and rifampicin) can cause different levels of atorvastatin plasma levels. 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.
5. Digoxin: When multiple doses of Lipitor are combined with digoxin, the steady-state plasma concentration of digoxin increases by about 20%, and patients should be properly monitored when taking digoxin.
6. Oral contraceptives: When Lipitor is used in combination with oral contraceptives, the AUCs of norethisterone 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.
7. Warfarin: Lipitor has no clinically significant effect on prothrombin time when patients receive long-term warfarin treatment.

Lipitor 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 Lipitor to plasma proteins, hemodialysis cannot significantly increase the clearance of Lipitor ^[2] .

Lipitor clinical trial

1. Prevention of vascular diseases:
The British Anglo-Scandinavian Heart Endpoint Study (ASCOT) evaluated the efficacy of Lipitor in lethal and non-lethal coronary heart disease. 10,305 hypertensive patients aged 40-80 years (mean 63 years) were enrolled. They had no previous history of myocardial infarction and their total cholesterol levels were 251 mg / dL (6.5 mmol / 1). In addition, all patients had at least three of the following cardiovascular risk factors: male (81.1%). Age 55 years (84.5%), smoking (33.2%), diabetes (24.3%), immediate family members with a history of coronary heart disease (26%), total cholesterol / high density lipoprotein ratio greater than 6 (14.3%), peripheral vascular disease (5.1%), left ventricular hypertrophy (14.4%), history of cerebrovascular disease (9.8%), specific electrocardiogram abnormalities (14.3%), proteinuria / albuminuria (62.4%). In this double-blind, placebo-controlled study, patients were receiving antihypertensive therapy (non-diabetic patients had a target blood pressure below 140 / 90mn Hg, and diabetic patients had a target blood pressure below 130/80 mmHg) and were randomized to receive Lipitor Treatment with 10 mg / day (n = 5168) or placebo (n = 5197) adjusted the release of nine baseline characteristics of selected patients using appropriate covariate adjustments to reduce imbalance between these characteristics between groups. The median patient follow-up period was 3.3 years.
The effect of Lipitor 10mg / day on blood lipid levels is similar to that observed in previous clinical studies.
Lipitor significantly reduces coronary events [fatal coronary heart disease (46 events in placebo group, 40 events in Lipitor group) or nonfatal myocardial infarction (108 events in placebo group, 60 events in Lipitor group )], With a 36% relative risk reduction [(1.9% in the Lipitor group and 3.0% in the placebo group), p = 0.0005 (see Figure 1)]. The risk reduction was consistent regardless of age, smoking status, obesity, or the presence of abnormal renal function. This effect of Lipitor is seen regardless of baseline LDL levels. With fewer incidents, women's results are uncertain.

Lipitor also significantly reduced the relative risk of vascular reconstruction by 42%. Although the reduction in fatal and non-fatal stroke did not reach a predetermined significant level (p = 0.01), a good trend of 26% relative risk reduction was observed (the incidence of the Lipitor group was 1.7% and the placebo group was 2.3% ). There was no significant difference between cardiovascular deaths (P = 0.51) and non-cardiovascular deaths (p = 0.17) between the two treatment groups.
The Atorvastatin Collaborative Diabetes Study (CARDS) evaluated the effect of Lipitor on cardiovascular disease (CVD) endpoints. 2838 patients were selected (94% were white and 68% were men). Those aged 40-75 years who were diagnosed with WHO type 2 diabetes mellitus had no history of cardiovascular disease. LDL 160mg / dL, triglycerides 600mg / dL. With the exception of diabetes, all patients have at least one of the following risk factors: smoking (23%), hypertension (80%), retinopathy (30%), microalbuminuria (9%), or massive albuminuria ( 3%). This study did not select patients for hemodialysis. In this multicenter, placebo-controlled, double-blind clinical study, patients were randomized to receive Lipitor 10mg / day (n = 1.429) or placebo (n = 1.411) at a 1: 1 ratio, with median follow-up years At 3.9 years, the primary endpoint was the occurrence of any major cardiovascular event: myocardial infarction. Death from acute coronary heart disease, unstable heart striate carcinoma, coronary revascularization or stroke. The primary analysis was when the primary endpoint first occurred.
The baseline characteristics of the patients were: mean age 62 years, mean glycated hemoglobin 7.7%: median low density lipoprotein cholesterol 120 mg / dL; median total cholesterol 207 mg / dL; median triglyceride 151 mg / dL; median The value is high density lipoprotein cholesterol 52mg / dL.
The effect of Lipitor 10mg / day on blood lipid levels is similar to that observed in previous clinical studies.
Lipitor significantly reduced the incidence of major cardiovascular events (primary end point events) (83 events in the Lipitor group and 127 events in the placebo group), with a relative risk reduction of 37%, a hazard ratio of 0.63, and a 95% confidence interval ( O.48, 0.83) (p = 0.001) (see Figure 2). Age, gender, or baseline lipid levels did not affect the effects of Lipitor.

Lipitor significantly reduced stroke risk by 48% (21 events in the atorvastat group vs. 39 events in the placebo group), HR 0.52, 95% CI (0.3l, 0.89) (p = 0.016), myocardial infarction The risk rate decreased by 42% (38 events in the atorvata group vs. 64 events in the placebo group), HR 0.58, 95% CI (0.39, 0.86) (0.007). There were no significant differences in angina pectoris, revascularization, and acute coronary heart disease death between the two groups.
There were 61 deaths in the Lipitor group and 82 deaths in the placebo group (HR 0.73, p = 0.059). In the New Target Therapy Study (TNT), the effects of Lipitor 80mg / day and 10mg / day on reducing cardiovascular events were evaluated. 10,000 (94% white, 81% male, 38% 65 years old) patients with clinical evidence of coronary heart disease were enrolled, and all patients had low density after 8 weeks of open-lead therapy with Lipitor 10mg / day Lipoprotein cholesterol levels reached less than 130 mg / dL. Patients were randomized to receive Lipitor 10 mg / day or 80 mg / day, with a median follow-up of 4.9 years. The primary endpoint was the time of first occurrence of any of the following major cardiovascular events (MCVE): coronary heart disease death, non-fatal myocardial infarction, cardiac arrest resuscitation, fatal and non-fatal stroke. After 12 weeks of treatment, the average levels of LDL cholesterol, total cholesterol, triglycerides, non-HDL and HDL cholesterol in the Lipitor 80mg / day treatment group were 73,145,128,98 and 47mg / dL, respectively. The Lipitor 10mg / day treatment group was 99,177,152,129 and 48mg / dL.
Lipitor 80mg / day significantly reduced the incidence of major cardiovascular events (434 events in the 80mg / day group and 548 events in the 10mg / day group), a relative risk reduction of 22%, a hazard ratio of 0.78, and a 95% confidence interval (0.69, 0.89), p = 0.0002 (see Figure 3 and Table 3). Overall risk reduction was consistent across ages (<65, 65) or gender.

a Atorvastatin 80mg. Atorvastatin 10mg
b Composition of other secondary endpoints * Secondary endpoints are not included in the primary endpoint. HR = hazard ratio; CHD = coronary heart disease; CI = confidence interval; MI = myocardial infarction: CHF = congestive heart failure; CV = cardiovascular; PVD = Peripheral vascular disease; CABG = confidence interval for the secondary endpoint of coronary artery bypass grafting, not adjusted using multiple comparisons. In the events included in the primary efficacy endpoint of stroke, Lipitor 80mg / day treatment significantly reduced non-fatality, Non-vascular operation-related myocardial death and fatal and non-fatal stroke rates, but did not reduce the incidence of coronary heart disease death or cardiac arrest resuscitation (Table 3). Lipitor 80mg 135 days in the scheduled secondary endpoint Treatment significantly reduced the incidence of coronary revascularization, angina pectoris, and hospitalization for heart failure, but did not reduce the incidence of peripheral vascular disease. The reduction in hospitalizations due to congestive heart failure was only observed in 8% of patients with a previous history of congestive heart failure.
There was no significant difference in all-cause mortality between the two treatment groups (Table 3). Cardiovascular death, including coronary heart disease death and fatal stroke, occurred in the Lipitor 80mg treatment group, and the number was not less than that of the Lipitor 10mg treatment group. The number of patients with non-cardiovascular death in the Lipitor 80mg group was greater than that in the Lipitor 10mg group.
In an intensive lipid-lowering further reduction clinical endpoint study (IDEAL), 8888 patients with a history of coronary heart disease under 80 years of age who received Lipitor 80 mg / day compared with simvastatin 20 to 40 mg / day evaluated whether they could reduce heart Vascular danger. The patients were mainly men (81%), whites (99%), average age 61.7 years, and mean LDL cholesterol was 121.5 mg / dL at random; 76% were treated with statins. There was no lead-in period in this prospective, randomized, open, blind endpoint (PROBE) study, and the median duration of follow-up was 4.8 years. After 12 weeks of treatment, the average levels of low-density lipoprotein cholesterol, total cholesterol, triglyceride, high-density lipoprotein, and non-high-density lipoprotein cholesterol in the Lipitor 80mg / day treatment group were 78, 145, and 115, respectively. 45 and 100 mg / dL, simvastatin 20-40 mg daily treatment groups were 105, 179, 142, 47 and 132 mg / dL, respectively.
There were no significant differences in the primary endpoints of the two treatment groups, namely the incidence of the first major coronary event (fatal coronary heart disease, non-fatal myocardial infarction, and cardiac arrest resuscitation): 411 (9.3%) in Lipitor 80mg / day treatment group , Stravastatin 20-40mg / day treatment group was 463 (10.4%), the hazard ratio was 0.89, 95% confidence interval (0.78, 1.01), p = 0.07.
There was no significant difference in all-cause mortality between the two treatment groups: 366 (82%) in the Lipitor 80mg / day treatment group and 374 (8.4%) in the Lipitor 80mg / day treatment group in the simvastatin 20-40mg / day treatment group. The proportion of patients with cardiovascular or non-cardiovascular deaths was similar in the group and the simvastatin 20-40 mg / day treatment group.
2. Hypercholesterolemia (heterozygous familial or nonfamilial) and mixed hyperlipidemia (Fredrickcon a and b)
Lipitor reduces total cholesterol, low density lipoprotein cholesterol, and very low density lipoprotein cholesterol in patients with hypercholesterolemia and mixed dyslipidemia. Apolipoprotein B, and triglycerides, raise high-density lipoprotein cholesterol. The effect can be seen in two weeks, and the maximum effect is usually reached within 4 weeks of treatment, and the long-term treatment can maintain the effect.
Lipitor is effective in patients with a variety of hypercholesterolemia, whether with or without hypertriglyceridemia, in men and women, and in the elderly. Use of pediatric patients is limited to homozygous familial hyperlipidemia.
In two multicenter, placebo-controlled, dose-effect studies of patients with hypercholesterolemia, a single dose of Lipitor for 6 weeks significantly reduced total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein D and triglycerides (see Table 4 for summary results).

a From the results of two dose-response studies.
Pooled data from 24 controlled studies of Fredrickson type IIa and type IIb hyperlipoproteinemia patients showed median HDL cholesterol compared with baseline at 10, 20, 40, and 80 mg of Lipitor (No. (25th and 75th percentiles) The percentage changes are 6.4 (-1.4,14), 8.7 (0.17) 7.8 (0,16), and 5.1 (-2.7,15). In addition, the analysis of the aggregate data showed that total cholesterase, low-density lipoprotein cholesterol, triglycerides, total cholesterol / high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol / high-density lipoprotein cholesterol were also consistently significantly reduced.
Lipitor and other statins were compared in three multicenter, double-blind patients with hyperlipidemia. After randomization, patients received Lipitor 10 mg / day or fixed-dose control for 16 weeks (Table 5).

1 Negative value of 95% confidence interval with 95% difference between treatments can be explained by atortastatin except HDL-C. Excluding the range of 0 indicates a statistically significant difference.
a. Significant difference compared with lovastatin ANCOVA, P0.05
b. Significant difference compared with pravastatin ANCOVA, P0.05
c. Significant difference compared with simvastatin ANCOVA, P0.05
The effect of the differences in lipid effects of various treatments on the clinical outcome in Table 5 is unclear. Table 5 does not include atorvastatin. 10 mg compared with higher doses of lovastatin, pravastatin and simvastatin data. The drugs compared in the studies summarized in the table are not interchangeable.
3. Hypertriglyceridemia (Fredrickson Type )
In several clinical studies involving 64 patients with pure hypertriglyceridemia, the efficacy of Lipitor is shown in the following table. The baseline triglyceride level of Lipitor is 565 (267-1502).

4. The role of -lipoproteinemia (Fredrickson type III):
Lipitor's open cross-over study of 16 patients with -lipoproteinemia (Fredrickson type III) (genotype: 14 apoE2 / E02 and 2 apoE3 / E2) is shown in the following table:

5. Homozygous familial hypercholesterolemia < br In a study without a control group, 29 homozygous familial hypercholesterolemia patients aged 6 to 37 years received a maximum daily dose of Lipitor of 20 to 80mg of treatment. The average reduction in LDL cholesterol in this study was 18%. The average effect of LDL cholesterol reduction in 25 patients was 20% (range 7% to 53%, with a median value of 24%); the remaining 4 patients increased LDL cholesterol by 7% to 24%. Five of the 29 patients had LDL function loss. Of these five patients, two patients with portal and vena cava shunts showed no significant reduction in LDL cholesterol. The remaining 3 receptor-negative patients had an average reduction in LDL-cholesterol of 22%.
6. Children with heterozygous familial hyperlipidemia < br In a study that started as a double-blind, placebo-controlled, open-label study, 187 were aged 10-17 (mean age 14.1 years) ) Heterozygous familial or severe hypercholesterolemia boys and girls after menarche were randomized to receive Lipitor (n = 140) or placebo (n = 47) for 26 weeks, then all patients received Lipitor treatment for 26 weeks. Inclusion criteria included 1) baseline low-density lipoprotein cholesterol level 190 mg / dL or 2) baseline low-density lipoprotein cholesterol level 160 mg / dl and family history of familial hypercholesterolemia positive or at first or second level Relatives have a positive family history of diagnosed early-onset coronary heart disease. The baseline mean LDL cholesterol level in the Lipitor group was 218.6 mg / dL (range: 138.5-385.0 mg / dL), and the placebo control group was 230.0 ng. / dL range: 160.0-324.5 mg / dL). The dose of Lipitor (once a day) is 10 mg in the first 4 weeks. If the LDL cholesterol level is greater than 130 mg / dL, adjust to 20 mg. After 4 weeks in the double-blind treatment period, the number of patients in the Lipitor group (57.1%) to be increased to 20 mg.
During the 26-week double-blind treatment period, Lipitor significantly reduced plasma total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B levels (see Table 8).

In the 26-week double-blind period, the average LDL-C in the Lipitor group reached 130.7 mg / dL (70.0 to 242.0 mg / dL) and the LDL-C level in the placebo group was 228.5 mg / Dl (152.0 to 385.0 mg / dL). .
The safety and effectiveness of Lipitor at doses above 20 mg have not been performed in a child-controlled study, and the long-term effectiveness of Lipitor for childhood treatment to reduce morbidity and mortality in adulthood has not been proven.

Lipitor Pharmacology and Toxicology

Clinical Pharmacology Mechanism of Action br Lipitor is a selective and competitive agent for 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 atherogenesis in humans. Cardiovascular disease risk factors, and high HDL cholesterol levels are associated with a reduced risk of cardiovascular disease.
In animal models, Lipitor reduces plasma cholesterol and lipoprotein levels by resisting the synthesis of HMG-CoA reductase and cholesterol in the liver, and enhances LDL uptake and Catabolism; Lipitor also reduces generation of lipoproteins and low-density lipoprotein 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.
Lipitor reduces total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels in patients with homozygous and heterozygous family hypercholesterolemia, nonfamily hypercholesterolemia, and mixed dyslipidemia. Lipitor also reduces very low-density lipoprotein protein cholesterol and triglyceride levels, and can use elevated levels of high-density lipoprotein cholesterol and apolipoprotein A-1. Lipitor reduces 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 density Lipoprotein alcohol can not leak water, Lipitor can reduce the intermediate density lipoprotein cholesterol in patients with lipoprotein abnormalities.
Pharmacodynamics Lipitor 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 depth of the systemic drug is more related to a reduction in LDL cholesterol. The individualized dose should be determined according to the efficacy of the treatment (see [Dosage and Administration]).
Non-clinical toxicology Carcinogenic , teratogenic, reproductive damage In a 2-year study in rats, the dose levels given to rats were 10, 30, and 100 mg / kg / day, at high levels Two rare tumors were found in the muscles of female rats at doses: one was rhabdomyosarcoma and the other was 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 carcinogenesis study in mice, the doses were 100,200. Or 400mg / kg / day. Leading to a significant increase in hepatic adenomas in high-dose 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, Atostatin 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 the fertility of the animals. 10 rats were given atorvastatin 100mg / kg / day (16 times the area under the curve when the 80mg dose was given to humans) for 3 months, of which 2 rats had epididymal hypoplasia and azoospermia; 30 and At 10 mg / kg / day, the testicular weight of the dose group decreased significantly, and the epididymal weight of the 100 mg dose group decreased. Atorvastatin was given to male rats at a dose of 100 mg / kg / day before mating for a total of 11 weeks. Sperm motility and sperm cell head concentration increased, while abnormal sperm increased. Administration of 10, 40, or 120 mg / kg / day atorvatin to dogs for two years did not adversely affect semen parameters or histopathology of the reproductive organs.

Lipitor pharmacokinetics

Pharmacokinetics and drug metabolism Absorption: Rapid absorption after oral administration of Lipitor: peak plasma concentration (Cmax) within 1 to 2 hours. The degree of absorption increases with the dose or proportionality of Lipitor. Lipitor (parent drug) has an absolute bioavailability of about 14% and a system bioavailability of HMG-CoA reductase inhibitory activity of about 30%. The lower system bioavailability is due to gastrointestinal mucosal clearance and / or liver first-pass effects before entering the systemic circulation. Compared to the morning dose, the plasma concentration at night was slightly lower (Cmax and AUC about 30%). However, no matter when it is administered throughout the day, the reduction in LDL cholesterol is the same (see [Dosage and Administration]).
Distribution: Lipitor's average distribution volume is approximately 381 liters. Plasma protein binding rate is 98%. A blood / plasma ratio of about 0.25 indicates that only a small amount of drug penetrates into the red blood cells. According to observations in rats, Lipitor may be secreted into human milk ([taboo], [drugs for pregnant and lactating women], and [notes], "lactating women").
Metabolism: Lipitor is extensively metabolized into ortho and para hydroxy derivatives and various beta oxidation products. In vitro experiments, the ortho- and para-hydroxylated metabolites inhibited HMG-CoA reductase similarly to Lipitor. About 70% of the circulating inhibitory activity on HMG-CoA reductase is produced by active metabolites. In vitro studies have shown the importance of cytochrome P450 3A4 in the metabolism of Lipitor, while taking the known isoenzyme inhibitor erythromycin is consistent with increased plasma concentration of Lipitor in the human body (see [Caution] [Drugs interact with each other]. In animals, the ortho-hydroxyl metabolites undergo a further glucouronic acid process.
Excretion: Lipitor and its metabolites are mainly cleared by the bile after hepatic and / or extrahepatic metabolism, but Lipitor does not appear to have significant hepato-enteric recirculation. Lipitor's average plasma elimination half-life in humans is about 14 hours, but because of its active metabolites, Lipitor's half-life of HMG-CoA reducing alcohol inhibitory activity is about 20-30 hours. After oral administration of Lipitor, the urine recovery rate was less than 2% of the dose.
Special populations < br Elderly patients: In healthy elderly people (age 65 years), the blood concentration of Lipitor is higher than that of young people (Cmax is about 40%, AUC is about 30%). Clinical data show that given any dose of Lipitor, the level of LDL-C reduction is significantly higher in the elderly than in young people (see [Notes], "Medication for the elderly")
Children: Pharmacokinetic data in children are not sufficient ^[2] .
Gender: Lipitor's plasma concentration varies by sex (in terms of Cmax, women are about 20% higher than men, and in terms of AUC, women are 10% lower than men). However, in clinical applications, there is no significant gender difference in the effect of Lipitor on LDL-C.
Patients with renal insufficiency: Kidney disease has no effect on Lipitor's plasma concentration and LDL-C effect, so patients with renal insufficiency do not need to adjust the dose (see [Dosage and Administration])
Patients on hemodialysis: Although patients with end-stage renal disease have not yet been studied, due to the extensive combination of these two drugs with plasma proteins, hemodialysis does not significantly improve clearance of Lipitor.
Patients with hepatic insufficiency: In patients with chronic alcoholic liver disease, Lipitor's plasma concentration increased significantly. In Childs-Pugh A patients, Cmax and AUC increased by 4 times, while in Childs-Pugh B patients AUC increased by 16 and 11 times, respectively (see [Contraindications]).

Lipitor R & D History

In 1985, Bruce Roth first synthesized atorvastatin calcium. 1997: Lipitor becomes the fifth statin approved by the FDA for the treatment of patients with high cholesterol. Lipitor was first approved for use in the United Kingdom and subsequently marketed in the United States. In the first three months of listing, Lipitor became a leader in the lipid-lowering market.
1998: Wall Street analysts call Lipitor "turbostatin." Lipitor becomes a statin leader in the United States.
2003: ASCOT trial results show Lipitor significantly reduces the risk of fatal and non-fatal heart attacks and strokes.
2004: FDA approves Lipitor's new indications. Lipitor reduces the risk of heart attack, revascularization, and angina pectoris in patients with normal or mildly elevated cholesterol and multiple cardiovascular risk factors.
2005: US FDA approves Lipitor for patients with type 2 diabetes who have no evidence of heart disease and other risk factors to reduce the risk of stroke and heart disease.
2005: Lipitor's TNT study shows that Lipitor can reduce the risk of cardiovascular and cerebrovascular events in patients with stable coronary heart disease when LDL-C is reduced below the current recommended level.
2006: Cardiac Association launches new guidelines suggesting: To achieve LDL-C below 100 mg / dL (2.6 mmol / L) or below 70 mg / dL (1.8 mmol / L), use statins as 2 Grade preventive treatment.
2007: FDA approves Lipitor's new indications. Patients with clear heart disease can use statins to:
Reduce the risk of non-fatal myocardial infarction;
Reduce the risk of fatal and non-fatal strokes;
Reduce the risk of revascularization;
Reduce the risk of hospitalization due to congestive heart failure;
Reduce the risk of angina pectoris;
The 2014 New England Journal of Medicine looks back on the 200-year history of modern medicine, and Liptop is on the list. The article states that atorvastatin treatment in patients with ACS can significantly reduce LDL-C and become the standard treatment for patients with ACS.

Lipitor storage

Keep tightly closed.

Lipitor packaging

Packed in aluminum / aluminum blister; boxed; 7 pieces / box, 10 pieces / box.

Lipitor validity

36 months.

Lipitor implementation standards

Import Drug Registration Standard JX20070073

Lipitor approval number

10mg: National Medicine Standard J20120050;
20mg: National Medicine Standard J20120049;
40mg: National Medicine Standard J20120051.

Lipitor Manufacturing

Pfizer Ireland Pharmaceuticals

Lipitor Packaging

Pfizer Pharmaceutical Co., Ltd.

Lipitor approval date

March 9, 2007

Lipitor revision date

December 11, 2007 March 11, 2009 April 20, 2011 October 08, 2012