What Are the Different Atorvastatin Side Effects?

Atorvastatin calcium capsules are indicated for patients with primary hypercholesterolemia. Including patients with familial hypercholesterolemia (hybrid subtype) or mixed hyperlipidemia (equivalent to Fredrickson classification || a and || b type). If the effects of diet and other non-drug treatments are not satisfactory, this product can be used to treat the increase of total cholesterol, low density lipoprotein cholesterol, apolipoprotein B and triglyceride. In homozygous familial hypercholesterolemia patients. Atorvastatin calcium can be used in combination with other lipid-lowering therapies or alone (when no other treatment is available) to reduce total cholesterol and low-density lipoprotein cholesterol.

Atorvastatin calcium capsules are indicated for patients with primary hypercholesterolemia. Including patients with familial hypercholesterolemia (hybrid subtype) or mixed hyperlipidemia (equivalent to Fredrickson classification || a and || b type). If the effects of diet and other non-drug treatments are not satisfactory, this product can be used to treat the increase of total cholesterol, low density lipoprotein cholesterol, apolipoprotein B and triglyceride. In homozygous familial hypercholesterolemia patients. Atorvastatin calcium can be used in combination with other lipid-lowering therapies or alone (when no other treatment is available) to reduce total cholesterol and low-density lipoprotein cholesterol.

Drug Name

Atorvastatin calcium capsules

Drug type

Prescription drugs, medicines for medical workers' injuries

Use classification

Lipid-lowering drugs

Atorvastatin calcium capsule ingredients

The main ingredients of this product are: atorvastatin calcium, its chemical name is [R- (R, R)]-2- (4-fluorophenyl) -, -dihydroxy-5- (1-methyl Ethyl) -3-phenyl-4-[(aniline) carbonyl] -1 hydrogen-pyrrole-1-heptanoic acid calcium trihydrate.
Its chemical structural formula is:

Molecular formula: C ₆₆ H ₆₈ CaF ₂ N ₄ O ₁₀ · 3H ₂ O
Molecular weight: 1209.42

Atorvastatin calcium capsule properties

This product is a hard cavity capsule with white granules or powder.

Atorvastatin calcium capsules specifications

(1) 10 mg (2) 20 mg (based on C ₃₃ H ₃₅ FN ₂ 0 ₅ )

Atorvastatin calcium capsules dosage

Before the patient starts treatment with this product. Should carry out standard low cholesterol diet control. A reasonable diet should also be maintained throughout the treatment period. The dose should be individualized according to the baseline level of LDL cholesterol and the treatment goals and the treatment effect of the patient.
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 80 mg once daily. Can be taken at any time of the day. Not affected by meals. For patients with confirmed coronary heart disease or other patients with increased risk of ischemic events, the treatment goals are LDL-C <3 mmol / L (or <115 mg / dL) and total cholesterol <5 mmol / L (or <190 mg / dL ). Treatment of Primary Hypercholesterolemia and Mixed Hyperlipidemia Most patients take atorvastatin calcium 10 mg once daily. Its blood lipid levels can be controlled. Significant results were seen within 2 weeks of treatment. Significant results were seen within 4 weeks of treatment. Long-term treatment can maintain the effect. The initial dose of 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 have not achieved satisfactory results, you can choose to adjust the dose to a large amount of 80 mg daily or 40 mg of this product with cholic acid mixture. Homozygous familial hypercholesterolemia is in a charity drug study involving 64 patients. Forty-six of these patients had corresponding LDL receptor information. The LDL-C of these 46 patients decreased by an average of 21%. The dose of this product can be increased to 80 mg per day. For patients with homozygous familial hypercholesterolemia. The recommended dose of this product is 10 to 80 mg per day. Atorvastatin calcium should be used as an adjunct to other lipid-lowering treatments, such as LDL plasma dialysis. Or when these treatment conditions are not available. This product can be used alone. Patients with renal insufficiency Dosage of kidney disease will not affect the plasma concentration of this product. It will not affect its lipid-lowering effect. So there is no need to adjust the dose.

Atorvastatin calcium capsule adverse reactions

The most common adverse reactions of this product are constipation, flatulence, indigestion and abdominal pain. It usually resolves after continued medication. Less than 2% of patients in clinical trials discontinued treatment due to adverse reactions associated with this product.
Based on clinical research data and extensive post-marketing experience. Adverse events of atorvastatin calcium are as follows. By convention, the estimated frequency of adverse events is: common (1 / 100. <1/10); uncommon (1 / 1000, <1/100); rare (1 / 10000, <1/1000) ; Very rare (<1/10000).
Gastrointestinal abnormalities are common: constipation. Flatulence, indigestion, nausea, diarrhea. Uncommon: anorexia, vomiting.
Blood and lymphatic system abnormalities are uncommon: thrombocytopenia. Immune system abnormalities: Common: Allergic reactions. Very rare: allergic reactions.
Endocrine disorders: Uncommon: Hair loss, hyperglycemia, hypoglycemia, pancreatitis. Spirit: Common: Insomnia. Uncommon: Amnesia.
Nervous system abnormalities: Common: headache, dizziness, paresthesia. Cancer is sluggish. Uncommon: peripheral neuropathy. Hepatobiliary abnormalities: rare: hepatitis, cholestatic jaundice.
Skin / limbs: Common: rash, itching. Uncommon: Rubella.
Very rare: angioedema, bullous rash (including erythema polymorphic, Stevens-Johnson syndrome, and toxic epidermolysis)
Ear loss labyrinth abnormal: uncommon: tinnitus. Skeletal muscle abnormalities: Common: Myalgia, arthralgia. Uncommon: Myopathy. Rare: Myositis, rhabdomyolysis.
Reproductive system abnormalities: Uncommon: Impotence. General abnormalities: Common: weakness, chest pain, back pain, peripheral edema. Uncommon: discomfort, weight gain.
Studies: As with other HMG-CoA reductase inhibitors, elevated serum aminotransferase levels have been reported in patients taking this product, but these changes are usually mild and transient and do not require treatment interruption. The clinically significant increase in serum transaminase (3 times the upper limit of normal) in patients receiving this product was 0.8%. These changes that occurred in all patients were dose related and reversible. It is similar to HMG-CoA reductase inhibitors in other clinical trials. 2.5% of patients taking this product experienced an increase in serum phosphocreatine kinase (CPK) more than three times the upper limit of normal. 0.4% of patients taking this product have a phosphocreatine kinase elevation that is 10 times greater than the upper limit of normal. (See [Precautions])

Atorvastatin calcium capsules contraindications

(1) Those who are allergic to any of the ingredients contained in this product are prohibited.
(2) Patients with active liver disease, serum aminotransferases that have risen more than 3 times the upper limit of normal and have unknown causes, myopathy, pregnancy, lactation and any women of childbearing age who have not taken appropriate contraceptive measures are contraindicated.

Atorvastatin calcium capsules precautions

1. Liver effects (1) Liver function tests should be done and reviewed regularly before starting treatment. Liver function should be checked in patients with any symptoms or signs suggesting liver damage. Patients with elevated aminotransferase levels should be monitored until normal. If the transaminase continues to rise more than 3 times the normal value, it is recommended to reduce the dose or discontinue this product (see [Adverse Reactions]). (2) Use this product with caution in patients with excessive alcohol consumption and / or history of liver disease.
2. Skeletal muscle effects Like other HMG-CoA reductase inhibitors, atorvastatin may affect skeletal muscle in rare cases, causing myalgia, myositis, and myopathy. May progress to life-threatening rhabdomyolysis. It is manifested as a significant increase in CPK (more than 10 times the upper limit of normal), myosinemia, and myosinuria, leading to renal failure.
Before treatment, atorvastatin should be used with caution in patients susceptible to rhabdomyolysis. CPK should be measured before treatment in the following cases:
Renal dysfunction, hypothyroidism, personal or family history of hereditary myopathy, previous history of statin or fibrate muscle injury, previous history of liver disease, and / or heavy alcohol consumption. To judge the necessity of the inspection.
In these cases, the risk of treatment-benefit ratio should be weighed and clinical monitoring recommended.
If baseline CPK levels are significantly elevated (5 times above the upper limit of normal), treatment should not be started.
Creatine Phosphokinase is measured when strenuous exercise or any factors that may increase CPK. CPK should not be measured. This can make interpretation of results difficult. If the CPK baseline level rises significantly (more than 5 times the upper limit of normal), it should be reviewed within 5 to 7 days to verify the results.
Patients should promptly report myalgia, cramps, or weakness during treatment (especially if accompanied by discomfort or fever).
If the above symptoms occur during medication, CPK should be measured. Once a significant increase is found (more than 5 times the upper limit of normal), treatment should be discontinued.
If muscle symptoms are severe and cause daily discomfort, even if the CPK level is 5 times the normal upper limit. Consideration should also be given to discontinuing treatment.
If symptoms ease and CPK levels return to normal, atorvastatin may be re-used or replaced with another type of statin under close monitoring, starting with the lowest dose.
If clinically occurring CPK levels exceed 10 times the upper limit of normal or definite diagnosis / suspected rhabdomyolysis, atorvastatin must be discontinued.
Atorvastatin can increase the risk of rhabdomyolysis in combination with the following drugs: cyclosporin, erythromycin, clarithromycin, itraconazole, ketoconazole, nefazodone, nicotinic acid, and gemfid Bezi, other fibric acid derivatives or HIV protease inhibitors (see [Drug Interactions] and [Adverse Effects]).
Patients with galactose intolerance, human lactose deficiency, or rare genetic diseases such as glucose-galactose malabsorption should not take this product.

Atorvastatin calcium capsules for pregnant and lactating women

Atorvastatin calcium is contraindicated in pregnant and lactating women. Women of childbearing age should take appropriate contraceptive measures. The safety of atorvastatin in pregnant and lactating women has not been proven. Animal experiments have confirmed that HMG-CoA reductase inhibitors may have effects on the growth and development of embryos and infants. When taking atorvastatin at a dose of more than 20 mg / kg / day (equivalent to the clinical human dose). The offspring of the rat are stunted, and the survival rate after birth is reduced.
The concentration of atorvastatin and its active metabolites in rat plasma was the same as that in its milk. Whether the drug and its active metabolites are secreted in human milk is unclear.

Atorvastatin calcium capsules for children

Use of this product by children should be determined by a specialist. 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 daily. Depending on the patient's response and tolerance, the dose can be increased to 80 mg per day. There is no data on the safety of this product for the growth and development of this population.

Atorvastatin calcium capsules for elderly

The recommended dose of atorvastatin calcium in elderly people over 70 years of age has no difference in efficacy and safety from the general population.

Atorvastatin calcium capsule drug interactions

The risk of myopathy increases when statins are combined with cyclosporin, fiber derivatives, macrolide antibiotics (including erythromycin), conazole antifungals, or niacin. In very rare cases. Can cause rhabdomyolysis with myosinuria followed by renal insufficiency. therefore. The combined risk-benefit ratio should be carefully weighed (see [Notes]).
Cytochrome P450 3A4 inhibitor: Atorvastatin is metabolized by cytochrome P450 3A4. This product is an inhibitor of cytochrome P450 3A4 (cyclosporin, macrolide antibiotics such as erythromycin and clarithromycin and kang Drug interactions may occur with azole antifungals such as itraconazole HIV protease inhibitors. Concomitant medications lead to increased plasma concentrations of atorvastatin, so special attention should be paid when combining atorvastatin with the above drugs (see [Precautions]).
P-glycoprotein inhibitors: Atorvastatin and atorvastatin metabolites are P-glycoprotein matrices. P-glycoprotein inhibitors (such as cyclosporin) can increase the bioavailability of atorvastatin.
Erythromycin, clarithromycin: Atorvastatin 10 mg once daily combined with cytochrome P4503A4 inhibitor erythromycin (500 mg. 4 times daily) or clarithromycin (500 mg, 2 times daily) Application, the plasma concentration of atorvastatin increased. Clarithromycin increased the maximum plasma concentration of atorvastatin and the area under the curve by 56% and 80%, respectively.
Itraconazole: The combination of atorvastatin 40 mg and itraconazole 200 mg / day can lead to a 3-fold increase in the former's AUC.
Protease inhibitors: Protease inhibitors, known cytochrome P450 3A4 inhibitors, increase atorvastatin blood levels when used in combination with atorvastatin.
Grapefruit Juice: Contains one or more ingredients that inhibit cytochrome P450 3A4, which can increase the plasma concentration of drugs metabolized by this enzyme. Ingestion of 240 ml of grapefruit juice increased the AUC of atorvastatin by 37% and reduced the active parahydroxy metabolite AUC by 20.4%. However, ingesting a large amount of grapefruit juice (drinking more than 1.2 liters per day for 5 consecutive days) increased atorvastatin and active (atorvastatin and metabolite) HMG-CoA reductase inhibitor AUC by 2.5 times and 1.3 times, respectively. Therefore, it is recommended that people taking atorvastatin should not consume large amounts of grapefruit juice at the same time.
Cytochrome P450 3A4 inducer: The effect of cytochrome P450 3A4 inducer (rifampin, phenytoin) on this product is unknown. The possible interactions between this product and other substrates of this isoenzyme are unknown, but attention should be paid to drugs with a narrow therapeutic index, such as anti | arrhythmic drugs (amiodarone).
Other combination therapies: Gefibezil / Fibric acid derivatives: Fibric acid derivatives increase the risk of atropine-induced myopathy. Based on the results of in vitro studies, gemfibrozil inhibits the glucuronide pathway of atorvastatin, which may lead to elevated plasma levels of atorvastatin (see [Cautions]).
Digoxin: When 10 mg of this product is combined with multiple doses of digoxin, the steady-state plasma concentration of digoxin is not affected. When combined with digoxin 80 mg once a day, the concentration of digoxin increased by about 20%. This is due to the inhibition of the cell membrane transporter p-glycoprotein. Patients taking digoxin should be properly monitored.
Oral contraceptives: When this product is used in combination with oral contraceptives, the plasma concentrations of norethisterones and ethinyl estradiol increase. When choosing oral contraceptives, attention should be paid to their increased concentrations.
Colestipol (cholestyramine): When colestipol is combined with this product, the plasma concentration of atorvastatin and its active metabolite is reduced by 25%. However, the lipid-lowering effect of a combination of two drugs is greater than that of a single drug.
Antacids: When this product is used in combination with oral antacid suspensions containing magnesium hydroxide and aluminum hydroxide, the plasma concentration of atorvastatin and its active metabolites is reduced by about 35%; however, it reduces low-density lipoprotein The effect of cholesterol was not affected.
Warfarin: This product is used in combination with warfarin. The prothrombin time decreases slightly in the first few days and returns to normal after 15 days. Even so, patients taking warfarin should be closely monitored when taking this product.
Atitriptyline: No multiple effects of this product in combination with atipibrine have been found to eliminate atipibine.
Cimetidine: Studies on the interaction between this product and cimetidine have not found an interaction between the two.
Amlodipine: The combination of atorvastatin 80 mg and amlodipine 10 mg has no change in the pharmacokinetics of atorvastatin at steady state concentrations.
Others: No clinically significant drug interactions have been found in clinical trials of this product in combination with antihypertensive drugs or hypoglycemic drugs.

Atorvastatin calcium capsules overdose

There is no special treatment for this drug overdose. Once overdose occurs, the patient should take symptomatic and supportive measures as needed. Patients' liver function should be checked and serum creatine phosphokinase levels monitored. Because a large number of drugs bind to plasma proteins, hemodialysis cannot significantly accelerate the clearance of atorvastatin.
[Impact on driving and machine operation ability]
There are no reports of adverse events suggesting that taking this product will have any effect on the patient's ability to drive and operate dangerous machines.

Atorvastatin calcium capsules pharmacology and toxicology

Pharmacodynamics Atorvastatin belongs to HMG-CoA reductase inhibitor.
Atorvastatin is a selective and competitive inhibitor of HMG-CoA reductase. HMG-CoA reductase is a rate-limiting enzyme that converts 3-hydroxy-3-methyl-glutaryl-CoA to Mevalonate (precursor of sterols including cholesterol). Triglycerides and cholesterol are combined in the liver into very low density lipoprotein cholesterol (VLDL) and released into the plasma for further transport to surrounding tissues. Low-density lipoprotein cholesterol (LDL) is formed from very low-density lipoprotein cholesterol (VLDL) and is primarily catabolized by the receptor for high affinity low-density lipoprotein cholesterol (LDL).
Atorvastatin reduces plasma cholesterol and serum lipoprotein concentrations by inhibiting the biosynthesis of HMG-CoA reductase and cholesterol in the liver, and enhances LDL uptake and metabolism by increasing liver LDL receptors on the cell surface.
Atorvastatin reduces LDL cholesterol production and LDL cholesterol particles. Atorvastatin results in a significant and persistent increase in LDL cholesterol receptor activity, which in turn results in beneficial changes in the mass of LDL cholesterol particles in the circulation. Atorvastatin can effectively reduce low-density lipoprotein cholesterol levels in patients with homozygous familial hypercholesterolemia, and lipid-lowering drugs are generally not effective for such patients.
Clinical safety data Atorvastatin has no carcinogenic effect on rats. Calculated in mg / kg, the maximum dose used in rats was 63 times higher than the maximum dose used in humans (80 mg / day); calculated from the AUC (0-24) value derived from the total inhibitory activity, the value in the rat group was higher 8.16 times. In a two-year study using mice, the maximum dose used in mice was 250 times higher than the maximum dose used in humans calculated as mg / kg of body weight. The incidence of hepatocellular adenoma in male mice and hepatocellular carcinoma in female mice was between Increase at maximum dose. Calculated by AUC (0-24), the systemic dosage of mice is 6-11 times higher than that of humans. Four in vivo tests and one in vitro test performed with and without metabolic activation conditions confirmed that atorvastatin was not genetically altered and caused chromosomal aberrations. In animal tests, male and female animals were used at doses as high as 175 mg / kg / day and 225 mg / kg / day, respectively. Atorvastatin did not have any effect on the fertility of the animals and was not teratogenic.

Atorvastatin calcium capsules pharmacokinetics

Absorption: Atorvastatin is absorbed quickly after oral administration: The plasma concentration reaches a peak within 1 to 2 hours. The degree of absorption increases in proportion to the dose of atorvastatin. Compared with oral solutions, atorvastatin calcium capsules have a bioavailability of 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 gastrointestinal mucosal clearance and / or liver first-pass effects before entering the systemic circulation.
Distribution: The average distribution volume of atorvastatin is approximately 381 liters. More than 98% of atorvastatin binds to plasma proteins.
Metabolism: Atorvastatin is metabolized by pigment cells P450 3A4 into ortho and para hydroxy derivatives and various oxidation products. Among other things, these products are metabolized by the glucuronidation process. In vitro experiments, the inhibitory effect of site and para-hydroxylated metabolites on HMG-CoA reductase was comparable to that of atorvastatin. About 70% of the circulating inhibitory activity on HMG-CoA reductase is produced by active metabolites.
Clearance: Atorvastatin is mainly cleared by the bile after liver 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 inhibitory activity is about 20-30 hours.
Special population elderly: The plasma concentrations of atorvastatin and its active metabolites are higher in healthy elderly subjects than in adult subjects, but the lipid-lowering effect is comparable to that of young patients.
Children: No pharmacokinetic data are available for children. Gender: The plasma concentration of atorvastatin and its active metabolites in women (Cmax increases by about 20% and AUC decreases by 10%) is different from that of men. These differences are not clinically significant, and therefore there are no clinically significant differences in lipid-lowering effects on men and women.
Patients with renal insufficiency: Kidney disease has no effect on the plasma concentration and lipid-lowering effect of atorvastatin and its active metabolites.
Patients with liver dysfunction: The plasma concentrations of atorvastatin and its active products are significantly increased in patients with chronic alcoholic liver disease (about 16 times Cmax and about 11 times AUC).

Atorvastatin calcium capsule storage

Shaded, sealed, and stored in a cool place (not exceeding 20 ° C).

Atorvastatin calcium capsule packaging

Polyvinyl chloride solid pharmaceutical tablets and pharmaceutical packaging are packed in aluminum foil, 7 tablets per plate; 10 tablets per plate.

Atorvastatin calcium capsules expiration date

36 months.

Atorvastatin calcium capsules

YBH00642007. ^[1]