Atorvastatin film-coated tablets 40 mg blister No. 30

Instructions Atorvastatin film-coated tablets 40 mg blister No. 30

Composition

active ingredient: atorvastatin;

1 film-coated tablet contains 10.36, 20.72 or 41.44 mg of atorvastatin calcium, corresponding to 10, 20 or 40 mg of atorvastatin, respectively;

excipients: mannitol (E 421), microcrystalline cellulose, calcium carbonate, povidone, croscarmellose sodium, sodium lauryl sulfate, colloidal anhydrous silica, magnesium stearate, hypromellose, titanium dioxide (E 171), macrogol 6000, talc.

Dosage form

Film-coated tablets.

Main physicochemical properties:

10 mg: film-coated tablets, white, round, biconvex, 7 mm in size.

20 mg: film-coated tablets, white, round, biconvex, 9 mm in size.

40 mg: film-coated tablets, white, oval, biconvex, 8.2×17 mm in size.

Pharmacotherapeutic group

Drugs that lower serum cholesterol and triglyceride levels. HMG-CoA reductase inhibitors. ATC code C10A A05.

Pharmacological properties

Pharmacodynamics.

Atorvastatin is a synthetic lipid-lowering drug. Atorvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early, rate-limiting step in cholesterol biosynthesis.

Atorvastatin is a selective competitive inhibitor of HMG-CoA reductase, an enzyme that regulates the rate of conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. Cholesterol and triglycerides circulate in the bloodstream complexed with lipoproteins. These complexes are separated by ultracentrifugation into HDL (high-density lipoprotein), LDL (intermediate-density lipoprotein), LDL (low-density lipoprotein), and VLDL (very-low-density lipoprotein) fractions. Triglycerides (TG) and cholesterol in the liver are incorporated into VLDL and released into the blood plasma for transport to peripheral tissues. LDL is formed from VLDL and catabolized by interaction with high-affinity LDL receptors. Clinical and pathological studies show that elevated plasma levels of total cholesterol (TC), LDL-cholesterol (LDL-C), and apolipoprotein B (apo B) contribute to the development of atherosclerosis in humans and are risk factors for cardiovascular disease, while elevated HDL-cholesterol levels are associated with a reduced risk of cardiovascular disease.

Elevated levels of total cholesterol, LDL cholesterol, and apo B (the membrane complex for LDL cholesterol) are associated with the development of atherosclerosis. Similarly, decreased levels of HDL cholesterol (and its transport complex, apo B) are associated with the development of atherosclerosis.

Epidemiological studies have established that cardiovascular morbidity and mortality vary directly proportionally with total cholesterol and LDL cholesterol levels and inversely proportionally with HDL cholesterol levels.

Atorvastatin reduces total cholesterol, LDL-cholesterol, and apo B in patients with homozygous and heterozygous familial hypercholesterolemia, nonfamilial hypercholesterolemia, and mixed dyslipidemia. Atorvastatin also reduces VLDL-cholesterol and TG, and causes transient increases in HDL-cholesterol and apolipoprotein A-1. Atorvastatin reduces total cholesterol, LDL-cholesterol, VLDL-cholesterol, apo B, triglycerides, and non-HDL-cholesterol, and increases HDL-cholesterol in patients with isolated hypertriglyceridemia. Atorvastatin reduces LDL-C in patients with dysbetalipoproteinemia.

Like LDL, cholesterol- and triglyceride-rich lipoproteins, including VLDL, HDL, and remnants, may also contribute to atherosclerosis. Elevated plasma triglyceride levels are often found in the triad of low HDL-C and small LDL particles, and in association with nonlipid metabolic risk factors for coronary heart disease. Total plasma triglycerides per se have not been consistently shown to be an independent risk factor for coronary heart disease. Furthermore, no independent effect of increasing HDL or decreasing triglycerides on the risk of coronary and cardiovascular morbidity and mortality has been established.

Atorvastatin, as well as some of its metabolites, are pharmacologically active in humans. The main site of action of atorvastatin is the liver, which plays a major role in cholesterol synthesis and LDL clearance. The dose of the drug, in contrast to the systemic concentration of the drug, correlates better with the reduction in LDL cholesterol levels. Individual selection of the dose of the drug should be carried out depending on the therapeutic response (see section "Method of administration and dosage").

Pharmacokinetics.

Atorvastatin is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. The extent of absorption is dose-proportional. The absolute bioavailability of atorvastatin (parent drug) is approximately 14%, and the systemic bioavailability of HMG-CoA reductase inhibitory activity is approximately 30%. The low systemic availability of the drug is attributed to presystemic clearance in the gastrointestinal mucosa and/or presystemic biotransformation in the liver. Although food reduces the rate and extent of absorption of the drug by approximately 25% and 9%, respectively, based on Cmax and AUC, the reduction in LDL-C is similar whether atorvastatin is taken with or without food. When atorvastatin was administered in the evening, its plasma concentration was lower (approximately 30% for Cmax and AUC) than when administered in the morning. However, the reduction in LDL-C was the same regardless of the time of administration (see section 4.2).

Distribution.

The mean volume of distribution of the drug is approximately 381 liters. More than 98% of the drug is bound to plasma proteins. The blood/plasma concentration ratio of approximately 0.25 indicates poor penetration of the drug into erythrocytes. Based on observations in rats, it is believed that atorvastatin is able to penetrate into breast milk (see sections “Contraindications”, “Use during pregnancy or lactation” and “Special instructions”).

Metabolism.

Atorvastatin is extensively metabolized to ortho- and parahydroxylated derivatives and various beta-oxidation products. In vitro studies have shown that the inhibition of HMG-CoA reductase by ortho- and parahydroxylated metabolites is equivalent to that of atorvastatin. Approximately 70% of the circulating inhibitory activity against HMG-CoA reductase is associated with the active metabolites. In vitro studies suggest the importance of metabolism by cytochrome P450 3A4, which is consistent with the increased plasma concentrations of atorvastatin in humans after concomitant administration with erythromycin, a known inhibitor of this isoenzyme (see section 4.5).

Excretion: Atorvastatin and its metabolites are eliminated primarily in the bile after hepatic and/or extrahepatic metabolism, but the drug does not appear to undergo enterohepatic recirculation. The mean elimination half-life of the drug from human plasma is approximately 14 hours, but the half-life of HMG-CoA reductase inhibitory activity is 20 to 30 hours due to the contribution of active metabolites. Less than 2% of the dose is excreted in the urine after oral administration.

Elderly patients.

Plasma concentrations of atorvastatin are higher (approximately 40% for Cmax and 30% for AUC) in healthy elderly patients (aged 65 years and older) than in young adults. Clinical data suggest that the degree of LDL-C reduction at any dose is greater in elderly patients compared with young subjects (see section 4.4).

Children: Pharmacokinetic data in pediatric patients are not available.

Gender: Plasma concentrations of atorvastatin in women differ from those in men (approximately 20% higher for Cmax and 10% lower for AUC). However, there is no clinically significant difference in LDL-C reduction between men and women with atorvastatin.

Kidney dysfunction.

Renal disease has no effect on plasma concentrations of atorvastatin or LDL-C reduction, and therefore no dose adjustment is required for patients with renal impairment (see sections 4.2 and 4.4).

Hemodialysis: Although studies have not been conducted in patients with end-stage renal disease, hemodialysis is not expected to significantly increase drug clearance because the drug is highly bound to plasma proteins.

Liver failure.

Plasma concentrations of atorvastatin are markedly increased in patients with chronic alcoholic liver disease. Cmax and AUC values are 4-fold higher in patients with Child-Pugh Class A liver disease. In patients with Child-Pugh Class B liver disease, Cmax and AUC values are increased approximately 16-fold and 11-fold, respectively (see Contraindications).

Clinical characteristics.

Indication

Prevention of cardiovascular disease

In adult patients without clinically apparent coronary heart disease but with multiple risk factors for coronary heart disease, such as age over 65 years, smoking, hypertension, low HDL, or a family history of early coronary heart disease, atorvastatin is indicated for:

-reducing the risk of myocardial infarction;

-reducing the risk of stroke;

-reducing the risk of needing revascularization procedures and the risk of angina.

-reducing the risk of myocardial infarction;

-reducing the risk of stroke.

In patients with clinically significant coronary heart disease, atorvastatin is indicated for:

-reducing the risk of non-fatal myocardial infarction;

-reducing the risk of fatal and non-fatal stroke;

-reducing the risk of needing revascularization procedures;

-reducing the risk of hospitalization due to congestive heart failure;

-reducing the risk of angina pectoris.

Hyperlipidemia

-As an adjunct to diet, to reduce elevated levels of total cholesterol, LDL cholesterol, apolipoprotein B and triglycerides, and to increase HDL cholesterol in patients with primary hypercholesterolemia (heterozygous familial and non-familial) and mixed dyslipidemia (types IIa and IIb according to the Fredrickson classification).

-As an adjunct to diet for the treatment of patients with elevated serum triglyceride levels (type IV according to the Fredrickson classification).

-For the treatment of patients with primary dysbetalipoproteinemia (type III according to the Fredrickson classification) in cases where diet is not effective enough.

-To reduce total cholesterol and LDL-cholesterol in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or as primary therapy if such treatments are unavailable.

-As an adjunct to diet to reduce total cholesterol, LDL cholesterol and apolipoprotein B levels in postmenarcheal boys and girls aged 10 to 17 years with heterozygous familial hypercholesterolemia, if, after appropriate diet therapy, the test results are as follows:

a) LDL cholesterol remains ≥ 190 mg/dL or

b) LDL cholesterol ≥ 160 mg/dL and:

· there is a family history of early cardiovascular disease or

· two or more other risk factors for cardiovascular disease

present in a pediatric patient.

Contraindication

- Active liver disease, which may include persistent elevations of hepatic transaminases of unknown etiology.

- Hypersensitivity to any of the components of this medicinal product.

Application features.

Skeletal muscles

Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with atorvastatin and other drugs in this class. A history of renal impairment is a risk factor for rhabdomyolysis. Such patients should be monitored closely for skeletal muscle abnormalities.

Atorvastatin, like other statins, has occasionally been associated with myopathy, defined as muscle pain or weakness in association with an elevation of creatine phosphokinase (CPK) >10 times the upper limit of normal. Concomitant use of higher doses of atorvastatin with certain medicinal products, such as cyclosporine and potent CYP3A4 inhibitors (e.g. clarithromycin, itraconazole and HIV protease inhibitors), increases the risk of myopathy/rhabdomyolysis.

There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy associated with statin use. IMMNM is characterized by the following features: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy reveals necrotizing myopathy without significant inflammation; and positive dynamics are observed with the use of immunosuppressive agents.

The risk of myopathy during treatment with drugs of this class is increased with concomitant use of cyclosporine, fibric acid derivatives, erythromycin, clarithromycin, the hepatitis C protease inhibitor telaprevir, combinations of HIV protease inhibitors, including saquinavir + ritonavir, lopinavir + ritonavir, tipranavir + ritonavir, darunavir + ritonavir, fosamprenavir and fosamprenavir + ritonavir, as well as niacin or azole antifungals. Physicians considering the combination of atorvastatin and fibric acid derivatives, erythromycin, clarithromycin, saquinavir + ritonavir, lopinavir + ritonavir, darunavir + ritonavir, fosamprenavir, fosamprenavir + ritonavir, azole antifungals, or lipid-modifying doses of niacin should carefully weigh the potential benefits and risks and monitor patients closely for any symptoms of muscle pain, tenderness, or weakness, especially during the initial months of therapy and during any up-titration periods of either drug. Low initial and maintenance doses of atorvastatin should be considered when co-administered with the above-mentioned drugs (see Interactions). In such situations, periodic CPK determination may be considered, but there is no guarantee that such monitoring will help prevent cases of severe myopathy.

Myopathy, including rhabdomyolysis, has been reported with concomitant use of atorvastatin with colchicine, therefore atorvastatin should be administered with caution to patients receiving colchicine (see section 4.5).

Atorvastatin therapy should be temporarily or permanently discontinued in any patient with an acute, serious condition suggestive of myopathy or in the presence of a risk factor for the development of renal failure secondary to rhabdomyolysis (e.g. severe acute infection, hypotension, surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures).

Liver dysfunction

Statins, like some other lipid-lowering therapeutic agents, have been shown to be associated with abnormal liver function tests. Persistent elevations in serum transaminases (>3 times the upper limit of normal, occurring on 2 or more occasions) have been observed in patients treated with atorvastatin in clinical trials.

One case of jaundice was reported. Elevations in liver function tests (LFTs) in other patients were not associated with jaundice or other clinical symptoms. After dose reduction, interruption, or discontinuation of the drug, transaminase levels returned to or near pretreatment levels without residual effects. More than half of the patients with persistent elevations in liver function tests continued treatment with atorvastatin at lower doses.

It is recommended that liver enzyme levels be obtained before initiating therapy with atorvastatin and repeated as clinically indicated. There have been rare post-marketing reports of fatal and non-fatal hepatic failure in patients receiving statins, including atorvastatin. If severe hepatic injury with clinical symptoms of hyperbilirubinemia or jaundice occurs during treatment with atorvastatin, treatment should be discontinued immediately. Unless an alternative etiology is identified, treatment with the drug should not be restarted.

Atorvastatin should be used with caution in patients who consume significant amounts of alcohol and/or have a history of liver disease. Atorvastatin is contraindicated in active liver disease or persistent elevations of hepatic transaminases of unknown etiology (see Contraindications).

Endocrine function

Increases in HbA1c and fasting serum glucose have been reported with HMG-CoA reductase inhibitors, including atorvastatin.

Statins inhibit cholesterol synthesis and theoretically may reduce adrenal and/or gonadal steroid secretion. Clinical studies have shown that atorvastatin does not reduce basal plasma cortisol levels or impair adrenal reserve. The effect of statins on sperm fertilisation has not been studied in a sufficient number of patients. It is not known how, or if, the drug affects the gonadal-pituitary-hypothalamic system in premenopausal women. Caution should be exercised when co-administering statins with drugs that may reduce the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone and cimetidine.

In a clinical trial in which atorvastatin 80 mg was administered to patients without coronary artery disease who had a history of stroke or transient ischemic attack within the previous 6 months, a higher incidence of hemorrhagic stroke was observed in the atorvastatin 80 mg group compared to the placebo group. The incidence of fatal hemorrhagic stroke was similar in all treatment groups. The incidence of non-fatal hemorrhagic stroke was significantly higher in the atorvastatin group compared to the placebo group. Several baseline characteristics, including the presence of hemorrhagic and lacunar stroke at baseline, were associated with a higher incidence of hemorrhagic stroke in the atorvastatin group (see section 4.8).

No differences in safety and efficacy were observed between patients aged 65 to 75 years and patients aged 75 years and older, and no differences in response to treatment were observed between elderly and younger patients; however, greater sensitivity of some older patients cannot be excluded. Since older age (>65 years) is a predisposing factor for myopathy, caution should be exercised when prescribing atorvastatin to the elderly.

Liver failure

Atorvastatin is contraindicated in patients with active liver disease, including persistent elevations of hepatic transaminases of unknown etiology (see sections 4.3 and 5.1).

Before starting treatment

Atorvastatin should be used with caution in patients with a predisposition to rhabdomyolysis. Before initiating statin treatment in patients with a predisposition to rhabdomyolysis, CK levels should be determined in:

-impaired kidney function;

-hypofunction of the thyroid gland;

-hereditary disorders of the muscular system in family or personal history;

-previous cases of muscle toxicity from statins or fibrates;

- history of liver disease and/or heavy alcohol consumption.

For elderly patients (70 years and older), the need for these measures should be assessed taking into account the presence of other predisposing factors for the development of rhabdomyolysis.

Increased plasma levels of the drug are possible, in particular in the case of interactions and use in special patient populations, including patients with hereditary diseases.

In such cases, it is recommended to assess the risk-benefit ratio of treatment and conduct clinical monitoring of the patient. If the CK level is significantly elevated (more than 5 times the upper limit of normal) before starting treatment, treatment should not be started.

Creatine kinase level measurement

Creatine kinase levels should not be measured after strenuous exercise or in the presence of any possible alternative causes of elevated CK levels, as this may complicate interpretation of the results. If CK levels are significantly elevated at baseline (>5 times the upper limit of normal), repeat testing should be performed in 5–7 days to confirm the result.

During treatment

Patients should be advised to immediately report the development of muscle pain, cramps, or weakness, especially when accompanied by malaise or fever.

If these symptoms occur during treatment with atorvastatin, the patient's CK level should be determined. If the CK level is significantly elevated (more than 5 times the upper limit of normal), treatment should be discontinued.

Discontinuation of treatment should also be considered if the CK level is less than five times the upper limit of normal, but muscle symptoms are severe and cause daily discomfort.

After symptoms resolve and CK levels normalize, resuming atorvastatin treatment or starting an alternative statin may be considered, provided the lowest possible dose is used and the patient is closely monitored.

Treatment with atorvastatin should be discontinued if a clinically significant increase in CK levels is observed (more than 10 times the upper limit of normal) or if rhabdomyolysis is diagnosed (or if rhabdomyolysis is suspected).

Concomitant use with other medications

If concomitant treatment with atorvastatin and these drugs is necessary, the benefits and risks of concomitant treatment should be carefully weighed. If patients are taking drugs that increase the plasma concentration of atorvastatin, it is recommended to reduce the dose of atorvastatin to the minimum. In addition, in the case of the use of potent CYP3A4 inhibitors, a lower initial dose of atorvastatin should be considered. Appropriate clinical monitoring of these patients is also recommended.

It is not recommended to prescribe atorvastatin and fusidic acid simultaneously, therefore it is worth considering the possibility of temporarily withdrawing atorvastatin for the period of treatment with fusidic acid.

Interstitial lung disease

Exceptional cases of interstitial lung disease have been reported with some statins (especially with long-term treatment). Symptoms include shortness of breath, non-productive cough and general malaise (fatigue, weight loss and fever). If interstitial lung disease is suspected, statin treatment should be discontinued.

Lipid-modifying drug therapy should be one of the components of complex therapy for patients with a significantly increased risk of developing atherosclerotic vascular diseases due to hypercholesterolemia. Drug therapy is recommended as an adjunct to diet when the result of following a diet that limits the intake of saturated fats and cholesterol, as well as using other non-drug measures, was insufficient. In patients with coronary heart disease or multiple risk factors for coronary heart disease, atorvastatin can be started simultaneously with diet.

Application restrictions

Atorvastatin has not been studied in conditions where the primary lipoprotein abnormality is elevated chylomicrons (Fredrickson types I and V).

Interaction with other medicinal products and other types of interactions

The risk of myopathy during statin treatment is increased by concomitant use of fibric acid derivatives, lipid-modifying doses of niacin, cyclosporine, or potent CYP 3A4 inhibitors (e.g. clarithromycin, HIV protease inhibitors, and itraconazole) (see sections 4.4 and 5.1).

Potent CYP 3A4 inhibitors. Atorvastatin is metabolized by cytochrome P450 3A4. Concomitant use of the drug with potent CYP 3A4 inhibitors may lead to increased plasma concentrations of atorvastatin (see detailed information below). The extent of interaction and potentiation depend on the variability of the effect on CYP 3A4. Concomitant use with potent CYP3A4 inhibitors (e.g. cyclosporine, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors including ritonavir, lopinavir, atazanavir, indinavir, darunavir) should be avoided whenever possible. If concomitant use of these drugs with atorvastatin cannot be avoided, lower initial and maximum doses of atorvastatin should be considered. Appropriate clinical monitoring of the patient is also recommended.

Moderate CYP3A4 inhibitors (e.g. erythromycin, diltiazem, verapamil and fluconazole) may increase plasma concentrations of atorvastatin. Concomitant use of erythromycin and statins is associated with an increased risk of myopathy. Drug interaction studies to evaluate the effects of amiodarone or verapamil on atorvastatin have not been conducted. Amiodarone and verapamil are known to inhibit CYP3A4 activity, and therefore, co-administration of these drugs with atorvastatin may result in increased exposure to atorvastatin. Therefore, lower maximum doses of atorvastatin should be considered when atorvastatin is co-administered with these moderate CYP3A4 inhibitors. Clinical monitoring of the patient is also recommended. Clinical monitoring of the patient is recommended after initiation of treatment with an inhibitor or after dose adjustment.

Grapefruit juice: Contains one or more components that inhibit CYP 3A4 and may increase plasma concentrations of atorvastatin, especially with excessive grapefruit juice consumption (more than 1.2 liters per day).

Clarithromycin.

Atorvastatin AUC was significantly increased when atorvastatin 80 mg was co-administered with clarithromycin (500 mg twice daily) compared to atorvastatin alone (see section 5.1). Therefore, atorvastatin doses above 20 mg should be used with caution in patients taking clarithromycin (see sections 4.4 and 4.2).

The AUC of atorvastatin was significantly increased when the drug was co-administered with several combinations of HIV protease inhibitors, as well as with the hepatitis C virus protease inhibitor telaprevir, compared to atorvastatin alone (see section 5.1). Therefore, concomitant use with atorvastatin should be avoided in patients taking the HIV protease inhibitors tipranavir + ritonavir or the hepatitis C virus protease inhibitor telaprevir. The drug should be prescribed with caution to patients taking the HIV protease inhibitors lopinavir + ritonavir and used at the lowest necessary dose. For patients taking the HIV protease inhibitors saquinavir + ritonavir, darunavir + ritonavir, fosamprenavir or fosamprenavir + ritonavir, the dose of atorvastatin should not exceed 20 mg, and these drugs should be used with caution (see sections 4.4 and 4.2). When used in patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, the dose of atorvastatin should not exceed 40 mg, and close clinical monitoring of the patient's condition is also recommended.

Itraconazole.

The AUC of atorvastatin was significantly increased when atorvastatin 40 mg was co-administered with itraconazole 200 mg (see section 5.1). Therefore, caution should be exercised when atorvastatin doses greater than 20 mg are administered to patients taking itraconazole (see sections 4.4 and 4.2).

Cyclosporine.

Atorvastatin and its metabolites are substrates of the OATP1B1 transporter. OATP1B1 inhibitors (e.g. cyclosporine) may increase the bioavailability of atorvastatin. The AUC of atorvastatin was significantly increased when 10 mg of the drug was co-administered with cyclosporine at a dose of 5.2 mg/kg/day compared to atorvastatin alone (see section 5.1). The concomitant use of atorvastatin and cyclosporine should be avoided (see section 4.4).

Medical recommendations for the use of interacting drugs are summarized in Table 1 (see also sections “Method of administration and dosage”, “Special instructions for use”).

Table 1.

Drug interactions associated with an increased risk of myopathy/rhabdomyolysis

*Use with caution and in the lowest dose necessary.

Gemfibrozil.

Due to the increased risk of myopathy/rhabdomyolysis when HMG-CoA reductase inhibitors are administered concomitantly with gemfibrozil, the concomitant use of atorvastatin with gemfibrozil should be avoided (see section 4.4).

Other fibrates.

Since it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased by concomitant use of other fibrates, atorvastatin should be used with caution when used concomitantly with other fibrates (see section 4.4).

Niacin.

The risk of skeletal muscle adverse events is increased when the drug is used in combination with niacin, and therefore, in such conditions, a dose reduction of atorvastatin should be considered (see section "Special warnings and precautions for use").

Rifampin or other cytochrome P450 3A4 inducers. Concomitant use of the drug with cytochrome P450 3A4 inducers (e.g. efavirenz, rifampin) may result in unstable decreases in atorvastatin plasma concentrations. Due to the dual interaction mechanism of rifampin, concomitant use of atorvastatin with rifampin is recommended, as delayed administration of the drug after rifampin administration has been shown to be associated with significant decreases in atorvastatin plasma concentrations.

Diltiazem hydrochloride

Simultaneous administration of atorvastatin (40 mg) and diltiazem (240 mg) is accompanied by an increase in the concentration of atorvastatin in the blood plasma.

Cimetidine

As a result of the conducted studies, no signs of interaction between atorvastatin and cimetidine were detected.

Antacids

Concomitant oral administration of atorvastatin and an antacid suspension containing magnesium and aluminum hydroxide resulted in a decrease in plasma atorvastatin concentrations of approximately 35%. The lipid-lowering effects of atorvastatin were not altered.

Colestipol

Plasma concentrations of atorvastatin were lower (approximately 25%) when atorvastatin and colestipol were coadministered. The lipid-lowering effect of the combination of atorvastatin and colestipol was not significantly reduced.