Atorvastatin-ALSI, 10 mg 30 pcs

Reducing cholesterol, Preventing heart attacks and strokes

Atorvastatin is used:

• .in combination with diet to reduce elevated levels of total cholesterol, cholesterol/LDL, apolipoprotein B and triglycerides and increase HDL cholesterol in patients with primary hypercholesterolemia, heterozygous familial and non-familial hypercholesterolemia and combined (mixed) hyperlipidemia (Fredrickson types IIa and IIb);
• in combination with diet for treatment of patients with increased serum levels of triglycerides (Fredrickson type IV) and patients with dysbetalipoproteinemia (Fredrickson type III), in which diet therapy is not effective
• For lowering total cholesterol and LDL-cholesterol levels in patients with homozygous familial hypercholesterolemia when diet therapy and other non-pharmacological methods of treatment are not effective enough.

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Active ingredient

Composition

One film-coated tablet contains:

the active substance:

atorvastatin calcium trihydrate – 10.85 mg, which corresponds to 10 mg of atorvastatin;

excipients:

calcium carbonate – 33.00 mg,

microcrystalline cellulose – 48.00 mg,

lactose monohydrate (milk sugar) – 23.85 mg,

Pregelatinized starch (starch 1500) – 32.80 mg,

Colloidal silica (aerosil) – 0.75 mg,

Magnesium stearate – 0.75 mg,

Polyvinyl alcohol – 2.50 mg,

Interaction

The risk of myopathy during treatment with other drugs of this class is increased with concomitant use of cyclosporine, fibrates, erythromycin, azole antifungals and nicotinic acid.

Concomitant oral administration of Atorvastatin and suspension containing magnesium and aluminum hydroxide decreased plasma concentrations of Atorvastatin by approximately 35%, but the degree of decrease in cholesterol/LDL levels was not changed.

In concomitant use Atorvastatin does not affect pharmacokinetics of antipyrine (phenazone), therefore, interaction with other drugs metabolized by the same cytochrome isoenzymes is not expected.

Concomitant use of colestipol decreased plasma concentrations of Atorvastatin by approximately 25%. However, the hypolipidemic effect of combination of Atorvastatin and colestipol was superior to that of each drug separately.

The equilibrium plasma concentrations of digoxin and Atorvastatin at a dose of 10 mg did not change when digoxin and Atorvastatin were repeatedly administered. However, when using digoxin in combination with Atorvastatin at a dose of 80 mg/day, digoxin concentrations increased by approximately 20%. Patients receiving digoxin in combination with Atorvastatin should be monitored.

In concomitant use of Atorvastatin and erythromycin (500 mg 4 times/day) or clarithromycin (500 mg 2 times/day), which inhibit cytochrome Р450 3A4, an increase in plasma concentration of Atorvastatin was observed.

Concomitant administration of Atorvastatin (10 mg once daily) and azithromycin (500 mg once daily) did not change Atorvastatin plasma concentration.

Atorvastatin had no clinically significant effect on plasma concentrations of terfenadine, which is metabolized primarily by cytochrome Р450 3А4; in this regard, it seems unlikely that Atorvastatin can significantly affect pharmacokinetic parameters of other cytochrome Р450 3А4 substrates.

In concomitant use of Atorvastatin and oral contraceptives containing norethindrone and ethinylestradiol, a significant increase in AUC of norethindrone and ethinylestradiol of approximately 30% and 20% respectively was observed. This effect should be considered when choosing an oral contraceptive for a woman receiving Atorvastatin.

Concomitant use with drugs that reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone) increases the risk of reduction of endogenous steroid hormones (caution should be exercised).

In studying the interaction of Atorvastatin with warfarin and cimetidine no signs of clinically significant interaction were found.

The pharmacokinetics of Atorvastatin 80 mg and amlodipine 10 mg in equilibrium have not changed.

There were no clinically significant adverse interactions between Atorvastatin and antihypertensive agents.

The concomitant use of Atorvastatin with protease inhibitors known as cytochrome P450 3A4 inhibitors was accompanied by an increase in plasma concentration of Atorvastatin.

Pharmaceutical incompatibility is not known.

Directions for use

Before Atorvastatin is prescribed, a standard hypolipidemic diet should be recommended for the patient, which the patient should continue to follow during the entire period of therapy.

The initial dose is on average 10 mg once daily. The dose varies from 10 to 80 mg once daily.

The drug can be taken at any time of the day with food or regardless of the time of meals. The dose is adjusted with regard to baseline cholesterol/LDL levels, the goal of therapy and individual effect. At the beginning of treatment and/or during dose increase of Atorvastatin it is necessary to monitor plasma lipid levels every 2-4 weeks and adjust the dose accordingly.

Primary hypercholesterolemia and mixed hyperlipidemia, as well as Fredrickson type III and IV.

In most cases a dose of 10 mg of Atorvastatin once daily is sufficient. Significant therapeutic effect is observed after 2 weeks, as a rule, and maximum therapeutic effect is usually observed after 4 weeks. With long-term treatment this effect is maintained.

Homozygous familial hypercholesterolemia.

Prescribe in a dose of 80 mg (4 tablets of 20 mg) once daily.

The use of the drug in patients with renal insufficiency and renal diseases does not influence the plasma level of Atorvastatin or the degree of decrease of cholesterol/LDL during its use; therefore no change in the dose of the drug is required.

In case of hepatic impairment, the dose should be reduced (see section “Caution” and “Special Precautions”).

There were no differences in safety, efficacy, or achievement of hypolipidemic therapy goals when using the drug in elderly patients compared to the general population.

Special Instructions

Before starting therapy with Atorvastatin, a standard hypocholesterolemic diet should be prescribed for the patient, which should be followed during the entire period of treatment.

The use of HMG-CoA reductase inhibitors to reduce blood lipid levels may lead to changes in biochemical parameters reflecting liver function. Liver function should be monitored before the start of therapy, at 6 weeks, 12 weeks after the start of Atorvastatin administration and after each dose increase as well as periodically, e.g., every 6 months. Elevation of serum hepatic enzymes activity may be observed during Atorvastatin therapy. Patients with increased enzyme levels should be monitored until enzyme levels return to normal. In case if values of alanine aminotransferase (ALT) or asparagine aminotransferase (AST) exceed more than 3 times the upper allowable limit, it is recommended to reduce Atorvastatin dose or discontinue treatment.

Atorvastatin should be used with caution in patients who abuse alcohol and/or have liver disease. Active liver disease or persistent increase in aminotransferase activity of unclear genesis are contraindications to Atorvastatin administration.

Treatment with Atorvastatin may cause myopathy. The diagnosis of myopathy (pain and weakness in muscles combined with an increase in creatine phosphokinase (CPK) activity more than 10 times the upper limit of normal) should be discussed in patients with widespread myalgia, muscle soreness or weakness and/or a marked increase in CPK activity. Patients should be warned to inform their physician immediately of unexplained muscle pain or weakness if accompanied by malaise or fever.

Atorvastatin therapy should be discontinued if there is a marked increase in CPK activity or if there is confirmed or suspected myopathy. Risk of myopathy during treatment by other drugs of this class was increased with concomitant use of cyclosporine, fibrates, erythromycin, nicotinic acid or azole antifungal agents. Many of these drugs inhibit cytochrome P450 3A4-mediated metabolism and/or drug transport. Atorvastatin is biotransformed by CYP 3A4.

When prescribing Atorvastatin in combination with fibrates, erythromycin, immunosuppressive agents, azole antifungal agents or nicotinic acid in hypolipidemic doses, the expected benefits and risks of treatment should be carefully weighed and patients should be regularly observed to detect muscle pain or weakness, especially during the first months of treatment and during periods of increasing doses of any drug. In such situations, periodic determination of CPK activity may be recommended, although such monitoring does not prevent the development of severe myopathy.

In Atorvastatin, as well as other drugs of this class, there have been cases of rhabdomyolysis with acute renal failure due to myoglobinuria. Atorvastatin therapy should be temporarily discontinued or completely discontinued in case of signs of possible myopathy or in presence of risk factor of renal failure during rhabdomyolysis (for example, severe acute infection, arterial hypotension, serious surgery, trauma, severe metabolic, endocrine and electrolyte disorders and uncontrolled convulsions).

Before starting therapy with Atorvastatin, an attempt should be made to achieve control of hypercholesterolemia through adequate dietary therapy, increased physical activity, weight reduction in obese patients and treatment of other conditions.

Patients should be warned to seek immediate medical attention if they experience unexplained muscle pain or weakness, especially if accompanied by malaise or fever.

Influence on driving and operating machinery

There have been no reports of adverse effects of Atorvastatin on driving and operating machinery.

Synopsis

Features

Absorption is high. Maximal concentration (Cmax) in plasma is reached after 1-2 hours, Cmax in women is 20% higher, area under the curve/concentration, time (AUC) – 10% lower; Cmax in patients with alcoholic cirrhosis is 16 times higher than normal, AUC – 11 times higher.

Food slightly reduces speed and duration of drug absorption (by 25% and 9%, respectively), but decrease of LDL cholesterol is similar to that with Atorvastatin without food. Concentration of Atorvastatin when administered in the evening is lower than in the morning (approximately by 30%). A linear relationship between the degree of absorption and the drug dose has been found.

Bioavailability is 12%, systemic bioavailability of HMG-CoA reductase inhibitory activity is 30%. Low systemic bioavailability is due to presystemic metabolism in the gastrointestinal mucosa and during “first passage” through the liver.

The average volume of distribution is 381 liters, the binding to plasma proteins is 98%. It is metabolized mainly in liver under the action of CYP3A4, CYP3A5 and CYP3A7 cytochrome with formation of pharmacological active metabolites (ortho- and parahydroxylated derivatives, beta-oxidation products). In vitro, ortho- and parahydroxylated metabolites have an inhibitory effect on HMG-CoA reductase, comparable with that of Atorvastatin. The inhibitory effect of the drug against HMG-CoA reductase is approximately 70% determined by the activity of circulating metabolites.

Extracted with bile after hepatic and/or extrahepatic metabolism (not subjected to marked intestinal-hepatic recirculation).

The elimination half-life is 14 hours. Inhibitory activity against HMG-CoA reductase persists for about 20-30 hours due to the presence of active metabolites. Less than 2% of the oral dose is detected in the urine. It is not excreted during hemodialysis.

Contraindications

Hypersensitivity to the components of the drug;

Active liver disease or increased “hepatic” enzyme activity of unclear origin (more than 3 times the upper limit of normal);

Hepatic failure (degree of severity according to Child-Pugh classification A and B)

Pregnancy;

Lactation period;

Age under 18 years (effectiveness and safety not established).

With caution: alcohol abuse, history of liver disease, severe electrolyte balance disorders, endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgical interventions, injuries, skeletal muscle diseases.

Overdose

Treatment: there is no specific antidote, symptomatic therapy is carried out.

Hemodialysis is ineffective.

Similarities