Torvacard, 40 mg 90 pcs

Hypolipidemic drug from the group of statins. Selective competitive inhibitor of HMG-CoA reductase – enzyme converting 3-hydroxy-3-methylglutaryl coenzyme A into mevalonic acid, which is a precursor of sterols, including cholesterol (CH). Triglycerides (TG) and CH in the liver are incorporated into LDL, enter the blood plasma, and are transported to peripheral tissues. LDL are formed from LDL in the course of interaction with LDL receptors.

Atorvastatin reduces plasma concentrations of CH and lipoproteins due to inhibition of HMG-CoA reductase, synthesis of CH in the liver and increasing number of hepatic LDL receptors on cell surface that leads to increase of capture and catabolism of LDL. Reduces LDL formation, causes a pronounced and persistent increase in LDL receptor activity.

Lower LDL concentration in patients with homozygous familial hypercholesterolemia, which usually does not respond to therapy with hypolipidemic agents. Reduces the concentration of total cholesterol by 30-46%, LDL by 41-61%, apolipoprotein B by 34-50% and TG by 14-33%; causes an increase in concentration of HDL-C and apolipoprotein A.

Dose-dependently reduces LDL concentration in patients with homozygous hereditary hypercholesterolemia resistant to therapy with other hypolipidemic agents.

Indications

Active ingredient

Composition

How to take, the dosage

Before prescribing Torvacard, the patient should be recommended a standard hypolipidemic diet, which he should continue to follow for the duration of therapy.

The initial dose is on average 10 mg once daily. The dose varies from 10 to 80 mg once daily. The drug may be taken at any time of the day with food or regardless of the time of meals. The dose is selected taking into account the initial levels of LDL-C, the purpose of therapy and individual effect. At the beginning of treatment and/or during dose increase of Torvacard it is necessary to monitor plasma lipid levels every 2-4 weeks and adjust the dose accordingly.

In primary hypercholesterolemia and mixed hyperlipidemia, a dose of 10 mg of Torvacard once daily is sufficient in most cases. Significant therapeutic effect is usually observed after 2 weeks, and the maximum therapeutic effect is usually observed after 4 weeks. With long-term treatment this effect is maintained.

The following guidelines may be used in determining a treatment goal.

The recommendations of the National Cholesterol Education Program (USA). Diagnosed vascular atherosclerosis* LDL cholesterol, mg/dL (mmol/L).

The goals of hypolipidemic therapy of the European Atherosclerosis Society In patients with a confirmed diagnosis of CHD and other patients at high risk of ischemic complications, the goal of treatment is to reduce cholesterol – LDL less than 115 mg/dL (less than 3 mmol/L) and total cholesterol less than 190 mg/dL (less than 5 mmol/L).

National treatment guidelines Homozygous familial hypercholesterolemia. In the study in adult patients with homozygous familial hypercholesterolemia the therapy with atorvastatin in dose of 80 mg in most cases resulted in decrease of HDL-C levels by more than 15% (18-45%). Administration of the drug in patients with renal insufficiency and renal diseases has no effect on plasma levels of atorvastatin or degree of LDL-cholesterol reduction during its use, therefore, no change in the drug dose is required. No differences in safety, efficacy or achievement of hypolipidemic therapy goals have been observed in elderly patients compared to the general population when using the drug.

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 niacin.

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 LDL cholesterol levels was not changed.

In concomitant use atorvastatin does not affect pharmacokinetics of antipyrine, therefore no interaction with other drugs metabolized by the same cytochrome isoenzymes is 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 alone.

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 require monitoring.

In concomitant use of atorvastatin and erythromycin (500 mg 4 times/day) or clarithromycin (500 mg 2 times/day), which inhibit CYP3A4 isoenzyme, increased plasma concentration of atorvastatin was observed.

When concomitant use of atorvastatin (10 mg once daily) and azithromycin (500 mg once daily) the plasma concentration of atorvastatin was not changed.

Atorvastatin had no clinically significant effect on plasma concentrations of terfenadine, which is metabolized primarily with participation of CYP3A4; in this regard it seems unlikely that atorvastatin can significantly affect pharmacokinetic parameters of other CYP3A4 substrates.

Concomitant use of atorvastatin and oral contraceptives containing norethindrone and ethinylestradiol. Concomitant use of atorvastatin and oral contraceptives containing norethindrone and ethinylestradiol has shown a significant increase in AUC of norethindrone and ethinylestradiol by approximately 30% and 20%, respectively. This effect should be considered when choosing an oral contraceptive for a woman receiving atorvastatin.

In studies of interactions of atorvastatin with warfarin and cimetidine, no evidence of clinically significant interaction was found.

In concomitant use of atorvastatin 80 mg and amlodipine 10 mg, pharmacokinetics of atorvastatin in equilibrium has not changed.

The concomitant use of atorvastatin with protease inhibitors, known as CYP3A4 isoenzyme inhibitors, was accompanied by an increase in plasma concentration of atorvastatin.

No clinically significant adverse interactions of atorvastatin and antihypertensive agents and with estrogens have been observed. Studies of interaction with all specific drugs have not been conducted.

Special Instructions

Before starting therapy with Torvacard, the patient should be prescribed a standard hypocholesterolemic diet, which must 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 therapy, at 6 weeks, 12 weeks after the start of Torvacard and after each dose increase, as well as periodically (e.g., every 6 months). Elevated serum liver enzyme activity may be observed during therapy with Torvacard. Patients with elevated transaminase levels should be monitored until enzyme levels return to normal. If ALT or AST values are more than 3 times the upper limit of normal, it is recommended to reduce the dose of Torvacard or discontinue treatment.

Torvacard treatment may cause myopathy. In patients with widespread myalgia, muscle soreness or weakness and/or marked increase in CPK activity, the possibility of myopathy (pain and weakness in the muscles combined with an increase in CPK activity of more than 10 times the upper limit of normal) should be kept in mind. Patients should be warned to tell their physician immediately about unexplained muscle pain or weakness if accompanied by malaise or fever.

Torvacard therapy should be discontinued if there is a marked increase in CPK activity or if there is confirmed or suspected myopathy. The risk of myopathy during treatment with other drugs of this class was increased with concomitant use of cyclosporine, fibrates, erythromycin, nicotinic acid or azole antifungals. Many of these drugs inhibit CYP3A4 isoenzyme-mediated metabolism and/or drug transport. Atorvastatin is biotransformed by CYP3A4. Prescribing atorvastatin in combination with fibrates, erythromycin, immunosuppressive agents, azole antifungals or nicotinic acid in hypolipidemic doses, the expected benefits and risks of treatment should be carefully weighed and patients should be regularly observed for muscle pain or weakness, especially during the first months of treatment and during periods of increasing dose of any drug. In these situations, periodic determination of CPK activity may be recommended, although such monitoring does not prevent the development of severe myopathy.

In the use of atorvastatin, as well as other drugs of this class, cases of rhabdomyolysis with acute renal failure due to myoglobinuria have been described. Therapy with Torvacard should be temporarily discontinued or completely canceled if there are signs of possible myopathy or a risk factor for renal failure in rhabdomyolysis (eg, severe acute infection, arterial hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders and uncontrolled convulsions). Before starting therapy with Torvacard, an attempt should be made to achieve control of hypercholesterolemia through adequate diet 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.

Features

Absorption is high. Cmax in blood plasma is reached after 1-2 hours, Cmax in women is 20% higher, AUC – 10% lower; Cmax in patients with alcoholic cirrhosis – 16 times higher, AUC – 11 times higher than normal.

Food slightly decreases rate and duration of drug absorption (by 25% and 9% respectively), but decrease of LDL-C 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 was 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 Vd is 381 l, the binding to plasma proteins is 98%. It is metabolized mainly in liver under the action of CYP3A4, CYP3A5 and CYP3A7 isoenzymes with formation of pharmacological active metabolites (ortho- and parahydroxylated derivatives, β-oxidation products). In vitro, ortho- and parahydroxylated metabolites have an inhibitory effect on HMG-CoA reductase that is comparable to that of atorvastatin. The inhibitory effect of the drug against HMG-CoA reductase is approximately 70% determined by the activity of circulating metabolites.

Extracted through the intestine with bile after hepatic and/or extrahepatic metabolism (not subject to marked intestinal-hepatic recirculation).

T1/2 – 14 h. Inhibitory activity against HMG-CoA reductase persists for about 20-30 h 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

Side effects

Overdose

Pregnancy use

Atorvastatin is contraindicated in pregnancy and during lactation (breastfeeding).

It is unknown whether atorvastatin is excreted with breast milk. Taking into account the possibility of adverse events in breastfed children, if it is necessary to use the drug during lactation, the question of stopping breastfeeding should be considered.

Women of reproductive age should use adequate contraceptive methods during treatment. Atorvastatin can be administered to women of reproductive age only if the likelihood of pregnancy is very low and the patient is informed about the possible risks of treatment for the fetus.

Similarities