Torvacard pills 10mg, 90pcs

Composition

1 tablet contains:

Active ingredient:  

atorvastatin (in the form of calcium salt) 10 mg;

Auxiliary substances:

magnesium oxide heavy,

microcrystalline cellulose,

lactose monohydrate,

sodium croscarmellose,

low-substituted hydroxypropylcellulose LH21,

colloidal silicon dioxide,

magnesium stearate.

Shell composition:

hypromellose 2910/5,

macrogol 6000,

titanium dioxide,

talc.

Pharmacological action

Torvacard – hypolipidemic.

Pharmacodynamics

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

Atorvastatin reduces the concentration of cholesterol and lipoproteins in blood plasma by inhibiting HMG-CoA reductase, CHOLESTEROL synthesis in the liver, and increasing the number of hepatic LDL receptors on the cell surface, which leads to increased LDL uptake and catabolism. Reduces the formation of LDL, causes a pronounced and persistent increase in the activity of LDL receptors. Reduces LDL concentrations in patients with homozygous familial hypercholesterolemia, which usually does not respond to lipid-lowering therapy. 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 the concentration of HDL-C and apolipoprotein A.

Dose-dependently reduces the concentration of LDL in patients with homozygous hereditary hypercholesterolemia, resistant to therapy with other lipid-lowering agents.

Pharmacokinetics

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

Food slightly reduces the rate and duration of drug absorption (by 25 and 9%, respectively), but the decrease in LDL-C is similar to that when using atorvastatin without food. The concentration of atorvastatin when used in the evening is lower than in the morning (by approximately 30%). A linear relationship was found between the degree of absorption and the dose of the drug.

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

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

It is excreted through the intestine with bile after hepatic and / or extrahepatic metabolism (does not undergo pronounced enterohepatic recirculation).

T1 / 2-14 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 of the drug is detected in the urine. It is not excreted during hemodialysis.

Indications

• of cardiovascular disease (in patients with elevated risk factors for coronary artery disease — elderly age over 55 years, Smoking, hypertension, diabetes mellitus, peripheral vascular disease, history of stroke, left ventricular hypertrophy, protein/albuminuria, ischemic heart disease in the immediate family), including on the background of dyslipidemia, secondary prevention is to reduce the total risk of death, myocardial infarction, stroke, re-hospitalization for about angina and need for the procedure of revascularization;
• in combination with diet to reduce elevated levels of total cholesterol, cholesterol/LDL, and apolipoprotein b, and TG and increased level of cholesterol/HDL in patients with primary hypercholesterolemia, heterozygous familial and non-family hypercholesterolemia and combined (mixed) hyperlipidemia (types IIa and IIb according to Fredrickson);
• in combination with diet for the treatment of patients with elevated serum TG levels (type IV according to Fredrickson) and patients with dysbetalipoproteinemia (type III Fredrickson), whose diet does not provide an adequate effect;
• to reduce levels of total cholesterol and cholesterol/LDL in patients with homozygous familial hypercholesterolemia, when diet and other non-pharmacological treatments are insufficiently effective (as an adjunct to lipid-lowering therapy, including cell saver purified LDL from the blood).

Use during pregnancy and lactation

Atorvastatin is contraindicated for use during pregnancy and lactation (breastfeeding).

It is not known whether atorvastatin is excreted in breast milk. Taking into account the possibility of adverse events in infants, if it is necessary to use the drug during lactation, the question of stopping breastfeeding should be decided.

Women of reproductive age should use adequate methods of contraception during treatment.

Atorvastatin can be prescribed to women of reproductive age only if the probability of pregnancy is very low, and the patient is informed about the possible risk of treatment for the fetus.

Contraindications

• acute liver diseases
• severe general condition of the patient
• hypersensitivity to Torvacard.

Side effects

Infectious and parasitic diseases:  often-nasopharyngitis.

Blood and lymphatic system disorders:  rarely-thrombocytopenia.

From the immune system:  often-allergic reactions; very rarely-anaphylaxis.

From the side of metabolism and nutrition:  often — hyperglycemia; infrequently-hypoglycemia, weight gain, anorexia.

From the side of the psyche:  infrequently — sleep disorders, including insomnia and nightmares.

Nervous system disorders:  often-headache; infrequently-dizziness, paresthesia, hypesthesia, perversion of taste, loss or loss of memory; rarely-peripheral neuropathy.

From the side of the visual organ:  infrequently-reduced visual clarity; rarely-visual impairment.

Hearing disorders and labyrinth disorders:  infrequently-tinnitus; very rarely-hearing loss.

Respiratory, thoracic and mediastinal disorders:  often — pain in the pharynx and trachea, nosebleeds.

From the digestive system:  often-constipation, flatulence, dyspepsia, nausea, diarrhea; infrequently-vomiting, pain in the upper and lower abdomen, belching, pancreatitis.

Liver and biliary tract disorders:  infrequently-hepatitis; rarely-cholestasis; very rarely-liver failure.

Skin and subcutaneous tissue disorders:  infrequently — urticaria, skin rash, pruritus, alopecia; rarely-angioedema, bullous dermatitis, including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders:  often — myalgia, arthralgia, pain in the extremities, muscle spasms, joint swelling, back pain; infrequently-neck pain, muscle weakness; rarely-myopathy, myositis, rhabdomyolysis, tendopathy (sometimes complicated by a torn tendon).

General disorders and disorders at the injection site:  infrequently — malaise, asthenia, chest pain, peripheral edema, fatigue, fever.

Laboratory and instrumental data:  often-increased activity of hepatic transaminases, increased activity of CPK; infrequently-leukocyturia, increased concentration of glycosylated hemoglobin.

Interaction

The risk of myopathy during treatment with other drugs in this class increases with concomitant use of cyclosporine, fibrates, erythromycin, antifungal drugs related to azoles, and niacin.

Concomitant oral administration of atorvastatin and a suspension containing magnesium and aluminum hydroxide reduced plasma concentrations of atorvastatin by approximately 35%, but the degree of reduction in LDL-C levels did not change.

Concomitant use of atorvastatin does not affect the pharmacokinetics of antipyrine, so interactions with other drugs metabolized by the same cytochrome isoenzymes are not expected.

Plasma concentrations of atorvastatin decreased by approximately 25% when colestipol was co-administered. However, the lipid-lowering effect of the combination of atorvastatin and colestipol exceeded that of each drug separately. When digoxin and atorvastatin were re-administered at a dose of 10 mg, the steady-state plasma concentrations of digoxin did not change.However, when digoxin was used in combination with atorvastatin at a dose of 80 mg/day, the digoxin concentration increased by about 20%. Patients receiving digoxin in combination with atorvastatin should be monitored.

Concomitant use of atorvastatin and erythromycin (500 mg 4 times / day) or clarithromycin (500 mg 2 times / day), which inhibit the CYP3A4 isoenzyme, an increase in the concentration of atorvastatin in blood plasma was observed.

Concomitant use of atorvastatin (10 mg 1 time/day) and azithromycin (500 mg 1 time/day) did not change the concentration of atorvastatin in blood plasma.

Atorvastatin did not have a clinically significant effect on the plasma concentration of terfenadine, which is mainly metabolized by CYP3A4; therefore, it seems unlikely that atorvastatin can significantly affect the pharmacokinetic parameters of other CYP3A4 substrates.

When atorvastatin was co-administered with an oral contraceptive containing norethindrone and ethinylestradiol, a significant increase in the AUC of norethindrone and ethinylestradiol was observed by approximately 30% and 20%, respectively. This effect should be considered when choosing an oral contraceptive for a woman receiving atorvastatin.

When studying the interaction of atorvastatin with warfarin and cimetidine, no signs of clinically significant interaction were found. Concomitant use of atorvastatin 80 mg and amlodipine 10 mg did not alter the pharmacokinetics of atorvastatin at steady state.

Concomitant use of atorvastatin with protease inhibitors, known as CYP3A4 inhibitors, was accompanied by an increase in the concentration of atorvastatin in blood plasma.

There was no clinically significant adverse interaction between atorvastatin and antihypertensive agents, as well as with estrogens. Interaction studies with all specific drugs have not been conducted.

Pharmaceutical incompatibility is unknown.

How to take, course of use and dosage

Before prescribing Torvacard, the patient should be recommended a standard lipid-lowering diet, which he should continue to follow throughout the entire period of therapy.

The initial dose is on average 10 mg 1 time/day. The dose varies from 10 to 80 mg 1 time/day. The drug can be taken at any time of the day with food or regardless of the time of meal. The dose is selected taking into account the initial LDL-C levels, the purpose of therapy, and the individual effect. At the beginning of treatment and/or during an increase in the dose of Torvacard, it is necessary to monitor blood lipid levels every 2-4 weeks and adjust the dose accordingly.

In primary hypercholesterolemia and mixed hyperlipidemia, in most cases, it is sufficient to prescribe a dose of 10 mg of Torvacard 1 time/day. A significant therapeutic effect is observed after 2 weeks, as a rule, and the maximum therapeutic effect is usually observed after 4 weeks. With long-term treatment, this effect persists.

Overdose

Symptoms: hypotension is possible.

Treatment: conducting symptomatic therapy.

There is no specific antidote. Hemodialysis is ineffective.

Special instructions

Before starting Torvacard therapy, the patient should be prescribed a standard hypocholesterolemic diet, which he must follow during the entire treatment period.

The use of HMG-CoA reductase inhibitors to reduce blood lipids may lead to changes in biochemical parameters that reflect liver function. Liver function should be monitored before starting therapy,6 weeks,12 weeks after starting Torvacard and after each dose increase, as well as periodically (for example, every 6 months). An increase in the activity of liver enzymes in the blood serum can be observed during therapy with Torvacard. Patients with elevated transaminase levels should be monitored until their enzyme levels return to normal. If the ALT or AST values are more than 3 times higher than the upper limit of normal (ULN), it is recommended to reduce the dose of Torvacard or stop treatment.

Torvacard should be used with caution in patients who abuse alcohol and / or have liver disease. Active liver disease or persistent increase in the activity of aminotransferases of unknown origin serve as contraindications to the appointment of Torvacard. Treatment with Torvacard may cause myopathy. Patients with advanced myalgia, muscle soreness or weakness, and / or a marked increase in CPK activity should be aware of the possibility of developing myopathy (pain and weakness in the muscles combined with an increase in CPK activity by more than 10 times compared to ULN).

Patients should be warned that they should immediately inform the doctor about the appearance of unexplained pain or weakness in the muscles, if they are accompanied by malaise or fever. Torvacard therapy should be discontinued if there is a marked increase in CPK activity or if there is a confirmed or suspected myopathy. The risk of myopathy associated with other drugs in this class was increased with concomitant use of cyclosporine, fibrates, erythromycin, nicotinic acid, or azole antifungal agents. Many of these drugs inhibit CYP3A4-mediated metabolism and / or drug transport. Atorvastatin is biotransformed by CYP3A4.

When prescribing atorvastatin in combination with fibrates, erythromycin, immunosuppressive agents, azole antifungal drugs or nicotinic acid in hypolipidemic doses, the expected benefit and risk of treatment should be carefully weighed and patients should be regularly monitored for muscle pain or weakness, especially during the first months of treatment and during periods of increasing the dose of any drug. In such situations, periodic monitoring of CPK activity can be recommended, although such monitoring does not prevent the development of severe myopathy.

When using atorvastatin, as well as other drugs of this class, cases of rhabdomyolysis with acute renal failure due to myoglobinuria have been described. Torvacard therapy should be temporarily discontinued or completely discontinued if there are signs of possible myopathy or the presence of a risk factor for developing renal failure on the background of rhabdomyolysis (for example, severe acute infection, hypotension, serious surgery, trauma, severe metabolic, endocrine and electrolyte disorders and uncontrolled seizures). Before starting Torvacard therapy, it is necessary to try to achieve control of hypercholesterolemia through adequate diet therapy, increased physical activity, weight loss 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 they are accompanied by malaise or fever.

Influence on the ability to drive a car and work with mechanisms

No adverse effects of Torvacard on the ability to drive a car or work with mechanisms have been reported.

Form of production

Film-coated tablets

Storage conditions

At a temperature of 10-30 °C

Shelf life

2 years

Active ingredient

Atorvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets