Torvas - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline 73.58 mg / 147.16 mg / 294.31 mg / 588.62 mg, lactose monohydrate 33.25 mg / 66.5 mg / 133 mg / 266 mg, croscarmellose sodium 2.5 mg / 5 mg / 10 mg / 20 mg, calcium carbonate 4 mg / 8 mg / 16 mg / 32 mg, magnesium stearate 0.81 mg / 1.62 mg / 3.25 mg / 6.5 mg;

tablet coating composition: opedrai white 5 mg / 10 mg / 20 mg / 40 mg [hypromellose 62.5%, macrogol 6.25%, titanium dioxide (E171) 31.25%], simethicone (emulsion) 0.05 mg / 0.1 mg / 0.2 mg / 0.4 mg.

Description:

Dosage of 10 mg: Biconvex tablets of oval form covered with a film membrane, white or almost white, with engraving "NK10" on one side.

Dosage of 20 mg: Biconvex tablets of oval form covered with a film membrane, white or almost white, with engraving "NL20" on one side.

Dosage of 40 mg: Biconvex tablets of oval form covered with a film membrane, white or almost white, with engraving "NM40" on one side.

Dosage of 80 mg: Biconvex oval tablets coated with a film shell, white or almost white, engraved with "TH80" on one side.

Pharmacotherapeutic group:Hypolipidemic agent - inhibitor of HMG-CoA reductase

ATX: & nbsp

C.10.A.A Inhibitors of HMG-CoA reductase

C.10.A.A.05 Atorvastatin

Pharmacodynamics:

Hypolipidemic agent from the group of HMG-CoA reductase inhibitors (statins). A selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonic acid, a precursor of styrenics, including cholesterol.Triglycerides (TG) and cholesterol in the liver are included in the composition of very low density lipoproteins (LGTONP), enter the blood plasma and transport to peripheral tissues. Low density lipoproteins (LDL) are formed from VLDL in the course of interaction with LDL receptors.

Atorvastatin reduces the concentration of cholesterol and lipoproteins in the blood plasma, inhibiting HMG-CoA reductase and the synthesis of cholesterol in the liver and increasing the number of "liver" LDL receptors on the cell surface, which leads to increased cholesterol-LDL capture and catabolism.

Reduces the formation of LDL, causes a pronounced and persistent increase in the activity of LDL receptors.

In a dose of 40 mg 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 cholesterol (lipoproteins of high density) and apolipoprotein A. The results of treatment are similar in patients with heterozygous familial hypercholesterolemia, non-family forms, hypercholesterolemia and mixed hyperlipidemia, including in patients with insulin-dependent diabetes mellitus.

Dose-dependent decreases the concentration of LDL in patients with homozygous hereditary hypercholesterolemia, resistant to therapy with other lipid-lowering drugs.

In patients with isolated hypertriglyceridemia atorvastatin reduces the concentration of total cholesterol, LDL cholesterol, cholesterol-VLDL, apolipoprotein B and TG and increases the level of HDL cholesterol. In patients with disbetalipoproteinemia atorvastatin reduces the content of intermediate density lipoprotein cholesterol.

Reliably reduces the risk of developing ischemic complications (including the development of death from myocardial infarction), the risk of re-hospitalization for angina accompanied by signs of myocardial ischemia. The therapeutic effect is achieved 2 weeks after the initiation of therapy, reaches a maximum after 4 weeks, and persists throughout the treatment period.

Pharmacokinetics:

Suction: after oral administration atorvastatin quickly absorbed from the gastrointestinal tract. Time to reach the maximum concentration (TCmah) - 1-2 hours. For women, the maximum concentration (Cmah) is higher by 20%, the area under the curve "concentration-time" (AUC) - 10% lower than that of men. Food slightly reduces the speed and duration of absorption of the drug (by 25% and 9%, respectively), but the reduction in LDL cholesterol is similar to that of atorvastatin without food.The concentration of atorvastatin when used in the evening is lower than in the morning (about 30%). A linear relationship between the degree of absorption and the dose of the drug has been revealed. Bioavailability - 14%, systemic bioavailability of inhibitory activity against HMG-CoA reductase - 30%. Low systemic bioavailability is due to presystemic metabolism in the mucous membrane of the gastrointestinal tract and during the "primary passage" through the liver.

Distribution: the average volume of distribution is 381 liters, the connection with plasma proteins is more than 98%. The ratio of the content in the erythrocytes / plasma is about 0.25, that is atorvastatin poorly penetrates into red blood cells.

Metabolism: metabolized primarily in the liver under the action of isoenzymes CYP3A4, CYP3A5 and CYP3A7 with the formation of pharmacologically active metabolites (ortho- and para-hydroxylated derivatives, beta-oxidation products). In vitro ortho- and para-hydroxylated metabolites have an inhibitory effect on HMG-CoA reductase, 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 and lasts about 20-30 hours due to their presence.

Excretion: atorvastatin and its metabolites are excreted mainly through the intestine after hepatic and / or extrahepatic metabolism (atorvastatin not subject to severe intestinal hepatic recirculation). The half-life (T1 / 2) is 14 hours. Less than 2% of the dose taken internally is determined in the urine.

It is not excreted during hemodialysis due to intensive binding to plasma proteins.

FROMmah and AUC of the drug in the elderly (65 years and older) by 40 and 30 %, respectively, higher than those in adult patients of young age (of no clinical significance).

Impaired renal function does not affect the concentration of the drug in the blood plasma.

The concentration of the drug is significantly increased (Cmah about 16 times, AUC - 11 times higher than normal) in patients with alcoholic cirrhosis of the liver (stage B according to the Child-Pugh classification).

Indications:

Primary hypercholesterolemia (heterozygous familial and non-family hypercholesterolemia IIbut of the type); combined (mixed) hyperlipidemia (IIa and IIb by Fredrickson); with increased concentration of triglycerides (TG) in blood plasma (type IV according to Fredrickson); dysetalopoproteinemia (type III) (as a supplement to the diet); family endogenous hypertriglyceridemia (type IV) only when the diet and other non-pharmacological treatments are insufficient effective.

Homozygous hereditary hypercholesterolemia (as an adjunct to hypolipidemic therapy).

Contraindications:

Hypersensitivity to atorvastatin or any other component of the drug, active liver disease, increased activity of "hepatic" transaminases of unknown origin (more than 3 times compared with the upper limit of normal), lactase deficiency, lactose intolerance, glucose-galactose malabsorption, pregnancy, period breastfeeding; children under 18 years of age (efficacy and safety not established).

Carefully:

Alcohol abuse, liver disease in history, endocrine and metabolic disorders, arterial hypotension, severe acute infection (sepsis), uncontrolled epilepsy, extensive surgical interventions, trauma.

Pregnancy and lactation:

Torvas is contraindicated in pregnancy.

Women of reproductive age during treatment should apply reliable methods of contraception. Atorvastatin can be prescribed to women of reproductive age only if the probability of pregnancy is very low, and the patient is informed of the potential risk of treatment for the fetus.In the case of diagnosing pregnancy during therapy, the drug should be discontinued immediately.

Atorvastatin is excreted in breast milk. If you need to use the drug, nursing mothers should stop breastfeeding.

Dosing and Administration:

Inside, taken at any time of the day, but at the same time, regardless of the time of ingestion. Before appointment Thorvas patient should be recommended a standard hypocholesterolemic diet, which he must continue to observe during the entire period of therapy.

The dose ranges from 10 mg to 80 mg per day. For most patients, the initial dose is 10 mg once a day. The dose is selected taking into account the initial concentrations of cholesterol, the purpose of therapy and individual response to ongoing therapy.

At the beginning of treatment and / or while increasing the dose of the drug, you should monitor every 2-4 weeks the concentration of lipids in the blood plasma and adjust the dose accordingly.

With primary hypercholesterolemia and combined (mixed) Hyperlipidemia is prescribed 10 mg once a day. Therapeutic effect is observed after 2 weeks, the maximum therapeutic effect is observed after 4 weeks.

With a homozygous family Hypercholesterolemia is taken on 40-80 mg once a day (lowering the LDL content by 18-45%).

If there is a violation of the liver, the dose of the drug should be reduced, with the constant monitoring of the activity of "liver" transaminases: aspartate aminotransferase (ACT) and alanine aminotransferase (ALT).

If there is a violation of kidney function and in elderly patients, dosage adjustment is not required.

When used simultaneously with cyclosporine, the dose of Torvas should not exceed 10 mg / day.

Side effects:

According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1 / 10000, <1/1000) and very rarely (> 1/10000), including individual messages; frequency unknown - according to available data to establish the frequency of occurrence was not possible.

From the central and peripheral nervous system: often: headache; infrequently: dizziness, sleep disturbances, including insomnia and nightmarish dreams, asthenic syndrome, weakness, paresthesia, hypoesthesia,loss or loss of memory; rarely: peripheral neuropathy.

From the digestive tract: often: constipation, flatulence, indigestion, nausea, diarrhea; infrequently: anorexia, vomiting, pancreatitis, hepatitis, abdominal pain; rarely: cholestatic jaundice (including obstructive jaundice); very rarely: liver failure.

From the side of the musculoskeletal system and connective tissue: often: myalgia, arthralgia, "swelling" of the joints, joint pain, back pain; infrequently: muscle cramps, pain in the muscles of the neck; rarely: myopathy, myositis, rhabdomyolysis, tendinopathy (sometimes complicated by a rupture of the tendon).

From the sense organs: infrequently: noise in the ears, blurred vision; very rarely: hearing loss.

From the skin and subcutaneous fat: infrequently: urticaria, skin rash and itching, allergic reactions, alopecia; rarely: angioedema, bullous rash, polymorphous exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (syndrome Lyell).

From the hematopoiesis: infrequently: thrombocytopenia.

From the respiratory system: often: nasopharyngitis, sore throat, nosebleeds.

Laboratory data: often: increased activity of "liver" transaminases, alkaline phosphatase and creatine phosphokinase (CK) in the blood plasma; infrequently: leukocyturia; frequency unknown: hyperglycemia, increased concentration of glycosylated hemoglobin.

Other: often: peripheral edema; infrequent: increased fatigue, impaired potency, weight gain, secondary renal failure, fever, chest pain; very rarely: gynecomastia, diabetes mellitus.

There are separate reports on the development of atonic fasciitis (a connection with the use of atorvastatin has not been accurately established); frequency unknown: depression, interstitial lung disease (especially with prolonged therapy), sexual dysfunction.

Overdose:

Symptoms: development of myopathy with subsequent rhabdomyolysis and acute renal failure. In this case, the drug should be immediately canceled.

Treatment: there is no specific antidote. Symptomatic therapy is performed. Take measures to maintain vital body functions and measures to prevent further absorption of the drug: gastric lavage, the reception of activated charcoal. Because the atorvastatin is largely associated with blood plasma proteins, hemodialysis is ineffective.

Interaction:

With the simultaneous administration of cyclosporine, fibrates, erythromycin, clarithromycin, immunosuppressive, antifungal preparations of azole derivatives and nicotinic acid in lipid-lowering doses (more than 1 g / day), the concentration of atorvastatin in the blood plasma (and the risk of myopathy) increases.

With simultaneous ingestion of atorvastatin and a suspension containing magnesium and aluminum hydroxide, atorvastatin concentrations in the blood plasma decrease by approximately 35%, however, the level of decrease in the level of cholesterol / LDL does not change.

Clinically significant interaction is not observed with simultaneous use with warfarin, cimetidine, phenazone.

With simultaneous application of colestipol, concentrations of atorvastatin in blood plasma decreased by approximately 25%. However, the hypolipidemic effect of the combination of atorvastatin and colestipol was superior to that of each drug individually.

When digoxin is used in combination with atorvastatin at a dose of 80 mg / day, the digoxin concentration increases by about 20%.

With the simultaneous use of atorvastatin and erythromycin (500 mg 4 times a day) or clarithromycin (500 mg twice a day), which inhibit cytochrome P450 AP4, there is an increase in the concentration of atorvastatin in the blood plasma.

With the simultaneous use of atorvastatin (10 mg once a day) and azithromycin (500 mg once a day), the concentration of atorvastatin in the blood plasma does not change.

At simultaneous application of atorvastatin in a dose of 80 mg / day and oral contraceptives containing norethisterone or ethinyl estradiol, there is an increase AUC norethisterone and ethinyl estradiol by approximately 30% and 20%, respectively.

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

With the simultaneous use of atorvastatin 80 mg and amlodipine 10 mg, the pharmacokinetics of atorvastatin did not change.

The simultaneous use of atorvastatin with protease inhibitors, known as isoenzyme inhibitors CYP3A4, is accompanied by an increase in the concentration of atorvastatin in plasma (with simultaneous use with erythromycin CmAtorvastatin increases by 40%). Because grapefruit juice contains one or more components that inhibit the cytochrome isoenzyme CYP3A4, its excessive consumption (more than 1.2 liters per day) can cause an increase in the concentration of atorvastatin in the blood plasma.

Joint use of atorvastatin in a dose of 40 mg with diltiazem at a dose of 240 mg, leads to an increase in the concentration of atorvastatin in blood plasma. Atorvastatin and its metabolites are substrates of the transport protein OATP1B1. Inhibitors of OATP1B1 (for example, ciclosporin) may increase the bioavailability of atorvastatin. Thus, the combined use of atorvastatin 10 mg and cyclosporine at a dose of 5.2 mg / kg / day leads to an increase in the concentration of atorvastatin in blood plasma by 7.7 times.

There was no clinically significant undesirable interaction of atorvastatin and antihypertensive agents.

The development of rhabdomyolysis with simultaneous use of atorvastatin and fusidic acid has been reported.

Special instructions:

The drug Torvas can cause an increase in activity of CK, which should be taken into account in the differential diagnosis of chest pain.It should be borne in mind that an increase in CK 10 times compared with the norm, accompanied by myalgia and muscle weakness may be associated with myopathy, treatment should be discontinued.

The liver function should be monitored before the start of treatment, 6 and 12 weeks after the start of taking the drug and after every dose increase, and periodically (every 6 months). Increased activity of "liver" transaminases is observed mainly in the first 3 months of the drug. In the event that ALT activity or ACT increases more than 3 times, it is recommended to reduce the dose of the drug Torvas or cancel the drug.

It is necessary to temporarily stop the use of the drug Torvas in the development of clinical symptoms, suggesting the presence of acute myopathy, or in the presence of factors predisposing to the development of acute renal failure against rhabdomyolysis (severe infections, low blood pressure, extensive surgery, trauma, metabolic, endocrine or severe electrolyte disturbances). Patients should be warned that they should immediately consult a doctor if unexplained pain or weakness in the muscles occurs, especially if they are accompanied by a malaise or fever.The risk of myopathy increases with simultaneous use of cyclosporine, fibroic acid derivatives, erythromycin, clarithromycin, nicotinic acid in lipid-lowering doses (more than 1 g / day) or antifungal preparations of azole derivatives.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and controlling mechanisms due to the risk of developing dizziness.

Form release / dosage:Tablets 10 mg, 20 mg, 40 mg, 80 mg.

Packaging:

Tablets 10 mg, 20 mg, 40 mg: 10 tablets per blister of A1 / A1 foil. For 1,3, 5 or 10 blisters together with instructions for use in a cardboard bundle.

Tablets 80 mg: 10 tablets per blister of A1 / A1 foil. For 1, 3, 5 or 10 blisters together with instructions for use in a cardboard bundle. 6 tablets per blister of A1 / A1 foil. For 5 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

In dry, dark place at a temperature of 15 ° C to 30 ° C. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:PL-000829

Date of registration:07.10.2011

The owner of the registration certificate:Ranbaxy Laboratories LimitedRanbaxy Laboratories Limited India

Manufacturer: & nbsp

TABUK PHARMACEUTICALS, MFG. Co. Saudi Arabia

Representation: & nbspRABBAYS LABORATORY LIMITEDRABBAYS LABORATORY LIMITED

Information update date: & nbsp25.12.2014

Illustrated instructions

Instructions

Torvas (Torvas)