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

Active substance - atorvastatin calcium trihydrate 10.36 mg, calculated as atorvastatin 10 mg or atorvastatin calcium trihydrate 20.72 mg, calculated as atorvastatin 20 mg.

Tablets, film-coated 10 mg

Excipients: corn starch, lactose monohydrate, povidone - K30, magnesium stearate, croscarmellose sodium.

Sheath: hypromellose, macrogol, talc, titanium dioxide, a brilliant blue dye.

Film-coated tablets 20 mg

Excipients: corn starch, lactose monohydrate, povidone-K30, magnesium stearate, croscarmellose sodium.

Sheath: hypromellose, macrogol, titanium dioxide.

Description:

Tablets, film-coated 10 mg: round, biconvex, covered with a film shell of blue color. On the cross-section are visible: film The shell is blue and the core is white or almost white.

Tablets, film-coated 20 mg: round, biconvex, film-coated tablets of white color. On the cross section are visible: a film shell of white or almost white color and a core of white or almost white color.

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:

A hypolipidemic agent from the group of 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 sterols, including cholesterol.

Triglycerides (TG) and cholesterol in the liver are included in the composition of very low density lipoproteins (VLDL), enter the plasma and are transported 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 by inhibiting HMG-CoA reductase, the synthesis of cholesterol in the liver, and the increase in the number of "liver" LDL receptors on the cell surface, which leads to an increase in the capture and catabolism of LDL. Reduces the formation of LDL, causes a pronounced and persistent increase in the activity of LDL receptors. Reduces the concentration of LDL 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 cholesterol-HDL and apolipoprotein A. Dozozavisimo lowers the concentration of LDL in patients with homozygous hereditary hypercholesterolemia, resistant to therapy with other lipid-lowering drugs.

Significantly reduces the risk of ischemic complications (including death from the development of myocardial infarction) by 16%, the risk of re-hospitalization for angina, accompanied by signs of myocardial ischemia - by 26%.

Does not have a carcinogenic and mutagenic effect.

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:

Absorption is high. Time to reach the maximum concentration (TCmax) - 1-2 hours, the maximum concentration (Cmah) in women is higher by 20%, AUC (area under the pharmacokinetic curve "concentration-time") - lower by 10%; FROMmah in patients with alcoholic cirrhosis of the liver 16 times, AUC - 11 times higher than normal. 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 with 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 in respect HMG-CoA reductase-30 %. Low systemic bioavailability is due to presystemic metabolism in the mucous membrane of the gastrointestinal tract (GIT) and at the "first passage" through the liver.

The average volume of distribution is 38.1 liters, the connection with plasma proteins is more than 98%. Metabolized mainly in the liver under the action of isoenzymes CYP3A4, FROMYP3A5 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. The half-life (T1 / 2) is 14 hours.

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

Renal failure does not affect the concentration of the drug in the plasma.

Indications:

- In combination with a diet to reduce the elevated concentrations of total cholesterol, cholesterol / LDL, apolipoprotein B and triglycerides, and increase HDL cholesterol concentrations in patients with primary hypercholesterolemia, heterozygous familial and non-family hypercholesterolemia, and combined hyperlipidemia (types IIa and IIb by Frederickson);

- In combination with a diet for the treatment of patients with elevated serum concentrations of triglycerides (familial endogenous hypertriglyceridemia of type IV according to Frederickson) and patients with disbetalipoproteinemia (type III according to Frederickson), in which diet therapy does not provide an adequate effect;

- To reduce the concentration of total cholesterol and LDL cholesterol in patients with homozygous familial hypercholesterolemia, when dietotherapy and other non-pharmacological treatments are not effective enough (as an adjunct to lipid-lowering therapy, including autohemotransfusion of LDL-purified blood);

- Diseases of the cardiovascular system (including patients without clinical manifestations of ischemic heart disease,but with increased risk factors for its occurrence - elderly age over 55, nicotine dependence, arterial hypertension, diabetes mellitus, peripheral vascular disease, stroke, left ventricular hypertrophy, protein / albuminuria, coronary heart disease in close relatives) h. on the background of dyslipidemia - secondary prophylaxis in order to reduce the total risk of death, myocardial infarction, stroke, repeated hospitalization for angina pectoris and the need for a revascularization procedure.

Contraindications:

Hypersensitivity to atorvastatin or other components of the drug, active liver disease or increased activity of "liver" transaminases (more than 3 times) of unknown origin, hepatic insufficiency (A and B severity on the Child-Pugh scale), women of reproductive age not using adequate methods of contraception, children under 18 years of age (efficacy and safety not established). Lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.

Carefully:

Alcoholism, liver disease in history, pronounced violations of water-electrolyte balance, endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgical interventions, injuries, skeletal muscle diseases.

Pregnancy and lactation:

The use of the drug Lipoford in women of reproductive age, it is possible only in. case of using reliable methods of contraception. The patient should be informed of the possible risk of treatment for the fetus.

Lipofort is contraindicated for use during pregnancy. Because cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefit of using the drug during pregnancy. When used by mothers in the first trimester pregnancy of lovastatin (inhibitor of HMG-CoA reductase) with dextroamphetamine are known cases of the birth of children with bone deformity, tracheo-esophageal fistula, atresia of the anus. In case of pregnancy in the course of therapy, the drug should be stopped immediately, and the patients are warned about the potential risk to the fetus.

If it is necessary to use the drug during lactation, taking into account the possibility of undesirable phenomena in infants, it is necessary to solve the problem of stopping breastfeeding.

Dosing and Administration:

Before starting treatment with Lipoford, the patient should be recommended a standard lipid-lowering diet, which he must continue for the entire period of therapy.

Lipford is taken orally, at any time of the day (but at the same time), regardless of food intake.

The recommended initial dose is 10 mg once a day. Then the dose is selected taking into account the initial concentrations of cholesterol / LDL, the purpose of therapy and individual effect. At the beginning of treatment and / or during a dose increase, Lipoford needs to monitor the lipid levels in the blood plasma every 2-4 weeks and adjust the dose accordingly. Change the dose should be at intervals of at least 4 weeks. The maximum daily dose is 80 mg per 1 dose.

In patients with a confirmed diagnosis of ischemic heart disease or a high risk of ischemic complications, the goal of treatment is to lower LDL cholesterol below 3 mmol / L (or less than 115 mg / dL) and total cholesterol below 5 mmol / L (or less than 190 mg / dL) .

Primary (heterozygous familial and non-family) hypercholesterolemia and mixed hyperlipidemia (type IIa and IIb).

Treatment begins with a recommended initial dose of 10 mg, which is increased after 4 weeks of therapy, depending on the patient's reaction. The maximum daily dose is 80 mg.

Homozygous hereditary hypercholesterolemia.

The range of doses is the same as for other types of hyperlipidemia. The initial dose is selected individually depending on the severity of the disease. In most patients with homozygous hereditary hypercholesterolemia, the optimal effect is observed when use of drug in a daily dose of 80 mg (once).

In patients with renal insufficiency and in elderly patients correction of doses of atorvastatin is not required.

In patients with impaired liver function care should be taken in connection with the delay in removing the drug from the body. Clinical and laboratory indicators should be closely monitored and, if significant pathological changes are detected, the dose should be reduced or treatment should be discontinued.

Side effects:

The incidence of adverse reactions listed below was determined according to the following (World Health Organization classification):

very often more than 1/10, often from more than 1/100 to less than 1/10, infrequently from more than 1/1000 to less than 1/100, rarely from more than 1/10000 to less than 1/1000, very rarely - from less than 1/10000, including individual messages.

From the central nervous system: often - headache, asthenia, insomnia; infrequently - dizziness, drowsiness, nightmarish dreams, amnesia ,. depression, peripheral neuropathy, ataxia, hypoesthesia, paresthesia.

From the digestive system: often - nausea, constipation or diarrhea, flatulence, gastralgia, abdominal pain; infrequently - anorexia or increased appetite, vomiting, hepatitis, pancreatitis, cholestatic jaundice.

From the musculoskeletal system: very often - myalgia; arthralgia; infrequently - myopathy; rarely - myositis, rhabdomyolysis, back pain, cramps of the calf muscles of the legs.

Allergic reactions: often - itchy skin, rash; infrequently - hives; very rarely - angioedema, anaphylactic shock, bullous eruptions, polymeric exudative erythema, incl.Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Laboratory indicators: infrequently - hyperglycemia, hypoglycemia, increase activity of serum creatine phosphokinase (CK), an increase in activity of aspartate aminotransferase (ACT) and alanine aminotransferase (ALT).

Other: often - chest pain, peripheral edema; rarely - impotence, secondary renal failure, alopecia, tinnitus, increase in body weight, malaise, fatigue, thrombocytopenia.

Overdose:There is no specific antidote, symptomatic therapy. Hemodialysis is ineffective.

Interaction:

With the simultaneous use of cyclosporine, fibrates, erythromycin, clarithromycin, immunosuppressive, antifungal agents (belonging to azoles), nicotinic acid, and nicotinamide, drugs inhibiting metabolism, cytochrome P4503A4-mediated plasma concentration of atorvastatin (and the risk of myopathy) is increasing. By prescribing these drugs, you should carefully weigh the expected benefit and risk of treatment, regularly observe patients to identify pain or weakness in the muscles,especially during the first months of treatment and during the period of increasing the dose of any drug, periodically to determine the activity of CKK, although such control does not prevent the development of severe myopathy. Lipofor therapy should be discontinued in the event of a marked increase in CK activity or in the presence of confirmed or suspected myopathy.

Atorvastatin did not have a clinically significant effect on the concentration of terfenadine in the blood plasma, which is metabolized, cytochrome P4503A4; in this connection, it seems unlikely that atorvastatin can significantly affect the pharmacokinetic parameters of other substrates of cytochrome P4503A4.

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

Antacids reduce the concentration by 35% (the effect on the content of LDL cholesterol does not change).

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

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

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%).

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

Increases the concentration (when administered with atorvastatin at a dose of 80 mg / day) of oral contraceptives containing norethisterone by 30% and ethinyl estradiol on 20 %.

The lipid-lowering effect of the combination with colestipol exceeds that for each drug alone, despite a decrease in the concentration of atorvastatin by 25% when it is used concomitantly with colestipol.

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

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

Special instructions:

Before starting therapy with Lipoford, you need to try to achieve control of hypercholesterolemia by adequate diet therapy, increased physical activity, weight loss in obese patients and treatment of other conditions.

The use of HMG-CoA reductase inhibitors to reduce lipid levels in the blood can lead to a change in the biochemical parameters of liver function that should be monitored before the start of therapy, 6 and 12 weeks after starting Lipford and after each dose increase, and periodically, for example , every 6 months.

An increase in the activity of "hepatic" transaminases can be observed mainly in the first three months of application of the drug. Patients who have an increased level of activity of "liver" transaminases should be monitored before the level of enzymes returns to normal. It is recommended to cancel the drug or reduce the dose with an increase in aspartate aminotransferase (ACT) and alanine aminotransferase (ALT) more than 3 times.

Treatment with Lipford can cause myopathy (pain and weakness in the muscles in combination with an increase in CKK activity by more than 10 times compared with the upper limit of the norm). Lipoford can cause an increase in serum CK values, which should be taken into account in the differential diagnosis of chest pain. 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 use of atorvastatin should be temporarily discontinued in the development of clinical symptoms suggesting the presence of acute myopathies, 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 disorders and uncontrolled convulsions). The risk of myopathy increases with the simultaneous use of cyclosporine, fibrolic acid derivatives, erythromycin, nicotinic acid or azole antifungal drugs.There are reports of the development of atonic fasciitis in the background of atorvastatin, however, the connection with the drug is possible, but has not been proven to date, the etiology is not known.

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

The adverse effect of Lipofford on the ability to drive vehicles and engage in other activities that require concentration and speed of psychomotor reactions have not been reported.

Form release / dosage:Tablets, film-coated, 10 mg, 20 mg.

Packaging:

For 14 tablets in a blister of PVC / aluminum foil.

For 1 or 2 blisters together with instructions for use in a pack of cardboard.

For 10 tablets in a blister of PVC / aluminum foil.

By 2, 3, 4 or 6 blisters together with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, protected place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009045/10

Date of registration:31.08.2010

Expiration Date:Unlimited

The owner of the registration certificate:Oxford Laboratories Pvt. Ltd.Oxford Laboratories Pvt. Ltd. India

Manufacturer: & nbsp

OXFORD Laboratories, Pvt. Ltd. India

Representation: & nbspOXFORD LABORATORY Pvt. Ltd. OXFORD LABORATORY Pvt. Ltd. India

Information update date: & nbsp10.04.2018

Illustrated instructions

Instructions

Lipford (Lipoford)