Tulip pills 10mg №90

Mechanism of action

Tulip - lipid-lowering.

Pharmacodynamics

Atorvastatin is a selective competitive inhibitor of HMG-CoA reductase, an enzyme involved in the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, the precursor of steroids, including cholesterol. Cholesterol and triglycerides (TG) circulate in the bloodstream in the composition of lipoprotein molecules. Triglycerides and cholesterol in the liver are synthesized by VLDL. From the liver, they enter the blood plasma and are delivered to peripheral tissues. LDLs are formed from VLDL, their catabolism is carried out mainly through interaction with LDL receptors. Atorvastatin reduces the synthesis and LDL cholesterol, total cholesterol, apolipoprotein B in patients with homozygous and heterozygous familial hypercholesterolemia, primary hypercholesterolemia and mixed hyperlipidemia. It also causes a decrease in VLDL and triglyceride cholesterol levels and an increase in HDL cholesterol and apolipoprotein A. Atorvastatin reduces total cholesterol, LDL cholesterol, VLDL cholesterol, apolipoprotein B, triglycerides and non-HDL cholesterol, and the level of the non-HDL cholesterol level, the level of the non-HDL cholesterol, LDL cholesterol, apolipoprotein B, triglycerides and non-HDL cholesterol, increases the levels of total cholesterol, LDL cholesterol, apolipoprotein A. patients with isolated hypertriglyceridemia, LPSP cholesterol level in patients with dysbetalipoproteinemia.Like LDL, cholesterol-rich and triglyceride-rich lipoproteins (VLDL, intermediate density lipoproteins, and chylomicron residues) can also contribute to the progression of atherosclerosis. Increased plasma triglycerides are often combined with a decrease in HDL levels and the appearance of small-sized LDL particles, as well as other non-lipid metabolic risk factors for CHD.

Pharmacokinetics

Absorption and distribution

Absorption is high. C_max in blood plasma after oral administration is achieved in 1-2 hours. C_max in women it is higher by 20%, in AUC - 10% lower than in men. C_max in patients with alcoholic cirrhosis of the liver (class B on the Child-Pugh scale) is 16 times, and AUC is 11 times higher than the norm.

Meal slightly reduces the rate and extent of absorption of the drug (by 25 and 9%, respectively), but lowering LDL cholesterol is similar to that when using atorvastatin without simultaneous ingestion of food.

After oral administration of atorvastatin in the evening, the plasma concentration is lower (C_max and AUC at about 30%) than after taking it in the morning, but lowering the concentration of LDL cholesterol does not depend on the time of day at which the drug is taken. A linear relationship was found between the degree of absorption and the dose of the drug.

Bioavailability is 12%, systemic bioavailability of inhibitory activity against HMG-CoA reductase is about 30%. Low systemic bioavailability is caused by presystemic metabolism in the gastrointestinal tract and during the first passage through the liver.

Medium V_d - 381 l, connection with plasma proteins - 98%.

It is metabolized mainly in the liver under the action of cytochrome P4503A4 with the formation of pharmacologically active metabolites (ortho and parahydroxylated derivatives, beta-oxidation products). Tulip^® (tablets of 10 and 20 mg) causes a decrease in total cholesterol by 29 and 33%, LDL-cholesterol by 39 and 43%, apolipoprotein B by 32 and 35% and triglycerides by 14 and 26%. Level LPVP-cholesterol at the same time increases respectively by 6 and 9%. It is mainly excreted in bile after hepatic and / or extrahepatic metabolism (atorvastatin does not undergo a pronounced enterohepatic recirculation, is not excreted by hemodialysis). T_1/2 - 14 h. The inhibitory activity against HMG-CoA reductase remains about 20-30 h due to the presence of active metabolites. Less than 2% of the ingested dose of the drug is determined in the urine.

Composition

1 pill contains:

Active ingredient: atorvastatin (in the form of Calcium salt) 10 mg;

Excipients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, hydroxypropyl cellulose, polysorbate 80, heavy Magnesium oxide, colloidal silicon dioxide, magnesium stearate;

The composition of the shell: hypromellose, hydropropylcellulose, titanium dioxide (E171), polyethylene glycol 6000, talc.

Interaction

Antacids: with simultaneous administration of atorvastatin and antacid drugs in the form of a suspension containing magnesium and aluminum hydroxide, the concentration of atorvastatin in the blood plasma decreases by approximately 35%, while the degree of lowering LDL cholesterol remains unchanged.

Colestipol: with simultaneous use of atorvastatin and colestipol, the concentration of atorvastatin in the blood plasma is reduced by approximately 25%, while the lipid-lowering effect of the combination of atorvastatin and colestipol exceeds that of each drug separately.

Digoxin: with repeated simultaneous intake of atorvastatin and Digoxin, the concentration of digoxin in the blood plasma increases by about 20%, and therefore the patient must be monitored.

Erythromycin: while taking atorvastatin and Erythromycin, which has an inhibitory effect on cytochrome P450 CYP3A4, plasma concentration of atorvastatin increases by approximately 40%.

Oral contraceptives: With simultaneous use of atorvastatin and oral contraceptive drugs, AUC values ​​increase by approximately 30% for norethisterone and 20% for ethinyl estradiol. These data should be considered when selecting contraceptives for patients taking atorvastatin.

Warfarin: in patients who take Warfarin for a long time, atorvastatin slightly reduces the prothrombin time in the first days after the start of its use, however, after 15 days, this figure returns to normal. After atorvastatin is prescribed, patients taking warfarin should be monitored more frequently than usual.

With the simultaneous appointment of cyclosporine, fibrates, Clarithromycin, antifungal drugs (related to azoles) and nicotinamide, the concentration of atorvastatin in the blood plasma (the risk of myopathy) increases.

Active substance

Atorvastatin

Mode of application

Before treatment, the patient should be transferred to a low cholesterol diet. Inside, at any time of the day, regardless of the meal.

The dose of the drug varies from 10 to 80 mg once a day, selecting it based on the initial levels of Xc-LDL, the goals of therapy and the individual effect. Change the dose should be at least 4 weeks apart.

Primary hypercholesterolemia and mixed hyperlipidemia

Recommended Initial Tulip Dose^® makes 10 mg once a day. Then an individual dose is selected, which is 10-80 mg of the drug per day, depending on the target level of cholesterol and the effectiveness of the drug. After 2-4 weeks after the start of treatment and / or selection of a dose of Tulip^®should determine the level of blood lipids and in accordance with him to adjust the dose of the drug.

Familial hypercholesterolemia is heterozygous. Initial dose of Tulip^® makes 10 mg a day, the dose can be increased to 80 mg a day.

- homozygous. The dose range is the same as with other types of hyperlipidemia. The initial dose is selected individually depending on the severity of the disease. The maximum daily dose of 80 mg.

Dosages for patients with renal insufficiency. If a patient has kidney disease, the concentration of atorvastatin in the blood plasma and its effect on LDL cholesterol levels do not change. In this regard, dose adjustment for patients with kidney disease is not required.

Dosages for patients with liver failure.In patients with impaired liver function, care must be taken in connection with the slowing down of the drug from the body. Clinical and laboratory findings should be carefully monitored and, if significant changes are detected, the dose should be reduced or treatment should be discontinued.

Patients of the older age group. Dose adjustment for patients older than 70 years is not required.

Overdose

There is no specific treatment in case of a Tulip overdose. Symptomatic treatment; take measures to maintain vital functions and prevent further absorption of the drug (gastric lavage, taking activated charcoal). Due to the fact that the drug is actively associated with plasma proteins, hemodialysis is not an effective way to accelerate its removal from the body.

Side effects

Digestive system: in more than 2% of cases - nausea; less than 2% - heartburn, constipation or diarrhea, flatulence, abdominal pain, anorexia, decreased or increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive and ulcerative lesions of the oral cavity, gastroenteritis, hepatitis, biliary colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, abnormal liver function, melena, gingival bleeding, tenesmus.

Respiratory system: in more than 2% of cases - bronchitis, rhinitis; less commonly, pneumonia, dyspnea, bronchial asthma, epistaxis.

Nervous system: in more than 2% of cases - insomnia, dizziness; less than 2% - headache, asthenia, malaise, drowsiness, unusual dreams, paresthesia, amnesia, emotional lability, peripheral neuropathy, ataxia, facial nerve paralysis, hyperkinesis, depression, hyperesthesia, loss of consciousness.

Musculoskeletal system: in more than 2% of cases - arthritis; in less than 2% - leg muscle cramps, bursitis, tenosynovitis, myositis, myopathy, arthralgia, myalgia, contractures of the joints, stiff neck muscles, rhabdomyolysis.

Allergic reactions: in less than 2% of cases - pruritus, skin rash, contact dermatitis; rarely - urticaria, anaphylaxis, angioedema, erythema multiforme exudative (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), photosensitization.

Skin: in less than 2% of cases - alopecia, sweating, eczema, seborrhea, ecchymosis, petechiae.

The urinogenital system: in more than 2% of cases - urogenital infections, peripheral edema; in less than 2% of cases - dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, imperative urination to urinate), nephritis, hematuria, vaginal bleeding, urolithiasis, epididymitis, decreased libido, impaired ejaculation, impotence, uterine diseases bleeding.

Sense organs: in less than 2% of cases - amblyopia, tinnitus, dry conjunctiva, disturbed accommodation, bleeding in the eyes, deafness, increased intraocular pressure, parosmia, taste perversion, loss of taste.

Cardiovascular system: in more than 2% of cases - chest pain; in less than 2% - palpitations, vasodilation, orthostatic hypotension, phlebitis, arrhythmia, angina pectoris, increased blood pressure.

Blood system: in less than 2% of cases - anemia, lymphadenopathy, thrombocytopenia.

Laboratory indicators: in less than 2% of cases - hyperglycemia, hypoglycemia, increased creatine phosphokinase (CPK), albuminuria.

Others: in less than 2% of cases - weight gain, gynecomastia, exacerbation of gout, mastodynia.

Indications

• elevated blood cholesterol
• coronary heart disease
• coronary atherosclerosis.

Use during pregnancy and lactation

Use during pregnancy and during breastfeeding is contraindicated.

Contraindications

• hypersensitivity to atorvastatin and other excipients of the drug;
• liver diseases in the active stage (including active chronic hepatitis, chronic alcoholic hepatitis); increased activity of ALT or AST (more than 3 times compared with the upper limit of the norm) of unclear genesis; liver failure (severity A and B on the Child-Pyuga scale);
• women of reproductive age who do not use adequate methods of contraception.

With caution: a history of liver disease, alcohol abuse, severe electrolyte imbalance, endocrine and metabolic disorders, arterial hypotension,severe acute infections (sepsis), uncontrolled epilepsy, diseases of skeletal muscles, extensive surgical interventions, injuries, children's age (efficacy and safety of use have not been established).

Special instructions

Liver dysfunction. The use of HMG-CoA reductase inhibitors to reduce the level of lipids in the blood can lead to changes in biochemical parameters reflecting the function of the liver.

Liver function should be monitored before starting treatment, after 6 weeks, 12 weeks after starting Tulip.^® and after each dose increase, as well as periodically, for example, every 6 months. Changes in the activity of liver enzymes are usually observed during the first three months after starting Tulip.^®. Patients with increased transaminase levels should be monitored until the level of enzymes returns to normal. In the event that the values ​​of ALT or AST are more than 3 times higher than the level of the upper permissible limit, it is recommended to reduce the dose of Tulip^® or stop treatment.

Skeletal musculature. Patients with diffuse myalgia, lethargy or muscle weakness and / or a significant increase in CPK are a risk group for the development of myopathy (defined as muscle pain with a concomitant increase in CPK levels of more than 10 times compared with the upper limit of normal).

In the appointment of combined therapy Tulip^® and cyclosporine, fibric acid derivatives, erythromycin, clarithromycin,immunosuppressants and antifungal drugs azole structure, as well as causing lipid lowering doses of niacin, it is necessary to compare the potential benefits and risks in this treatment and monitor patients who have signs or symptoms of muscle pain, lethargy or weakness, especially during the first months treatment and with increasing doses of any of the drugs.

Tulip treatment^® should be temporarily suspended or discontinued when a serious condition develops, which may result from myopathy, as well as with risk factors for the development of acute renal failure due to rhabdomyolysis (for example, acute severe infection, hypotension, extensive surgery, trauma, severe metabolic and endocrine disturbances and electrolyte imbalances).

The patient should immediately consult a doctor if there are unexplained pains or weakness in the muscles, especially if they are accompanied by indisposition and fever. Women of reproductive age should use reliable methods of contraception.

Influence on the ability to drive and other activities that require concentration and speed of psychomotor reactions

Tulip^® does not affect the ability to drive a car and mechanisms.

Shelf life

2 years

Pharmacy sales terms

On prescription

Storage conditions

At a temperature not higher than 25 ° C