Tulip, 40 mg 30 pcs.

Tulip is hypolipidemic.

Pharmacodynamics

Atorvastatin is a selective competitive inhibitor of HMG-CoA reductase, the enzyme involved in the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A into mevalonate, a precursor of steroids, including cholesterol.including cholesterol. Cholesterol and triglycerides (TG) circulate in the vascular bed as part of lipoprotein molecules. From triglycerides and cholesterol, LDL are synthesized in the liver. From the liver they enter blood plasma and are delivered to peripheral tissues. LDL are formed from LDLNP, their catabolism is carried out mainly through interaction with LDL receptors.

Atorvastatin reduces LDL cholesterol synthesis and content, total cholesterol content, apolipoprotein B in patients with homozygous and heterozygous familial hypercholesterolemia, primary hypercholesterolemia and mixed hyperlipidemia. It also causes decreases in LDL cholesterol and triglyceride levels and increases in HDL-cholesterol and apolipoprotein A levels.

. Atorvastatin reduces total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein B, triglycerides and non-LDL-cholesterol levels and increases HDL-cholesterol levels in patients with isolated hypertriglyceridemia, LDL-cholesterol levels in patients with dysbetalipoproteinemia. Like LDL, cholesterol-rich and triglyceride-rich lipoproteins (LDLNP, intermediate-density lipoproteins, and chylomicron residues) may also contribute to the progression of atherosclerosis. Elevated plasma triglyceride levels are often combined with decreased HDL levels and the appearance of small LDL particles, as well as other non-lipid metabolic risk factors for CHD.

Pharmacokinetics

Absorption and distribution

Absorption is high. C_max in plasma after oral administration is reached after 1-2 h. C_max in women is 20% higher, AUC is 10% lower than in men. C_max in patients with alcoholic liver cirrhosis (class B according to Child-Pugh scale) is 16 times higher, and AUS is 11 times higher than normal.

Eating slightly reduces the rate and degree of absorption of the drug (by 25 and 9%, respectively), but the decrease in LDL-cholesterol is similar to that of atorvastatin without concomitant food intake.

After oral administration of atorvastatin in the evening, plasma concentrations are lower (C_max and AUC approximately by 30%) than after administration in the morning, but decrease in LDL-cholesterol concentration is independent of the time of day in which the drug is taken. A linear correlation between the degree of absorption and the dose of the drug was found.

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

The average V_d is 381 liters and the binding to plasma proteins is 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^® (10 and 20 mg tablets) causes decreases 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%.

The level of HDL-cholesterol in this case increases by 6 and 9%, respectively. It is excreted mainly with bile after hepatic and/or extrahepatic metabolism (atorvastatin does not undergo marked intestinal-hepatic recirculation, it is not excreted with hemodialysis). T_1/2 – 14 h. 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 determined in the urine.

Indications

Active ingredient

Composition

1 tablet contains:

The active ingredient:

atorvastatin (in the form of calcium salt) 40 mg;

Associates:

microcrystalline cellulose,

lactose monohydrate,

magnesium oxide heavy,

colloidal silicon dioxide,

magnesium stearate;

Composition of the shell:

Hypromellose, hydropropyl cellulose, titanium dioxide (E171), polyethylene glycol 6000, talc.

How to take, the dosage

The patient should be switched to a cholesterol-lowering diet before starting treatment. Orally, at any time of the day, regardless of meals.

The dose of the drug is varied from 10 to 80 mg once daily, adjusted for baseline LDL-C levels, the goal of therapy, and individual effect. The dose should be changed at intervals of at least 4 weeks.

Primary hypercholesterolemia and mixed hyperlipidemia

The recommended starting dose of Tulip® is 10 mg once daily. The dose is then individually adjusted to 10-80 mg of the drug per day, depending on the target cholesterol level and the effectiveness of the drug. After 2-4 weeks after the treatment start and/or after adjusting the dose of Tulip ® the blood lipid level should be determined and the dose of the preparation should be adjusted in accordance with it.

Familial hypercholesterolemia is heterozygous. The initial dose of Tulip® is 10 mg per day, the dose may be increased to 80 mg per day.

Homozygous. The dose range is the same as for other types of hyperlipidemia. The initial dose is chosen individually depending on the severity of the disease. The maximum daily dose is 80 mg.

Dosages for patients with renal insufficiency. In patients with renal impairment plasma concentration of atorvastatin and its effect on LDL cholesterol levels do not change. In this regard, no dose adjustment is required for patients with renal disease.

Dosages for patients with hepatic impairment. In patients with hepatic impairment caution should be observed due to delayed elimination of the drug from the body. Clinical and laboratory parameters should be carefully monitored and if significant changes are detected, the dose should be reduced or treatment discontinued.

Patients in the older age group. No dose adjustment is required for patients over 70 years of age.

Interaction

Antacids: in concomitant administration of atorvastatin and antacids in the form of magnesium and aluminum hydroxide suspensions, plasma concentration of atorvastatin decreases by approximately 35%, while the degree of LDL cholesterol level reduction remains unchanged.

Colestipol: concomitant use of atorvastatin and colestipol decreases plasma concentration of atorvastatin by approximately 25%, with hypolipidemic effect of combination of atorvastatin and colestipol exceeding that of each drug separately.

Digoxin: Multiple concomitant administration of atorvastatin and digoxin increases plasma concentrations of digoxin by approximately 20%, therefore, the patient should be monitored.

Eritromycin: Concomitant administration of atorvastatin and erythromycin, which has an inhibitory effect on cytochrome P450 CYP3A4, increases plasma concentration of atorvastatin by approximately 40%.

Peroral contraceptives: In concurrent use of atorvastatin and oral contraceptives AUC values increase by approximately 30% for norethisterone and 20% for ethinylestradiol. These data should be considered when selecting contraceptives for patients taking atorvastatin.

Warfarin: in patients taking warfarin for a long time, atorvastatin slightly decreases prothrombin time in the first days after the beginning of its use, but after 15 days this figure is normalized. After administration of atorvastatin, patients taking warfarin should be monitored more frequently than usual.

The concomitant administration of cyclosporine, fibrates, clarithromycin, antifungal drugs (related to azoles) and nicotinamide will increase plasma concentrations of atorvastatin (risk of myopathy).

Special Instructions

Disorders of liver function. 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 starting treatment, 6 weeks, 12 weeks after starting Tulip® and after each dose increase, and periodically, such as every 6 months. Changes in liver enzyme activity are usually seen within the first three months after starting Tulip®. 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 tolerance, it is recommended to reduce the dose of Tulip® or discontinue treatment.

Skeletal Musculature. Patients with diffuse myalgia, muscle laxity or weakness and/or significant elevation of CPK are at risk for myopathy (defined as muscle pain with concomitant elevation of CPK levels more than 10 times the upper limit of normal).

When administering combination therapy with Tulip® and cyclosporine, fibric acid derivatives, erythromycin, clarithromycin, immunosuppressants, and azole antifungals and lipid-lowering doses of niacin, the potential benefit and risk of this treatment should be compared and patients who show signs or symptoms of muscle pain, lethargy, or weakness should be monitored, particularly during the first months of treatment and when the dose of any of the drugs is increased.

The treatment with Tulip® should be temporarily suspended or discontinued if a serious condition that may result from myopathy develops and if there are risk factors for acute renal failure due to rhabdomyolysis (e.g., acute severe infection, arterial hypotension, extensive surgery, trauma, severe metabolic and endocrine disorders, and electrolyte imbalances).

The patient should seek immediate medical attention if unexplained muscle pain or weakness occurs, especially if accompanied by malaise and fever. Women of reproductive age should use reliable methods of contraception.

Impact on the ability to drive vehicles and engage in other activities requiring concentration and quick psychomotor reactions

Tulip® has no effect on the ability to drive and operate machinery.

Contraindications

With caution: history of liver disease, alcohol abuse, severe electrolyte balance disorders, endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), uncontrolled epilepsy, skeletal muscle disease, major surgical interventions, trauma, childhood (effectiveness and safety of use are not established).

Side effects

The digestive system: In more than 2% of cases, nausea; In 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 mouth, gastroenteritis, hepatitis, biliary colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, impaired liver function, melena, bleeding gums, tenesmus.

Respiratory system: in more than 2% of cases – bronchitis, rhinitis; less frequently – pneumonia, dyspnea, bronchial asthma, nasal bleeding.

Nervous system: in more than 2% of cases, insomnia, dizziness; in less than 2%, headache, asthenia, malaise, somnolence, unusual dreams, paraesthesia, amnesia, emotional lability, peripheral neuropathy, ataxia, facial nerve palsy, hyperkinesias, depression, hyperesthesia, unconsciousness.

Musculoskeletal system: in more than 2% of cases – arthritis; in less than 2% – leg muscle cramps, bursitis, tenosynovitis, myositis, myopathy, arthralgia, myalgia, joint contractures, neck muscle stiffness, rhabdomyolysis.

Allergic reactions: in less than 2% of cases – skin itching, skin rash, contact dermatitis; rarely – urticaria, anaphylaxis, Quincke’s edema, erythema multiforme (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), photosensitization.

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

Urogenital system: in more than 2% of cases – urogenital infections, peripheral edema; in less than 2% of cases – dysuria (including Pollakiuria, nycturia, urinary incontinence or urinary retention, imperative urge to urinate), nephritis, hematuria, vaginal bleeding, urolithiasis, epididymitis, decreased libido, ejaculation disorders, impotence, uterine bleeding.

Sensory organs: in less than 2% of cases – amblyopia, tinnitus, dry conjunctiva, accommodation disorders, bleeding in the eyes, deafness, increased intraocular pressure, parosmia, perversion of taste, loss of taste sensation.

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

Hematopoietic system: in less than 2% of cases – anemia, lymphadenopathy, thrombocytopenia.

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

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

Overdose

There is no specific treatment in case of Tulip® overdose. Treatment is symptomatic; measures are taken to maintain vital functions and prevent further absorption of the drug (gastric lavage, intake of activated charcoal). Due to the fact that the drug is actively bound to blood plasma proteins, hemodialysis is not an effective way to accelerate its elimination from the body.

Pregnancy use

The use in pregnancy and during breastfeeding is contraindicated.

Similarities