Tulip, pills 10mg, 90pcs

Composition

1 tablet contains:

Active ingredient:

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

Auxiliary substances:

microcrystalline cellulose,

lactose monohydrate,

sodium croscarmellose,

hydroxypropylcellulose,

polysorbate 80,

heavy magnesium oxide,

colloidal silicon dioxide,

magnesium stearate;

Shell composition:  

hypromellose, hydropropylcellulose, titanium dioxide (E 171), polyethylene glycol 6000, talc.

Pharmacological action

Tulip – hypolipidemic.

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, a precursor of steroids, including cholesterol. Cholesterol and triglycerides (TG) circulate in the vascular bed as part of lipoprotein molecules. VLDL is synthesized from triglycerides and cholesterol in the liver. From the liver, they enter the blood plasma and are delivered to peripheral tissues. LDL is formed from VLDL, and its catabolism is mainly carried out through interaction with LDL receptors.

Atorvastatin reduces the synthesis and content of LDL cholesterol, total cholesterol, and apolipoprotein B in patients with homozygous and heterozygous familial hypercholesterolemia, primary hypercholesterolemia, and mixed hyperlipidemia. It also causes a decrease in VLDL cholesterol and triglycerides 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 increases HDL cholesterol in patients with isolated hypertriglyceridemia, and LDL cholesterol 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. Elevated plasma triglycerides are often associated with a decrease in HDL 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. _Cmax in blood plasma after oral use is reached in 1-2 hours_{. Cmax} in women is 20% higher, and AUC is 10% lower than in men. _Cmax in patients with alcoholic cirrhosis of the liver (class B on the Child-Pugh scale) is 16 times, and the AUC is 11 times higher than normal.

Food intake slightly reduces the rate and degree of absorption of the drug (by 25 and 9%, respectively), but the reduction in LDL cholesterol is similar to that when using atorvastatin without simultaneous food intake.

After oral use of atorvastatin in the evening, the concentration in blood plasma is lower (_cmax and AUC are approximately 30%) than after taking it in the morning, but the decrease in LDL cholesterol concentration 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.

The bioavailability is 12%, and 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 at the first passage through the liver.

Mean Vd — 381 l, plasma protein binding-98%.

It is mainly metabolized 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) reduces 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 increases by 6 and 9%, respectively. It is mainly excreted in bile after hepatic and / or extrahepatic metabolism (atorvastatin does not undergo pronounced enterohepatic recirculation, is not excreted by 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 detected in the urine.

Indications

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

Use during pregnancy and lactation

Use during pregnancy and lactation is contraindicated.

Contraindications

• hypersensitivity to atorvastatin and other auxiliary substances of the drug;
• liver disease in the active stage (including chronic active hepatitis, chronic alcoholic hepatitis); increased activity of ALT or AST (more than 3 times compared with the upper limit of normal) of unknown origin; hepatic failure (severity and scale of child-Pyuga);
• women of reproductive age not using adequate contraceptive methods.

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

Side effects

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 oral cavity, gastroenteritis, hepatitis, biliary colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, liver dysfunction, melena, bleeding gums, tenesmus.

Respiratory system:  in more than 2% of cases — bronchitis, rhinitis; less often-pneumonia, dyspnoea, bronchial asthma, nosebleeds.

The nervous system:  in more than 2% of cases — insomnia, dizziness; in 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, joint contractures, neck muscle rigidity, rhabdomyolysis.

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

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

Genitourinary 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), 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, eye hemorrhage, deafness, increased intraocular pressure, parosmia, taste distortion, loss of taste sensations.

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.

The 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), albuminuria.

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

Interaction

Antacids:  when atorvastatin is co-administered with antacids in the form of a suspension containing magnesium and aluminum hydroxide, the concentration of atorvastatin in blood plasma decreases by approximately 35%, while the degree of reduction in LDL cholesterol remains unchanged.

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

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

Erythromycin:  with simultaneous use of atorvastatin and erythromycin, which has an inhibitory effect on cytochrome P450 CYP3A4, the concentration of atorvastatin in blood plasma increases by approximately 40%.

Oral contraceptives:  when atorvastatin is co-administered with oral contraceptives, the AUC values increase by approximately 30% for norethisterone and 20% for ethinyl estradiol.These data should be taken into account when selecting contraceptives for patients taking atorvastatin.

Warfarin: in patients taking 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 indicator normalizes. After prescribing atorvastatin, patients taking warfarin should be monitored for PV more often than usual.

Concomitant use of cyclosporine, fibrates, clarithromycin, antifungal drugs (related to azoles) and nicotinamide increases the concentration of atorvastatin in blood plasma (risk of myopathy).

How to take, course of use and dosage

Before starting treatment, the patient should be switched to a low-cholesterol diet. Inside, at any time of the day, regardless of food intake.

The dose of the drug is varied from 10 to 80 mg once a day, choosing it taking into account the initial levels of LDL-C, the purpose of therapy and the 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. Then the dose is individually selected, which is 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 starting treatment and/or selecting the dose of Tulip®, the blood lipid level should be determined and the dose of the drug adjusted accordingly.

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

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

Dosages for patients with renal insufficiency. If the patient has kidney disease, the concentration of atorvastatin in blood plasma and its effect on LDL cholesterol do not change. Therefore, no dose adjustment is required for patients with kidney disease.

Dosages for patients with hepatic insufficiency. In patients with impaired liver function, caution should be exercised in connection with slowing the 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 should be discontinued.

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

Overdose

There is no specific treatment for overdose with Tulipom.

Treatment is symptomatic; measures are taken to maintain vital functions and prevent further absorption of the drug (gastric lavage, taking activated charcoal).

Due to the fact that the drug actively binds to plasma proteins, hemodialysis does not seem to be an effective way to speed up its elimination from the body.

Special instructions

Impaired liver function. 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 treatment,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 within the first three months after starting Tulip®. Patients with elevated transaminase levels should be monitored until their enzyme levels return to normal. In the event that the ALT or AST values are more than 3 times higher than the upper permissible limit, it is recommended to reduce the dose of Tulip® or discontinue treatment.

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

When prescribing concomitant therapy with Tulip® and cyclosporine, fibric acid derivatives, erythromycin, clarithromycin, immunosuppressants and azole-based antifungal drugs, as well as lipid-lowering doses of niacin, it is necessary to compare the potential benefits and risks of this treatment and monitor patients who show signs or symptoms of muscle pain, lethargy or weakness, especially during the first months of treatment and when increasing the dose of any of the drugs.

Treatment with Tulip® should be temporarily suspended or discontinued if a serious condition develops that may result from myopathy, as well as if there are 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 disorders, as well as electrolyte balance disorders).

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

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

Toolip® it does not affect the ability to drive a car and mechanisms.

Form of production

Film-coated tablets

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

2 years

Active ingredient

Atorvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Atherosclerosis, Prevention of heart attacks and strokes