Tulip - instructions for use, analogs, reviews and release forms (tablets 10 mg, 20 mg and 40 mg) of the statin drug for the treatment of hypercholesterolemia and blood cholesterol lowering in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Tulip. There are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Tulip in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Tulip in the presence of existing structural analogues.The use of statin for the treatment of hypercholesterolemia and the reduction of cholesterol in the blood in adults, children, as well as during pregnancy and lactation. Composition of the preparation.

 

Tulip - a hypolipidemic agent.

 

Atorvastatin (the active substance of Tulip) is 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 (Xc) are included in the composition of very low density lipoproteins (VLDL) in liver synthesis, 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.

 

Studies have shown that an increase in the concentrations of total cholesterol, LDL, and apolipoprotein B (apo-B) in the blood plasma contributes to the development of atherosclerosis and is part of a group of risk factors for cardiovascular disease, while an increase in the concentration of high-density lipoprotein (HDL) reduces the risk development of cardiovascular diseases.

 

Atorvastatin reduces the concentration of Xs 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 "hepatic" LDL receptors on the cell surface, which leads to an increase in the capture and catabolism of LDL (according to preclinical research).

 

Atorvastatin reduces the synthesis and concentration of Xc-LDL, total Xc, apo-B in patients with homozygous and heterozygous familial hypercholesterolemia, primary hypercholesterolemia and mixed hyperlipidemia.

 

It also causes a decrease in the concentration of cholesterol-VLDL and TG and an increase in the concentration of cholesterol-HDL and apolipoprotein A-1 (apo-A).

 

In patients with disbetalipoproteinemia, the concentration of intermediate-density lipoproteins is decreased.

 

Atorvastatin in doses of 10 mg and 20 mg reduces the concentration of total cholesterol by 29% and 33%, LDL by 39% and 43%, apo-B by 32% and 35% and TG by 14% and 26%, respectively; causes an increase in the concentration of cholesterol-HDL and apo-A.

 

Atorvastatin in doses of 40 mg reduces the concentration of total XC by 37%, LDL by 50%, apo-B by 42% and TG by 29%; causes an increase in the concentration of Xc-HDL and apo-A.

 

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

 

Does not have a carcinogenic and mutagenic effect.

 

The therapeutic effect develops 2 weeks after the initiation of therapy, reaches a maximum after 4 weeks, and persists throughout the treatment period.

 

Composition

 

Atorvastatin (in the form of Atorvastatin calcium) + auxiliary substances.

 

Pharmacokinetics

 

Absorption is high. Cmax in the blood plasma after ingestion is achieved after 1-2 hours. Food intake somewhat reduces the rate and extent of absorption of the drug (by 25% and 9%, respectively), but the decrease in X-LDL is similar to that with atorvastatin without simultaneous ingestion. After ingestion of atorvastatin in the evening, its concentration in the blood plasma is lower (Cmax and AUC approximately 30%) than after taking in the morning, whereas the decrease in the concentration of LDL-C is independent of the time of day of the drug. A linear relationship between the degree of absorption and the dose of the drug has been revealed. Bioavailability is 12-14%, the systemic bioavailability of inhibitory activity against HMG-CoA reductase is about 30%. Low systemic bioavailability is due to the presystemic metabolism in the gastrointestinal tract and the effect of the first passage through the liver.The ratio of atorvastatin concentration in erythrocytes / plasma is about 0.25, which indicates a poor penetration of atorvastatin into erythrocytes.

 

Atorvastatin is metabolized predominantly in the liver under the action of isoenzymes CYP3A4, CYP3A5 and CYP3A7 with the formation of pharmacologically active metabolites (ortho- and parahydroxylated derivatives, beta-oxidation products). In vitro, ortho- and parahydroxylated 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, which persists for about 20-30 hours, due to their presence.

 

It is derived mainly through the intestine after hepatic and / or extrahepatic metabolism (the drug is not subjected to severe intestinal hepatic recirculation). Less than 2% of the dose taken internally is determined in urine. It is not excreted during hemodialysis due to intensive binding to blood plasma proteins.

 

Pharmacokinetics in special clinical cases

 

In females Cmax is higher by 20%, AUC is lower by 10% than in men, which has no clinical significance.

 

In patients with alcoholic cirrhosis (class B on the Child-Pugh scale), the liver Cmax is 16 times, and the AUC is 11 times higher than normal.

 

Cmax and AUC in elderly patients (over 65 years) are 40% and 30% higher, respectively, than in young patients, but this does not affect the degree of lowering LDL cholesterol.

 

Impaired renal function does not affect the concentration of the drug in the blood plasma, the degree of decrease in LDL cholesterol.

 

Indications

• in combination with a hypocholesterolemic diet to reduce elevated concentrations of total XC, Xc-LDL, apo-B and TG, and an increase in HDL-C concentration in patients with primary hypercholesterolemia, heterozygous familial and non-family hypercholesterolemia, and combined (mixed) hyperlipidemia (type 2a and 2b by classification Fredrickson), when dietetics and other non-pharmacological methods of treatment are not effective enough;
• to reduce the concentration of total Xc and Xc-LDL in patients with homozygous familial hypercholesterolemia, when diet therapy and other non-pharmacological treatments are not effective enough;
• primary prevention of cardiovascular complications in patients without clinical signs of IHD,but having several risk factors for its development: age over 55, nicotine dependence, arterial hypertension, diabetes mellitus, retinopathy, albuminuria, low concentrations of HDL-C in the blood plasma, genetic predisposition, incl. against dyslipidemia;
• secondary prophylaxis of cardiovascular complications in patients with ischemic heart disease in order to reduce the total death rate, myocardial infarction, stroke, re-hospitalization for angina pectoris and the need for revascularization.

 

Forms of release

 

Tablets coated with 10 mg, 20 mg and 40 mg.

 

Instructions for use and dosage

 

Before starting the Tulip drug, the patient should be recommended a standard hypocholesterolemic diet, which he must continue to observe during the entire period of therapy with the drug.

 

The drug is taken orally regardless of the time of ingestion. The dose of Tulip drug varies from 10 mg to 80 mg per day, and is selected taking into account the initial concentrations of LDL-C, the purpose of therapy and individual therapeutic response to the therapy.

 

For most patients, the initial dose is 10 mg once a day.

 

At the beginning of treatment, after 2-4 weeks of therapy and / or after increasing the dose of Tulip, it is necessary to monitor the concentration of lipids in the blood plasma and, if necessary, adjust the dose of the drug.

 

The maximum daily dose is 80 mg per day.

 

Primary (heterozygous hereditary and polygenic) hypercholesterolemia (type 2a) and mixed hyperlipidemia (type 2b)

 

In most cases, it is enough to use the drug Tulip in a dose of 10 mg 1 time per day (atorvastatin can be used in tablets of 10 and 20 mg). If necessary, it is possible to gradually increase the dose to 80 mg (2 tablets of 40 mg), depending on the patient's response at 2-4 weeks intervals, since the therapeutic effect occurs after 2 weeks, and the maximum therapeutic effect after 4 weeks. With prolonged treatment, this effect persists.

 

Homozygous hereditary hypercholesterolemia

 

The drug Tulip in most cases used in a dose of 80 mg (2 tablets of 40 mg) once a day.

 

Prevention of cardiovascular disease

 

Tulip is used in a dose of 10 mg once a day. If the optimal concentration of LDL in the plasma is not achieved, an increase in the dose of the drug to 80 mg per day is possible, depending on the patient's reaction with an interval of 2-4 weeks.

 

Side effect

• allergic reactions;
• anaphylaxis;
• headache;
• dizziness;
• sleep disorders, including insomnia and nightmares;
• asthenic syndrome;
• weakness;
• paresthesia;
• hypoesthesia;
• a violation of taste sensitivity;
• loss or loss of memory;
• peripheral neuropathy;
• noise in ears;
• blurred vision;
• impaired vision;
• loss of hearing;
• constipation, diarrhea;
• flatulence;
• dyspepsia;
• nausea, vomiting;
• anorexia;
• pancreatitis;
• hepatitis;
• abdominal pain;
• eructation;
• Cholestatic jaundice (including obstructive);
• liver failure;
• myalgia;
• arthralgia;
• swelling of the joints;
• joint pain;
• backache;
• muscular spasm;
• pain in the muscles of the neck;
• muscle weakness;
• myopathy;
• myositis;
• rhabdomyolysis;
• tendinopathy (sometimes complicated by a ruptured tendon);
• immuno-mediated necrotizing myopathy;
• hives;
• skin rash and itching;
• alopecia;
• angioedema;
• bullous rash;
• multi-form exudative erythema (including Stevens-Johnson syndrome);
• toxic epidermal necrolysis (Lyell's syndrome);
• hyperglycemia, hypoglycemia;
• thrombocytopenia;
• nasopharyngitis;
• a sore throat;
• nose bleed;
• leukocyturia;
• increase in the concentration of glycosylated hemoglobin;
• increased fatigue;
• depression;
• violation of potency;
• sexual dysfunction;
• secondary renal failure;
• increased body temperature;
• chest pain;
• peripheral edema;
• increase in body weight;
• gynecomastia;
• diabetes;
• interstitial lung disease (especially with prolonged therapy).

 

Contraindications

• liver disease in the active stage or an increase in the activity of hepatic transaminases in blood plasma (more than 3 times as compared with VGN) of an unknown genesis;
• pregnancy;
• lactation period;
• age under 18 years (effectiveness and safety not established);
• deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome (because the composition contains lactose);
• increased sensitivity to atorvastatin and other auxiliary components of the drug.

 

Application in pregnancy and lactation

 

The drug Tulip 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.

 

In case of diagnosing pregnancy during treatment with Tulip, its reception should be stopped as soon as possible, and the patient should be warned about the potential risk to the fetus.

 

Tulip drug can be used in women of reproductive age only if the probability of pregnancy is very low, and the patient is informed of the possible risk to the fetus during treatment.

 

Women of reproductive age during treatment with Tulip should use reliable methods of contraception.

 

Atorvastatin is excreted in breast milk, therefore it is contraindicated for use in the period of breastfeeding. If you need to use Tulip during lactation breastfeeding should be discontinued.

 

Use in children

 

Contraindicated in childhood and adolescence under 18 years (efficacy and safety not established).

 

special instructions

 

Effects on the liver

 

As with the use of other inhibitors of HMG-Co-reductase (statins), in the treatment with Tulip, a moderate (more than 3-fold compared to HGV) increase in the serum activity of hepatic transaminases: ACT and ALT.

 

Before the start of therapy, after 6 weeks and 12 weeks after starting the Tulip drug or after increasing its dose, it is necessary to monitor the liver function (ACT, ALT). The liver function should also be monitored when there are clinical signs of liver damage. In the case of increased activity of ACT and ALT, their activity should be monitored until it is normalized. Tulip should be used with caution in patients who abuse alcohol and / or have a history of liver disease.

 

Diseases of the liver in the active stage or an increase in the activity of hepatic transaminases of blood plasma of unknown origin are contraindication for the use of Tulip.

 

Prevention of stroke with intensive lipid-lowering therapy (SPARCL)

 

In a retrospective analysis of the various subspecies of stroke in non-CHD patients who recently suffered a stroke or transient ischemic attack (TIA), a higher risk of hemorrhagic stroke was found in patients taking atorvastatin 80 mg compared with placebo. Especially high risk was observed in patients who had hemorrhagic stroke or lacunar infarction at the time of the beginning of the study.For patients who underwent hemorrhagic stroke or lacunar infarction and taking atorvastatin at a dose of 80 mg, the risk / benefit ratio is ambiguous, and the potential risk of hemorrhagic stroke should be carefully assessed before treatment begins.

 

Action on skeletal muscles

 

With the use of Tulip, the development of myalgia is possible. The diagnosis of myopathy (pain and weakness in muscles in combination with an increase in CKK activity by more than 10 times compared to IGN) is possible in patients with diffuse myalgia, muscle soreness or weakness, and / or a marked increase in CKK activity. Therapy with Tulip should be discontinued in the event of a marked increase in the activity of CKK or in the presence of confirmed or suspected myopathy.

 

When using other inhibitors of HMG-Co-reductase (statins), an increase in the risk of myopathy can be possible with simultaneous application with cyclosporine, fibrates, erythromycin, nicotinic acid in lipid-lowering doses (more than 1 g per day) or antifungal agents of the azole group. Applying the drug Tulip in combination with fibrates, erythromycin, immunosuppressants,antifungal drugs of the azole group or nicotinic acid in lipid-lowering doses (more than 1 g per day), it is necessary to weigh the expected benefit and risk from treatment with Tulip.

 

Very rarely reported cases of immunosupplemented necrotizing myopathy during or after treatment with statins, including atorvastatin. Immuno-mediated necrotizing myopathy is clinically characterized by muscle weakness in the upper limbs and increased concentration of CK of plasma, which persists despite the cessation of statin treatment.

 

If combination therapy is required, the use of these drugs in lower initial and maintenance doses should be considered. Periodic monitoring of the activity of CK is recommended.

 

The combined use of atorvastatin and fusidic acid is not recommended, therefore, a temporary discontinuation of therapy with atorvastatin during the administration of fusidic acid should be considered.

 

Patients should be warned that they should immediately consult a doctor if unexplained pain or muscle weakness occurs, especially if they are accompanied by a malaise or fever.

 

In applying the drug Tulip, as well as other HMG-Co reductase inhibitors (statins) are described rare cases of rhabdomyolysis with acute renal failure caused by myoglobinuria.

 

If you have symptoms of possible myopathy or presence of renal failure factor risk against the background of rhabdomyolysis (eg, severe acute infection, hypotension, major surgery, trauma, severe metabolic, electrolyte and endocrine disorders, and uncontrolled seizures) therapy with Tulip should suspend or cancel .

 

Interstitial lung disease

 

It reported only rare cases of interstitial lung disease with the use of some statins, especially with long-term therapy. Clinical manifestations include dyspnea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). In case of suspected development of interstitial lung disease, treatment with statins should be discontinued.

 

Diabetes

 

Data from some studies suggest that the use of statins, as a class,can lead to an increase in blood glucose, and in some patients with an increased risk of developing diabetes in the future can cause hyperglycemia, which requires standard antidiabetic therapy. However, such a risk is insignificant compared with a reduction in the risk of vascular risk when taking statins, and therefore should not be the reason for the abolition of statin treatment. Patients in the risk group (with a fasting glucose concentration of 5.6-6.9 mmol / L, a BMI greater than 30 kg / m2, elevated triglycerides, elevated blood pressure) should be monitored, both clinically and biochemically, in accordance with national standards for medical care .

 

Impact on the ability to drive vehicles and manage mechanisms

 

During treatment with Tulip, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

 

Drug Interactions

 

The risk of myopathy during treatment with HMG-CoA reductase inhibitors increases with simultaneous use with cyclosporine, erythromycin,clarithromycin, immunosuppressive, antifungal agents (azole derivatives) due to a possible increase in the concentration of atorvastatin in the blood serum.

 

When used simultaneously with HIV protease inhibitors - indinavir, ritonavir - the risk of myopathy increases.

 

A similar interaction is possible with the simultaneous use of atorvastatin with fibrates and nicotinic acid in lipid-lowering doses (more than 1 g per day).

 

Inhibitors of the isoenzyme CYP3A4

 

Since atorvastatin is metabolized by the CYP3A4 isoenzyme, the combined use of Tulip with inhibitors of this isoenzyme can lead to an increase in the concentration of atorvastatin in the blood plasma. The degree of interaction and the effect of increasing the concentration of atorvastatin are determined by the variability of the effect on the isoenzyme CYP3A4.

 

Inhibitors of transport protein OATP1B1

 

Atorvastatin and its metabolites are substrates of the transport protein OATP1B1. Inhibitors of OATP1B1 (eg, cyclosporin) may increase the bioavailability of atorvastatin. Thus, the use of atorvastatin in a dose of 10 mg and cyclosporine at a dose of 5.2 mg / kg per day leads to an increase in the concentration of atorvastatin in blood plasma by 7.7 times.

 

Erythromycin / clarithromycin

 

With simultaneous use of atorvastatin 10 mg and Erythromycin (500 mg 4 times a day) or Clarithromycin (500 mg twice a day), which inhibit the cytochrome CYP3A4 isoenzyme, an increase in the concentration of atorvastatin in blood plasma (by 40% - when used with erythromycin and 56% - when applied with clarithromycin).

 

Inhibitors of proteases

 

Simultaneous use of atorvastatin with protease inhibitors, known as cytochrome CYP3A4 isoenzyme inhibitors, is accompanied by an increase in the concentration of atorvastatin in the blood plasma (with simultaneous application with erythromycin-Cmax, atorvastatin is increased by 40%).

 

Diltiazem

 

Joint application of Tulip in a dose of 40 mg with diltiazem in a dose of 240 mg leads to an increase in the concentration of atorvastatin in blood plasma.

 

Cimetidine

 

Clinically significant interaction of atorvastatin with cimetidine was not revealed.

 

Itraconazole

 

Simultaneous use of atorvastatin in doses of 20 mg to 40 mg and Itraconazole at a dose of 200 mg conducts to a 3-fold increase in the value of AUC atorvastatin.

 

Grapefruit juice

 

Since grapefruit juice contains one or more components that inhibit the CYP3A4 isoenzyme, its excessive intake (more than 1.2 liters per day for 5 days) can cause an increase in the concentration of atorvastatin in the blood plasma.

 

Inductors of the isoenzyme CYP3A4

 

The combined use of atorvastatin with inducers of the isoenzyme SURDA4 (eg, efavirenz or rifampicin) can lead to a decrease in the concentration of atorvastatin in the blood plasma. Due to the dual mechanism of interaction with rifampicin (inducer of the isoenzyme CYP3A4 and the inhibitor of the hepatocyte transport protein OATP1B1), simultaneous use of atorvastatin and rifampicin is not recommended, since delayed administration of atorvastatin after taking rifampicin results in a significant decrease in the concentration of atorvastatin in the blood plasma.

 

Antacids

 

With simultaneous administration of Tulip and a suspension containing magnesium and aluminum hydroxides, the concentration of atorvastatin in the plasma is reduced by about 35%, but the degree of decrease in the concentration of LDL-C is not changed.

 

Fenazone

 

Atorvastatin does not affect the pharmacokinetics of phenazone, therefore interaction with other drugs metabolized by the same isoenzymes is not expected.

 

Kolestypol

 

The lipid-lowering effect of the combination with colestipol is greater than that of each drug alone, despite a decrease in the concentration of atorvastatin by 25% with its simultaneous application with colestipol.

 

Fusidic acid

 

Studies on the interaction of Tulip and fusidic acid have not been conducted. As in the case of other statins, post-marketing studies of combined use of atorvastatin and fusidic acid reported side effects on muscles, including rhabdomyolysis. The mechanism of interaction is unknown. Such patients require careful follow-up and, possibly, a temporary discontinuation of atorvastatin.

 

Colchicine

 

Although studies of the interaction of atorvastatin and colchicine have not been carried out, cases of myopathy have been reported when combined with colchicine, and caution should be exercised when atorvastatin and colchicine are given concomitantly.

 

Digoxin

 

When repeated use of Digoxin and atorvastatin in a dose of 10 mg of Css digoxin in the blood plasma does not change. However, when using digoxin in combination with atorvastatin at a dose of 80 mg per day, the concentration of digoxin in the blood plasma increases by approximately 20%. Patients taking digoxin in combination with atorvastatin require control of digoxin concentration in the blood plasma.

 

Azithromycin

 

With the simultaneous use of atorvastatin at a dose of 10 mg 1 time per day and Azithromycin at a dose of 500 mg once a day, the concentration of atorvastatin in the blood plasma does not change.

 

Oral contraceptives

 

With the simultaneous use of atorvastatin and an oral contraceptive containing norethisterone and ethinylestradiol, there is a significant increase in the AUC of norethisterone and ethinylestradiol by about 30% and 20%, respectively, which should be considered when choosing an oral contraceptive.

 

Terfenadine

 

Atorvastatin with simultaneous application with terfenadine does not have a clinically significant effect on the pharmacokinetics of terfenadine.

 

Warfarin

 

In patients who take long-acting warfarin, atorvastatin at a dose of 80 mg per day somewhat shortens prothrombin time in the early days of joint use. This effect disappears after 15 days of simultaneous application of these drugs. Although very rarely reported clinically significant changes in the anticoagulant effect, prothrombin time should be determined in patients taking coumarin anticoagulants before and often at the beginning of atorvastatin treatment to ensure no significant changes in prothrombin time. Once a stable prothrombin time is recorded, it can be checked at intervals common to patients,taking coumarin anticoagulants. When changing the dose or discontinuing treatment, these measures should be repeated. There was no association between the use of atorvastatin and bleeding or a change in prothrombin time in patients not taking anticoagulants.

 

Amlodipine

 

With the simultaneous use of atorvastatin in a dose of 80 mg and Amlodipine at a dose of 10 mg, the pharmacokinetics of atorvastatin in the equilibrium state does not change.

 

Other lipid-lowering drugs

 

With the simultaneous use of Tulip with other lipid-lowering medications (for example, ezetimibe, gemfibrozil, fibrolic acid derivative) in lipid-lowering doses, the risk of rhabdomyolysis increases.

 

Other concomitant therapy

 

With the simultaneous use of atorvastatin with antihypertensive agents and estrogens (as a substitute therapy), no clinically significant interaction has been identified.

 

Analogues of drug Tulip

 

Structural analogs for the active substance:

• Anistat;
• Atokord;
• Atomax;
• Ator;
• Atorvastatin;
• Atorvastatin calcium;
• Atorvastatin calcium trihydrate;
• Atorvox;
• Atoris;
• The Vasator;
• Lipon;
• Lipofford;
• Liprimar;
• Liptonorm;
• Novostat;
• TG tor;
• Torvacard;
• Torvalip;
• Torvas.

 

Analogues for the pharmacological group (statins):

• Akorta;
• Aktalipid;
• Apexstatin;
• Atherostat;
• Atorvastatin;
• Vazilip;
• Zocor;
• Zokor forte;
• Zorstat;
• Cardiostatin;
• The Cross;
• Leskol;
• Leskol Fort;
• Lipobay;
• Lipopraim;
• Lipostat;
• Lovacor;
• Lovastatin;
• Lovasterol;
• Mevakor;
• Medostatin;
• Mertenil;
• Ovenkor;
• Pravastatin;
• Ro-statin;
• Rovacor;
• Rosart;
• Rosystark;
• Rosuvastatin;
• Rosewood;
• Rosulip;
• Roxer;
• Rustor;
• Simva Hexal;
• Simvakol;
• Simvale;
• Simvastatin;
• Simvastol;
• Symvor;
• Simgal;
• Simlo;
• Sinquard;
• Suvardio;
• Tevastor;
• Holvasim;
• Holletar.

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