Tulip pills 10mg №30

Indications

- in combination with a cholesterol-lowering diet to reduce elevated concentrations of total Xc, Xc-LDL, apo-B and TG and increase the concentration of Xc-HDL in patients with primary hypercholesterolemia, heterozygous familial and non-familial hypercholesterolemia and combined (mixed) hyperlipidemia (type IIa) according to the Fredrickson classification), when diet therapy and other non-pharmacological treatment methods are not sufficiently effective;

- to reduce the concentration of total CS and LDL-LDL in patients with homozygous familial hypercholesterolemia, when diet therapy and other non-pharmacological treatment methods are not sufficiently effective;

- primary prevention of cardiovascular complications in patients without clinical signs of CHD, but having several risk factors for its development: age over 55 years old, nicotine dependence, arterial hypertension, diabetes mellitus, retinopathy, albuminuria, low concentrations of HDL-C HDL, genetic predisposition, incl. against dyslipidemia;

- secondary prevention of cardiovascular complications in patients with coronary artery disease in order to reduce the overall mortality rate, myocardial infarction, stroke, re-hospitalization for angina and the need for revascularization.

Dosage and administration

Before starting to use the drug Tulip ^® the patient should be recommended a standard cholesterol-lowering diet, which he must continue to follow throughout the entire period of drug therapy.

It is recommended to use the drug Tulip^® inside regardless of meal times. Tulip dose^® varies from 10 mg to 80 mg per day, and is selected based on the initial concentration of Xc-LDL, the goal of therapy and the individual therapeutic response to the therapy.

For most patients, the initial dose is 10 mg 1 time / day.

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

The maximum daily dose is 80 mg / day.

Primary (heterozygous hereditary and polygenic) hypercholesterolemia (type IIa) and mixed hyperlipidemia (type IIb)

In most cases, it is enough to use a dose of 10 mg 1 time / day. If necessary, a gradual increase in the dose to 80 mg is possible, depending on the response of the patient with an interval of 2-4 weeks, since the therapeutic effect is observed after 2 weeks, and the maximum therapeutic effect after 4 weeks. With long-term treatment, this effect persists.

Homozygous hereditary hypercholesterolemia

Tulip drug^® used in a daily dose of 10 to 80 mg 3 times / day.

Prevention of the development of cardiovascular diseases

Tulip^® used at a dose of 10 mg 1 time / day. If the optimal concentration of LDL in plasma is not reached, an increase in the dose of the drug to 80 mg / day is possible, depending on the response of the patient with an interval of 2-4 weeks.

Correction dose of the drug Tulip^® at patients with impaired renal function and in elderly patients not required.

Have patients with impaired liver function slowing the elimination of the drug Tulip^® from the body, so it is recommended to use it with caution with constant monitoring of the activity of hepatic transaminases: ACT and ALT. If the observed increase in the activity of ACT or ALT is more than 3 times compared with VGN is maintained, a dose reduction or withdrawal of the drug Tulip is recommended.^®.

Adverse effects

According to WHO, undesirable effects are classified according to their frequency of development as follows: often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10 000, < 1/1000) and very rarely (<1/10 000), including individual messages.

From the central and peripheral nervous system: often - headache; infrequently - dizziness, insomnia, asthenic syndrome, malaise, weakness, paresthesia, hypoesthesia, amnesia, nightmarish dreams; rarely, peripheral neuropathy.

From the digestive tract: often - constipation, flatulence, dyspepsia, nausea, diarrhea; infrequently - anorexia, vomiting, pancreatitis, hepatitis, abdominal pain; rarely - cholestatic jaundice (including obstructive); very rarely - liver failure.

Musculoskeletal system: often - myalgia, arthralgia, pain in the joints, back pain; infrequently - muscle cramps, pain in the muscles of the neck; rarely - myopathy, myositis, rhabdomyolysis, tendinopathy (sometimes complicated by tendon rupture).

From the senses: infrequently - tinnitus, blurred vision; very rarely - hearing loss.

From the skin and subcutaneous fat: infrequently - urticaria, skin rash and itching, allergic reactions, alopecia; rarely - angioedema, bullous rash, polymorphic exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

On the part of the endocrine system: often - hyperglycemia, increased activity of serum CPK, increased activity of hepatic transaminases; infrequently - hypoglycemia.

From the side of blood-forming organs: infrequently - thrombocytopenia.

Other: often - sore throat, nosebleeds, peripheral edema; infrequently - increased fatigue, weight gain, impaired potency, secondary renal failure, fever, chest pain; very rarely - gynecomastia, diabetes. There are separate reports on the development of atonic fasciitis (the association with the use of Atorvastatin has not been precisely established). The frequency is unknown - sexual dysfunction, depression, interstitial lung disease (especially with long-term therapy).

Contraindications

- liver disease in the active stage or increased activity of hepatic transaminases in the blood plasma (more than 3 times compared with VGN) of unclear genesis;

- pregnancy;

- lactation period;

- age up to 18 years (efficiency and safety have not been established);

- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (because the composition contains lactose);

- Hypersensitivity to atorvastatin and other auxiliary components of the drug.

WITH caution

Alcohol abuse, a history of liver diseases, muscular system diseases (in history from the use of other members of the HMG-CoA reductase inhibitor group), severe electrolyte imbalances, endocrine (hyperthyroidism) and metabolic disorders, arterial hypotension, high risk of developing diabetes, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgical interventions, injuries, aggressive lipid-lowering therapy (atorvastatin 80 mg) for secondary prevention of insul in patients with a hemorrhagic or lacunar stroke in history.

Use during pregnancy and lactation

Tulip drug^® contraindicated during pregnancy. Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of inhibition of HMG-CoA reductase exceeds the benefits of using the drug during pregnancy.

In the case of diagnosing pregnancy in the course of therapy with Tulip^®, its reception should be stopped as soon as possible, and the patient is 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 during breastfeeding, if necessary, the use of the drug Tulip^® during lactation, breastfeeding should be discontinued.

Application for violations of the liver

Patients with impaired liver function the drug is prescribed with caution in connection with the slowdown of its elimination from the body. In this situation, control of clinical and laboratory parameters is shown, and if significant pathological changes are detected, the dose should be reduced or treatment should be discontinued.

Application for violations of kidney function

Patients with impaired renal function correction dosage is not required.

Use in children

Contraindicated in children and adolescents under 18 years of age (efficacy and safety have not been established).

special instructions

As with the use of other inhibitors of HMG-Co-reductase (statins), during therapy with Tulip^® perhaps a moderate (more than 3 times compared with VGN) increase in serum activity of hepatic transaminases: ACT and ALT.

Before the start of therapy, after 6 weeks and 12 weeks after the start of taking Tulip^® or after increasing its dose, it is necessary to monitor indicators of liver function (ACT, ALT).Liver function should also be monitored when clinical signs of liver damage appear. In the case of increased activity of ACT and ALT, their activity should be monitored until it normalizes. If the observed increase in the activity of ACTi or ALT is more than 3 times as compared with VGN is maintained, a dose reduction or withdrawal of the drug Tulip is recommended.^®.

Tulip^® It 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 increased activity of hepatic transaminases of blood plasma of unknown origin are a contraindication for the use of the drug Tulip^®.

Action on skeletal muscle

When using the drug Tulip^®may develop myalgia. The diagnosis of myopathy (pain and weakness in the muscles in combination with an increase in the activity of CPK more than 10 times compared with VGN) may be suggested in patients with diffuse myalgia, muscle soreness or weakness and / or a pronounced increase in the activity of CPK. Therapy with Tulip^® should be stopped in case of a pronounced increase in the activity of CPK or in the presence of confirmed or suspected myopathy.

The use of other HMG-Co-reductase inhibitors (statins) may increase the risk of myopathy while using it with cyclosporine, fibrates, Erythromycin, nicotinic acid in lipid-lowering doses (more than 1 g / day) or azole antifungal drugs. Using the drug Tulip^® in combination with fibrates, erythromycin, immunosuppressants, azole antifungal drugs or nicotinic acid in lipid-lowering doses (more than 1 g / day), it is necessary to weigh the expected benefit and risk from treatment with Tulip^®.

If necessary, combination therapy should consider the possibility of using these drugs in lower initial and maintenance doses.

Periodic monitoring of CPK activity and serum glucose concentration is recommended.

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

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

If symptoms of possible myopathy appear or there is a risk factor for the development of renal failure in the presence of rhabdomyolysis (for example, severe acute infection, arterial hypotension, extensive surgical intervention, trauma, serious metabolic, electrolyte and endocrine disorders and uncontrolled seizures), Tulip preparation^® should be suspended or completely canceled.

Special precautions when disposing of unused medication

No need for special precautions when destroying unused Tulip^®.

Influence on ability to drive motor transport and control mechanisms

During the period of treatment with Tulip^® Care must be taken when driving and engaging in other potentially hazardous activities that require increased concentration and psychomotor speed.

Overdose

There is no specific antidote for the treatment of overdose.

In case of overdose, symptomatic treatment should be carried out. Hemodialysis is not effective (because the drug is significantly associated with plasma proteins).

Drug interaction

The risk of myopathy during treatment with HMG-CoA reductase inhibitors increases while being used with cyclosporine, erythromycin, Clarithromycin, immunosuppressive, antifungal drugs (azole derivatives) due to a possible increase in serum atorvastatin concentrations.

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

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

Inhibitors of the isoenzyme CYP3A4

Since atorvastatin is metabolized by the isoenzyme CYP3A4, the joint use of the drug Tulip^® with inhibitors of this isoenzyme can lead to an increase in plasma atorvastatin concentrations. The degree of interaction and the effect of increasing the concentration of atorvastatin are determined by the variability of exposure to the CYP3A4 isoenzyme.

Inhibitors of the transport protein OATP1B1

Atorvastatin and its metabolites are substrates of the transport protein OATP1B1. OATR1B1 inhibitors (for example, cyclosporin) can increase the bioavailability of atorvastatin. Thus, the use of atorvastatin at a dose of 10 mg and cyclosporine at a dose of 5.2 mg / kg / day leads to an increase in the concentration of atorvastatin in the blood plasma 7.7 times.

Erythromycin / clarithromycin

With simultaneous use of atorvastatin 10 mg and erythromycin (500 mg 4 times / day) or clarithromycin (500 mg 2 times / day), which inhibit the cytochrome CYP3A4 isoenzyme, plasma concentrations of atorvastatin are increased (by 40% when used with erythromycin and 56% when used with clarithromycin).

Protease inhibitors

The simultaneous use of atorvastatin with protease inhibitors, known as inhibitors of cytochrome CYP3A4 isoenzyme, is accompanied by an increase in plasma concentrations of atorvastatin (with simultaneous use with erythromycin - C_max atorvastatin is increased by 40%).

Diltiazem

The combined use of atorvastatin at a dose of 40 mg with diltiazem at a dose of 240 mg leads to an increase in plasma atorvastatin concentration.

Cimetidine

Clinically significant interaction of atorvastatin with cimetidine was not detected.

Itraconazole

The simultaneous use of atorvastatin in doses of 20 mg to 40 mg and itraconazole at a dose of 200 mg leads to a 3-fold increase in the value of the AUC of atorvastatin.

Grapefruit juice

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

Inductors of isoenzyme CYP3A4

The combined use of atorvastatin with inducers of the isoenzyme SURZA4 (for example, efavirenz or rifampicin) can lead to a decrease in plasma levels of atorvastatin. Due to the dual mechanism of interaction with rifampicin (CYP3A4 isoenzyme inducer and hepatocyte transport protein inhibitor OATP1B1), simultaneous use of atorvastatin and rifampicin is not recommended, since delayed atorvastatin administration after taking rifampicin leads to a significant decrease in atorvastatin concentration in the blood plasma.

Antacids

With simultaneous oral administration of atorvastatin and a suspension containing Magnesium and aluminum hydroxides, the concentration of atorvastatin in plasma decreases by approximately 35%, however, the degree of decrease in the concentration of Xc-LDL does not change.

Phenazole

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

Colestipol

The hypolipidemic effect of the combination with colestipol is superior to that for each drug separately, despite the decrease in the concentration of atorvastatin by 25% with its simultaneous use with colestipol.

Digoxin

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

Azithromycin

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

Oral contraceptives

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

Terfenadine

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

Warfarin

In patients who take Warfarin for a long time, atorvastatin at a dose of 80 mg / day shortens the prothrombin time somewhat in the first days of combined use.This effect disappears after 15 days of simultaneous use of these drugs.

Amlodipine

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

Other lipid-lowering drugs

With simultaneous use of atorvastatin with other lipid-lowering drugs (for example, ezetimib, gemfibrozil, a derivative of fibric acid) in lipid-lowering doses increases the risk of developing rhabdomyolysis.

Other concomitant therapy

With the joint use of atorvastatin with antihypertensive drugs and estrogen (as a replacement therapy) - clinically significant interaction was not detected.

Terms and conditions of storage

The drug should be stored out of the reach of children at a temperature not higher than 25 ° C.