Tevastor

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Tevastor: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Instructions for the use of Tevastor: method and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Testimonials to Tevastora
19. Price of Tevastor in pharmacies

Latin name: Tevastor

ATX code: C10AA07

Active ingredient: rosuvastatin (rosuvastatin)

Manufacturer: Teva Pharmaceutical Enterprises Ltd. (TEVA Pharmaceutical Industries, Ltd.) (Israel)

Description and photo update: 2018-25-10

Tevastor is a lipid-lowering drug, a selective inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, which reduces the concentration of lipids in tissues and body fluids.

Release form and composition

Tevastor is produced in the form of film-coated tablets (10 pcs. In blisters, in a cardboard box of 3 or 9 blisters):

dosage 5 mg: round, biconvex; engraving on one side - "N", on the other side - "5"; a film shell from light yellow-orange to orange (a grayish tint is allowed), a core from almost white to white stands out at the fracture;
dosage 10 mg: round, biconvex; engraving on one side - "N", on the other side - "10"; the film membrane is from light pink to pink, at the fracture the core is distinguished from almost white to white;
dosage 20 mg: round, biconvex; engraving on one side - "N", on the other side - "20"; the film membrane is from light pink to pink, at the fracture the core is distinguished from almost white to white;
dosage 40 mg: oval, engraved on one side - "N", on the other side - "40"; the film membrane is from light pink to pink; at the fracture, a core is distinguished from almost white to white.

1 tablet at a dosage of 5 mg contains:

active ingredient: rosuvastatin in the form of rosuvastatin calcium - 5.21 mg;
auxiliary components: microcrystalline cellulose, lactose, povidone-KZO, crospovidone, sodium stearyl fumarate;
shell Opadray II 85P23426 orange: titanium dioxide (E171), partially hydrolyzed polyvinyl alcohol, talc, macrogol-3350, black iron oxide dye (E172), yellow iron oxide dye (E172), sunset yellow dye (E110).

In 1 tablet at a dosage of 10; 20 or 40 mg contains:

active ingredient: rosuvastatin in the form of rosuvastatin calcium - 10.42; 20.83 or 41.67 mg;
auxiliary components: microcrystalline cellulose, lactose, povidone-KZO, crospovidone, sodium stearyl fumarate;
shell Opadray II 85P24155 pink: titanium dioxide (E171), partially hydrolyzed polyvinyl alcohol, talc, macrogol-3350, dyes - yellow iron oxide (E172), red iron oxide (E172), indigo carmine aluminum varnish (E132), azorubin aluminum varnish (E 122).

Pharmacological properties

Pharmacodynamics

The active component of Tevastor, rosuvastatin, has a hypolipidemic effect by selective competitive inhibition of HMG-CoA reductase, an enzyme that transforms 3-hydroxy-3-methylglutaryl coenzyme A into mevalonate, an intermediate in the chain of Xc (cholesterol) biosynthesis. Rosuvastatin specifically acts in the liver, inhibiting the synthesis of Xc, and also providing catabolism of LDL (low density lipoproteins), by increasing the number of their hepatic receptors on the cell surface, which increases the uptake followed by dissimilation of LDL. As a result of this efficiency, the synthesis of VLDL (very low density lipoproteins) decreases, thereby reducing the total amount of LDL and VLDL. Rosuvastatin reduces elevated levels of total cholesterol, LDL-C, TG (thyroglobulin);increases the level of HDL-cholesterol (high-density lipoprotein cholesterol), lowers the level of ApoB (apolipoprotein B), VLDL-C, non-HDL cholesterol, TG-VLDL and increases the level of ApoA-1 (apolipoprotein A-1). Tevastor helps to reduce the following ratios: total Hs / Hs-HDL, Xs-LDL / Hs-HDL, Xs-non-HDL / Hs-HDL and ApoV / ApoA-1.

The therapeutic effect of rosuvastatin is manifested within 1 week after the start of taking the drug, after 2 weeks from the start of therapy it reaches up to 90% of the maximum possible effect, which usually occurs by 4 weeks, and is supported by regular intake of the drug.

Pharmacokinetics

Pharmacokinetic characteristics of rosuvastatin:

absorption: reaching Cmax (maximum concentration) in blood plasma occurs approximately 5 hours after oral administration of the drug; the absolute bioavailability indicator is about 20%;
distribution: up to 90% of rosuvastatin binds to plasma proteins, to a greater extent to albumin; the substance accumulates mainly in the liver (the main organ of Xc synthesis and catabolism of Xc-LDL), the volume of distribution (Vd) is approximately 134 liters;
metabolism: rosuvastatin is biotransformed slightly (up to 10% of the dose taken), since it is a non-core substrate in the metabolic processes of enzymes of the cytochrome P450 system. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9. To a lesser extent, isoenzymes CYP2C19, CYP3A4 and CYP2D6 are involved in the process. The main identified metabolites of rosuvastatin: N-dismethyl - the activity of which is half that of rosuvastatin; lactone metabolites - which are pharmacologically inactive. Inhibition of circulating HMG-CoA reductase in more than 90% is provided by the pharmacological activity of rosuvastatin, the rest is by its metabolites;
elimination: the half-life (T _1/2) is about 19 hours. The T _1/2 value does not change with increasing dose. Up to 90% of the drug is excreted with feces unchanged, the rest of the substance is excreted in the urine. Average plasma clearance is ~ 50 l / h (with a coefficient of variation - 21.7%). In the process of hepatic uptake of rosuvastatin, as in the case of other inhibitors of HMG-CoA reductase, the anionic membrane transporter Xc is involved, which is assigned an important role in the hepatic elimination of the substance.

Pharmacokinetics of rosuvastatin in special patient groups:

renal failure: mild and moderate - the plasma concentration indicators of rosuvastatin and N-dismethyl do not change significantly; strongly pronounced, with a creatinine clearance (CC) of less than 30 ml / min, - the plasma concentration of rosuvastatin is 3 times higher, its active metabolite, N-dysmethyl, is 9 times higher, and in hemodialysis patients the indicator is about 50% higher, than in healthy volunteers;
liver failure (points on the Child-Pugh scale): ≤ 7 points - no increase in T _1/2 was detected; 8–9 - at least 2 patients had an increase in T _1/2, at least 2 times; ≥ 9 - no experience of use;
Race: Japanese and Chinese people in Asia have approximately double the average area under the concentration-time curve (AUC) compared with European patients living in Europe and Asia. The influence of genetic characteristics and environmental factors on these differences in pharmacokinetic parameters was not revealed. The analysis conducted among different ethnic groups of patients: Hispanics, Europeans, blacks, African Americans - did not reveal clinically significant differences in pharmacokinetic characteristics;
age and gender: they have no clinically significant effect on the pharmacokinetic characteristics of rosuvastatin.

Indications for use

primary or mixed hypercholesterolemia according to the Fredrickson classification type IIb: in addition to dietary nutrition, when food regimen and other non-drug methods of therapy (weight loss, exercise) are insufficient;
homozygous FHC (familial hypercholesterolemia): an addition to dietary nutrition and other types of lipid-lowering treatment, as well as with its insufficient effectiveness;
hypertriglyceridemia according to the Fredrickson classification type IV: addition to dietary food;
atherosclerosis: to slow the progression of the disease, in addition to dietary nutrition aimed at reducing the level of total cholesterol and LDL cholesterol;
major cardiovascular diseases, such as heart attack, stroke, arterial revascularization, in adult patients without clinical signs of coronary artery disease (ischemic heart disease), but with an increased likelihood of its development [age over 50 years for men and over 60 years for women; increased concentration of CRP (C-reactive protein) - from 2 mg / l or more; the presence of at least one of the associated risk factors - arterial hypertension, smoking, low concentration of HDL-C, family history of early coronary heart disease): for primary prevention.

Contraindications

5, 10 and 20 mg tablets

Absolute:

severe liver dysfunction (≥ 9 points on the Child-Pugh scale), due to lack of experience with use;
liver disease in the active stage, including a persistent increase in the activity of liver enzymes or an increase in indicators by more than 3 times compared with the upper limit of normal (UHN);
severe renal dysfunction (CC <30 ml / min);
simultaneous use with cyclosporine;
myopathy;
the period of pregnancy and breastfeeding;
lack of reliable methods of contraception in women of childbearing age;
lactase deficiency, lactose intolerance, glucose-galactose malabsorption (due to the presence of lactose in the tablets);
children and adolescents under 18 years of age, due to lack of experience in use;
hypersensitivity to rosuvastatin and the auxiliary components of Tevastor.

Relative contraindications for tablets at a dosage of 5, 10 and 20 mg, conditions / diseases in which the drug should be taken with caution: risk of myopathy / rhabdomyolysis (hypothyroidism, renal failure, personal / family history of genetic muscle diseases and a previous history of muscle toxicity from use other inhibitors of HMG-CoA reductase or fibrates); alcohol abuse; conditions in which there is an increase in the plasma concentration of rosuvastatin; belonging to the Asian race; application simultaneously with fibrates; history of liver disease; arterial hypotension; sepsis; extensive surgery and trauma; severe metabolic, endocrine or electrolyte disturbances; uncontrolled seizures; advanced age over 65 years.

Tablets at a dosage of 40 mg

Absolute:

severe liver dysfunction (≥ 9 points on the Child-Pugh scale), due to lack of experience with use;
liver disease in the active stage, including a persistent increase in the activity of liver enzymes or an increase in indicators by more than 3 times compared with the upper limit of normal (UHN);
simultaneous use with fibrates;
impaired renal function (CC <60 ml / min);
the risk of myopathy / rhabdomyolysis: hypothyroidism, renal failure, concomitant use with cyclosporine, personal / family history of genetic muscle diseases and a previous history of muscle toxicity from the use of other HMG-Co-A reductase inhibitors or fibrates;
alcohol abuse;
conditions in which there is an increase in the plasma concentration of rosuvastatin;
use in patients of Asian race;
the period of pregnancy and breastfeeding;
lack of reliable methods of contraception in women of childbearing age;
lactase deficiency, lactose intolerance, glucose-galactose malabsorption (due to the presence of lactose in the tablets);
children and adolescents under 18 years of age, due to lack of experience in use;
hypersensitivity to rosuvastatin and auxiliary components of the drug.

Relative contraindications: tablets at a dosage of 40 mg should be taken with caution in case of renal failure (CC> 60 ml / min), history of liver disease, sepsis, arterial hypotension, major surgical interventions, trauma, severe metabolic, endocrine or electrolyte disturbances, uncontrolled convulsive seizures and in old age over 65 years.

Instructions for the use of Tevastor: method and dosage

Tevastor is intended for oral administration. The tablets should not be chewed or crushed; they must be swallowed whole and washed down with water. If you want to take rosuvastatin 5 mg, the 10 mg tablet should be halved. The dosage regimen does not depend on the circadian rhythm, as well as the diet.

Before taking Tevastor, the patient needs to start following the classic lipid-lowering diet, which should be continued throughout the treatment.

The dose of rosuvastatin is selected individually and depends on the clinical indications and the therapeutic response of the patient, taking into account the current recommendations for target lipid levels.

For patients starting to take the drug, or transferred from taking other HMG-CoA reductase inhibitors, an initial dose of 5 or 10 mg once a day is recommended. Its choice depends on the content of cholesterol and the potential risk of developing cardiovascular complications and the likelihood of developing side effects. If necessary, the dose of Tevastor can be increased after 4 weeks.

In the case of severe hypercholesterolemia and with a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia), when the desired result was not achieved with rosuvastatin therapy at a dose of 20 mg for 4 weeks, the dose should be increased to 40 mg under the supervision of a physician (due to the increased risk of adverse reactions). Patients receiving 40 mg tablets require particularly careful regular monitoring. After increasing the dose of the drug and / or 2-4 weeks of taking Tevastor, it is necessary to monitor the parameters of lipid metabolism.

For patients belonging to the Asian race, it is recommended to start therapy with Tevastor with a dose of 5 mg, tablets at a dosage of 40 mg are contraindicated.

Tevastor should not be taken at a dose of 40 mg to patients with a predisposition to the development of myopathy, and when prescribing tablets of 10 and 20 mg, it is recommended to start treatment with a dose of 5 mg.

Genetic polymorphism: carriers of genotype SLC01B1 (OATP1B1) c.521CC and genotype ABCG2 (RSCR) C.421AA have increased exposure (AUC) to rosuvastatin in comparison with carriers of genotype SLC01B1 C.521TT and genotype ABCG2 c.421CC. Therefore, for patients with c.521СС and C.421AA genotypes, it is recommended to take Tevastor once a day at a maximum dose of 20 mg.

Due to the binding of rosuvastatin to various transport proteins (for example, with OATP1B1 and BCRP), the simultaneous use of Tevastor with cyclosporine and HIV protease inhibitors (including ritonavir in combination with atazanavir, lopinavir) increases the likelihood of myopathy / rhabdomyolysis. Which requires considering alternative treatment or stopping the drug. If it is not possible to avoid the simultaneous use of these drugs, it is necessary to assess the benefit / risk ratio of concomitant therapy and consider reducing the dose of Tevastor.

Side effects

The side effects observed with rosuvastatin are usually mild and transient, and the frequency of their occurrence, as in the case of the use of other HMG-CoA reductase inhibitors, is predominantly dose-dependent.

The frequency of side effects by systemic organ classes (on a scale: more than 1/100, but less than 1/10 - often; more than 1/1000, but less than 1/100 - infrequently; more than 1/10 000, but less than 1/1000 - rare; less than 1/10 000 - extremely rare; cannot be calculated from the available data - the frequency is unknown):

immune system: rarely - hypersensitivity reactions, up to angioedema;
endocrine system: often - type 2 diabetes mellitus;
central nervous system: often - dizziness, headaches;
digestive system: often - nausea, constipation, abdominal pain; rarely - pancreatitis;
skin and subcutaneous fat: infrequently - rash, pruritus, urticaria;
musculoskeletal system: often - myalgia; rarely - myopathy (including myositis), rhabdomyolysis; the use of Tevastor in all dosages (especially more than 20 mg) - myalgia, myopathy (including myositis); in rare cases - rhabdomyolysis with / without acute renal failure, dose-dependent increase in the activity of creatine phosphokinase (CPK), in most episodes - insignificant, asymptomatic and temporary. With an increase in VGN activity of CPK 5 times or more, therapy with rosuvastatin should be temporarily interrupted;
urinary system: proteinuria - significant changes in urine protein content (from complete absence or presence in trace amounts, to ++ or more) were recorded in less than 1% of patients receiving 10–20 mg of rosuvastatin, and in ~ 3% of patients receiving a dose 40 mg. For the most part, proteinuria decreases or disappears during treatment and does not lead to an exacerbation or progression of existing kidney disease;
hepatobiliary system: in some patients, a dose-dependent increase in the activity of hepatic transaminases, for the most part insignificant, asymptomatic and temporary;
laboratory results: increased levels of bilirubin, glucose, serum activity of gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), thyroid dysfunction;
other reactions: often - asthenic syndrome.

The frequency of side effects of Tevastor according to post-marketing use data:

blood and lymphatic system: frequency unknown - thrombocytopenia;
digestive system: rarely - increased activity of liver enzymes; extremely rare - jaundice, hepatitis; frequency unknown - diarrhea;
musculoskeletal system: extremely rare - arthralgia; frequency unknown - immune-mediated necrotizing myopathy;
central nervous system: extremely rare - polyneuropathy, memory loss.
respiratory system: frequency unknown - shortness of breath, cough;
urinary system: extremely rare - hematuria;
skin and subcutaneous fat: frequency unknown - Stevens-Johnson syndrome;
reproductive system: frequency unknown - gynecomastia;
other reactions: frequency unknown - peripheral edema.

As a result of the use of some statins, the following side effects were observed: sexual dysfunction, depression, sleep disturbances (including insomnia and nightmares); in isolated cases - interstitial lung disease, especially as a result of prolonged use of drugs.

Overdose

The simultaneous administration of several daily doses of rosuvastatin does not change its pharmacokinetic characteristics.

For the treatment of an overdose, if necessary, carry out symptomatic therapy, provide control of CPK activity and liver function. The specific antidote is unknown. Hemodialysis is ineffective.

special instructions

Proteinuria, mainly of renal origin, diagnosed during testing, is observed in patients taking the drug at a dose of 40 mg or more, most often it is of a transient nature and is not a symptom of progressive or acute renal failure. All serious renal complications are observed when taking rosuvastatin at a dose of 40 mg, therefore, the use of Tevastor at a dose of 40 mg requires monitoring of renal function indicators.

Skeletal muscle lesions such as myalgia, myopathy and, in isolated cases, rhabdomyolysis, are observed in patients taking Tevastor at a dose of 20 mg or more. Rarely, episodes of rhabdomyolysis have been reported with the combined use of ezetimibe and HMG-CoA reductase inhibitors. The risk of developing rhabdomyolysis, both with rosuvastatin therapy and with other HMG-CoA reductase inhibitors, increases with a dose of 40 mg.

It is not necessary to determine the activity of CPK after intense physical exertion, as well as in the presence of other possible reasons for an increase in its activity due to the probable distortion of indicators. When the initial CPK activity is significantly increased (≥ 5 VGN), the measurement must be repeated after 5-7 days. You should not start taking Tevastor if a second check confirms an initial increased CPK activity (≥ 5 VGN).

Patients should be aware of the need to immediately inform the doctor about the appearance of previously unremarked symptoms, muscle pain of unknown etiology, weakness and / or seizures, especially when they are combined with malaise and fever. Therapy is stopped when the CPK activity is 5 times higher than the VGN or in the presence of serious muscle ailments that cause constant discomfort. After the disappearance of symptoms and the normalization of CPK activity, the question of using rosuvastatin in a minimum dose and under close supervision should be re-considered. It is inappropriate to conduct routine monitoring of CPK activity in the absence of symptoms.

Before starting treatment and for 3 months of therapy, it is recommended to carry out a functional diagnosis of the liver.

Influence on the ability to drive vehicles and complex mechanisms

Studies of the effect of rosuvastatin on the ability to concentrate and the speed of psychomotor reactions have not been conducted. But when performing potentially hazardous activities, including driving vehicles, it must be borne in mind that during therapy with Tevastor, dizziness may develop.

Application during pregnancy and lactation

Tevastor is contraindicated for the treatment of pregnant and breastfeeding women. And if pregnancy is diagnosed during therapy, the drug must be stopped immediately.

Women of reproductive age need to use reliable methods of protection. Cholesterol, as well as the products of its biosynthesis, play an important role in the development of the fetus, therefore, the risk of inhibition of HMG-CoA reductase significantly exceeds the potential benefit from the use of Tevastor.

Studies on the release of rosuvastatin into breast milk have not been conducted, and therefore, if it is necessary to use Tevastor during lactation, breastfeeding should be discontinued.

Pediatric use

Tevastor is contraindicated for the treatment of children and adolescents under 18 years of age.

With impaired renal function

Patients with mild to moderate renal disease do not require dose adjustment of rosuvastatin. In case of severe renal failure (CC <30 ml / min), the use of Tevastor in any dosage is contraindicated.

With moderate renal impairment (CC <60 ml / min), it is recommended to start therapy with a dose of 5 mg, and a dose of 40 mg is contraindicated for use.

For violations of liver function

According to the instructions, Tevastor is contraindicated for use in liver diseases in the active phase, including a persistent increase in the activity of hepatic transaminases, or any increase in their activity by 3 or more times over VGN.

There is no experience with the use of Tevastor in severe liver dysfunction (on the Child-Pugh scale - 9 points and higher).

Use in the elderly

In old age over 65 years, Tevastor should be prescribed with caution; it is recommended to start treatment with a dose of 5 mg.

Drug interactions

cyclosporine: AUC of rosuvastatin increases on average by 7 times in comparison with the values recorded in healthy volunteers; the plasma concentration of cyclosporine does not change;
vitamin K antagonists (warfarin): at the beginning of joint therapy with rosuvastatin or with an increase in the dose of the drug, an increase in the International Normalized Ratio (MHO) is possible; when rosuvastatin is canceled or its dose is reduced, a decrease in MHO is possible, in such situations it is recommended to control this indicator;
ezetimibe: its use at a dose of 10 mg simultaneously with rosuvastatin at a dose of 10 mg increases the AUC of the latter in patients with hypercholesterolemia. Possible increased risk of side effects due to pharmacodynamic interactions;
gemfibrozil, fenofibrate, other fibrates and nicotinic acid in hypolipidemic doses increase the likelihood of myopathy occurring if used in combination with HMG-CoA reductase inhibitors (possibly due to the fact that statins can cause myopathy when used as monotherapy); gemfibrozil: increases Cmax and AUC of rosuvastatin by 2 times; in the course of special studies, there was no corresponding pharmacokinetic interaction of rosuvastatin with fenofibrate, but their pharmacodynamic interaction is likely;
protease inhibitors: the mechanism of their interaction with rosuvastatin is not exactly known, but complex use can cause a sustained increase in the effectiveness of Tevastor. According to pharmacokinetic studies on healthy volunteers, it was determined that the combined use of rosuvastatin at a dose of 20 mg and a complex of protease inhibitors (lopinavir 400 mg + ritonavir 100 mg) increased AUC by 2 times and Cmax by 5 times. In this connection, the simultaneous use of rosuvastatin and protease inhibitors is not recommended in the treatment of patients with HIV;
suspensions of antacids containing aluminum and magnesium hydroxide: reduce the plasma concentration of rosuvastatin by about 50%; weakening of the effect is observed when taking antacids 2 hours after rosuvastatin. The study of the clinical effectiveness of the interaction has not been conducted;
erythromycin: reduces the AUC of rosuvastatin by 20% and its Cmax by 30%, this effect is possibly associated with increased intestinal motility due to the intake of erythromycin;
oral contraceptives: rosuvastatin increases the AUC of ethinyl estradiol by 26% and norgestrel by 34%; when selecting a dose of oral contraceptives, such an increase in plasma concentration should be taken into account while using Tevastor;
digoxin: no clinically significant interaction with rosuvastatin was found in studies.

As a result of the studies carried out both in vivo and in vitro, it was revealed that rosuvastatin is neither an inducer nor an inhibitor for isoenzymes of the cytochrome P450 system. But it is a weak substrate for these isoenzymes. Interactions that would be of clinical significance were also not observed in rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4) and ketoconazole (an inhibitor of CYP2A6 and CYP3A4). Therefore, the interaction of rosuvastatin with the cytochrome P450 system is not expected.

Analogs

The analogues of Tevastor are Acorta, Lipoprime, Crestor, Mertenil, Ro-statin, Rosart, Reddistatin, Rosistark, Rosuvastatin, Rustor, Rosulip, Rosufast, Rosucard, Roxera, Suvardio, etc.

Terms and conditions of storage

Keep out of the reach of children. Store at a temperature not exceeding 25 ° C.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Tevastor

According to reviews, Tevastor is an effective drug for lowering cholesterol, improving the condition and normalizing these analyzes. But many patients complain about its high cost and the long course required for recovery.

Patients recommend taking pills only at night, since during the day rosuvastatin is quickly excreted from the body and does not give the expected effect.

The price of Tevastor in pharmacies

Estimated price for Tevastor film-coated tablets:

dosage 5 mg: 30 pcs. - 368 rubles;
dosage 10 mg: 30 pcs. - 539 rubles; 90 pcs. - 1126 rubles;
dosage 20 mg: 30 pcs. - 668 rubles; 90 pcs. - 1601 rubles.

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!