Polvasterol 30s 5 mg coated tablets
- $11.20
Polvasterol
the Trade name
Polvasterol
Mezhdunarodnoye the unlicensed
name Rosuvastatin Dosage Form
of the Tablet, coated 5 mg, 10 mg, 20 mg, 40 mg
Structure
One tablet contains
active agent –
calcium rosuvastatin
(it is equivalent to rosuvastatin)
5.20 (5.00)
10.40
(10.00) 20.80 (20.00) 41.60 (40.00)
excipients: lactoses monohydrate (type 1), lactoses monohydrate (type 2), cellulose microcrystalline, sodium citrate, krospovidon type B, silicon dioxide colloidal anhydrous, magnesium stearate.
The description
of the Tablet, film coated white or almost white color of round shape, with a biconvex surface, with an engraving 5 on one party (for a dosage of 5 mg).
Tablets, film coated white or almost white color of round shape, with a biconvex surface, with an engraving 10 on one party (for a dosage of 10 mg).
Tablets, film coated white or almost white color of round shape, with a biconvex surface, with an engraving 20 on one party (for a dosage of 20 mg).
Tablets, film coated white or almost white color of round shape, with a biconvex surface, with an engraving 40 on one party (for a dosage of 40 mg).
The pharmacotherapeutic group
Hypolipidemic drugs of HMG-CoA reductase inhibitors
the ATX C10A A07 Code
the Pharmacological
Pharmacokinetics Rosuvastatin properties is a selection, competitive inhibitor of HMG-CoA reductase - the enzyme turning 3-hydroxy-3-metilglutarilkoenzim A in mevalonat, the predecessor of cholesterol. The main target of effect of rosuvastatin is the liver where synthesis of cholesterol (XC) and catabolism of lipoproteins of the low density (LDL) is carried out.
Rosuvastatin increases number of hepatic receptors of LDL by surfaces of cells, increasing capture and catabolism of LDL that leads to inhibition of synthesis of lipoproteins of very low density (LPONP), reducing thereby total amount of LDL and LPONP. The maximum concentration of rosuvastatin in blood plasma is reached approximately in 5 hours after oral administration. The absolute bioavailability is about 20%. Rosuvastatin is absorbed, mainly, by a liver. The volume of distribution of rosuvastatin is about 134 l. About 90% of rosuvastatin contact proteins of plasma, generally albumine. Rosuvastatin is exposed to limited metabolism (about 10%). Rosuvastatin is non-core substrate for metabolism by enzymes of a system of P450 cytochrome. The main isoenzyme participating in rosuvastatin metabolism is CYP2C9. CYP2C19, CYP3A4 and CYP2D6 enzymes are involved in metabolism to a lesser extent.
The main revealed metabolites of rosuvastatin are N-dismetil and lactonic metabolites. N-dismetil for about 50% is less active, than rosuvastatin, lactonic metabolites are pharmacological not active. More than 90% of pharmacological activity on inhibition of the circulating HMG-CoA reductase are provided with rosuvastatin, the rest – its metabolites.
About 90% of a dose of rosuvastatin are removed in not changed view with excrements (including the absorbed and not absorbed rosuvastatin). The rest is removed with urine. Plasma elimination half-life (T ½) makes about 19 hours. Elimination half-life does not change at increase in a dose of drug. The average geometrical plasma clearance is about 50 liters/hour (coefficient of variation of 21.7%). As well as in case of other inhibitors of HMG-CoA reductase, the membrane carrier of cholesterol who is carrying out an important role in hepatic elimination of rosuvastatin is involved in process of hepatic capture of rosuvastatin.
System exposure of rosuvastatin increases in proportion to a dose.
The therapeutic effect appears within one week after the beginning of therapy by rosuvastatin, in 2 weeks of treatment reaches 90% of the greatest possible effect. The maximum therapeutic effect is usually reached by 4th week and maintained at regular reception.
The pharmacodynamics
Polvasterol reduces the increased content of cholesterol-LDL (HS-LPNP), the general cholesterol, triglycerides (TG), increases the content of cholesterol of lipoproteins of the high density (HS-LPVP) and also reduces apolipoprotein B content (ApoV), HS-neLPVP, HS-LPONP, TG-LPONP also increases the level of A-I apolipoprotein (ApoA-I), reduces a ratio of HS-LPNP/HS-LPVP, the general HS/HS-LPVP and HS-neLPVP/HS-LPVP and a ratio of ApoB/ApoA-I.
Polvasterol is effective at adult patients with a hypercholesterolemia with or without gipertriglitseridemiya, regardless of race, a floor or age, and with a family hypercholesterolemia.
Indications
- primary hypercholesterolemia (the IIa type, including a family heterozygous hypercholesterolemia) or the mixed dislipidemiya (IIb type) as addition to a diet when the diet and other non-drug methods of treatment (for example, physical exercises, decrease in body weight) are insufficient
- a family homozygous hypercholesterolemia as addition to a diet and other lipidsnizhayushchy therapy (for example, LPNP-aferez), or in cases when similar therapy is not suitable the patient
- as addition to a diet for delay of progressing of atherosclerosis at adult patients as a part of therapy for decrease in levels of the LPNP general cholesterol (OHS) and XC to target levels
- prevention of cardiovascular complications at adult patients with the increased risk of developing an atherosclerotic cardiovascular disease as auxiliary therapy.
A route of administration and doses
Inside not to chew and not to crush a tablet, to swallow entirely, washing down with water. It can be appointed irrespective of meal. Prior to the beginning of and during therapy by Polvasterol the patient has to keep to a standard hypolipidemic diet. The dose of drug has to be selected individually depending on the purposes of therapy and the response to treatment.
The recommended initial dose for the patients beginning to take the drug or for the patients transferred from intake of other inhibitors of HMG-CoA reductase has to make 5 or 10 mg of Polvasterol of 1 times a day. When choosing an initial dose it is necessary to be guided by the level of content of cholesterol and to take possible risk of cardiovascular complications into account and also it is necessary to estimate potential risk of development of side effects. In case of need, the dose can be increased after 4 weeks of administration of drug. To raise a dose of drug gradually.
Due to the possible development of side effects at reception of a dose of 40 mg, increase in a dose to the maximum 40 mg can be considered only at patients with a heavy hypercholesterolemia and with high risk of cardiovascular complications (especially at patients with a family hypercholesterolemia) at which the desirable result of therapy at reception of a dose of 20 mg was not achieved. Observation of the patients receiving drug in a dose of 40 mg is recommended.
Purpose of a dose of 40 mg is not recommended to the patients who were earlier not taking the drug. After 2-4 week therapies and/or at increase in a dose of Polvasterol the control of indicators of lipidic exchange is necessary (if necessary dose adjustment is required).
Prevention of cardiovascular complications at adult patients with the increased risk of developing an atherosclerotic cardiovascular disease as auxiliary therapy
the Recommended dose - 20 mg once a day.
Elderly patients
dose adjustment is not required. To patients 70 years are more senior the initial dose of drug of 5 mg is recommended.
Patients with a renal failure
with a renal failure easy or moderate severity dose adjustment is not required From patients, the recommended initial dose of drug of 5 mg. At patients with moderate renal failures (clearance of creatinine less than 60 ml/min.) - use of drug in a dosage of 40 mg is contraindicated. At patients with the profound renal failure (clearance of creatinine less than 30 ml/min.) - drug Polvasterol use is contraindicated.
Patients with a liver failure
the Experience of use of drug for patients with point higher than 9 on a scale of Chayld-Pyyu is absent.
Special populations. Ethnic groups
When studying the pharmacokinetic Polvasterola parameters at the patients belonging to different ethnic groups the increase in system concentration of rosuvastatin at Japanese and Chinese is noted. It is necessary to consider this fact when prescribing rosuvastatin to these groups of patients. The recommended initial dose for patients of Asian race makes 5 mg.
The patients predisposed to a myopathy
prescribing of drug in a dose of 40 mg is contraindicated to patients with the factors predisposed to development of a myopathy. The recommended initial dose for this group of patients makes 5 mg.
Side effects
Often (> 1/100, <>
- a headache, dizziness
- nausea, an abdominal pain, a constipation
- myalgias
- an asthenic syndrome
- diabetes (patients with level have a glucose in blood on an empty stomach 5.6 - 6.9
mmol/l)
Infrequently (> 1/1000, <>
- an itching, rash, urticaria
Seldom (> 1/10,000,
- hypersensitivity reactions, including a Quincke's disease
- a myopathy, a rhabdomyolysis
- increase in level of hepatic transaminases, pancreatitis
Very seldom (
-jaundice, hepatitis
- polyneuropathy
- memory loss
- a hamaturia
- arthralgias
- a depression, sleep disorders
- sexual dysfunction
Isolated cases
- interstitial diseases of lungs
At the patients receiving Polvasterol can come to light a proteinuria. In most cases the proteinuria decreases or disappears in the course of therapy and does not mean emergence sharp or progressing of the existing disease of kidneys. As well as at use of other inhibitors of GMG-KoA-reduktazy, the frequency of emergence of side effects has dose-dependent character.
Contraindications
- hypersensitivity to rosuvastatin or any of drug components
- liver diseases in an active phase, including permanent increase
in serumal activity of transaminases and any increase in activity
of transaminases in blood serum (more than by 3 times in comparison with the upper
bound of norm)
- an acute renal failure (clearance of creatinine less than 30 ml/min.)
- myopathies
- a concomitant use of cyclosporine
- pregnancy, the lactation period, lack of adequate methods of contraception
- predisposition to development of miotoksichesky complications
- hereditary intolerance of a galactose, lactose
- insufficiency or a sprue of glucose and a galactose
For a dose of 40 mg
- a renal failure of moderate severity (clearance of creatinine less than 60 ml/min.)
- a hypothyroidism
- states which can lead to increase in plasma concentration of rosuvastatin
- a concomitant use of fibrat
- patients of Asian race
- muscular diseases in the anamnesis
- a miotoksichnost against the background of intake of other GMG-KoA inhibitors –
- reductase or fibrat in the anamnesis
- an alcohol abuse
Medicinal interactions
Cyclosporine:
During combined use of cyclosporine and rosuvastatin, the PPK levels of rosuvastatin were on average 7 times higher, than the levels observed at healthy volunteers.
Joint reception does not affect concentration of cyclosporine in plasma.
Antagonists of vitamin K:
As well as with others of GMG-KoA-reduktazy inhibitors, the initiation of treatment or increase in a dosage for the patients accepting at the same time antagonists of vitamin K (for example, warfarin or other anticoagulant of coumarin) can lead to increase in the International Normalized Coefficient (INR). The termination of reception or a dose decline of rosuvastatin can lead to reduction of the International Normalized Coefficient. In such cases the corresponding control of the International Normalized Coefficient is necessary.
Ezetimib:
As a result of combined use of rosuvastatin PPK or Cmax of each drug also change. However the impact of pharmaceutical adynamic interaction between drugs on emergence of side effects cannot be found out.
Gemfibrozil and other lipidoponizhayushchy drugs:
As a result of combined use of rosuvastatin and a gemfibrozil increase twice Cmax and PPK of rosuvastatin (see Section 4.4).
On the basis of data on studying interaction, the corresponding interaction with fenofibraty is not expected. However there can be a pharmakodinamichesky interaction.
Gemfibrozil, fenofibrat, other fibrata and lipidoponizhayushchy doses (> or it is equal to 1 g/day) Niacinum (niacin) enhance risk of a myopathy at joint reception from GMG-KoA-reduktazy inhibitors, it is possible because they can cause a myopathy at separate use. The dose of 40 mg is contraindicated at combined use with fibraty (cm Section 4.3 and 4.4). These patients have to begin with a dose 5 mg also.
Protease inhibitors:
In spite of the fact that the exact mechanism of interaction is unknown, sharing of inhibitor of protease can strengthen effect of rosuvastatin considerably. In a pharmacokinetic research joint reception of 20 mg of rosuvastatin and a combination of drug with 2 inhibitors of protease (400 mg of a lopinavir of/100 mg of an irtonavir) at healthy volunteers (0-24) rosuvastatin and Cmax respectively were associated with approximately 2-fold and 5-fold increase in a homeostasis of PPK. Thus, sharing of rosuvastatin at patients from the HIV accepting protease inhibitors is not recommended.
Antacids:
Simultaneous use of rosuvastatin with the suspension of an antacid containing hydroxide of aluminum and magnesium leads to reduction of concentration of rosuvastatin in plasma approximately for 50%.
This effect was softened when the antacid was accepted in 2 hours after intake of rosuvastatin. The clinical importance of this interaction was not studied.
Erythromycin:
Simultaneous use of rosuvastatin and erythromycin leads to 20% to reduction of PPK (0-t) and 30% to reduction of Cmax of rosuvastatin. This interaction can be caused by strengthening of the vermicular movement of intestines caused by erythromycin.
Oral contraceptives / gormozamestitelnaya therapy:
Simultaneous use of rosuvastatin and oral contraceptives leads to increase in PPK of ethinylestradiol and Norgestrelum by 26% and 34%, respectively. This increase in level in plasma has to be taken into account when choosing doses of an oral kontratsepitv. Pharmacokinetic data on the persons accepting at the same time rosuvastatin and gormozamestitelny therapy are unavailable, thus, similar effects cannot be excluded. However, the combination is widely used at women in clinical trials and well transferred.
Other medications:
On the basis of data on special researches of interaction clinically significant interaction with digoxin is not expected.
P450 cytochrome enzymes:
Results of the researches in vitro and in Vivo show that rosuvastatin is not either inhibitor, or the inductor of isoenzymes of P450 cytochrome. Besides, rosuvastatin is not nutritious substrate for these isoenzymes. Clinically significant interaction between rosuvastatin and flukonazoly (CYP2C9 and CYP3A4 inhibitor) or ketonazoly was not observed (CYP2A6 and CYP3A4 inhibitor). As a result of joint intake of rosuvastatin and an itrakonazol (CYP3A4 inhibitor) and PPK of rosuvastatin increases by 28%. This small increase is not considered clinically significant. Thus, interaction of drugs as a result of P450 cytochrome metabolism is not expected.
Special instructions
With care
For doses less than 40 mg: the personal or family anamnesis of hereditary muscular diseases and the previous anamnesis of muscular toxicity when using other inhibitors of GMG-KoA-reduktazy or fibrat, excessive alcohol intake, a hypothyroidism, race (Asian race), co-administration from fibrata.
Presence of risk of developing a myopathy/rhabdomyolysis - a renal failure, age is more senior than 70 years, states at which increase in plasma concentration of rosuvastatin, liver diseases in the anamnesis, sepsis, arterial hypotension, extensive surgical interventions, injuries, heavy metabolic, endocrine or electrolytic disturbances or uncontrollable epilepsy is noted.
Use in pediatric practice
the Efficiency and safety of use of drug for children up to 18 years is not completely established.
From the musculoskeletal system
At Polvasterol's use in all dosages and, in particular at reception of the doses of drug exceeding 20 mg it was reported about the following impacts on the musculoskeletal system: myalgia, myopathy, in rare instances rhabdomyolysis.
Definition of a kreatinfosfokinaza
of KFK should not be carried out after intensive physical activities or in the presence of other possible reasons of increase in KFK, can lead to incorrect interpretation of the received results. In case the KFK initial level is significantly increased (5 times higher, than the upper bound of norm), in 5 - 7 days it is necessary to take repeated measurement. It is not necessary to begin therapy if the repeated test confirms the KFK initial level (more than 5 times higher in comparison with the upper bound of norm).
It is necessary to inform the patient on need of the immediate message to the doctor about cases of unexpected appearance of muscular pains, muscle weakness or spasms, especially in combination with an indisposition and fever. At such patients it is necessary to determine the KFK level. Therapy has to be stopped if the KFK level is considerably increased (more than by 5 times in comparison with the upper bound of norm) or if symptoms from muscles are pronounced and cause daily discomfort (even if the KFK level is 5 times less in comparison with the upper bound of norm). If symptoms disappear and the KFK level returns to norm, it is necessary to consider a question of repeated appointment of Polvasterol or other inhibitors of GMG-KoA-reduktazy in smaller doses at careful observation of the patient. Routine control of KFK in the absence of symptoms is not reasonable.
Signs of increase in impact on skeletal muscles at Polvasterol's reception and the accompanying therapy are noted. It was reported about increase in number of cases of a miositis and a myopathy at the patients accepting other inhibitors of GMG-KoA-reduktazy in combination with derivatives of fibrinous acid, including gemfibrozit, cyclosporine, niacin, azolny antifungal means, inhibitors of proteases and makrolidny antibiotics. Gemfibrozil increases risk of emergence of a myopathy at the combined appointment with some inhibitors of GMG-KoA-reduktazy. Thus, co-administration of Polvasterol and a gemfibrozil is not recommended. The ratio of risk and possible advantage at combined use of Polvasterol and fibrat or Niacinum has to be carefully weighed.
In 2-4 weeks after an initiation of treatment and/or at increase in a dose of Polvasterol the control of indicators of lipidic exchange is necessary (if necessary dose adjustment is required).
The liver
Is recommended to carry out definition of indicators of function of a liver prior to therapy and in 3 months after the beginning of therapy. Polvasterol's reception it is necessary to stop or reduce a drug dose if the level of activity of transaminases in blood sera by 3 times exceeds the upper bound of norm. At patients with a hypercholesterolemia owing to a hypothyroidism or a nephrotic syndrome therapy of basic diseases has to be carried out prior to treatment by Polvasterol.
The interstitial disease of lungs
At use of statines was reported about single cases of an interstitial disease of lungs, especially, when long therapy was carried out. The described signs can include short wind, dry cough and the general aggravation of symptoms (fatigue, loss of weight and fever). If there are suspicions on development in the patient of an interstitial disease of lungs, therapy by statines it is necessary to stop.
Diabetes
At patients with glucose level in blood on an empty stomach of 5.6 - 6.9 mmol/l, treatment by rosuvastatin contacted the diabetes raised by risk of a disease.
Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms
During the driving or work with mechanisms need to be considered that during therapy there can be dizziness.
Overdose
Symptoms - expressiveness of symptoms of side effects.
Treatment - symptomatic and the supporting actions. Control of function of a liver and the KFK level is necessary. It is improbable that the hemodialysis will be effective.
The form of release and packing
On 10 tablets place in blister strip packaging from a foil soft, from the opaque party laminated by polyamide, from the brilliant party laminated by a film of polyvinylchloride and aluminum foil (AL/OPA/AL/PVH).
On 3 planimetric packs together with the instruction for medical use in the state and Russian languages place in a cardboard pack.
To Store storage conditions in the dry, protected from light place at a temperature not over 30 of 0C to Store in places inaccessible for children!
A period of storage
2 years
not to use drug after expiry date
Prescription status
According to the prescription
the Producer
the Pharmaceutical plant POLFARMA of the joint-stock company, Poland
of st. of Pelplinsk 19, 83-200 Starogard Gdanski
the Owner of the registration certificate
of JSC Khimfarm,
to Develop Kazakhstan
the Trade name
Polvasterol
Mezhdunarodnoye the unlicensed
name Rosuvastatin Dosage Form
of the Tablet, coated 5 mg, 10 mg, 20 mg, 40 mg
Structure
One tablet contains
active agent –
calcium rosuvastatin
(it is equivalent to rosuvastatin)
5.20 (5.00)
10.40
(10.00) 20.80 (20.00) 41.60 (40.00)
excipients: lactoses monohydrate (type 1), lactoses monohydrate (type 2), cellulose microcrystalline, sodium citrate, krospovidon type B, silicon dioxide colloidal anhydrous, magnesium stearate.
The description
of the Tablet, film coated white or almost white color of round shape, with a biconvex surface, with an engraving 5 on one party (for a dosage of 5 mg).
Tablets, film coated white or almost white color of round shape, with a biconvex surface, with an engraving 10 on one party (for a dosage of 10 mg).
Tablets, film coated white or almost white color of round shape, with a biconvex surface, with an engraving 20 on one party (for a dosage of 20 mg).
Tablets, film coated white or almost white color of round shape, with a biconvex surface, with an engraving 40 on one party (for a dosage of 40 mg).
The pharmacotherapeutic group
Hypolipidemic drugs of HMG-CoA reductase inhibitors
the ATX C10A A07 Code
the Pharmacological
Pharmacokinetics Rosuvastatin properties is a selection, competitive inhibitor of HMG-CoA reductase - the enzyme turning 3-hydroxy-3-metilglutarilkoenzim A in mevalonat, the predecessor of cholesterol. The main target of effect of rosuvastatin is the liver where synthesis of cholesterol (XC) and catabolism of lipoproteins of the low density (LDL) is carried out.
Rosuvastatin increases number of hepatic receptors of LDL by surfaces of cells, increasing capture and catabolism of LDL that leads to inhibition of synthesis of lipoproteins of very low density (LPONP), reducing thereby total amount of LDL and LPONP. The maximum concentration of rosuvastatin in blood plasma is reached approximately in 5 hours after oral administration. The absolute bioavailability is about 20%. Rosuvastatin is absorbed, mainly, by a liver. The volume of distribution of rosuvastatin is about 134 l. About 90% of rosuvastatin contact proteins of plasma, generally albumine. Rosuvastatin is exposed to limited metabolism (about 10%). Rosuvastatin is non-core substrate for metabolism by enzymes of a system of P450 cytochrome. The main isoenzyme participating in rosuvastatin metabolism is CYP2C9. CYP2C19, CYP3A4 and CYP2D6 enzymes are involved in metabolism to a lesser extent.
The main revealed metabolites of rosuvastatin are N-dismetil and lactonic metabolites. N-dismetil for about 50% is less active, than rosuvastatin, lactonic metabolites are pharmacological not active. More than 90% of pharmacological activity on inhibition of the circulating HMG-CoA reductase are provided with rosuvastatin, the rest – its metabolites.
About 90% of a dose of rosuvastatin are removed in not changed view with excrements (including the absorbed and not absorbed rosuvastatin). The rest is removed with urine. Plasma elimination half-life (T ½) makes about 19 hours. Elimination half-life does not change at increase in a dose of drug. The average geometrical plasma clearance is about 50 liters/hour (coefficient of variation of 21.7%). As well as in case of other inhibitors of HMG-CoA reductase, the membrane carrier of cholesterol who is carrying out an important role in hepatic elimination of rosuvastatin is involved in process of hepatic capture of rosuvastatin.
System exposure of rosuvastatin increases in proportion to a dose.
The therapeutic effect appears within one week after the beginning of therapy by rosuvastatin, in 2 weeks of treatment reaches 90% of the greatest possible effect. The maximum therapeutic effect is usually reached by 4th week and maintained at regular reception.
The pharmacodynamics
Polvasterol reduces the increased content of cholesterol-LDL (HS-LPNP), the general cholesterol, triglycerides (TG), increases the content of cholesterol of lipoproteins of the high density (HS-LPVP) and also reduces apolipoprotein B content (ApoV), HS-neLPVP, HS-LPONP, TG-LPONP also increases the level of A-I apolipoprotein (ApoA-I), reduces a ratio of HS-LPNP/HS-LPVP, the general HS/HS-LPVP and HS-neLPVP/HS-LPVP and a ratio of ApoB/ApoA-I.
Polvasterol is effective at adult patients with a hypercholesterolemia with or without gipertriglitseridemiya, regardless of race, a floor or age, and with a family hypercholesterolemia.
Indications
- primary hypercholesterolemia (the IIa type, including a family heterozygous hypercholesterolemia) or the mixed dislipidemiya (IIb type) as addition to a diet when the diet and other non-drug methods of treatment (for example, physical exercises, decrease in body weight) are insufficient
- a family homozygous hypercholesterolemia as addition to a diet and other lipidsnizhayushchy therapy (for example, LPNP-aferez), or in cases when similar therapy is not suitable the patient
- as addition to a diet for delay of progressing of atherosclerosis at adult patients as a part of therapy for decrease in levels of the LPNP general cholesterol (OHS) and XC to target levels
- prevention of cardiovascular complications at adult patients with the increased risk of developing an atherosclerotic cardiovascular disease as auxiliary therapy.
A route of administration and doses
Inside not to chew and not to crush a tablet, to swallow entirely, washing down with water. It can be appointed irrespective of meal. Prior to the beginning of and during therapy by Polvasterol the patient has to keep to a standard hypolipidemic diet. The dose of drug has to be selected individually depending on the purposes of therapy and the response to treatment.
The recommended initial dose for the patients beginning to take the drug or for the patients transferred from intake of other inhibitors of HMG-CoA reductase has to make 5 or 10 mg of Polvasterol of 1 times a day. When choosing an initial dose it is necessary to be guided by the level of content of cholesterol and to take possible risk of cardiovascular complications into account and also it is necessary to estimate potential risk of development of side effects. In case of need, the dose can be increased after 4 weeks of administration of drug. To raise a dose of drug gradually.
Due to the possible development of side effects at reception of a dose of 40 mg, increase in a dose to the maximum 40 mg can be considered only at patients with a heavy hypercholesterolemia and with high risk of cardiovascular complications (especially at patients with a family hypercholesterolemia) at which the desirable result of therapy at reception of a dose of 20 mg was not achieved. Observation of the patients receiving drug in a dose of 40 mg is recommended.
Purpose of a dose of 40 mg is not recommended to the patients who were earlier not taking the drug. After 2-4 week therapies and/or at increase in a dose of Polvasterol the control of indicators of lipidic exchange is necessary (if necessary dose adjustment is required).
Prevention of cardiovascular complications at adult patients with the increased risk of developing an atherosclerotic cardiovascular disease as auxiliary therapy
the Recommended dose - 20 mg once a day.
Elderly patients
dose adjustment is not required. To patients 70 years are more senior the initial dose of drug of 5 mg is recommended.
Patients with a renal failure
with a renal failure easy or moderate severity dose adjustment is not required From patients, the recommended initial dose of drug of 5 mg. At patients with moderate renal failures (clearance of creatinine less than 60 ml/min.) - use of drug in a dosage of 40 mg is contraindicated. At patients with the profound renal failure (clearance of creatinine less than 30 ml/min.) - drug Polvasterol use is contraindicated.
Patients with a liver failure
the Experience of use of drug for patients with point higher than 9 on a scale of Chayld-Pyyu is absent.
Special populations. Ethnic groups
When studying the pharmacokinetic Polvasterola parameters at the patients belonging to different ethnic groups the increase in system concentration of rosuvastatin at Japanese and Chinese is noted. It is necessary to consider this fact when prescribing rosuvastatin to these groups of patients. The recommended initial dose for patients of Asian race makes 5 mg.
The patients predisposed to a myopathy
prescribing of drug in a dose of 40 mg is contraindicated to patients with the factors predisposed to development of a myopathy. The recommended initial dose for this group of patients makes 5 mg.
Side effects
Often (> 1/100, <>
- a headache, dizziness
- nausea, an abdominal pain, a constipation
- myalgias
- an asthenic syndrome
- diabetes (patients with level have a glucose in blood on an empty stomach 5.6 - 6.9
mmol/l)
Infrequently (> 1/1000, <>
- an itching, rash, urticaria
Seldom (> 1/10,000,
- hypersensitivity reactions, including a Quincke's disease
- a myopathy, a rhabdomyolysis
- increase in level of hepatic transaminases, pancreatitis
Very seldom (
-jaundice, hepatitis
- polyneuropathy
- memory loss
- a hamaturia
- arthralgias
- a depression, sleep disorders
- sexual dysfunction
Isolated cases
- interstitial diseases of lungs
At the patients receiving Polvasterol can come to light a proteinuria. In most cases the proteinuria decreases or disappears in the course of therapy and does not mean emergence sharp or progressing of the existing disease of kidneys. As well as at use of other inhibitors of GMG-KoA-reduktazy, the frequency of emergence of side effects has dose-dependent character.
Contraindications
- hypersensitivity to rosuvastatin or any of drug components
- liver diseases in an active phase, including permanent increase
in serumal activity of transaminases and any increase in activity
of transaminases in blood serum (more than by 3 times in comparison with the upper
bound of norm)
- an acute renal failure (clearance of creatinine less than 30 ml/min.)
- myopathies
- a concomitant use of cyclosporine
- pregnancy, the lactation period, lack of adequate methods of contraception
- predisposition to development of miotoksichesky complications
- hereditary intolerance of a galactose, lactose
- insufficiency or a sprue of glucose and a galactose
For a dose of 40 mg
- a renal failure of moderate severity (clearance of creatinine less than 60 ml/min.)
- a hypothyroidism
- states which can lead to increase in plasma concentration of rosuvastatin
- a concomitant use of fibrat
- patients of Asian race
- muscular diseases in the anamnesis
- a miotoksichnost against the background of intake of other GMG-KoA inhibitors –
- reductase or fibrat in the anamnesis
- an alcohol abuse
Medicinal interactions
Cyclosporine:
During combined use of cyclosporine and rosuvastatin, the PPK levels of rosuvastatin were on average 7 times higher, than the levels observed at healthy volunteers.
Joint reception does not affect concentration of cyclosporine in plasma.
Antagonists of vitamin K:
As well as with others of GMG-KoA-reduktazy inhibitors, the initiation of treatment or increase in a dosage for the patients accepting at the same time antagonists of vitamin K (for example, warfarin or other anticoagulant of coumarin) can lead to increase in the International Normalized Coefficient (INR). The termination of reception or a dose decline of rosuvastatin can lead to reduction of the International Normalized Coefficient. In such cases the corresponding control of the International Normalized Coefficient is necessary.
Ezetimib:
As a result of combined use of rosuvastatin PPK or Cmax of each drug also change. However the impact of pharmaceutical adynamic interaction between drugs on emergence of side effects cannot be found out.
Gemfibrozil and other lipidoponizhayushchy drugs:
As a result of combined use of rosuvastatin and a gemfibrozil increase twice Cmax and PPK of rosuvastatin (see Section 4.4).
On the basis of data on studying interaction, the corresponding interaction with fenofibraty is not expected. However there can be a pharmakodinamichesky interaction.
Gemfibrozil, fenofibrat, other fibrata and lipidoponizhayushchy doses (> or it is equal to 1 g/day) Niacinum (niacin) enhance risk of a myopathy at joint reception from GMG-KoA-reduktazy inhibitors, it is possible because they can cause a myopathy at separate use. The dose of 40 mg is contraindicated at combined use with fibraty (cm Section 4.3 and 4.4). These patients have to begin with a dose 5 mg also.
Protease inhibitors:
In spite of the fact that the exact mechanism of interaction is unknown, sharing of inhibitor of protease can strengthen effect of rosuvastatin considerably. In a pharmacokinetic research joint reception of 20 mg of rosuvastatin and a combination of drug with 2 inhibitors of protease (400 mg of a lopinavir of/100 mg of an irtonavir) at healthy volunteers (0-24) rosuvastatin and Cmax respectively were associated with approximately 2-fold and 5-fold increase in a homeostasis of PPK. Thus, sharing of rosuvastatin at patients from the HIV accepting protease inhibitors is not recommended.
Antacids:
Simultaneous use of rosuvastatin with the suspension of an antacid containing hydroxide of aluminum and magnesium leads to reduction of concentration of rosuvastatin in plasma approximately for 50%.
This effect was softened when the antacid was accepted in 2 hours after intake of rosuvastatin. The clinical importance of this interaction was not studied.
Erythromycin:
Simultaneous use of rosuvastatin and erythromycin leads to 20% to reduction of PPK (0-t) and 30% to reduction of Cmax of rosuvastatin. This interaction can be caused by strengthening of the vermicular movement of intestines caused by erythromycin.
Oral contraceptives / gormozamestitelnaya therapy:
Simultaneous use of rosuvastatin and oral contraceptives leads to increase in PPK of ethinylestradiol and Norgestrelum by 26% and 34%, respectively. This increase in level in plasma has to be taken into account when choosing doses of an oral kontratsepitv. Pharmacokinetic data on the persons accepting at the same time rosuvastatin and gormozamestitelny therapy are unavailable, thus, similar effects cannot be excluded. However, the combination is widely used at women in clinical trials and well transferred.
Other medications:
On the basis of data on special researches of interaction clinically significant interaction with digoxin is not expected.
P450 cytochrome enzymes:
Results of the researches in vitro and in Vivo show that rosuvastatin is not either inhibitor, or the inductor of isoenzymes of P450 cytochrome. Besides, rosuvastatin is not nutritious substrate for these isoenzymes. Clinically significant interaction between rosuvastatin and flukonazoly (CYP2C9 and CYP3A4 inhibitor) or ketonazoly was not observed (CYP2A6 and CYP3A4 inhibitor). As a result of joint intake of rosuvastatin and an itrakonazol (CYP3A4 inhibitor) and PPK of rosuvastatin increases by 28%. This small increase is not considered clinically significant. Thus, interaction of drugs as a result of P450 cytochrome metabolism is not expected.
Special instructions
With care
For doses less than 40 mg: the personal or family anamnesis of hereditary muscular diseases and the previous anamnesis of muscular toxicity when using other inhibitors of GMG-KoA-reduktazy or fibrat, excessive alcohol intake, a hypothyroidism, race (Asian race), co-administration from fibrata.
Presence of risk of developing a myopathy/rhabdomyolysis - a renal failure, age is more senior than 70 years, states at which increase in plasma concentration of rosuvastatin, liver diseases in the anamnesis, sepsis, arterial hypotension, extensive surgical interventions, injuries, heavy metabolic, endocrine or electrolytic disturbances or uncontrollable epilepsy is noted.
Use in pediatric practice
the Efficiency and safety of use of drug for children up to 18 years is not completely established.
From the musculoskeletal system
At Polvasterol's use in all dosages and, in particular at reception of the doses of drug exceeding 20 mg it was reported about the following impacts on the musculoskeletal system: myalgia, myopathy, in rare instances rhabdomyolysis.
Definition of a kreatinfosfokinaza
of KFK should not be carried out after intensive physical activities or in the presence of other possible reasons of increase in KFK, can lead to incorrect interpretation of the received results. In case the KFK initial level is significantly increased (5 times higher, than the upper bound of norm), in 5 - 7 days it is necessary to take repeated measurement. It is not necessary to begin therapy if the repeated test confirms the KFK initial level (more than 5 times higher in comparison with the upper bound of norm).
It is necessary to inform the patient on need of the immediate message to the doctor about cases of unexpected appearance of muscular pains, muscle weakness or spasms, especially in combination with an indisposition and fever. At such patients it is necessary to determine the KFK level. Therapy has to be stopped if the KFK level is considerably increased (more than by 5 times in comparison with the upper bound of norm) or if symptoms from muscles are pronounced and cause daily discomfort (even if the KFK level is 5 times less in comparison with the upper bound of norm). If symptoms disappear and the KFK level returns to norm, it is necessary to consider a question of repeated appointment of Polvasterol or other inhibitors of GMG-KoA-reduktazy in smaller doses at careful observation of the patient. Routine control of KFK in the absence of symptoms is not reasonable.
Signs of increase in impact on skeletal muscles at Polvasterol's reception and the accompanying therapy are noted. It was reported about increase in number of cases of a miositis and a myopathy at the patients accepting other inhibitors of GMG-KoA-reduktazy in combination with derivatives of fibrinous acid, including gemfibrozit, cyclosporine, niacin, azolny antifungal means, inhibitors of proteases and makrolidny antibiotics. Gemfibrozil increases risk of emergence of a myopathy at the combined appointment with some inhibitors of GMG-KoA-reduktazy. Thus, co-administration of Polvasterol and a gemfibrozil is not recommended. The ratio of risk and possible advantage at combined use of Polvasterol and fibrat or Niacinum has to be carefully weighed.
In 2-4 weeks after an initiation of treatment and/or at increase in a dose of Polvasterol the control of indicators of lipidic exchange is necessary (if necessary dose adjustment is required).
The liver
Is recommended to carry out definition of indicators of function of a liver prior to therapy and in 3 months after the beginning of therapy. Polvasterol's reception it is necessary to stop or reduce a drug dose if the level of activity of transaminases in blood sera by 3 times exceeds the upper bound of norm. At patients with a hypercholesterolemia owing to a hypothyroidism or a nephrotic syndrome therapy of basic diseases has to be carried out prior to treatment by Polvasterol.
The interstitial disease of lungs
At use of statines was reported about single cases of an interstitial disease of lungs, especially, when long therapy was carried out. The described signs can include short wind, dry cough and the general aggravation of symptoms (fatigue, loss of weight and fever). If there are suspicions on development in the patient of an interstitial disease of lungs, therapy by statines it is necessary to stop.
Diabetes
At patients with glucose level in blood on an empty stomach of 5.6 - 6.9 mmol/l, treatment by rosuvastatin contacted the diabetes raised by risk of a disease.
Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms
During the driving or work with mechanisms need to be considered that during therapy there can be dizziness.
Overdose
Symptoms - expressiveness of symptoms of side effects.
Treatment - symptomatic and the supporting actions. Control of function of a liver and the KFK level is necessary. It is improbable that the hemodialysis will be effective.
The form of release and packing
On 10 tablets place in blister strip packaging from a foil soft, from the opaque party laminated by polyamide, from the brilliant party laminated by a film of polyvinylchloride and aluminum foil (AL/OPA/AL/PVH).
On 3 planimetric packs together with the instruction for medical use in the state and Russian languages place in a cardboard pack.
To Store storage conditions in the dry, protected from light place at a temperature not over 30 of 0C to Store in places inaccessible for children!
A period of storage
2 years
not to use drug after expiry date
Prescription status
According to the prescription
the Producer
the Pharmaceutical plant POLFARMA of the joint-stock company, Poland
of st. of Pelplinsk 19, 83-200 Starogard Gdanski
the Owner of the registration certificate
of JSC Khimfarm,
to Develop Kazakhstan
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