Description overdue on 08/13/2014
- Latin name: Roxera
- ATC code: C10AA07
- Active substance: Rosuvastatin (Rosuvastatinum)
- Manufacturer: KRKA, Slovenia
- Composition
- Product form
- Pharmacological action
- Pharmacodynamics and pharmacokinetics
- Indications
- Contraindications
- Side effects
- Tablets Roxer: instructions for use, route of administration and dosing regimen
- Overdose
- Cooperation
- Terms of sale
- Storage conditions
- Shelf life
- Analogs
- Reviews
- Price, where to buy
Composition
The composition of one tablet Roxer includes 5, 10, 15, 20, 30 or 40 mg rosuvastatin as rosuvastatin calcium and auxiliary components:
- microcrystalline cellulose;
- lactose anhydrous;
- crospovidone;
- colloidal anhydrous silica;
- magnesium stearate.
The shell, which is coated tablet contains in its composition:
- butyl methacrylate, dimethylaminoethyl metilkrilata copolymer in the ratio 1: 2: 1;
- macrogol 6000;
- titanium dioxide;
- lactose monohydrate.
Product form
Roxer produced in the form of tablets, coated white film coating, which differ in appearance depending on the concentration of the active substance:
- Tablets of rosuvastatin at a dose of 5, 10 or 15 mg are round, biconvex, with bevelled. On one side is made marking the corresponding dose of the active substance, "5", "10" and "15" respectively.
- Tablets of rosuvastatin at a dose of 20 mg are round, biconvex, with bevelled.
- Tablets of rosuvastatin at a dose of 30 mg, biconvex, shape and have kapsulovidnuyu risks of the two sides.
- Tablets of rosuvastatin at a dose of 40 mg, biconcave have kapsulovidnuyu form.
To cut the tablets are well looked through two layers, the inner - white.
Pharmacological action
The pharmacological action of the drug Roxer directed to:
- Suppressing the activity of microsomal enzyme hydroxymethylglutaryl-CoA reductase , Which performs the function of limiting the early stages of catalyst synthesis cholesterol .
- Normalization of the lipid profile ( hypolipidemic effect ) Due to a decline in blood concentrations of total cholesterol . triglycerides . Lipoprotein low density, and improve concentration indicators Lipoprotein high density.
The drug belongs to the pharmacological group " Statins ".
Pharmacodynamics and pharmacokinetics
Once in the body, rosuvastatin triggers the following effects:
- Helps reduce high concentrations low density lipoprotein cholesterol ;
- Helps reduce elevated concentrations of total cholesterol ;
- Helps reduce elevated triglyceride concentrations;
- Improves concentration HDL cholesterol ;
- It helps reduce the concentration low density lipoprotein apolipoprotein ( apolipoprotein B );
- It helps reduce the concentration low density lipoprotein cholesterol ;
- It helps reduce the concentration cholesterol, very low density lipoproteins ;
- It helps reduce the concentration triglycerides, very low density lipoproteins ;
- Improves concentration plasma apolipoprotein A1 ;
- Lowers cholesterol ratios LDL to high density lipoprotein cholesterol ;
- It reduces the overall ratios cholesterol to high density lipoprotein cholesterol ;
- Reduces ratios low density lipoprotein cholesterol to high density lipoprotein cholesterol;
- Reduces ratios low density lipoprotein apolipoprotein ( apolipoprotein B ) To apolipoprotein A1 .
Marked clinical effect of the Roxer develops a week after the start of the course of treatment. Approximately 90% of the maximum effect of the therapy is celebrated two weeks later.
To achieve the maximum effect takes usually four weeks, after which it is maintained throughout the subsequent treatment period.
The maximum plasma concentration rosuvastatin It says five hours after taking the pill, the rate of absolute bioavailability is 20%.
Rosuvastatin extensively biotransformed in liver Which is the primary focus of synthesizing cholesterol and metabolizing LDL cholesterol .
The index of the matter distribution is approximately 134 liters. About 90% rosuvastatin binds plasma proteins (mainly albumin ).
Rosuvastatin metabolized limited (about 10%). Carried out in vitro using a human hepatocyte research metabolism substance showed that it is subject only to minimum metabolism based cytochrome P450 enzyme system . Moreover, this metabolism can not be considered clinically important.
The main isoenzyme Participating in the metabolism of rosuvastatin Is CYP 2C9. To a lesser extent take part in the process isozymes 2C19, 3A4 and 2D6.
In the process of metabolizing it was identified two main metabolite :
- N-desmethyl ;
- lactone .
N-desmethyl It characterized at about one-half as compared to the activity rosuvastatin . As for lactone , It is considered clinically inactive form.
Rosuvastatin It has more than 90% inhibitory activity against hydroxymethylglutaryl-CoA reductase (HMG-CoA-reductase) that circulates in the human body in the general circulation.
Most enter the body rosuvastatin (about 90%) is output unchanged with the contents bowel . Thus excreted both absorbed and unabsorbed active substance.
The residue rosuvastatin excreted by the kidneys in the urine (approximately 5% - unchanged).
Half-life of the substance is about 20 hours and depends on the increase in dose. The average clearance of plasma is about 50 liters per hour. Indicator variation relative to the mean value (coefficient of variation) - 21, 7%.
As is the case with other agents that suppress the activity hydroxymethylglutaryl-CoA reductase , The capture of the liver rosuvastatin promotes attraction membrane transporter OATR-C, which plays an important role in the process of removing a substance from liver .
Rosuvastatin characterized by a dose-dependent systemic exposure, which increases in proportion to the dose of the substance.
Repeated daily application of the drug does not cause any changes of its pharmacokinetic characteristics of the active substance.
The patient's age and sex of no influence on the pharmacokinetics. This study showed that patients Mongoloid race the AUC and maximum plasma concentration rosuvastatin approximately twice as high as in patients belonging to the Caucasian race.
Indians have similar rates higher than those for Caucasians approximately 1, 3 times. There are no clinically significant differences between indicators for blacks and Caucasians are missing.
Patients with renal failure in mild or moderate form of indicators and the highest concentration of rosuvastatin N-desmethyl plasma remains essentially unchanged.
In severe forms renal failure index higher plasma concentrations rosuvastatin increased by about three times, and the rate of the highest plasma concentrations N-desmethyl - About nine times compared to the number reported in healthy volunteers.
Indicators plasma concentrations rosuvastatin patients who were on hemodialysis , Higher than in healthy volunteers approximately doubled.
At hepatic insufficiency Caused by chronic alcoholic liver disease, plasma concentrations of indicators rosuvastatin moderately increased.
Patients whose disease is a Class A for Child-Pugh , The rate of the highest concentrations rosuvastatin at plasma and the AUC increased by 60 and respectively by 5% in comparison with patients liver which is healthy.
If the disease liver It belongs to category B by Child-Pugh , Corresponding figures increased by 100 and 21%. For patients whose disease is classified as C, data are not available, due to the lack of experience with them rosuvastatin.
Indications
Roxer shows:
- For treatment of patients suffering from primary hypercholesterolemia type (including family g iperholesterinemii II-A by type Fredrickson ) Or dyslipidemia mixed type (type II-b). The drug is appropriate to prescribe when the expected therapeutic effect can not achieve the purpose of non-drug therapies: diet, correction of the patient's weight, exercise, etc ..
- For the treatment of patients diagnosed with family homozygous hypercholesterolaemia . Roxer prescribed as an adjunct to therapy, the aim of which is to reduce the level lipids As an adjunct to diet and in those cases where the previously assigned treatment does not give positive results.
- For patients who have been diagnosed atherosclerosis . The drug is used as an adjunct to diet assigned to slow the progression of the disease, as well as to decrease the total cholesterol and low density lipoprotein cholesterol to the desired level.
- As a prophylactic agent, preventing the development of disease complications hearts and vessels patients with a predisposition to the development of atherosclerotic vascular lesions .
Contraindications
Contraindications to tablets with a content of rosuvastatin Roxer at doses of 5, 10 and 15 mg, are:
- hypersensitivity to one or more components of the drug;
- reactive liver abnormalities (including inter alia the nature of the disease of unknown origin), as well as conditions characterized by steady increase in the level of hepatic transaminases And a state in which either hepatic transaminases It increases not less than three times;
- renal disease In which the clearance creatinine does not exceed the rate of 30 ml / min;
- chronic progressive hereditary neuromuscular diseases Which are characterized by a primary lesion of the muscles ( myopathy );
- concomitant use of anti-depressant Cyclosporine ;
- diagnosed in a patient at increased risk for miotoksicheskih complications ;
- intolerance lactose ;
- lactase deficiency ;
- galactose malabsorption glucose ;
- pregnancy (as the drug is not prescribed to women of reproductive age, if they do not use contraceptives );
- lactation;
- age 18 years.
Tablets of dosage rosuvastatin 30 and 40 mg are contraindicated:
- patients with a hypersensitivity to one or more components of the drug;
- patients with active forms liver abnormalities (including inter alia the nature of the disease of unknown origin), as well as conditions characterized by steady increase in the level of hepatic transaminases And a state in which either hepatic transaminases It increases not less than three times;
- renal disease In which the clearance creatinine does not exceed the rate of 60 ml / min;
- chronic progressive hereditary neuromuscular diseases Which are characterized by a primary lesion of the muscles ( myopathy );
- hypothyroidism ;
- concomitant use of anti-depressant Cyclosporine ;
- diagnosed in a patient at increased risk for miotoksicheskih complications (when the patient has a history of a mark on the toxicity from the muscle, which provoked another drug inhibitor hydroxymethylglutaryl-CoA reductase or drugs that are derivatives fibric acid );
- alcohol addiction;
- severe hepatic insufficiency ;
- affiliation of the patient to the Mongoloid race;
- Simultaneous reception fibrates ;
- intolerance lactose ;
- lactase deficiency ;
- galactose malabsorption glucose ;
- pregnancy (as the drug is not prescribed to women of reproductive age, if they do not use contraceptives);
- lactation;
- age 18 and older than 70 years.
Side effects
The treatment Roxer may experience the following side effects:
- dysfunction immune system Including the reactions caused by hypersensitivity to Rosuvastatin or other ingredients of the drug, including the development of angioedema ;
- dysfunction Digestive System , Expressed in the form of frequent constipation, epigastric pain, nausea; in rare cases can develop pancreatitis ;
- violations arising from the skin and subcutaneous tissue and is expressed in the form of a skin rash, pruritus, hives ;
- dysfunction of skeletal muscle that occur in the form of myalgia (often) and sometimes myopathy and rhabdomyolysis ;
- violation of a general nature, the most common of which is asthenia ;
- dysfunction kidney and urinary tract Which are often accompanied by increased concentrations of protein in urine.
Roxer can influence change in laboratory parameters. So, after taking the drug can increase the activity CK , Concentration indices Glucose . bilirubin , Liver enzyme gamma-glutamyl . alkaline phosphatase And changing parameters of plasma hormone concentrations Thyroid .
The frequency and severity of side effects are dose-dependent quantities.
Tablets Roxer: instructions for use, route of administration and dosing regimen
Before the appointment of the drug the patient is recommended to switch to a standard diet, the aim of which is to reduce the level cholesterol . Sticking to this diet is necessary and throughout the course of treatment.
Dose selected individually by the attending physician depending on the purpose of therapy and its effectiveness. Take the drug is allowed at any time, without being tied to meal times.
The tablet is swallowed whole without crushing, without chewing and drinking enough water.
Patients with hypercholesterolemia should start taking the drug with doses of 5 or 10 mg rosuvastatin . Tablets are given orally for one day. And this condition is maintained for patients who are not in treatment statins And for patients who have already completed a course of treatment with drugs that suppress the activity hydroxymethylglutaryl-CoA reductase .
In determining the initial dose Roxer, the doctor draws attention to the concentration indices cholesterol And assesses the risks of cardiovascular complications and side effects.
Where necessary, the dose may be adjusted to the next level, however, such adjustment is carried out not earlier than 4 weeks after the first administration.
Given that side reactions are dose-dependent, and upon receiving 40 mg of rosuvastatin occur more frequently than when taking it in smaller quantities, increasing the daily dose to 30 mg or 40 should be carried out with special care for:
- patients with severe hypercholesterolemia ;
- patients likely to develop complications from the function hearts and vascular system (in particular, if a patient is diagnosed familial hypercholesterolemia ).
If receiving lower doses rosuvastatin these categories of patients did not give the expected result, after the appointment of Roxer at a dose of 30 or 40 mg per day, patients must necessarily be kept under the control of the doctor treating them.
Also, regular monitoring by a doctor shown in cases where treatment is initiated immediately with a dose of 30 mg or 40 mg.
In accordance with the instructions for use, 20 mg Roxer shown as the starting dose for the prevention of diseases hearts and vascular patients Who have an increased risk of development of such pathologies.
People with moderate to severe impairment kidney adjust the dose is not required, however, this group of patients administered the drug with caution.
When dysfunction kidney moderate severity when clearance creatinine is in the range of 60 ml / min, treatment is initiated with a dose of 5 mg. High doses of the drug (30 and 40 mg) to appoint contraindicated.
Patients with severe dysfunction kidney prohibited use of the drug in any dosage.
In appointing the patients with Roxer liver disease Whose exponents of Child-Pugh do not exceed the 7, is not observed to increase systemic exposure rosuvastatin .
If the figures dysfunction liver equal to 8 or 9 points on Child-Pugh , Systemic exposure increases. Therefore, before assigning them to the drug in such patients require additional investigation function kidney .
The experience of treating patients, figures which exceed 9 points on Child-Pugh , absent.
Overdose
The clinical manifestations that may arise in excess of the recommended dosage instructions are not described. After receiving a single dose of Roxer, several times larger than the daily, clinically relevant changes in the pharmacokinetics rosuvastatin was observed.
In case of overdose and appearance symptoms of intoxication organism is shown symptomatic treatment and - if necessary - the appointment of the complex support measures.
It is also recommended to control the level of activity CK and carrying out the test to assess the functionality of liver .
Expediency destination Hemodialysis It is considered unlikely.
Cooperation
When assigning Roxer in combination with Cyclosporine significantly increased performance AUC rosuvastatin (approximately seven times), the plasma concentration cyclosporine It remains unchanged.
When concomitant administration with drugs that are antagonists Vitamin K or medications that suppress the activity hydroxymethylglutaryl-CoA reductase At the beginning of treatment, as well as an increase of the daily dose through its titration, there may be an increase INR (international normalized ratio).
As a rule, due to lower dose titration or total withdrawal of the drug, this figure is reduced.
Simultaneous treatment with lipid-lowering drugs Ezetimibe It does not cause changes in the AUC and peak plasma concentrations of both drugs, however, the possibility of pharmacodynamic interactions are not excluded.
In combination with Gemfibrozil and other drugs that help to reduce lipids It provokes a twofold increase in the AUC and maximum plasma concentration rosuvastatin .
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Terms of sale
Storage conditions
Shelf life
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