Liprimar® (Atorvastatin) 20 mg, 30 tablets
- $89.50
The instruction for medical use
of LIPRIMAR® medicine
the Trade name
of Liprimar®
the International unlicensed
name Atorvastatin Lekarstvennaya
the Tablet form, film coated, 10 mg, 20 mg, 40 mg and 80 mg
Structure
One tablet contains
active agent – calcium of an atorvastatin of 10.85 mg, 21.70 mg, 43.40 mg and 86.80 mg equivalent to an atorvastatin of 10 mg, 20 mg, 40 mg and 80 mg respectively,
excipients: calcium carbonate, cellulose microcrystalline, lactoses monohydrate, sodium of a kroskarmelloz, polysorbate 80, hydroxypropyl cellulose, magnesium stearate,
film covering: hydroksipropilmetiltsellyuloza, polyethyleneglycol 8000, titan dioxide (E 171), talc, emulsion of a simetikon.
The description
Round tablets, film coated white color, with an engraving 10 on one party and ATV - on another (a dosage of 10 mg).
Round tablets, film coated white color, with an engraving 20 on one party and ATV - on another (a dosage of 20 mg).
Round tablets, film coated white color, with an engraving 40 on one party and ATV - on another (a dosage of 40 mg).
Round tablets, film coated white color, with an engraving 80 on one party and ATV - on another (a dosage of 80 mg).
Pharmacotherapeutic group
Hypolipidemic drugs. Gipokholesterinemichesky and gipotriglitseridemichesky drugs. KoA-reductase GMG inhibitors.
Atorvastatin.
The ATX C10AA 05 code
the Pharmacological
Atorvastatin Pharmacokinetics Absorption properties is quickly soaked up after intake, concentration it in blood plasma reaches a maximum in 1-2 hours. Extent of absorption and concentration of an atorvastatin in blood plasma raise in proportion to a dose. The absolute bioavailability of an atorvastatin is about 14%, and system bioavailability of the inhibiting activity in the relation 3-hydroxy-3-methylglutaryl coenzyme of A-reductase (GMG-KoA-reduktazy) - about 30%. The low system bioavailability is caused by presistemny metabolism in a mucous membrane of digestive tract and/or at 'the first passing' through a liver.
Food reduces the speed and extent of absorption of drug a little (by 25% and 9%, respectively, what results of definition of Cmax and AUC testify to), however decrease in cholesterol of lipoproteids of the low density (Hs-LPNP) is similar to that at reception of an atorvastatin on an empty stomach. After reception of an atorvastatin in the evening its concentration in blood plasma is lower (Cmax and AUC approximately for 30%), than after reception in the morning. The linear dependence between extent of absorption and a dose of drug is revealed.
Distribution
the Average volume of distribution of an atorvastatin makes about 381 l. Communication with proteins of blood plasma not less than 98%. The relation of maintenance of an atorvastatin in erythrocytes/plasma makes about 0.25, i.e. atorvastatin badly gets into erythrocytes.
Metabolism
Atorvastatin is substantially metabolized with education orto- and para-hydroxylated derivatives and various products of beta oxidation. Orto- and para-hydroxylated metabolites have inhibiting effect on GMG-KoA-reduktazu. About 70% of decrease of the activity of GMG-KoA-reduktazy happen due to action of the active circulating metabolites. In metabolism of an atorvastatin liver P450 3A4 cytochrome plays an important role: concentration of an atorvastatin in blood plasma of the person at a concomitant use of erythromycin which is inhibitor of this isoenzyme increases. In turn atorvastatin is weak inhibitor of P450 3A4 cytochrome. Atorvastatin has no clinically significant impact on concentration in blood plasma of a terfenadin who is metabolized, mainly, by P450 3A4 cytochrome therefore it is improbable that atorvastatin has significant effect on pharmacokinetics of other substrates of P450 3A4 cytochrome.
Removal
Atorvastatin and his metabolites are removed, mainly, with bile as a result of hepatic and/or extrahepatic metabolism (atorvastatin is not exposed to the significant enterohepatic recirculation). Elimination half-life of an atorvastatin makes about 14 h. The inhibiting activity concerning GMG-KoA-reduktazy remains about 20-30 h, thanks to existence of active metabolites. After intake in urine less than 2% of an atorvastatin are found.
Special groups of patients
Elderly: concentration of an atorvastatin in blood plasma at aged people of 65 years are also more senior above (Cmax approximately for 40%, AUC approximately for 30%), than at adult patients of young age, differences in safety, efficiency or achievement of the goals of hypolipidemic therapy at elderly people in comparison with the general population it is not revealed.
Children: in an open 8 weeks research the patients of children's age with a stage a polovogotrazvitiya on Tannera 1 (N = 15) and ≥ 2 (N = 24) (at the age of 6–17 years) with a heterozygous family hypercholesterolemia and the H-LPNP initial level ≥ 4 mmol/l received, respectively, atorvastatin in doses 5 or 10 mg in the form of chewable tablets or 10 or 20 mg in the form of tablets, film coated once a day once a day. Body weight was the only significant variable in population FC of model of an atorvastatin. The seeming oral clearance of an atorvastatin at patients of children's age was similar to that at adults at allometrichesky scaling in body weight. In the range of exposures of an atorvastatin and about-hydroksiatorvastatina steady decrease in levels of H-LPNP and OH was observed.
Floor: concentration of an atorvastatin in blood plasma at women differs (Cmax is about 20% higher, and AUC 10% lower) from that at men, however clinically significant distinctions of influence of drug on lipidic exchange at men and women are not revealed.
Renal failure: the disease of kidneys does not affect concentration of an atorvastatin in blood plasma or its impact on indicators of lipidic exchange, in this regard change of a dose with a renal failure is not required from patients.
Hemodialysis: it is improbable that the hemodialysis will lead to significant increase in clearance of an atorvastatin as drug is substantially connected with proteins of blood plasma.
Liver failure: concentration of an atorvastatin considerably increases (Cmax approximately by 16 times, AUC approximately by 11 times) at patients with alcoholic cirrhosis (Chayld-Pyyu C).
The polymorphism of SLOC1B1
Hepatic metabolism of all inhibitors of GMG-KoA-reduktazy, including atorvastatin, is carried out with the assistance of the carrier of OATP1B1. Patients with polymorphism of SLOC1B1 have a risk of the increased exposure of an atorvastatin that can result in the increased risk of a rhabdomyolysis. The polymorphism in the gene coding protein OATP1B1 (SLCO1B1c.521CC) causes 2.4-fold increase in AUC value of an atorvastatin in comparison with that at the people who do not have the called genetic option (page 521TT). At this group of patients the genetic defect of capture of an atorvastatin liver cells is also possible. Possible consequences of influence on efficiency are not known.
A pharmacodynamics
of Liprimar® – synthetic hypolipidemic drug, a selection competitive inhibitor of GMG-KoA-reduktazy – the key enzyme turning 3-hydroksi-3-metilglutaril-KoA into mevalonovy acid – the predecessor of steroids, including cholesterol. At patients with a homozygous and heterozygous family hypercholesterolemia, single forms of a hypercholesterolemia and the mixed dislipidemiya, Liprimar® reduces the content in blood plasma of the general cholesterol (Hs), cholesterol of lipoproteids of low density and apolipoprotein B and also cholesterol of lipoproteids of very low density (Hs-LPONP) and triglycerides, causes unstable increase in content of cholesterol of lipoproteids of the high density (Hs-LPVP).
In a liver triglycerides and cholesterol are included lipoproteids of very low density (LPONP), come to blood plasma and are transferred to peripheral fabrics. Lipoproteids of the low density (LDL) which catabolize in interaction with high-affine receptors of LDL are formed of LPONP.
Липримар® reduces concentration of cholesterol and lipoproteids in blood plasma, inhibiting GMG-KoA-reduktazu and synthesis of cholesterol in a liver and increasing number of 'hepatic' receptors of LDL by surfaces of cells that leads to strengthening of capture and catabolism of LDL cholesterol.
Indications
- in combination with a diet for treatment of patients with the increased content in blood plasma of the general cholesterol, Hs-LPNP, apolipoprotein B and triglycerides and increases in maintenance of Hs-LPVP patients with primary hypercholesterolemia (heterozygous family and single hypercholesterolemia) combined (mixed) lipidemia (the IIa and IIb types across Frederikson), with the increased content of triglycerides in blood plasma (type IV across Frederikson) and patients with a disbetalipoproteinemiya (type III across Frederikson), in case of lack of adequate effect at a dietotherapy
- for decrease in content in blood plasma of the general cholesterol and Hs-LPNP at patients with a homozygous family hypercholesterolemia at insufficient efficiency of a dietotherapy and other not pharmacological methods of treatment
- for reduction of risk of lethal outcomes of an ischemic heart disease and risks of developing a myocardial infarction, stenocardia, a stroke and for reduction of need of holding procedures of revascularization at patients with cardiovascular diseases and/or a dislipidemiya and also if these diseases are not revealed, but have not less than three risk factors of development of an ischemic heart disease, such as age more than 55 years, smokings, arterial hypertension, low concentration in Hs-LPVP blood plasma, cases of prematurity of an ischemic heart disease for relatives
- in combination with a diet for treatment of children at the age of 10-17 years with the increased content in blood plasma of the general cholesterol, Hs-LPNP and apolipoprotein B with a heterozygous family hypercholesterolemia if after an adequate dietotherapy the Hs-LPNP level remains also to gt, 190mg/dl or the Hs-LPNP level remains also to gt, 160mg/dl, but at the same time there are cases of prematurity of cardiovascular diseases at relatives or two and more risk factors of developing cardiovascular diseases at the child
the Route of administration and doses
Before an initiation of treatment of Liprimarom® it is necessary to try to achieve control of a hypercholesterolemia by means of a diet, physical exercises and decrease in body weight from patients with obesity and also treatment of a basic disease. When prescribing drug the patient needs to recommend a standard gipokholesterinemichesky diet which he has to observe during treatment.
The drug is taken at any time, irrespective of meal. The dose of drug is varied by from 10 to 80 mg once a day, selecting it taking into account the initial maintenance of Hs-LPNP, the purpose of therapy and individual effect. In an initiation of treatment and/or during increase in a dose of Liprimara® it is necessary to control each 2-4 weeks the maintenance of lipids in blood plasma and as appropriate to adjust a dose.
Primary hypercholesterolemia and the combined (mixed) lipidemia: for most of patients - 10 mg once a day, therapeutic action is shown within 2 weeks and usually reaches a maximum within 4 weeks, at long-term treatment the effect remains.
Homozygous family hypercholesterolemia: 80 mg once a day (in most cases therapy led to decrease in maintenance of Hs-LPNP by 18-45%).
Heavy dislipidemiya at pediatric patients: the recommended starting dose – 10 mg once a day. The dose can be increased up to 80 mg a day according to the clinical answer and shipping. Doses have to be picked up individually taking into account the recommended therapy purpose.
Use for patients with liver diseases: see. Contraindications.
A dosage at patients with a renal failure: the disease of kidneys does not influence concentration of Liprimara® in blood plasma or extent of decrease in maintenance of Hs-LPNP therefore correction of a dose of drug is not required.
Use for elderly people: differences in safety, efficiency or achievement of the goals of hypolipidemic therapy at elderly people in comparison with the general population are not revealed.
Side effects
Often (from & gt, 1/100 to & lt, 1/10)
- a headache
- a nasopharyngitis
- a hyperglycemia
- throat and throat pain, nasal bleeding
- dyspepsia, nausea, a constipation, a meteorism, diarrhea
- an arthralgia, extremity pain, myotonia, myalgia, swelling of joints, a dorsodynia
- abnormal indicators of function of a liver, increase in a serumal kreatinfosfokinaza (KFK)
- allergic reactions
Infrequently (from ≥1/1000 to & lt, 1/100)
- a hypoglycemia, increase in body weight, anorexia
- dreadful dreams, insomnia
- dizziness, paresthesia, a hypesthesia, a dysgeusia, amnesia
- indistinct sight
- sonitus
- vomiting, pain in the upper and lower part of a stomach, an eructation
- pancreatitis, hepatitis
- urticaria, skin rash, an itching, an alopecia
- neck pain, muscular fatigue
- an indisposition, an asthenia, thorax pain, peripheral hypostasis, increased fatigue, fever
- emergence of leukocytes in urine
Is rare (from ≥1/10000 to & lt, 1/1000)
- thrombocytopenia
- peripheral neuropathy
- a disorder of vision
- a cholestasia
- a Quincke's disease, bullous dermatitis including a polymorphic erythema, Stephens-Johnson's syndrome and a toxic epidermal necrolysis
- a myopathy, a miositis, a rhabdomyolysis, a tendinopatiya sometimes complicated with a gap
Very seldom (from ≤1/10000)
- an anaphylaxis
- a hearing loss
- a liver failure
- a gynecomastia
Is unknown (it is impossible to determine by the available data).
- the immunomediated necrotizing myopathy
the Following side effects were revealed in patients of children's age:
Often (from & gt, 1/100 to & lt, 1/10)
- a headache
- an abdominal pain
- increase in levels of alaninaminotranspherase and a serumal kreatinfosfokinaza (KFK)
At intake of some statines:
- sexual dysfunction
- a depression
- exclusively exceptional cases of an interstitial pulmonary disease, especially at long-term therapy
- diabetes: frequency will depend on existence or lack of risk factors (glucose in blood on an empty stomach of ≥5.6 mmol/l, BMI & gt, 30 kg/sq.m, the increased levels of triglycerides, arterial hypertension in the anamnesis)
Contraindications
- hypersensitivity to any of drug components
- an active disease of a liver or increase in activity of transaminases of serum (more than by 3 times in comparison with the upper bound of norm) not clear genesis
- pregnant women and the feeding women and also women of reproductive age who are not using adequate methods of contraception
- patients with a hereditary lactose intolerance, deficiency of enzyme of LAPP lactase, glucose galactose malabsorption
Medicinal interactions
Risk of development of a myopathy raises during treatment by inhibitors of GMG-KoA-reduktazy and simultaneous use of cyclosporine, derivatives of fibroyevy acid, botsepreviry, niacin and inhibitors of P450 3A4 cytochrome (erythromycin, antifungal drugs relating to azoles). At the patients who are at the same time accepting atorvastatin and botseprevir it is recommended to use the drug Liprimar® in lower initial dose and to carry out clinical monitoring. During the combined use with botsepreviry the daily dose of an atorvastatin should not exceed 20 mg.
Very rare messages about the immunomediated necrotizing myopathy (INM) in time or after treatment by statines, including atorvastatiny were registered. INM is clinically characterized by weakness of proximal muscles and the increased creatine kinase level in serum which remain, despite the therapy termination by statines.
P450 3A4 inhibitors: atorvastatin it is metabolized by P450 3A4 cytochrome. Simultaneous use of Liprimara® and inhibitors of P450 3A4 cytochrome can lead to increase in concentration of an atorvastatin in blood plasma. Extent of interaction and potentiation of effect depends on variability of action on P450 3A4 cytochrome.
Simultaneous use of strong P450 3A4 inhibitors (for example, cyclosporine, a telitromitsin, a klaritromitsin, a delavirdin, a stiripentol, a ketokonazol, a vorikonazol, an itrakonazol, a pozakonazol and inhibitors of HIV protease, including ritonavir, lopinavir, atazanavir, indinavir, darunavir, etc.) should be avoided as far as possible. In cases when simultaneous use of these medicines with atorvastatiny cannot be avoided, it is recommended to appoint lower initial and maximum doses of an atorvastatin and also to carry out appropriate clinical monitoring of a condition of the patient.
Moderate P450 3A4 inhibitors (for example, erythromycin, diltiazem, verapamil and flukonazol) can increase concentration of an atorvastatin in plasma. When using erythromycin in combination with statines the increased risk of a myopathy is observed. The researches of interactions estimating influence of Amiodaronum or verapamil on atorvastatin were not conducted. Both Amiodaronum, and verapamil inhibit activity of P450 3A4, and their combined use with atorvastatiny can lead to the increased exposure of an atorvastatin. Thus, at simultaneous use with moderate P450 3A4 inhibitors it is recommended to appoint lower maximum dose of an atorvastatin and to carry out the corresponding clinical monitoring at the patient. The corresponding clinical monitoring is recommended after the beginning of therapy or after inhibitor dose adjustment.
Conveyor inhibitors: atorvastatin and its metabolites are OATP1B1 conveyor substrates. OATP1B1 inhibitors (for example, cyclosporine) can increase bioavailability of an atorvastatin. Simultaneous use of 10 mg of Liprimara® and cyclosporine (5.2 mg/kg/days) leads to increase in exposure of an atorvastatin by 7.7 times.
At simultaneous use of an atorvastatin and inhibitors of an isoenzyme CYP3A4 or proteins carriers the increase in concentration of an atorvastatin in blood plasma and increase in risk of a myopathy is possible. The risk can also increase at simultaneous use of an atorvastatin with other medicines capable to cause a myopathy, such as derivatives of fibroyevy acid and ezetimib.
Erythromycin / klaritromitsin: at simultaneous use of Liprimara® and erythromycin (500 mg four times a day) or a klaritromitsina (500 mg two times a day) which inhibit P450 3A4 cytochrome, increase in concentration of an atorvastatin in blood plasma was observed.
Inhibitors of proteases: simultaneous use of Liprimara® with the inhibitors of proteases known as inhibitors of P450 3A4 cytochrome, was followed by increase in concentration of an atorvastatin in blood plasma.
Diltiazem hydrochloride: simultaneous use of Liprimara® (40 mg) and diltiazem (240 mg) leads to increase in concentration of an atorvastatin in blood plasma.
Cimetidinum: the research of interaction Liprimara® and Cimetidinum was conducted, clinically significant interactions it is not revealed.
Itrakonazol: (20mg-40mg) and the itrakonazola (200 mg) leads simultaneous use of Liprimara® to increase in AUC of an atorvastatin.
Grapefruit juice: contains one or two components which inhibit CYP 3A4 and can increase concentration of an atorvastatin in blood plasma, especially at overconsumption of grapefruit juice (more than 1.2 liters a day).
Inductors of P450 3A4 cytochrome: simultaneous use of Liprimara® with inductors of P450 3A4 cytochrome (efavirenz, Rifampinum and drugs of a St. John's wort) can lead to decrease in concentration of an atorvastatin in blood plasma. In view of the double mechanism of effect of Rifampinum (induction of P450 3A4 cytochrome and inhibition of OATP1B1 enzyme carrier in a liver), it is recommended to appoint Liprimar® along with Rifampinum as reception of Liprimara® after intake of Rifampinum leads to considerable decrease in level of an atorvastatin in blood plasma.
Antacids: the concomitant use in the suspension containing magnesium and aluminum hydroxides reduced concentration of an atorvastatin in blood plasma approximately by 35%, however extent of reduction of maintenance of Hs-LPNP at the same time did not change.
Antipyrine: Липримар® does not influence antipyrine pharmacokinetics therefore interaction with other drugs, the metabolized same isoenzymes of cytochrome, is not expected.
Gemfibrozil / derivatives of fibroyevy acid: monotherapy of a fibratama in certain cases is followed by the undesirable phenomena from muscles, including a rhabdomyolysis. The risk of emergence of these phenomena can be raised at co-administration of derivatives of fibroyevy acid and an atorvastatin. If simultaneous use cannot be avoided, for achievement of the therapeutic purpose it is necessary to use the lowest doses of an atorvastatin and to carry out appropriate monitoring at patients.
Ezetimib: monotherapy ezetimiby is followed by the undesirable phenomena from muscles, including a rhabdomyolysis. Therefore, the risk of these phenomena can be increased at co-administration of an ezetimib and atorvastatin. It is recommended to carry out appropriate monitoring at such patients.
Kolestipol: at simultaneous use of a kolestipol the concentration of an atorvastatin in blood plasma decreased approximately by 25%, however the hypolipidemic effect of a combination of an atorvastatin and kolestipol exceeded that of each drug separately.
Digoxin: At repeated intake of digoxin and Liprimara® in a dose of 10 mg the equilibrium concentration of digoxin in blood plasma did not change. However at use of digoxin in a combination with Liprimarom® in a dose of 80 mg/days the concentration of digoxin increased approximately by 20%. The patients receiving digoxin in combination with Liprimarom® demand the corresponding observation.
Azithromycin: at simultaneous use of Liprimara® (10 mg once a day) and azithromycin (500 mg once a day) concentration of an atorvastatin in plasma did not change.
Oral contraceptives: at simultaneous use of Liprimara® and oral contraceptive containing norethindrone and ethinylestradiol the substantial increase of AUC norethindrone and ethinylestradiol approximately for 30% and 20%, respectively was observed. This effect should be considered when choosing an oral contraceptive for the woman accepting Liprimar®.
Warfarin: in clinical trial at the patients receiving long therapy by warfarin, the combined use of an atorvastatin in a dose of 80 mg a day with warfarin caused small decrease in a prothrombin time approximately for 1.7 seconds during the first 4 days of treatment which returned to normal within 15 days of treatment atorvastatiny. Though only very exceptional cases of clinically significant interaction with anticoagulants, at the patients accepting coumarinic anticoagulants are registered, the prothrombin time should be defined before an initiation of treatment atorvastatiny and is rather frequent at early stages of therapy to make sure of lack of significant changes of a prothrombin time. After the stable prothrombin time is registered, it can be controlled with the frequency which is usually recommended for the patients receiving coumarinic anticoagulants. The same procedure should be repeated at change of a dose of an atorvastatin or its cancellation. Therapy atorvastatiny was not followed by cases of bleeding or changes of a prothrombin time at the patients
who are not accepting anticoagulants.
Warfarin: signs of clinically significant interaction of Liprimara® with warfarin are not revealed.
Amlodipin: at simultaneous use of Липримара® 80 mg and an amlodipina of 10 mg the pharmacokinetics of an atorvastatin in an equilibrium state did not change.
Colchicine: though researches of interactions of an atorvastatin and colchicine were not conducted, it was reported about myopathy cases at combined use of an atorvastatin and colchicine.
Fusidic acid: researches on interaction of Liprimara® and fusidic acid were not conducted, however in post-market researches it was reported about rhabdomyolysis cases at their simultaneous use. Therefore patients have to be under control and in case of need therapy of Liprimarom® can be temporarily suspended.
Other accompanying therapy: in clinical trials of Liprimar® applied in combination with antihypertensive drugs and estrogen which appointed with the replaceable purpose, signs of clinically significant undesirable interaction are noted.
The special
instructions Action on a liver
After treatment of Liprimarom® noted considerable (more than by 3 times in comparison with the upper bound of norm) increase in serumal activity of 'hepatic' transaminases.
Increase in activity of 'hepatic' transaminases usually was not followed by jaundice or other clinical manifestations. At a dose decline of Liprimara®, temporary or full drug withdrawal the activity of 'hepatic' transaminases was restored to initial level. Most of patients continued reception of Liprimara® in a reduced dose without any consequences.
It is necessary to control indicators of function of a liver during all course of treatment, especially at emergence of clinical signs of damage of a liver. In case of increase in content of 'hepatic' transaminases, their activity should be controlled before achievement of limits of norm. If increase in activity of nuclear heating plant or ALT more than by 3 times in comparison with the upper bound of norm remains, the dose decline or drug withdrawal is recommended.
Action
Appointing Liprimar® in hypolipidemic doses in combination with derivatives of fibroyevy acid, erythromycin, immunodepressants, azolny antifungal drugs or niacin to skeletal muscles, the doctor has to weigh carefully expected advantage and risk of treatment and to regularly observe patients for the purpose of detection of pains or weakness in muscles, especially within the first months of treatment and during the periods of increase in a dose of any drug. In similar situations it is possible to recommend periodic determination of activity of KFK though such monitoring does not allow to prevent development of a heavy myopathy. Липримар® can cause increase in activity of a kreatinfosfokinaza.
At use of Liprimara®, exceptional cases of a rhabdomyolysis with the acute renal failure caused by a myoglobinuria and a myoglobinemia are described. Therapy of Liprimarom® should be stopped temporarily or to cancel completely at emergence of signs of a possible myopathy or presence of risk factor of developing a renal failure against the background of a rhabdomyolysis (for example, a heavy acute infection, arterial hypotension, serious operation, an injury, metabolic, endocrine and electrolytic disturbances and uncontrollable spasms).
Information for the patient: patients need to be warned that they should see immediately a doctor at appearance of inexplicable pains or weakness in muscles, especially if they are followed by an indisposition or fever.
With care to apply at the patients abusing alcohol and/or having a liver disease (in the anamnesis).
The hemorrhagic stroke
the Analysis of a research of 4731 patients without the coronary heart disease (CHD) who had a stroke or the tranzitorny ischemic attack in the previous 6 months and who began to accept Липримар® 80 mg revealed high percent of hemorrhagic strokes in the group accepting 80 mg of Liprimara® in comparison with placebo (55 on Liprimare® against 33 on placebo). At patients with a hemorrhagic stroke the increased risk of developing a repeated stroke was observed (7 on Liprimare® against 2 on placebo). However at the patients accepting Липримар® 80 mg the smaller quantity of strokes of any types (265 against 311) and smaller number of an ischemic heart disease was observed.
An interstitial pulmonary disease
At use of some statines, especially at long-term therapy, exclusively exceptional cases of an interstitial pulmonary disease were registered. The shown signs can include in dispnoe, unproductive cough and deterioration in the general state of health (fatigue, loss of body weight and fever). In the presence of suspicion about development in the patient of an interstitial pulmonary disease the therapy by statines should be cancelled.
Diabetes
Some data demonstrate that statines as a class, increase glucose level in blood and at some patients with high risk level of development of diabetes in the future can lead to the hyperglycemia level at which it is reasonable to begin treatment of diabetes. Nevertheless, this risk is outweighed by advantage of risk reduction for vessels when using statines and therefore should not be the reason of the termination of treatment by statines. Patients of risk group (glucose level on an empty stomach of 5.6-6.9 mmol/l, BMI & gt, 30 kg/sq.m, the increased level of triglycerides, arterial hypertension)
have to is under observation both clinically, and biochemical according to national recommendations.
Use at pregnancy and feeding
during treatment have to use a breast of the Woman of reproductive age adequate methods of contraception. Липримар® women of reproductive age can appoint only if pregnancy probability at them very low, and the patient is informed on possible risk for a fruit during treatment.
Features of influence of medicine on ability to run the vehicle and potentially dangerous mechanisms
Considering side effects of drug, it is necessary to be careful at control of motor transport and other potentially dangerous mechanisms.
Overdose
Symptoms: strengthening of side effects.
Treatment: there is no specific antidote for treatment of overdose of Liprimara®. In case of overdose as required it is necessary to carry out symptomatic treatment (on doctor's orders). As drug actively contacts proteins of blood plasma, significant increase in clearance of Liprimara® at a hemodialysis is improbable.
Form of release and packing
of the Tablet, film coated, 10 mg, 20 mg, 40 mg and 80 mg. On 10 tablets in blister strip packaging from polyvinylchloride and aluminum foil. On 3 planimetric packs together with the instruction for medical use in the state and Russian languages in a cardboard pack.
To Store storage conditions at a temperature not higher than 25 wasps.
To store out of children's reach!
3 years
not to apply a period of storage after expiry date.
Prescription status
According to the prescription
Pfizer Pharmasyyutikals ElElSi Producer,
Puerto Rico Road 689, Km 1.9
Vega Baya Puerto Rico 00693
Upakovshchik Pfizer Manufacturing Doychland GmbH
of Moosvaldali, 1
79090 Freyburg, Germany
the Owner of the registration certificate
of Pfizer HCP Corporation, the USA
the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods):
Representative office of Pfizer HCP Corporation (USA) Almaty, Abylay Ave. of the khan, 141
ph. (727) 272-27-01, 250-09-16
fax (727) 272-04-06
To develop
of LIPRIMAR® medicine
the Trade name
of Liprimar®
the International unlicensed
name Atorvastatin Lekarstvennaya
the Tablet form, film coated, 10 mg, 20 mg, 40 mg and 80 mg
Structure
One tablet contains
active agent – calcium of an atorvastatin of 10.85 mg, 21.70 mg, 43.40 mg and 86.80 mg equivalent to an atorvastatin of 10 mg, 20 mg, 40 mg and 80 mg respectively,
excipients: calcium carbonate, cellulose microcrystalline, lactoses monohydrate, sodium of a kroskarmelloz, polysorbate 80, hydroxypropyl cellulose, magnesium stearate,
film covering: hydroksipropilmetiltsellyuloza, polyethyleneglycol 8000, titan dioxide (E 171), talc, emulsion of a simetikon.
The description
Round tablets, film coated white color, with an engraving 10 on one party and ATV - on another (a dosage of 10 mg).
Round tablets, film coated white color, with an engraving 20 on one party and ATV - on another (a dosage of 20 mg).
Round tablets, film coated white color, with an engraving 40 on one party and ATV - on another (a dosage of 40 mg).
Round tablets, film coated white color, with an engraving 80 on one party and ATV - on another (a dosage of 80 mg).
Pharmacotherapeutic group
Hypolipidemic drugs. Gipokholesterinemichesky and gipotriglitseridemichesky drugs. KoA-reductase GMG inhibitors.
Atorvastatin.
The ATX C10AA 05 code
the Pharmacological
Atorvastatin Pharmacokinetics Absorption properties is quickly soaked up after intake, concentration it in blood plasma reaches a maximum in 1-2 hours. Extent of absorption and concentration of an atorvastatin in blood plasma raise in proportion to a dose. The absolute bioavailability of an atorvastatin is about 14%, and system bioavailability of the inhibiting activity in the relation 3-hydroxy-3-methylglutaryl coenzyme of A-reductase (GMG-KoA-reduktazy) - about 30%. The low system bioavailability is caused by presistemny metabolism in a mucous membrane of digestive tract and/or at 'the first passing' through a liver.
Food reduces the speed and extent of absorption of drug a little (by 25% and 9%, respectively, what results of definition of Cmax and AUC testify to), however decrease in cholesterol of lipoproteids of the low density (Hs-LPNP) is similar to that at reception of an atorvastatin on an empty stomach. After reception of an atorvastatin in the evening its concentration in blood plasma is lower (Cmax and AUC approximately for 30%), than after reception in the morning. The linear dependence between extent of absorption and a dose of drug is revealed.
Distribution
the Average volume of distribution of an atorvastatin makes about 381 l. Communication with proteins of blood plasma not less than 98%. The relation of maintenance of an atorvastatin in erythrocytes/plasma makes about 0.25, i.e. atorvastatin badly gets into erythrocytes.
Metabolism
Atorvastatin is substantially metabolized with education orto- and para-hydroxylated derivatives and various products of beta oxidation. Orto- and para-hydroxylated metabolites have inhibiting effect on GMG-KoA-reduktazu. About 70% of decrease of the activity of GMG-KoA-reduktazy happen due to action of the active circulating metabolites. In metabolism of an atorvastatin liver P450 3A4 cytochrome plays an important role: concentration of an atorvastatin in blood plasma of the person at a concomitant use of erythromycin which is inhibitor of this isoenzyme increases. In turn atorvastatin is weak inhibitor of P450 3A4 cytochrome. Atorvastatin has no clinically significant impact on concentration in blood plasma of a terfenadin who is metabolized, mainly, by P450 3A4 cytochrome therefore it is improbable that atorvastatin has significant effect on pharmacokinetics of other substrates of P450 3A4 cytochrome.
Removal
Atorvastatin and his metabolites are removed, mainly, with bile as a result of hepatic and/or extrahepatic metabolism (atorvastatin is not exposed to the significant enterohepatic recirculation). Elimination half-life of an atorvastatin makes about 14 h. The inhibiting activity concerning GMG-KoA-reduktazy remains about 20-30 h, thanks to existence of active metabolites. After intake in urine less than 2% of an atorvastatin are found.
Special groups of patients
Elderly: concentration of an atorvastatin in blood plasma at aged people of 65 years are also more senior above (Cmax approximately for 40%, AUC approximately for 30%), than at adult patients of young age, differences in safety, efficiency or achievement of the goals of hypolipidemic therapy at elderly people in comparison with the general population it is not revealed.
Children: in an open 8 weeks research the patients of children's age with a stage a polovogotrazvitiya on Tannera 1 (N = 15) and ≥ 2 (N = 24) (at the age of 6–17 years) with a heterozygous family hypercholesterolemia and the H-LPNP initial level ≥ 4 mmol/l received, respectively, atorvastatin in doses 5 or 10 mg in the form of chewable tablets or 10 or 20 mg in the form of tablets, film coated once a day once a day. Body weight was the only significant variable in population FC of model of an atorvastatin. The seeming oral clearance of an atorvastatin at patients of children's age was similar to that at adults at allometrichesky scaling in body weight. In the range of exposures of an atorvastatin and about-hydroksiatorvastatina steady decrease in levels of H-LPNP and OH was observed.
Floor: concentration of an atorvastatin in blood plasma at women differs (Cmax is about 20% higher, and AUC 10% lower) from that at men, however clinically significant distinctions of influence of drug on lipidic exchange at men and women are not revealed.
Renal failure: the disease of kidneys does not affect concentration of an atorvastatin in blood plasma or its impact on indicators of lipidic exchange, in this regard change of a dose with a renal failure is not required from patients.
Hemodialysis: it is improbable that the hemodialysis will lead to significant increase in clearance of an atorvastatin as drug is substantially connected with proteins of blood plasma.
Liver failure: concentration of an atorvastatin considerably increases (Cmax approximately by 16 times, AUC approximately by 11 times) at patients with alcoholic cirrhosis (Chayld-Pyyu C).
The polymorphism of SLOC1B1
Hepatic metabolism of all inhibitors of GMG-KoA-reduktazy, including atorvastatin, is carried out with the assistance of the carrier of OATP1B1. Patients with polymorphism of SLOC1B1 have a risk of the increased exposure of an atorvastatin that can result in the increased risk of a rhabdomyolysis. The polymorphism in the gene coding protein OATP1B1 (SLCO1B1c.521CC) causes 2.4-fold increase in AUC value of an atorvastatin in comparison with that at the people who do not have the called genetic option (page 521TT). At this group of patients the genetic defect of capture of an atorvastatin liver cells is also possible. Possible consequences of influence on efficiency are not known.
A pharmacodynamics
of Liprimar® – synthetic hypolipidemic drug, a selection competitive inhibitor of GMG-KoA-reduktazy – the key enzyme turning 3-hydroksi-3-metilglutaril-KoA into mevalonovy acid – the predecessor of steroids, including cholesterol. At patients with a homozygous and heterozygous family hypercholesterolemia, single forms of a hypercholesterolemia and the mixed dislipidemiya, Liprimar® reduces the content in blood plasma of the general cholesterol (Hs), cholesterol of lipoproteids of low density and apolipoprotein B and also cholesterol of lipoproteids of very low density (Hs-LPONP) and triglycerides, causes unstable increase in content of cholesterol of lipoproteids of the high density (Hs-LPVP).
In a liver triglycerides and cholesterol are included lipoproteids of very low density (LPONP), come to blood plasma and are transferred to peripheral fabrics. Lipoproteids of the low density (LDL) which catabolize in interaction with high-affine receptors of LDL are formed of LPONP.
Липримар® reduces concentration of cholesterol and lipoproteids in blood plasma, inhibiting GMG-KoA-reduktazu and synthesis of cholesterol in a liver and increasing number of 'hepatic' receptors of LDL by surfaces of cells that leads to strengthening of capture and catabolism of LDL cholesterol.
Indications
- in combination with a diet for treatment of patients with the increased content in blood plasma of the general cholesterol, Hs-LPNP, apolipoprotein B and triglycerides and increases in maintenance of Hs-LPVP patients with primary hypercholesterolemia (heterozygous family and single hypercholesterolemia) combined (mixed) lipidemia (the IIa and IIb types across Frederikson), with the increased content of triglycerides in blood plasma (type IV across Frederikson) and patients with a disbetalipoproteinemiya (type III across Frederikson), in case of lack of adequate effect at a dietotherapy
- for decrease in content in blood plasma of the general cholesterol and Hs-LPNP at patients with a homozygous family hypercholesterolemia at insufficient efficiency of a dietotherapy and other not pharmacological methods of treatment
- for reduction of risk of lethal outcomes of an ischemic heart disease and risks of developing a myocardial infarction, stenocardia, a stroke and for reduction of need of holding procedures of revascularization at patients with cardiovascular diseases and/or a dislipidemiya and also if these diseases are not revealed, but have not less than three risk factors of development of an ischemic heart disease, such as age more than 55 years, smokings, arterial hypertension, low concentration in Hs-LPVP blood plasma, cases of prematurity of an ischemic heart disease for relatives
- in combination with a diet for treatment of children at the age of 10-17 years with the increased content in blood plasma of the general cholesterol, Hs-LPNP and apolipoprotein B with a heterozygous family hypercholesterolemia if after an adequate dietotherapy the Hs-LPNP level remains also to gt, 190mg/dl or the Hs-LPNP level remains also to gt, 160mg/dl, but at the same time there are cases of prematurity of cardiovascular diseases at relatives or two and more risk factors of developing cardiovascular diseases at the child
the Route of administration and doses
Before an initiation of treatment of Liprimarom® it is necessary to try to achieve control of a hypercholesterolemia by means of a diet, physical exercises and decrease in body weight from patients with obesity and also treatment of a basic disease. When prescribing drug the patient needs to recommend a standard gipokholesterinemichesky diet which he has to observe during treatment.
The drug is taken at any time, irrespective of meal. The dose of drug is varied by from 10 to 80 mg once a day, selecting it taking into account the initial maintenance of Hs-LPNP, the purpose of therapy and individual effect. In an initiation of treatment and/or during increase in a dose of Liprimara® it is necessary to control each 2-4 weeks the maintenance of lipids in blood plasma and as appropriate to adjust a dose.
Primary hypercholesterolemia and the combined (mixed) lipidemia: for most of patients - 10 mg once a day, therapeutic action is shown within 2 weeks and usually reaches a maximum within 4 weeks, at long-term treatment the effect remains.
Homozygous family hypercholesterolemia: 80 mg once a day (in most cases therapy led to decrease in maintenance of Hs-LPNP by 18-45%).
Heavy dislipidemiya at pediatric patients: the recommended starting dose – 10 mg once a day. The dose can be increased up to 80 mg a day according to the clinical answer and shipping. Doses have to be picked up individually taking into account the recommended therapy purpose.
Use for patients with liver diseases: see. Contraindications.
A dosage at patients with a renal failure: the disease of kidneys does not influence concentration of Liprimara® in blood plasma or extent of decrease in maintenance of Hs-LPNP therefore correction of a dose of drug is not required.
Use for elderly people: differences in safety, efficiency or achievement of the goals of hypolipidemic therapy at elderly people in comparison with the general population are not revealed.
Side effects
Often (from & gt, 1/100 to & lt, 1/10)
- a headache
- a nasopharyngitis
- a hyperglycemia
- throat and throat pain, nasal bleeding
- dyspepsia, nausea, a constipation, a meteorism, diarrhea
- an arthralgia, extremity pain, myotonia, myalgia, swelling of joints, a dorsodynia
- abnormal indicators of function of a liver, increase in a serumal kreatinfosfokinaza (KFK)
- allergic reactions
Infrequently (from ≥1/1000 to & lt, 1/100)
- a hypoglycemia, increase in body weight, anorexia
- dreadful dreams, insomnia
- dizziness, paresthesia, a hypesthesia, a dysgeusia, amnesia
- indistinct sight
- sonitus
- vomiting, pain in the upper and lower part of a stomach, an eructation
- pancreatitis, hepatitis
- urticaria, skin rash, an itching, an alopecia
- neck pain, muscular fatigue
- an indisposition, an asthenia, thorax pain, peripheral hypostasis, increased fatigue, fever
- emergence of leukocytes in urine
Is rare (from ≥1/10000 to & lt, 1/1000)
- thrombocytopenia
- peripheral neuropathy
- a disorder of vision
- a cholestasia
- a Quincke's disease, bullous dermatitis including a polymorphic erythema, Stephens-Johnson's syndrome and a toxic epidermal necrolysis
- a myopathy, a miositis, a rhabdomyolysis, a tendinopatiya sometimes complicated with a gap
Very seldom (from ≤1/10000)
- an anaphylaxis
- a hearing loss
- a liver failure
- a gynecomastia
Is unknown (it is impossible to determine by the available data).
- the immunomediated necrotizing myopathy
the Following side effects were revealed in patients of children's age:
Often (from & gt, 1/100 to & lt, 1/10)
- a headache
- an abdominal pain
- increase in levels of alaninaminotranspherase and a serumal kreatinfosfokinaza (KFK)
At intake of some statines:
- sexual dysfunction
- a depression
- exclusively exceptional cases of an interstitial pulmonary disease, especially at long-term therapy
- diabetes: frequency will depend on existence or lack of risk factors (glucose in blood on an empty stomach of ≥5.6 mmol/l, BMI & gt, 30 kg/sq.m, the increased levels of triglycerides, arterial hypertension in the anamnesis)
Contraindications
- hypersensitivity to any of drug components
- an active disease of a liver or increase in activity of transaminases of serum (more than by 3 times in comparison with the upper bound of norm) not clear genesis
- pregnant women and the feeding women and also women of reproductive age who are not using adequate methods of contraception
- patients with a hereditary lactose intolerance, deficiency of enzyme of LAPP lactase, glucose galactose malabsorption
Medicinal interactions
Risk of development of a myopathy raises during treatment by inhibitors of GMG-KoA-reduktazy and simultaneous use of cyclosporine, derivatives of fibroyevy acid, botsepreviry, niacin and inhibitors of P450 3A4 cytochrome (erythromycin, antifungal drugs relating to azoles). At the patients who are at the same time accepting atorvastatin and botseprevir it is recommended to use the drug Liprimar® in lower initial dose and to carry out clinical monitoring. During the combined use with botsepreviry the daily dose of an atorvastatin should not exceed 20 mg.
Very rare messages about the immunomediated necrotizing myopathy (INM) in time or after treatment by statines, including atorvastatiny were registered. INM is clinically characterized by weakness of proximal muscles and the increased creatine kinase level in serum which remain, despite the therapy termination by statines.
P450 3A4 inhibitors: atorvastatin it is metabolized by P450 3A4 cytochrome. Simultaneous use of Liprimara® and inhibitors of P450 3A4 cytochrome can lead to increase in concentration of an atorvastatin in blood plasma. Extent of interaction and potentiation of effect depends on variability of action on P450 3A4 cytochrome.
Simultaneous use of strong P450 3A4 inhibitors (for example, cyclosporine, a telitromitsin, a klaritromitsin, a delavirdin, a stiripentol, a ketokonazol, a vorikonazol, an itrakonazol, a pozakonazol and inhibitors of HIV protease, including ritonavir, lopinavir, atazanavir, indinavir, darunavir, etc.) should be avoided as far as possible. In cases when simultaneous use of these medicines with atorvastatiny cannot be avoided, it is recommended to appoint lower initial and maximum doses of an atorvastatin and also to carry out appropriate clinical monitoring of a condition of the patient.
Moderate P450 3A4 inhibitors (for example, erythromycin, diltiazem, verapamil and flukonazol) can increase concentration of an atorvastatin in plasma. When using erythromycin in combination with statines the increased risk of a myopathy is observed. The researches of interactions estimating influence of Amiodaronum or verapamil on atorvastatin were not conducted. Both Amiodaronum, and verapamil inhibit activity of P450 3A4, and their combined use with atorvastatiny can lead to the increased exposure of an atorvastatin. Thus, at simultaneous use with moderate P450 3A4 inhibitors it is recommended to appoint lower maximum dose of an atorvastatin and to carry out the corresponding clinical monitoring at the patient. The corresponding clinical monitoring is recommended after the beginning of therapy or after inhibitor dose adjustment.
Conveyor inhibitors: atorvastatin and its metabolites are OATP1B1 conveyor substrates. OATP1B1 inhibitors (for example, cyclosporine) can increase bioavailability of an atorvastatin. Simultaneous use of 10 mg of Liprimara® and cyclosporine (5.2 mg/kg/days) leads to increase in exposure of an atorvastatin by 7.7 times.
At simultaneous use of an atorvastatin and inhibitors of an isoenzyme CYP3A4 or proteins carriers the increase in concentration of an atorvastatin in blood plasma and increase in risk of a myopathy is possible. The risk can also increase at simultaneous use of an atorvastatin with other medicines capable to cause a myopathy, such as derivatives of fibroyevy acid and ezetimib.
Erythromycin / klaritromitsin: at simultaneous use of Liprimara® and erythromycin (500 mg four times a day) or a klaritromitsina (500 mg two times a day) which inhibit P450 3A4 cytochrome, increase in concentration of an atorvastatin in blood plasma was observed.
Inhibitors of proteases: simultaneous use of Liprimara® with the inhibitors of proteases known as inhibitors of P450 3A4 cytochrome, was followed by increase in concentration of an atorvastatin in blood plasma.
Diltiazem hydrochloride: simultaneous use of Liprimara® (40 mg) and diltiazem (240 mg) leads to increase in concentration of an atorvastatin in blood plasma.
Cimetidinum: the research of interaction Liprimara® and Cimetidinum was conducted, clinically significant interactions it is not revealed.
Itrakonazol: (20mg-40mg) and the itrakonazola (200 mg) leads simultaneous use of Liprimara® to increase in AUC of an atorvastatin.
Grapefruit juice: contains one or two components which inhibit CYP 3A4 and can increase concentration of an atorvastatin in blood plasma, especially at overconsumption of grapefruit juice (more than 1.2 liters a day).
Inductors of P450 3A4 cytochrome: simultaneous use of Liprimara® with inductors of P450 3A4 cytochrome (efavirenz, Rifampinum and drugs of a St. John's wort) can lead to decrease in concentration of an atorvastatin in blood plasma. In view of the double mechanism of effect of Rifampinum (induction of P450 3A4 cytochrome and inhibition of OATP1B1 enzyme carrier in a liver), it is recommended to appoint Liprimar® along with Rifampinum as reception of Liprimara® after intake of Rifampinum leads to considerable decrease in level of an atorvastatin in blood plasma.
Antacids: the concomitant use in the suspension containing magnesium and aluminum hydroxides reduced concentration of an atorvastatin in blood plasma approximately by 35%, however extent of reduction of maintenance of Hs-LPNP at the same time did not change.
Antipyrine: Липримар® does not influence antipyrine pharmacokinetics therefore interaction with other drugs, the metabolized same isoenzymes of cytochrome, is not expected.
Gemfibrozil / derivatives of fibroyevy acid: monotherapy of a fibratama in certain cases is followed by the undesirable phenomena from muscles, including a rhabdomyolysis. The risk of emergence of these phenomena can be raised at co-administration of derivatives of fibroyevy acid and an atorvastatin. If simultaneous use cannot be avoided, for achievement of the therapeutic purpose it is necessary to use the lowest doses of an atorvastatin and to carry out appropriate monitoring at patients.
Ezetimib: monotherapy ezetimiby is followed by the undesirable phenomena from muscles, including a rhabdomyolysis. Therefore, the risk of these phenomena can be increased at co-administration of an ezetimib and atorvastatin. It is recommended to carry out appropriate monitoring at such patients.
Kolestipol: at simultaneous use of a kolestipol the concentration of an atorvastatin in blood plasma decreased approximately by 25%, however the hypolipidemic effect of a combination of an atorvastatin and kolestipol exceeded that of each drug separately.
Digoxin: At repeated intake of digoxin and Liprimara® in a dose of 10 mg the equilibrium concentration of digoxin in blood plasma did not change. However at use of digoxin in a combination with Liprimarom® in a dose of 80 mg/days the concentration of digoxin increased approximately by 20%. The patients receiving digoxin in combination with Liprimarom® demand the corresponding observation.
Azithromycin: at simultaneous use of Liprimara® (10 mg once a day) and azithromycin (500 mg once a day) concentration of an atorvastatin in plasma did not change.
Oral contraceptives: at simultaneous use of Liprimara® and oral contraceptive containing norethindrone and ethinylestradiol the substantial increase of AUC norethindrone and ethinylestradiol approximately for 30% and 20%, respectively was observed. This effect should be considered when choosing an oral contraceptive for the woman accepting Liprimar®.
Warfarin: in clinical trial at the patients receiving long therapy by warfarin, the combined use of an atorvastatin in a dose of 80 mg a day with warfarin caused small decrease in a prothrombin time approximately for 1.7 seconds during the first 4 days of treatment which returned to normal within 15 days of treatment atorvastatiny. Though only very exceptional cases of clinically significant interaction with anticoagulants, at the patients accepting coumarinic anticoagulants are registered, the prothrombin time should be defined before an initiation of treatment atorvastatiny and is rather frequent at early stages of therapy to make sure of lack of significant changes of a prothrombin time. After the stable prothrombin time is registered, it can be controlled with the frequency which is usually recommended for the patients receiving coumarinic anticoagulants. The same procedure should be repeated at change of a dose of an atorvastatin or its cancellation. Therapy atorvastatiny was not followed by cases of bleeding or changes of a prothrombin time at the patients
who are not accepting anticoagulants.
Warfarin: signs of clinically significant interaction of Liprimara® with warfarin are not revealed.
Amlodipin: at simultaneous use of Липримара® 80 mg and an amlodipina of 10 mg the pharmacokinetics of an atorvastatin in an equilibrium state did not change.
Colchicine: though researches of interactions of an atorvastatin and colchicine were not conducted, it was reported about myopathy cases at combined use of an atorvastatin and colchicine.
Fusidic acid: researches on interaction of Liprimara® and fusidic acid were not conducted, however in post-market researches it was reported about rhabdomyolysis cases at their simultaneous use. Therefore patients have to be under control and in case of need therapy of Liprimarom® can be temporarily suspended.
Other accompanying therapy: in clinical trials of Liprimar® applied in combination with antihypertensive drugs and estrogen which appointed with the replaceable purpose, signs of clinically significant undesirable interaction are noted.
The special
instructions Action on a liver
After treatment of Liprimarom® noted considerable (more than by 3 times in comparison with the upper bound of norm) increase in serumal activity of 'hepatic' transaminases.
Increase in activity of 'hepatic' transaminases usually was not followed by jaundice or other clinical manifestations. At a dose decline of Liprimara®, temporary or full drug withdrawal the activity of 'hepatic' transaminases was restored to initial level. Most of patients continued reception of Liprimara® in a reduced dose without any consequences.
It is necessary to control indicators of function of a liver during all course of treatment, especially at emergence of clinical signs of damage of a liver. In case of increase in content of 'hepatic' transaminases, their activity should be controlled before achievement of limits of norm. If increase in activity of nuclear heating plant or ALT more than by 3 times in comparison with the upper bound of norm remains, the dose decline or drug withdrawal is recommended.
Action
Appointing Liprimar® in hypolipidemic doses in combination with derivatives of fibroyevy acid, erythromycin, immunodepressants, azolny antifungal drugs or niacin to skeletal muscles, the doctor has to weigh carefully expected advantage and risk of treatment and to regularly observe patients for the purpose of detection of pains or weakness in muscles, especially within the first months of treatment and during the periods of increase in a dose of any drug. In similar situations it is possible to recommend periodic determination of activity of KFK though such monitoring does not allow to prevent development of a heavy myopathy. Липримар® can cause increase in activity of a kreatinfosfokinaza.
At use of Liprimara®, exceptional cases of a rhabdomyolysis with the acute renal failure caused by a myoglobinuria and a myoglobinemia are described. Therapy of Liprimarom® should be stopped temporarily or to cancel completely at emergence of signs of a possible myopathy or presence of risk factor of developing a renal failure against the background of a rhabdomyolysis (for example, a heavy acute infection, arterial hypotension, serious operation, an injury, metabolic, endocrine and electrolytic disturbances and uncontrollable spasms).
Information for the patient: patients need to be warned that they should see immediately a doctor at appearance of inexplicable pains or weakness in muscles, especially if they are followed by an indisposition or fever.
With care to apply at the patients abusing alcohol and/or having a liver disease (in the anamnesis).
The hemorrhagic stroke
the Analysis of a research of 4731 patients without the coronary heart disease (CHD) who had a stroke or the tranzitorny ischemic attack in the previous 6 months and who began to accept Липримар® 80 mg revealed high percent of hemorrhagic strokes in the group accepting 80 mg of Liprimara® in comparison with placebo (55 on Liprimare® against 33 on placebo). At patients with a hemorrhagic stroke the increased risk of developing a repeated stroke was observed (7 on Liprimare® against 2 on placebo). However at the patients accepting Липримар® 80 mg the smaller quantity of strokes of any types (265 against 311) and smaller number of an ischemic heart disease was observed.
An interstitial pulmonary disease
At use of some statines, especially at long-term therapy, exclusively exceptional cases of an interstitial pulmonary disease were registered. The shown signs can include in dispnoe, unproductive cough and deterioration in the general state of health (fatigue, loss of body weight and fever). In the presence of suspicion about development in the patient of an interstitial pulmonary disease the therapy by statines should be cancelled.
Diabetes
Some data demonstrate that statines as a class, increase glucose level in blood and at some patients with high risk level of development of diabetes in the future can lead to the hyperglycemia level at which it is reasonable to begin treatment of diabetes. Nevertheless, this risk is outweighed by advantage of risk reduction for vessels when using statines and therefore should not be the reason of the termination of treatment by statines. Patients of risk group (glucose level on an empty stomach of 5.6-6.9 mmol/l, BMI & gt, 30 kg/sq.m, the increased level of triglycerides, arterial hypertension)
have to is under observation both clinically, and biochemical according to national recommendations.
Use at pregnancy and feeding
during treatment have to use a breast of the Woman of reproductive age adequate methods of contraception. Липримар® women of reproductive age can appoint only if pregnancy probability at them very low, and the patient is informed on possible risk for a fruit during treatment.
Features of influence of medicine on ability to run the vehicle and potentially dangerous mechanisms
Considering side effects of drug, it is necessary to be careful at control of motor transport and other potentially dangerous mechanisms.
Overdose
Symptoms: strengthening of side effects.
Treatment: there is no specific antidote for treatment of overdose of Liprimara®. In case of overdose as required it is necessary to carry out symptomatic treatment (on doctor's orders). As drug actively contacts proteins of blood plasma, significant increase in clearance of Liprimara® at a hemodialysis is improbable.
Form of release and packing
of the Tablet, film coated, 10 mg, 20 mg, 40 mg and 80 mg. On 10 tablets in blister strip packaging from polyvinylchloride and aluminum foil. On 3 planimetric packs together with the instruction for medical use in the state and Russian languages in a cardboard pack.
To Store storage conditions at a temperature not higher than 25 wasps.
To store out of children's reach!
3 years
not to apply a period of storage after expiry date.
Prescription status
According to the prescription
Pfizer Pharmasyyutikals ElElSi Producer,
Puerto Rico Road 689, Km 1.9
Vega Baya Puerto Rico 00693
Upakovshchik Pfizer Manufacturing Doychland GmbH
of Moosvaldali, 1
79090 Freyburg, Germany
the Owner of the registration certificate
of Pfizer HCP Corporation, the USA
the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods):
Representative office of Pfizer HCP Corporation (USA) Almaty, Abylay Ave. of the khan, 141
ph. (727) 272-27-01, 250-09-16
fax (727) 272-04-06
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