Krestor

Krestor – drug with hypolipidemic action.

Form of release and structure

Krestor release in the form of tablets: biconvex; on 5 mg: round, yellow, with the engraved text of "ZD4522 5" on one of the parties; on 10 mg: round, pink, with the engraved text of "ZD4522 10" on one of the parties; on 20 mg: round, pink, with the engraved text of "ZD4522 20" on one of the parties; on 40 mg: oval, pink, with the engraved text of "ZD4522" on one of the parties, on another – "40" (on 7 or 14 pieces in blisters, on 1, 2 or 4 blisters in a cardboard pack).

Is a part of 1 tablet:

• Active agent: розувастатин – 5, 10, 20 or 40 mg (in the form of a rozuvastatin of calcium);
• Auxiliary components (for tablets on 5/10/20/40 mg respectively): monohydrate of lactose – 93,08/89,5/179/164,72 mg, microcrystallic cellulose – 31,02/29,82/59,64/54,92 mg, calcium phosphate – 11,32/10,9/21,8/20 mg, кросповидон – 7,5/7,5/15/15 mg, magnesium stearate – 1,88/1,88/3,76/3,76 mg.

Structure of a film cover: monohydrate of lactose – 1,8/1,8/3,6/3,6 mg, a gipromelloza – 1,26/1,26/2,52/2,52 mg, glycerin triacetate (triacetin) – 0,036/0,36/0,72/0,72 mg, titanium dioxide – 0,9/1,06/2,11/2,11 mg, dye iron oxide yellow – 0,18 mg (for tablets on 5 mg), dye iron oxide red (for tablets on 10/20/40 mg) – 0,02/0,05/0,05 mg.

Indications to use

• Primary hypercholesterolemia (the increased content of cholesterol in serum) across Fredrikson (the IIa type, including a family heterozygous hypercholesterolemia) or the mixed hypercholesterolemia (IIb type) – as additional therapy to a diet in cases when the diet and other non-drug ways of treatment (for example, physical exercises, decrease in body weight) are insufficient;
• Family homozygous hypercholesterolemia – as additional therapy to a diet and other lipidosnizhayushchy therapy (for example, LPNP-aferez) or at insufficiency of similar treatment;
• Gipertriglitseridemiya (across Fredrikson – type IV) – as addition to a diet;
• Atherosclerosis (for progressing delay) – as addition to a diet at patients with existence of indications to performing therapy for decrease in concentration of the general XC (cholesterol) and HS-LPNP (cholesterol of lipoproteins of low density);
• The main cardiovascular complications, including arterial revascularization, a heart attack, a stroke (primary prevention) at adult patients without clinical symptoms of coronary heart disease, but with existence of high risk of its development (for men age – of 50 years, for women – of 60 years, the increased concentration of S-reactive protein (≥2 mg/l) in the presence of even at least one of accessory factors of risk: arterial hypertension, low concentration of HS-LPVP, smoking, family anamnesis of the early beginning of coronary heart disease).

Contraindications

• The liver diseases proceeding in an active phase including permanent increase in serumal activity of transaminases and any increase in activity of transaminases in blood serum (it is more than by 3 times in comparison with the upper bound of norm);
• Concomitant use with cyclosporine;
• Deficit of lactase, lactose intolerance or glyukozo-galaktozny malabsorption (lactose is Krestor's part);
• Age up to 18 years;
• Pregnancy, the period of breastfeeding (lactation), lack of adequate methods of contraception at women;
• Hypersensitivity to drug components.

Additional contraindications for a daily dose of 5, 10 or 20 mg are:

• The expressed functional disturbances of kidneys (the clearance of creatinine is less than 30 ml in a minute);
• Myopathy;
• Predisposition to emergence of miotoksichesky complications.

Contraindications for a daily dose of 40 mg are (in addition):

• Excessive alcohol intake;
• Existence of risk factors of emergence рабдомиолиза / myopathies, namely: moderate severity a renal failure (the clearance of creatinine is less than 60 ml in a minute), a hypothyroidism, the family or personal anamnesis of muscular diseases, a miotoksichnost against the background of use of fibrat or other inhibitors of GMG-KOA-reduktazy in the anamnesis;
• States at which plasma concentration of a rozuvastatin can increase;
• Concomitant use from fibrata;
• Belonging to Mongoloid race.

In the presence of the states/diseases described above Krestor in a daily dose of 5, 10 and 20 mg it is necessary to take with caution (under medical observation).

With caution Krestor in all dosages it is necessary to take in the presence of the following states / diseases:

• Uncontrollable convulsive attacks;
• Liver diseases in the anamnesis;
• Arterial hypotension;
• Sepsis;
• The endocrine, metabolic or electrolytic disturbances proceeding in a severe form;
• Injuries, extensive surgical interventions;
• Age of 65 years.

Krestor in a daily dose of 40 mg at weak severity of a renal failure (the clearance of creatinine is more than 60 ml in a minute) it is necessary to take with caution.

There is no experience of use of Krestor for patients with a liver failure and with more than 9 points on a scale of Chayld-Pyyu.

Route of administration and dosage

Krestor accept inside, regardless of meal and at any time. Tablets need to be swallowed entirely (without crushing and without chewing), washing down with water.

Before a course of treatment it is necessary to keep to a standard gipokholesterinemichesky diet (it should be continued throughout all therapy).

The doctor selects Krestor's dose individually, it is defined by the purposes of the carried-out treatment and the therapeutic response to treatment with the current recommendations about target concentration of lipids.

The recommended initial daily dose for the patients beginning to accept Krestor, or for other inhibitors of GMG-KOA-reduktazy of patients transferred from reception has to make 5 or 10 mg, frequency rate of reception – once a day. At selection of an initial dose it is necessary to be guided by individual concentration of cholesterol and to consider possible risk of development of cardiovascular complications and side effects. If necessary increase in a dose in 4 weeks is possible.

Because of high risk of development of side effects, increase in a dose up to 40 mg (after additional reception of a dose is higher recommended initial within 4 weeks of treatment) can be carried out only at patients with heavy degree of a hypercholesterolemia and with high risk of development of cardiovascular complications (especially at patients with a family hypercholesterolemia) at which at reception of a dose of 20 mg the desirable result was not achieved and which will be under observation of the doctor. Especially careful observation is recommended for the patients receiving Krestor in a dose of 40 mg.

Purpose of a daily dose of 40 mg is not recommended to patients who did not see a doctor earlier. In 14-28 days of treatment and/or at increase in a dose of Krestor it is necessary to control indicators of lipidic exchange (if necessary dose adjustment can be required).

Krestor's use is contraindicated to patients with a heavy renal failure (at clearance of creatinine it is less than 30 ml in a minute). Easy or moderate severity dose adjustment is not required to patients with a renal failure. Krestor's use in a dose of 40 mg is contraindicated to patients with moderate renal failures (at clearance of creatinine of 30-60 ml a minute). The patient with moderate functional disturbances of kidneys drug is recommended to accept 5 mg in an initial dose.

Krestor it is contraindicated to patient to accept with the liver diseases proceeding in an active phase.

Dose adjustment is not required to elderly patients.

At purpose of doses of 10 and 20 mg the recommended initial dose for patients of Mongoloid race, and also for patients with predisposition to a myopathy should not exceed 5 mg (Krestor's use in a dose of 40 mg is contraindicated).

Side effects

The side effects arising at Krestor's use, as a rule, have slight and passing character. As well as at use of other inhibitors of GMG-KOA-reduktazy, the frequency of their development has generally dozozavisimy character (> 1/100, <1/10 – it is frequent;> 1/1000, <1/100 – infrequently;> 1/10000, <1/1000 – it is rare; <1/10000, including separate cases – it is very rare):

• Central nervous system: often – dizziness, a headache;
• Immune system: seldom – hypersensitivity reactions, including development of a Quincke's disease;
• Urinary system: a proteinuria (changes of amount of protein in urine are observed less than at 1% of the patients receiving 10-20 mg of Krestor, and approximately at 3% of the patients receiving 40 mg). As a rule, the proteinuria decreases or disappears during therapy, and acute or progressing of the existing disease of kidneys does not mean emergence;
• Endocrine system: often – a diabetes mellitus of type 2;
• Digestive tract: often – nausea, a lock, abdominal pains; seldom – pancreatitis;
• Musculoskeletal system: a mialgiya, a myopathy, including a miositis (at Krestor's use in all dosages and, in particular, at reception of doses it is more than 20 mg); in rare instances – рабдомиолиз with an acute renal failure or without it; at insignificant number of patients – dozozavisimy increase in activity of a kreatinfosfokinaza (insignificant, asymptomatic and temporary; at increase it is more, than by 5 times in comparison with the highest limit of norm, therapy is interrupted);
• Liver: at insignificant number of patients – dozozavisimy increase in activity of hepatic transaminases (insignificant, asymptomatic and temporary);
• Integuments: infrequently – rash, a skin itch, a small tortoiseshell;
• Laboratory indicators: increase in concentration of bilirubin, glucose, activity gamma глутамилтрансферазы, alkaline phosphatase, symptoms of dysfunction of a thyroid gland;
• Others: often – an asthenic syndrome.

When carrying out post-market researches messages on development of the following side effects arrived:

• Central nervous system: very seldom – memory loss, polyneuropathy;
• Respiratory system: with not specified frequency – short wind, cough;
• Digestive tract: very seldom – jaundice, hepatitis; seldom – increase in activity of hepatic transaminases; with not specified frequency – diarrhea;
• Urinary system: very seldom – a hamaturia;
• Reproductive system and mammary glands: with not specified frequency – a gynecomastia;
• Integuments and hypodermic fatty tissue: with not specified frequency – Stephens-Johnson's syndrome;
• Musculoskeletal system: very seldom – an arthralgia; with not specified frequency – the immunomediated necrotizing myopathy;
• Others: with not specified frequency – peripheral hypostases.

During use of some statines messages on development of the following side effects arrived: a depression, sexual dysfunction, sleep disorders, including dreadful dreams and sleeplessness. It was reported about isolated cases of an intersticial disease of lungs, in particular at long therapy.

Special instructions

At receiving high doses (generally 40 mg) Krestor patients development of a canalicular proteinuria which, as a rule, was tranzitorny was noted and did not confirm an acute disease of kidneys or progressing of a disease of kidneys. At purpose of drug in a dose of 40 mg during treatment it is recommended to control indicators of function of kidneys.

At Krestor's use in all dosages (in particular higher than 20 mg) development of a mialgiya, myopathy, in rare instances – a rabdomioliza is possible.

If the initial level of a kreatinfosfokinaza is significantly increased (by 5 times exceeds the highest limit of norm), in 5-7 days it is necessary to take repeated measurement. If the repeated test confirms initial level, it is impossible to begin therapy. After intensive exercise stresses or in the presence of other possible reasons of increase in a kreatinfosfokinaza, its definition should not be carried out as it can lead to incorrect interpretation of the received results.

With risk factors of emergence of a myopathy / рабдомиолиза Krestor it is possible to take with caution after advantage ratio assessment with possible risk.

At unexpected emergence of muscular pains, muscular weakness or spasms, in particular in combination with fever and an indisposition, it is necessary to see a doctor. The possibility of continuation of therapy is defined by degree of manifestation of muscular pains and level of a kreatinfosfokinaza. After normalization of level of a kreatinfosfokinaza it is possible to consider a question of repeated appointment of Krestor in smaller doses at careful observation of a condition of the patient.

In 2-4 weeks after the beginning of therapy and/or increase in a dose it is necessary to carry out control of indicators of lipidic exchange (a dose if necessary adjust).

Prior to Krestor's reception and in 3 months after an initiation of treatment it is recommended to carry out definition of functional indicators of a liver. If the level of activity of transaminases in blood serum is 3 times higher than the upper bound of norm, the dose is reduced or cancel therapy.

At the hypercholesterolemia connected with a hypothyroidism or a nephrotic syndrome, therapy of the main diseases needs to be carried out prior to Krestor's use.

At use of some statines, in particular it is long, there were messages on isolated cases of development of the intersticial disease of lungs which is shown such symptoms as unproductive cough, an asthma and deterioration in overall health (weight reduction, fever and weakness). In these cases therapy is cancelled.

At concentration of glucose of 5,6 - 6,9 mmol/l Krestor's use was associated with the increased risk of development of a diabetes mellitus of type 2.

During treatment at control of motor transport or the performance of work connected with the increased concentration of attention and the psychomotor reactions demanding speed it is necessary to be careful (there is a probability of development of dizziness).

Medicinal interaction

At simultaneous use of Krestor with some medicines there can be following effects (AUC – total concentration of medicine in a blood plasma; _Cmax — the maximum concentration of drug in blood):

• Cyclosporine: significant increase in AUC of a rozuvastatin (the combination of drugs is contraindicated);
• Antagonists of vitamin K: increase INR (the international normalized relation);
• Gemfibrozil and other hypolipidemic drugs: increase _{in Cmax} and AUC of a rozuvastatin, perhaps pharmakodinamichesky interaction;
• Fenofibrat, gemfibrozit both other fibrata and lipidsnizhayushchy doses of niacin: increase in risk of development of a myopathy (the recommended initial dose of Krestor – 5 mg);
• Inhibitors of proteases: significant increase in exposure of a rozuvastatin;
• Antacids: significant decrease in plasma concentration of a rozuvastatin (this effect is expressed more weakly in cases if antacids are applied 2 hours later after reception of a rozuvastatin);
• Erythromycin: reduction of AUC and _Cmax of a rozuvastatin;
• Gormonozamestitelny therapy / oral contraceptives: increase in their AUC (it is necessary to consider at selection of doses of oral contraceptives).

Terms and storage conditions

To store in the place, unavailable to children, at a temperature up to 30 °C.

Period of validity – 3 years.