Zorstat - instructions for use, doses, side effects, contraindications

Excipients: butylhydroxyanisole, ascorbic acid, citric acid, lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch, silicon dioxide colloid, magnesium stearate, vegetable hydrogenated oil; shell: hypromellose, iron dye red oxide (E172), titanium dioxide (E171), polysorbate 80, talc.

Description:

10 mg - round light pink tablets with a risk on one side and labeling "Pliva" with another.

20 mg - round, red-brown tablets with a risk.

Pharmacotherapeutic group:Hypolipidaemic agent - HMG-CoA reductase inhibitor

ATX: & nbsp

C.10.A.A Inhibitors of HMG-CoA reductase

C.10.A.A.01 Simvastatin

Pharmacodynamics:

A hypolipidemic preparation obtained synthetically from a fermentation product Aspergillus terreus. It is an inactive lactone, it undergoes hydrolysis in the body with the formation of the main metabolite, the hydroxy-acid derivative. The active metabolite inhibits 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), an enzyme that catalyzes the initial, limiting stage of cholesterol biosynthesis. Since the conversion of HMG-CoA to mevalonate is an early stage in the synthesis of cholesterol, the use of Zorstat does not cause the accumulation of potentially toxic sterols in the body. HMG-CoA is easily metabolized to acetyl-CoA, which is involved in many synthesis processes in the body. Reduces the content of triglycerides (TG), low-density lipoproteins (LDL) and very low density (VLDL) and total cholesterol in the blood plasma. Increases the concentration of high density lipoprotein (HDL) and reduces the ratio of LDL / HDL cholesterol and total cholesterol / HDL (in cases of heterozygous familial and non-family forms of hypercholesterolemia,with mixed hyperlipidemia, when elevated cholesterol is a risk factor).

Reduces the level of total cholesterol and LDL cholesterol in cases of heterozygous familial and non-family forms of hypercholesterolemia, with mixed hyperlipidemia, when elevated cholesterol is a risk factor. The onset of the effect is observed within 2 weeks and the maximum therapeutic effect is within 4-6 weeks after the start of treatment. The effect remains only during the period of application of the drug, with the cessation of therapy the cholesterol content gradually returns to the initial level.

Pharmacokinetics:

Absorption of Zorstat is high. After oral intake quickly absorbed: the maximum concentration of the drug is observed after 1.3-2.4 hours, after 12 hours it is reduced by 90%. Communication with plasma proteins is 95%. Food does not affect the absorption of the drug.

Metabolized in the liver, has the effect of "first passage" through the liver, where it is hydrolyzed to active metabolites, the half-life of which is 1.9 hours. Excretion mainly through the intestine (60%) in the form of metabolites; 10-15% of the administered dose is excreted by the kidneys in an inactive form.

Indications:

Primary hypercholesterolemia IIa and IIb type in the ineffectiveness of diet therapy with low cholesterol and other non-drug measures (physical activity and weight loss) in patients with an increased risk of coronary atherosclerosis.

Combined hypercholesterolemia and hypertriglyceridemia; hyperlipoproteinemia, which can not be corrected by a special diet and exercise. Homozygous hereditary hypercholesterolemia (as an adjunct to hypolipidemic therapy).

Secondary prophylaxis to reduce the overall risk of mortality, myocardial infarction (to slow the progression of coronary atherosclerosis), stroke and transient cerebral circulation, slow the progression of coronary artery atherosclerosis, reduce the risk of revascularization procedures.

Contraindications:

- Hypersensitivity to simvastatin and other components of the drug (including hereditary lactose intolerance), as well as to other drugs of the statin series (inhibitors of GMC-CoA reductase) in the anamnesis;

- liver disease in the active phase or persistent increase in "hepatic" transaminases in the serum of unclear etiology;

- diseases of skeletal muscles (myopathy);

- concomitant therapy with drugs that inhibit CYP3A4;

- age under 18 years (safety and efficacy not established);

- Pregnancy and lactation (safety and efficacy not established).

Carefully:

Age over 70 years, uncompensated hypothyroidism, alcohol abuse or liver disease in history, patients after organ transplant who undergo immunosuppressant therapy (due to an increased risk of rhabdomyolysis and renal insufficiency), rhabdomyolysis in a history, an increased risk of rhabdomyolysis and renal insufficiency due to severe acute infection, arterial hypotension, major surgery, trauma,destruction of water-electotytic balance, severe metabolic and endocrine disorders), simultaneous administration of immunosuppressants (ciclosporin), as well as derivatives of fibroic acid or nicotinic acid (risk of myopathy), patients with increased or decreased tone of skeletal muscles of unclear etiology, epilepsy.

Pregnancy and lactation:

Zorstat can have an adverse effect on the fetus and is contraindicated in pregnant women. There are rare reports of the development of anomalies in newborns whose mothers were taking simvastatin. The use of the drug is not recommended in women of childbearing age who do not use contraceptives. If during the treatment the pregnancy does come, Zorstat should be canceled, and the woman is warned about the possible danger to the fetus.

Despite the fact that there is no data on the penetration of simvastatin into breast milk, breast-feeding while taking the drug is not recommended.

Dosing and Administration:

Inside, once, in the evening, with plenty of water.

Before starting treatment and during the course of therapy, patients should observe a diet with a low cholesterol content.

With hypercholesterolemia: the initial dose - 5 mg, with severe hypercholesterolemia - 10 mg. If necessary, the dose can be increased no earlier than 4 weeks. The maximum daily dose is 80 mg. Changes (selection) of the dose should be carried out at intervals of 4 weeks. In most patients, the optimal effect is achieved when taking the drug at doses up to 20 mg per day.

With ischemic heart disease: the initial dose is 20 mg; if necessary, the dose is gradually increased every 4 weeks to 40 mg.

If the LDL content is less than 75 mg / dl (1.94 mmol / l) and the total cholesterol content is less than 140 mg / dL (3.6 mmol / L), the dose should be reduced.

Patients with homozygous hereditary hypercholesterolemia the drug is prescribed in a single dose of 40 mg / day (in the evening) or 80 mg / day, divided into 3 doses: 20, 20 and 40 mg. Patients with chronic renal insufficiency (creatinine clearance less than 30 ml / min) or receiving ciclosporin, fibrates, nicotinamide: the initial dose of the preparation is 5 mg, and the maximum daily dose is 10 mg.

In elderly patients and in patients with mild or moderate degree of renal failure, dose adjustment is not required.

For patients receiving amiodarone or verapamil simultaneously with Zorstat, the daily dose should not exceed 20 mg.

Side effects:

Very often more than 10/100, often more than 1/100 and less than 1/10, infrequently more than 1/1000 and less than 1/100, rarely more than 1/10000 and less than 1/1000, very rarely less than 1 / 10000.

From the digestive tract: rarely - dyspepsia, nausea, vomiting, abdominal pain, constipation, diarrhea, flatulence, hepatitis, cholestatic jaundice, increased activity of "liver" transaminases, alkaline phosphatase, creatine phosphokinase (CK), acute pancreatitis.

Very rarely - liver failure.

From the nervous system and sensory organs: rarely - dizziness, asthenic syndrome, headache, paresthesia, peripheral neuropathy, convulsions, insomnia, blurred vision, a violation of taste.

From the musculoskeletal system: rarely - myalgia, myopathy, muscle weakness, rhabdomyolysis.

Allergic and immunopathological reactions: rarely - hypersensitivity, rheumatic polymyalgia, angioedema, lupus-like syndrome, urticaria, vasculitis, arthritis, arthralgia, photosensitivity, fever, skin hyperemia, "hot flushes" to the face, dyspnea, thrombocytopenia, eosinophilia, increased ESR.

Dermatological reactions: rarely - skin rash, itching, alopecia, dermatomyositis.

Other: rarely - anemia, palpitations, acute renal failure (due to rhabdomyolysis), decreased potency.

Overdose:

Symptoms: specific clinical manifestations are absent.

Treatment: symptomatic, it is necessary to induce vomiting, rinse the stomach, the appointment of activated charcoal, control of liver function and activity of creatinine phosphokinase; there is no specific antidote.

In the development of myopathy with rhabdomyolysis and acute renal failure, the drug should be discontinued immediately and the diuretic and sodium bicarbonate (intravenous infusion) administered to the patient. Perhaps the development of hyperkalemia, which is eliminated by intravenous infusion of calcium chloride or calcium gluconate, glucose infusion with insulin, the use of potassium ion-exchange sorbents. Hemodialysis is not effective.

Interaction:

Cytotoxic drugs, antifungal drugs (ketoconazole, itraconazole), fibrates, high doses of nicotinic acid, immunosuppressants, erythromycin, clarythromycin, telithromycin, HIV protease inhibitors, amiodarone, verapamil, nefazodone increase the risk of rhabdomyolysis and acute renal failure (with simultaneous appointment should not be prescribed simvastatin in a dose of more than 10 mg / day).

When co-administered with cyclosporine or danazol, the risk of myopathy / rhabdomyolysis increases.

The risk of developing myopathy also increases with the co-administration of other lipid-lowering drugs that are not potent inhibitors CYP3A4, but capable of causing myopathy under conditions of monotherapy.Such as gemfibrozil and other fibrates (except fenofibrate), as well as niacin (a nicotinic acid) in a dose ≥ 1 g per day.

The risk of developing myopathy increases with a joint appointment with fusidic acid. When prescribing fusidic acid, patients are advised to temporarily stop taking simvastatin.

The risk of myopathy is slightly increased in patients receiving diltiazem simultaneously with Zorstat in a dose of 80 mg.

Strengthens the effect of indirect anticoagulants and increases the risk of bleeding, which requires monitoring the coagulability of the blood before the treatment, and often enough in the initial period of therapy. Once a stable prothrombin time indicator or International Normalized Ratio (MNO) is reached, its further control should be performed at intervals recommended for patients receiving anticoagulant therapy.

Increases the concentration of digoxin in the blood serum.

Kolestyramin and colestipol reduce bioavailability (the use of simvastatin is possible in 2-4 hours after taking these drugs, with an additive effect noted).Grapefruit juice inhibits cytochrome P450 3A4, when taken in large quantities, Cmax and AUC simvastatin and, accordingly, the risk of myopathy increases, so their simultaneous use is not recommended.

Special instructions:

At the beginning of Zorstat therapy, a reversible increase in the level of "liver" enzymes is possible. Before starting treatment, it is necessary to conduct a study of liver function (monitor the activity of "liver" transaminases every 6 weeks for the first 3 months, then every 8 weeks for the remaining first year and then 1 time in six months). Patients receiving simvastatin in a daily dose of 80 mg, liver function is monitored once in 3 months. In those cases, when the activity of "hepatic" transaminases increases (exceeding the upper limit of the norm by 3 times), treatment is canceled.

Before starting treatment, the patient should be warned about the risk of developing myopathy and rhabdomyolysis, a serious complication, which in rare cases can occur when taking drugs from the statin group, especially in high doses. Before beginning treatment with the drug and further 2 times a year during the first year of treatment or within a year after the last rise of the dose, it is recommended to perform a study of liver function.

In patients who are experiencing an increase in the level of transaminases, it should be more often monitor their concentration. When taking the drug in a daily dose of 80 mg, liver function is monitored once in 3 months. In the event that the level of transaminases continues to grow, and if it exceeds the norm by 3 times, the drug should be canceled.

Zorstat, like other inhibitors of HMG-CoA reductase, should not be used at an increased risk of rhabdomyolysis and renal insufficiency (against severe acute infection, arterial hypotension, planned large surgery, trauma, severe metabolic disorders).

The abolition of lipid-lowering drugs during pregnancy does not have a significant effect on the results of long-term treatment of primary hypercholesterolemia.

In patients with a reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome), when the level of cholesterol is increased, the underlying disease should first be treated.

The drug is administered with caution to people who abuse alcohol and / or have a history of liver disease.

Before and during treatment, the patient should be on a hypocholesterol diet. Simultaneous reception of grapefruit juice can increase the severity of side effects associated with taking Zorstat, therefore, they should be avoided at the same time. With hypertriglyceridemia I, IV and V types Zorstat is not recommended.

Treatment with Zorstat can cause myopathy, leading to rhabdomyolysis and renal failure. The risk of this pathology increases in patients receiving simultaneously with Zorstat one or more of the following medicines: fibrates (gemfibrozil, fenofibrate), ciclosporin, nefazadone, macrolides (erythromycin, clarithromycin), antifungal agents from the group of "azoles" (ketoconazole, itraconazole) and HIV protease inhibitors (ritonavir). The risk of developing myopathy is also increased in patients with severe renal failure.

All patients starting Zorstat therapy, as well as patients who need to increase the dose of the drug, should be warned about the possibility of myopathy and the need to immediately seek medical attention in the event of unexplained pain,muscle soreness, lethargy or muscle weakness, especially if it is accompanied by a malaise or fever. The drug should be discontinued immediately if myopathy is diagnosed or suspected.

In order to diagnose the development of myopathy, it is recommended that CK values be measured regularly.

During the treatment, it is possible to increase the content of serum CK, which should be taken into account in the differential diagnosis of chest pain. The criterion for the discontinuation of the drug is an increase in serum levels of CK in more than 10 times the upper limit of the norm.

In patients with diffuse myalgias, increased muscular sensitivity and / or pronounced increase in activity of creatinine phosphokinase, treatment with the drug is stopped. In patients with homozygous familial hypercholesterolemia, in which there is a complete absence of LDL receptors, Zorstat's treatment, as a rule, does not have an effect.

When Zorstat is simultaneously taken with coumarin anticoagulants, regular monitoring of prothrombin time should be performed before treatment and during therapy.

Despite the limited experience of using simvastatin in elderly patients, they did not show an increase in the incidence of adverse events, both clinical and laboratory.

If drowsiness and dizziness occur when taking the drug, the patient should refrain from driving and from work involving increased attention.

Effect on the ability to drive transp. cf. and fur:If drowsiness and dizziness occur when taking the drug, the patient should refrain from driving and from work involving increased attention.

Form release / dosage:

Tablets, film-coated, 10 mg, 20 mg.

Packaging:

For 7 tablets in a blister of PVC / PVDC / aluminum foil.

For 4 blisters together with instructions for use in a cardboard box.

Storage conditions:

In a dry place at a temperature of no higher than 25 ° C. Keep out of the reach of children!

Shelf life:2 of the year.

Do not use after the expiration datequality of life.

Terms of leave from pharmacies:On prescription

Registration number:P N 015618/01

Date of registration:08.04.2009

Expiration Date:Unlimited

The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia

Manufacturer: & nbsp

PLIVA HRVATSKA, d.o.o. Croatia

Representation: & nbspPliva of Hvartska dooPliva of Hvartska doo

Information update date: & nbsp18.10.2017

Illustrated instructions

Instructions

Zorstat® (Zorstat®)