Torvazin - instructions for use, dose, side effects, contraindications

Composition:Each tablet contains 10 mg, 20 mg or 40 mg of the active ingredient atorvastatin (in the form of atorvastatin calcium 10.36 mg, 20.72 mg or 41.44 mg respectively); excipients: lactose monohydrate (119,44 / 238,88 / 477,76 mg), crospovidone (9/18/36 mg), povidone-KZO (4,5 / 9/18 mg), magnesium stearate (1.5 (3/6 mg), calcium carbonate 95 MD - Ultra 250 (5.2 / 10.4 / 20.8 mg): calcium carbonate (95.2%), maltodextrin (4.7%), polysorbate-80 (0.1%); film sheath: opadrai Y-I-7000 white (2/4/8 mg): hypromellose-2910 (62.5%), titanium dioxide (31.25%), macrogol-400 (6.25%).

Description:

Tablets 10 mg: White or almost white, round, biconvex tablets coated with a film sheath, engraved with E 541 on one side of the tablet, without or almost odorless.

Tablets 20 mg: White or almost white, round, biconvex tablets coated with a film sheath, engraved with E 542 on one side of the tablet, without or almost odorless.

40 mg tablets: White or almost white, biconvex oblong film-coated tablets, with a risk on one side of the tablet, with engraved E 543 on the other side of the tablet, with little or no odor.

Pharmacotherapeutic group:Hypolipidemic agent - inhibitor of HMG-CoA reductase

ATX: & nbsp

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

C.10.A.A.05 Atorvastatin

Pharmacodynamics:

Atorvastatin is a selective competitive inhibitor of HMG-CoA reductase, the enzyme responsible for the conversion of 3-hydroxy-3-methyl-glutaryl-coenzyme A to mevalonate. Mevalonate is a precursor of sterols, in particular cholesterol.In the liver, triglycerides and cholesterol constitute a fraction of very low density lipoproteins (VLDL), are released into the systemic circulation and are delivered to peripheral tissues. Low density lipoproteins (LDL) are formed from VLDL and undergo catabolism primarily by binding to receptors that have a high affinity for LDL (LDL) receptors.

Atorvastatin reduces the concentration of cholesterol in the blood plasma and the concentration of lipoproteins in the blood serum due to the inhibition of HMG-CoA reductase and the biosynthesis of cholesterol in the liver. Besides, atorvastatin promotes an increase in the number of LDL receptors on the surface of the liver cells, thereby improving the capture and catabolism of LDL.

Atorvastatin reduces LDL production and reduces the amount of LDL particles. On the background of therapy with atorvastatin, a pronounced and persistent increase in the activity of LDL receptors is observed along with positive changes in the quality of the circulating LDL particles. Atorvastatin dose-dependently reduces the concentration of LDL cholesterol in patients with hereditary homozygous hypercholesterolemia, resistant to therapy with other lipid-lowering drugs.

Atorvastatin is able to reduce the concentration of total cholesterol (30-46%), LDL cholesterol (41-61%), apolipoprotein B (34-50%) and triglycerides (14-33%). Wherein atorvastatin can increase the concentration of high-density lipoprotein cholesterol (HDL) and apolipoprotein A1 in varying degrees.

These results were similar in patients with heterozygous familial hypercholesterolemia, non-family forms of hypercholesterolemia, and mixed hyperlipidemia, including patients with type 2 diabetes.

In connection with a decrease in the concentration of total cholesterol, LDL cholesterol and apolipoprotein B, the risk of cardiovascular diseases decreases.

Pharmacokinetics:

Suction

Atorvastatin is rapidly absorbed after oral administration. The maximum concentration of the drug in the blood plasma (C_m_Oh) is achieved 1-2 hours after ingestion. The intensity of absorption of atorvastatin increases in proportion to its dose. The absolute bioavailability of atorvastatin is about 12%, and the systemic bioavailability of the active fraction of the HMG-CoA reductase inhibitor is approximately 30%. Low systemic bioavailability of the drug is due to the presystemic clearance of atorvastatin in the mucosa of the gastrointestinal tract and / or the systemic metabolism of atorvastatin in the liver.Food slightly reduces the speed and degree of absorption.

Distribution

The average volume of atorvastatin distribution is approximately 381 liters. The degree of binding of atorvastatin to plasma proteins> 98%.

Metabolism

Atorvastatin is metabolized with the participation of cytochrome P450 ZA4 with the formation of ortho- and para-hydroxylated derivatives and various beta-oxidation products. Along with other metabolic pathways, these atorvastatin derivatives are further subjected to glucuronidation. The ability of ortho- and para-hydroxylated atorvastatin derivatives to inhibit HMG-CoA reductase in vitro comparable to that of atorvastatin. The active metabolites of atorvastatin provide approximately 70% of the inhibitory activity of the drug against HMG-CoA reductase.

Excretion

Atorvastatin and its metabolites are excreted mainly with bile after hepatic and / or extrahepatic metabolism. It is not subject to severe intestinal hepatic recirculation. The half-life is about 14 hours. The half-life of the active fraction of the inhibitor of HMG-CoA reductase is from 20 to 30 hours.

The concentration of atorvastatin and its active metabolites in the blood plasma of elderly patients older than 65 years is higher than in young patients,whereas the hypolipidemic effect of the drug is approximately the same.

The experience of using the drug in the children's population is limited to a small number of patients (aged 4 to 17 years) with severe dyslipidemias, such as hereditary homozygous hypercholesterolemia, so the pharmacokinetic properties of atorvastatin for children are not well understood.

In women Cmoh about 20 % above, and the area under the curve "concentration of active substance-time" (AUC) about 10% lower than in men. Clinically significant differences in the concentration of lipids in the plasma of men and women are absent.

Impaired renal function does not affect the concentration of atorvastatin in the blood plasma or the lipid metabolism of the drug and its active metabolites.

In patients with alcoholic liver cirrhosis (grade B on the Child-Pugh scale) C_m_Oh and AUC respectively, 16 and 11 times higher.

Indications:

Primary hypercholesterolemia (heterozygous familial and non-family hypercholesterolemia (type IIbut according to Fredrickson's classification), combined (mixed) hyperlipidemia (IIa and IIb type according to Fredrickson's classification), Disbetalipoproteinemia (type III according to Fredrickson's classification) (as a supplement to the diet), family endogenous hypertriglyceridemia (type IV according to Fredrickson classification), resistant to diet.

Homozygous hereditary hypercholesterolemia with insufficient effectiveness of diet therapy and other non-pharmacological methods of treatment.

Primary prophylaxis of cardiovascular complications in patients without clinical manifestations of coronary heart disease (CHD), but having increased risk factors for its occurrence - elderly age over 55, nicotine dependence, arterial hypertension, diabetes, genetic predisposition, incl. against dyslipidemia secondary prophylaxis of cardiovascular complications in patients with ischemic heart disease in order to reduce the total death rate, myocardial infarction, stroke, re-hospitalization for angina pectoris and the need for revascularization procedures.

Contraindications:

Hypersensitivity to the components of the drug; active liver disease or increased activity of "hepatic" transaminases of unknown origin (more than 3times higher than the upper limit of the norm - VGN); myopathy; pregnancy; lactation period; in women with a safe reproductive potential, not using appropriate contraceptive measures; age under 18 years (due to insufficient clinical data, efficacy and safety are not established); deficiency of lactase, lactose intolerance, glucose-galactose malabsorption (see section "Special instructions").

Carefully:

Alcohol abuse, liver disease in history, severe water-electrolyte balance disorders, endocrine and metabolic disorders, arterial hypotension, severe acute infection (sepsis), uncontrolled epilepsy, extensive surgical interventions, injuries, skeletal muscle diseases.

Pregnancy and lactation:

TORVAZIN® is contraindicated in pregnancy and during breastfeeding.

It is not known whether atorvastatin with breast milk. Given the potential for adverse effects in infants, if necessary, use during lactation should decide the issue of termination of breastfeeding. Atorvastatin can be prescribed to women of reproductive age only if the probability of pregnancy is very low (women should have adequate contraception during treatment) and the patient is informed of the possible risk of treatment for the fetus.

Dosing and Administration:

TORVAZIN® in the form of tablets is taken orally, at any time of the day, regardless of food intake.

When appointing the drug, the patient should recommend a standard hypocholesterolemic diet, which he must adhere to throughout the period of therapy.

The dose should be selected individually on the basis of the initial values of the concentration of LDL cholesterol in the blood plasma, the purpose of therapy and the effect of treatment. The recommended initial dose of TORVAZIN® tablet is 10 mg once a day. Correction of the dose should be performed at intervals of four weeks or more. The maximum dose of the drug is 80 mg once a day.

In the treatment of patients with clinical manifestations of atherosclerosis, as well as patients with diabetes mellitus with an increased risk of developing adverse events from the cardiovascular system,the target LDL cholesterol concentrations are <2.5 mmol / L (100 mg / dL) and <2 mmol / L (80 mg / dl), respectively, and the target total cholesterol concentration is respectively <4.5 mmol / l (175 mg / dL) and <4.0 mmol / L (155 mg / dl).

It is recommended to use the current guidelines to determine the individual target concentration.

With primary hypercholesterolemia and combined (mixed) hyperlipidemia prescribe TORVAZIN® 10 mg once a day. Therapeutic effect manifests itself within 2 weeks, and the maximum effect usually develops by week 4. The effect remains on the background of maintenance treatment with the drug.

Hereditary heterozygous hypercholesterolemia

The recommended initial dose of TORVAZIN® is 10 mg once a day. Further correction of the dose is carried out individually. Correction of the dose should be performed at intervals of 4 weeks. Once a dose of 40 mg per day is reached, it can be increased to a maximum dose of 80 mg per day or supplemented with a sequestrant of bile acids.

For treatment hereditary homozygous hypercholesterolemia TORVAZIN® can be used in doses ranging from 10 to 80 mg per day.The drug should be prescribed as an adjunct to other types of lipid-lowering therapy (for example, apheresis of LDL), and also in cases when these kinds of therapy are not available.

Primary prevention of cardiovascular disease

Primary preventive therapy is 10 mg per day. In order to achieve the target concentration of cholesterol (LDL) in primary prevention, an increase in the dose to 80 mg per day may be necessary.

In patients with renal insufficiency correction of the dose is not required, because renal dysfunction does not affect the concentration of atorvastatin in the blood plasma or the degree of lipid lowering when it is used.

When hepatic insufficiency you may need to reduce the dose or cancel the drug.

In elderly patients, dose adjustment is not required.

At the beginning of therapy and / or during an increase in the dose of the drug, it is necessary to monitor the concentration of lipids every 2-4 weeks and adjust the dose accordingly. When used simultaneously with cyclosporine, the daily dose of the drug should not exceed 10 mg.

Side effects:

Undesirable effects are presented according to the following criteria for grouping by frequency: often (> 1/100 to <1/10), infrequently (from> 1/1000 to <1/100), rarely (from> 1/10000 to <1 / 1000),Very rarely (<1/10000) adverse reactions, with an unidentified prevalence (prevalence can not be determined based on available clinical data).

Most often observed undesirable phenomena from the side digestive system, including Constipation, flatulence, dyspepsia and pain in a stomach. As a rule, with further treatment of these undesirable phenomena regress.

From the side of the central nervous system and the peripheral nervous system: often: sleep disturbances, including insomnia and nightmarish dreams, headache, asthenic syndrome; infrequent: malaise, fatigue, dizziness, loss or loss of memory, paresthesia, peripheral neuropathy, hypoesthesia; very rarely: a violation of taste perception.

From the digestive system: often: nausea, diarrhea, abdominal pain, indigestion, flatulence, constipation (usually these phenomena weaken as the treatment continues); dyspepsia; infrequently: vomiting, pancreatitis, anorexia; rarely: hepatitis, cholestatic jaundice; very rarely: liver failure.

From the osteomuscular system: often: myalgia, arthralgia; infrequently: back pain, myopathy; rarely: rhabdomyolysis, myositis,muscle cramps; Very rarely: tendopathy (in some cases with a rupture of the tendon), swelling of the joints, cases of immunosuppressed necrotizing myopathy.

Allergic reactions: often: itching, rash; infrequently: urticaria; very rare: anaphylaxis, bullous rash, polymorphic exudative erythema (including Stevens-Johnson syndrome), Lyell's syndrome, angioedema.

On the part of the organs of hematopoiesis: infrequently: thrombocytopenia.

From the side of metabolism: infrequently: hypo- or hyperglycemia, increase in the concentration of glycosylated hemoglobin, increased activity of serum creatine phosphokinase (CK), peripheral edema, weight gain.

Laboratory indicators: rarely: an increase in the activity of "liver" transaminases in the blood serum.

Other: infrequent: sexual dysfunction, chest pain, visual impairment, sore throat, epistaxis, belching, alopecia, tinnitus, very rarely: gynecomastia, hearing loss, secondary renal insufficiency.

With the use of some inhibitors of HMG-CoA reductase (statins), the following undesirable effects were recorded: depression; single cases of interstitial lung disease.Usually, such cases were observed in patients who received therapy with HMG-CoA reductase inhibitors (statins) for a long time.

Overdose:

There is no specific antidote. In case of an overdose, the necessary symptomatic and supportive therapy should be carried out. It is necessary to monitor the liver function and the activity of CKK in the serum. Hemodialysis is ineffective.

Interaction:

The risk of myopathy when treated with HMG-CoA reductase inhibitors is increased when used in combination with cyclosporine, fibrates, macrolide antibiotics (including erythromycin), antifungal agents with azole derivatives or nicotinic acid in lipid-lowering doses (more than 1 g / day).

In some rare cases, these combinations cause rhabdomyolysis, accompanied by renal failure in connection with myoglobinuria. In this regard, a careful assessment of the risk-benefit ratio of combined treatment is necessary.

Atorvastatin metabolism is carried out with the participation of isoenzyme CYP3A4. When using atorvastatin in combination with isoenzyme inhibitors CYP3A4 (E.g., cyclosporine, antibiotics, macrolides, e.g., erythromycin and clarithromycin, nefazodone, antifungal azole derivatives, for example, itraconazole and HIV protease inhibitors) may increase atorvastatin plasma concentration. The degree of influence and potentiation effect is determined by the variability of the effect on the isoenzyme CYP3A4. In this regard, care should be taken with the appointment of atorvastatin in combination with the above drugs.

Atorvastatin and its metabolites are substrates for P-glycoprotein. Inhibitors of the transport protein OATP1B1 (for example, ciclosporin) may increase the bioavailability of atorvastatin.

The simultaneous use of drugs, which reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone), increases the risk of reducing the level of endogenous steroid hormones (while the application requires caution).

With simultaneous application of atorvastatin and erythromycin (500 mg four times a day) or clarithromycin (500 mg, 2 times a day), which inhibits isozyme CYP3A4, an increase in the concentration of atorvastatin in the blood plasma was observed.

With the simultaneous use of atorvastatin in a dose of 40 mg and itraconazole at a dose of 200 mg 1 time / day, there was an increase AUC up to a value exceeding that of monotherapy in 3 times.

With the simultaneous use of atorvastatin (10 mg 1 time / day) and azithromycin (500 mg 1 time / day), the concentration of atorvastatin in plasma did not change.

Simultaneous use of atorvastatin with inhibitors of proteases, which are inhibitors of the isoenzyme CYP3A4, was accompanied by an increase in the concentration of atorvastatin in blood plasma.

Effects of drugs that induce isoenzyme CYP3A4 (for example, rifampicin and phenazone), on atorvastatin is unknown. The interaction with atorvastatin and other substrates of this isoenzyme is not known, but the possibility of such interaction should be taken into account when using drugs with a low therapeutic index, in particular, class III antiarrhythmics, for example, amiodarone.

The risk of myopathy caused by atorvastatin may increase with the concomitant use of fibrates. Research m vitro suggest that gemfibrozil can also interact with atorvastatin by inhibiting its glucuronation, which can cause an increase in atorvastatin concentrations in the plasma. With repeated administration of digoxin and atorvastatin at a dose of 10 mg, the equilibrium concentrations of digoxin in the blood plasma did not change. However, when using digoxin in combination with atorvastatin at a dose of 80 mg / day, the digoxin concentration increased by about 20%. Patients receiving digoxin simultaneously with atorvastatin, should be observed. Taking atorvastatin concomitantly with an oral contraceptive containing norethisterone and ethinyl estradiol, caused an increase in the concentrations of norethisterone and ethinyl estradiol in plasma. These increases in concentration should be considered when choosing doses of oral contraceptives. With the simultaneous use of atorvastatin and a contraceptive for oral administration containing norethisterone and ethinyl estradiol, there was a significant increase AUC norethisterone and ethinyl estradiol by approximately 30% and 20%, respectively. This effect should be considered when choosing an oral contraceptive for a woman receiving atorvastatin.

With the introduction of colestipol in combination with atorvastatin, there was a decrease in the concentration of atorvastatin in the blood plasma by approximately 25%. However, with the combined use of atorvastatin and colestipol, the effect on lipids was more pronounced than with each of these drugs alone.

With simultaneous ingestion of atorvastatin and a suspension containing magnesium and aluminum hydroxide, the concentration of atorvastatin in blood plasma decreased by about 35 %; however, the degree of decrease in LDL-C level did not change at the same time.

When taking atorvastatin in combination with warfarin, there was a slight decrease in prothrombin time in the first days of atorvastatin administration; but in the next 15 days the prothrombin time returned to normal. However, in the case of simultaneous use of atorvastatin and warfarin, patients should be carefully monitored.

With simultaneous application atorvastatin does not affect the pharmacokinetics of phenazone, therefore interaction with other agents metabolized by the same cytochrome isoenzymes is not expected.

The study of simultaneous administration of cimetidine and atorvastatin did not reveal a significant interaction between these drugs.

With the simultaneous administration of atorvastatin in a dose of 80 mg and amlodipine at a dose of 10 mg, there was no change in the pharmacokinetic parameters of atorvastatin in the equilibrium state.

There was no clinically significant undesirable interaction of atorvastatin and antihypertensive agents. Studies of interaction with all specific drugs have not been conducted.

Atorvastatin had no clinically significant effect on the concentration of terfenadine in the blood plasma, which is metabolized mainly by isoenzyme CYP3A4; in this connection it seems unlikely that atorvastatin can significantly affect the pharmacokinetic parameters of other isoenzyme substrates CYP3A4.

With the simultaneous administration of atorvastatin at a dose of 80 mg per day and amlodipine at a dose of 10 mg, the pharmacokinetics of atorvastatin did not change in the equilibrium state.

Simultaneous administration of atorvastatin at a dose of 40 mg per day and diltiazem in a dose of 240 mg leads to an increase in the concentration of atorvastatin in the blood plasma.

Grapefruit juice contains at least one ingredient that is an inhibitor CYP3A4, and can cause an increase in plasma concentrations of those drugs that are metabolized CYP3A4. At a daily intake of 240 ml of grapefruit juice, there was an increase AUC atorvastatin by 37% and decrease AUC active orthohydroxy metabolite by 20.4%. When consuming a large amount grapefruit juice (more than 1.2 liters per day for 5 days) value AUC atorvastatin increased by 2.5 times, a AUC active inhibitors of HMG-CoA reductase (atorvastatin and its metabolites) - 1.3 times. In this regard, the consumption of large quantities of grapefruit juice during treatment with atorvastatin is not recommended.

Special instructions:

Before starting therapy with TORVAZIN, the patient should be given a standard hypocholesterolemic diet, which he must follow during the entire treatment period.

The use of HMG-CoA reductase inhibitors to reduce lipid levels in the blood can lead to a change in biochemical indicators that reflect the liver. The liver status should be monitored before the start of therapy, 6 weeks, 12 weeks after the start of TORVAZIN® and after each dose increase, and periodically, for example, every 6 months.Increased activity of hepatic enzymes in blood serum can be observed during therapy with TORVAZIN®. Patients with elevated levels of enzymes should be monitored until the enzyme level returns to normal. In the case of a persistent increase in the values of alanine aminotransferase (ALT) or aspartate aminotransferase (ACT) to a level exceeding more than 3 times the IGN, it is recommended to reduce the dose of TORVAZIN® or to stop treatment.

TORVAZIN® should be used with caution in patients who abuse alcohol and / or have liver disease.

Treatment with TORVAZIN®, like other HMG-CoA reductase inhibitors, can cause myopathy, which in the case of progression leads to rhabdomyolysis. Rhabdomyolysis is a life-threatening condition that is characterized by a pronounced increase in the activity of CKK (more than 10 times compared with HHV), myoglobinemia and myoglobinuria with the development of renal failure. The diagnosis of myopathy (pain and weakness in muscles in combination with increased activity of CK) should be discussed in patients with common myalgia or muscle weakness and / or a marked increase in CKK activity.Patients should be warned that they should immediately inform the doctor of unexplained pain or weakness in the muscles if they are accompanied by a malaise or fever. Therapy with atorvastatin should be discontinued in the event of a marked increase in the activity of CK or in the presence of confirmed or suspected myopathy.

Patients with factors predisposing to the development of rhabdomyolysis, TORVAZIN should be administered with caution. In the following cases, before the start of statin therapy, it is necessary to determine the activity of CKK in the blood serum: renal dysfunction, hypothyroidism, the history of the musculoskeletal system in history, the toxic effect of statin or fibrate therapy on the musculoskeletal system in the history, elderly patients over 65 years old For this category of patients other factors predisposing to the development of rhabdomyolysis are also characteristic. If the patient initially determined significantly increased activity of CK in the serum, exceeding the VGN by more than 5 times, therapy with TORVAZIN® can not be started.

The risk of rhabdomyolysis increases with simultaneous use of TORVAZIN® anddrugs that can increase the concentration of atorvastatin in the blood serum: ciclosporin, erythromycin, clarithromycin, fibrates, a nicotinic acid in lipid-lowering doses (more than 1 g / day), antifungal agents, azole derivatives, immunosuppressive agents, HIV protease inhibitors. If possible, these drugs should be replaced by analogues that do not enter into a drug interaction with atorvastatin. When taking drugs that increase the concentration of atorvastatin in the blood serum, it is recommended to reduce the initial dose of the latter and regularly observe patients to identify pain or weakness in the muscles, especially during the first months of treatment and during periods of increasing the dose of any drug. In such situations, it is possible to recommend a periodic determination of the activity of CKK, although such control does not prevent the development of severe myopathy.

The activity of CK should not be determined after intensive physical exertion, as well as in the presence of other reasons for increasing the concentration of this enzyme, since in such situations the interpretation of the results of laboratory testing is difficult.If initially the activity of CK exceeds the VGN by more than 5 times, after 5-7 days it is necessary to perform a control study.

According to the results of a secondary analysis of subtypes of acute cerebral circulation disorder in patients without ischemic heart disease (CHD) who had recently suffered acute cerebrovascular accident or transient ischemic attack, a higher prevalence of hemorrhagic strokes was observed in the atorvastatin 80 mg group compared with the placebo group . The highest risk was typical for patients with anamnestic data in favor of a previous hemorrhagic stroke or lacunar infarction of the brain. For such patients, the balance of benefit and risk of atorvastatin therapy at a dose of 80 mg is not accurately established, therefore, before the start of treatment, it is necessary to carefully evaluate the risk of developing an acute cerebrovascular accident by hemorrhagic type.

With the use of some statins, rare cases of interstitial pulmonary tissue development have been reported. Most often, interstitial lung damage was observed against the background of long-term therapy with statins and manifested itself as dyspnea,unproductive cough and worsening of the general condition (increased fatigue, weight loss and fever). If the patient is suspected of interstitial lung involvement, therapy with TORVAZIN® should be discontinued.

Tablets of the drug TORVAZIN® contains lactose, this must be taken into account when treating patients with lactose intolerance. TORVAZIN® should not be taken patients with rare hereditary intolerance to galactose, lactase deficiency and malabsorption syndrome of glucose and galactose.

Effect on the ability to drive transp. cf. and fur:

There were no reports of the effect of TORVAZIN® on vehicle management or working with mechanisms. However, some patients may experience drowsiness and dizziness at the beginning of treatment. When they occur, the patient must observe special precautions when driving vehicles and working with mechanisms.

Form release / dosage:

Tablets film-coated 10 mg, 20 mg, 40 mg.

Packaging:10 tablets in a blister of a combination film "cold" (polyamide / aluminum foil / PVC) // aluminum foil.3 blisters together with instructions for use in a cardboard bundle.

Storage conditions:At a temperature of no higher than 25 ° C.
Keep out of the reach of children.

Shelf life:3 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000776

Date of registration:29.09.2011

Date of cancellation:2016-11-17

The owner of the registration certificate:Egis Pharmaceutical Plant OJSCEgis Pharmaceutical Plant OJSC Hungary

Manufacturer: & nbsp

EGIS PHARMACEUTICALS, Plc Hungary

Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Information update date: & nbsp17.11.2016

Illustrated instructions

Instructions

Torvazin® (Torvazin®)