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

Core: Betadex (beta-cyclodextrin) - 15.0 mg; Copovidone 9.0 mg; corn starch pregelatinized starch - 75.0 mg; silicon dioxide colloid (aerosil brand A-300) - 1.5 mg; sodium stearyl fumarate 4.5 mg; magnesium carbonate 4.5 mg.

Finished water-soluble film shell: hypromellose (hydroxypropylmethylcellulose) - 7.79 mg; ferric oxide yellow oxide - 0.45 mg; dye iron oxide red - 0.15 mg; macrogol 6000 - 1.50 mg; talc - 0.24 mg; titanium dioxide - 0.37 mg.

Description:

Round, biconvex tablets, covered with a film membrane from light brown to dark brown. On the cross-section the nucleus is white or white with a yellowish tint of color.

Pharmacotherapeutic group:Antibiotic-oxazolidinone

ATX: & nbsp

J.01.X.X.08 Linezolid

J.01.X.X Other antibacterial drugs

Pharmacodynamics:

Linezolid, a synthetic antibacterial drug, belongs to a new class of antimicrobial agents, oxazolidinones, active in vitro in relation to aerobic Gram-positive bacteria, certain gram-negative bacteria and anaerobic microorganisms. Linezolid selectively inhibits protein synthesis in bacteria.By binding to the bacterial ribosome, it prevents formation of a functional initiation complex 70SWhich is an essential component of the translation process of protein synthesis.

Sensitivity

The drug is active in vitro and in vivo.

Gram-positive aerobes:

Enterococcus faecium (Including strains resistant to vancomycin)

Staphylococcus aureus (including methicillin-resistant strains)

Streptococcus agalactiae

Streptococcus pneumoniae (including multidrug-resistant strains)

Streptococcus pyogenes

The drug is active in vitro.

Gram-positive aerobes:

Enterococcus faecalis (including strains, resistant to vancomycin)

Enterococcus faecium (strains sensitive to vancomycin)

Staphylococcus epidermidis (including methicillin-resistant strains)

Staphylococcus haemolyticus

Streptococcus spp. groups Viridans

Gram-negative aerobes:

Pasteurella multocida

Resistant to linezolid microorganisms:

Haemophilus influenzae

Moraxella catarrhalis

Neisseria spp.

Enterobacteriaceae spp.

Pseudomonas spp.

Resistance

Linezolid action mechanism is different from the mechanisms of action of antimicrobial agents of other classes (e.g., aminglikozidov, beta-lactams, folic acid antagonists, glycopeptides, lincosamides, quinolones, rifamycins, streptogramins, tetracycline and chloramphenicol), so that cross-resistance between linezolid and these drugs do not exist. Linezolid is active against pathogenic microorganisms, both sensitive and resistant to these drugs. Resistance to linezolid develops slowly through a multistage mutation 23S ribosomal RNA and occurs at a frequency of less than 1x10^-9 - 1 x 10^-11.

Pharmacokinetics:

Suction

After oral administration linezolid quickly and intensively absorbed from the gastrointestinal tract. Eating does not affect the absorption of the drug. Absolute bioavailability is about 100%.

Distribution

The equilibrium concentration (Css) linezolid in the blood is achieved on the 2-3 day of application. Rapidly distributed in tissues with good perfusion. The volume of distribution of linezolid at equilibrium concentration in a healthy adult is on the average 40-50 liters, which is approximately equal to the total water content in the body. Binding to plasma proteins is 31% and does not depend on the concentration of linezolid in the blood.

Metabolism

It is established that cytochrome P450 isoenzymes do not participate in the metabolism of linezolid in vitro. Linezolid does not inhibit and does not potentiate the activity of clinically important isoenzymes of cytochrome P450 (1A2, 2C9, 2C19, 2D6, 2E1, 3A4).Metabolic oxidation leads to the formation of two inactive metabolites - hydroxyethyl glycine (the main metabolite in humans, formed as a result of a non-enzymatic process) and aminoethoxyacetic acid (formed in smaller amounts). Other inactive metabolites are also described.

Excretion

The extrarenal clearance is about 65% of the linezolid clearance. With increasing dose of linezolid, a small degree of nonlinearity of clearance is noted. This can be explained by a decrease in renal and extrarenal clearance with a high dose of linezolid. However, the differences in clearance are small and do not affect the apparent half-life.

Linezolid in patients with normal renal function and with renal insufficiency of mild and moderate degree is excreted by the kidneys in the form of hydroxyethyl glycine (40%), aminoethoxyacetic acid (10%) and unchanged (30-35%). The intestine is excreted as hydroxyethyl glycine (6%) and aminoethoxyacetic acid (3%).

Unchanged linezolid practically not excreted by the intestine. The half-life of linezolid is 5-7 hours on average.

Pharmacokinetics in selected groups of patients

Patients with renal insufficiency

After a single dose of 600 mg of linezolid in patients with severe renal insufficiency (creatinine clearance <30 ml / min), the plasma concentration of its two main metabolites increased by 7-8 times. However, the increase in the area under the pharmacokinetic curve "concentration-time" (AUC) of the starting drug was not noted. Despite the fact that some basic metabolites were removed during hemodialysis, their plasma concentration after taking 600 mg of linezolid and carrying out the dialysis procedure remained significantly higher than the plasma concentration in patients with normal renal function, mild or moderate renal insufficiency.

Patients with hepatic insufficiency

There is limited evidence that the pharmacokinetics of linezolid and its two major metabolites do not change in patients with mild and moderate hepatic insufficiency (A and B classes according to the Child-Pugh classification). The pharmacokinetics of linezolid in patients with severe hepatic insufficiency (class C according to the Child-Pugh classification) has not been studied. However, since linezolid it is not metabolized by a non-enzyme route, it is not expected to significantly impair its metabolism in liver failure.

Adolescents (12-17 years old)

In adolescents, the pharmacokinetics of linezolid did not differ from the kinetics in adults. Thus, with the appointment of the drug every 12 hours, the concentration of linezolid in the blood plasma will be the same as in adults with the same dose.

Elderly

In elderly patients aged 65 years and older, the pharmacokinetics of linezolid do not change significantly.

Women

In women, the distribution of the drug is somewhat lower than that of men; they also reduced by 20% the average clearance in terms of body weight. The concentration of linezolid in the blood plasma of women is higher than that of men, which can partly be explained by differences in body weight. However, since the half-life of linezolid in men and women does not differ significantly, there is no reason to expect an increase in the concentration of linezolid in the blood of women above the tolerated value, so no dose adjustment is required.

Indications:

Treatment of infectious inflammatory diseases, if known or suspected, that they are caused by aerosol and anaerobic Gram-positive microorganisms sensitive to linezolid (including infections accompanied by bacteremia):

- Community-acquired pneumonia Streptococcus pneumoniae (including multidrug-resistant strains), including cases accompanied by bacteraemia, or Staphylococcus aureus (only methicillin-sensitive strains);

- hospital pneumonia caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains) or Streptococcus pneumoniae (including multidrug-resistant strains);

- complicated skin and soft tissue infections, including infections with diabetic foot syndrome not accompanied by osteomyelitis, caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains), Streptococcus pyogenes or Streptococcus agalactiae;

- Uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (only methicillin-sensitive strains) or Streptococcus pyogenes;

- infections caused by Enterococcus faecium (strains resistant to vancomycin), including those accompanied by bacteremia.

Contraindications:

- Hypersensitivity to linezolid and / or other components of the drug;

- Simultaneous use of linezolid with monoamine oxidase A or B inhibitors (eg, phenelzine, isocarboxazide) for 14 days before or after termination of linezolid therapy;

- In the absence of careful monitoring of patients and monitoring of blood pressure, linezolid should not be prescribed:

- patients with uncontrolled arterial hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome, bipolar disorders, schizoaffective disorders and acute confusion;

- patients receiving the following types of drugs: adrenomimetics (for example, pseudoephedrine, phenylpropanolamine, epinephrine, norepinephrine, dobutamine), dopaminomimetics (eg, dopamine), serotonin reuptake inhibitors, tricyclic antidepressants, 5-H agonistsT₁ receptors (triptans), meperidine, or buspirone;

- Children under 12 years (for this form of release).

Carefully:

Patients with renal insufficiency

Due to the unexplained clinical significance of the two primary metabolites of linezolid in patients with severe renal insufficiency linezolid should be used with caution in such patients, and only if the intended benefit exceeds the potential risk.

Patients with hepatic insufficiency

There are limited clinical data that recommend the use of linezolid in such patients only if the intended benefit exceeds the potential risk.

Linezolid should be used with caution in patients with systemic infections that pose a risk to life, such as those associated with venous catheters in intensive care units.

Pregnancy and lactation:

Pregnancy

Studies of the safety of linezolid in pregnancy have not been carried out, therefore the use of linezolid in pregnancy is possible only if the expected benefit from therapy for the mother exceeds the potential risk to the fetus.

Breast-feeding

Linezolid penetrates into the breast milk of nursing women, so if you need to use the drug during lactation should stop breastfeeding.

Dosing and Administration:

The drug can be taken both during meals and between meals. Patients who at the beginning of therapy linezolid it was prescribed intravenously, in the future it can be transferred to any dosage form of linezolid for oral administration, while dose selection is not required, since the bioavailability of linezolid upon ingestion is almost 100%. The duration of treatment depends on the pathogen, the localization and severity of the infection, and also on the clinical effect.

Recommended dosing regimen for adults and adolescents (12-17 years)

Indications (including infections accompanied by bacteremia)	Single dose and multiplicity of administration	Recommended duration of treatment
- community-acquired pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant strains), including cases accompanied by bacteraemia, or Staphylococcus aureus (only methicillin-sensitive strains);	600 mg orally every 12 hours	10-14 days
- hospitalized pneumonia caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains) or Streptococcus pneumoniae (including multidrug-resistant strains);	600 mg orally every 12 hours	10-14 days
- complicated skin and soft tissue infections, including infections with diabetic foot syndrome not accompanied by osteomyelitis, caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains), Streptococcus pyogenes or Streptococcus agalactiae;	600 mg orally every 12 hours	10-14 days
- uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (only methicillin-sensitive strains) or Streptococcus pyogenes;	600 mg orally every 12 hours	10-14 days
- infections caused by Enterococcus faecium (strains resistant to vancomycin), including those accompanied by bacteremia.	600 mg every 12 hours	14-28 days

The maximum dose for adults and adolescents (12 - 17 years) - 1.2 g / day. Dose adjustment for elderly patients is not required.

Patients with renal insufficiency do not need dose adjustment. Patients who are on hemodialysis, the drug should be administered after the end of the procedure for hemodialysis.

Patients with hepatic insufficiency do not need dose adjustment.

Side effects:

The frequency of side effects listed below was determined according to the following (World Health Organization classification): very often (> 1/10); often (> 1/100 - <1/10); infrequently (> 1/1000 - <1/100); rarely (> 1/10000 - <1/1000); very rarely (<1/10000), the frequency is unknown (according to available data, it is impossible to estimate the frequency of development). The undesirable phenomena associated with the use of linezolid are usually of mild or moderate severity. Most often, diarrhea, headache, nausea and vomiting are noted.

Adult patients

Infectious and parasitic diseases: often - candidiasis (including candidiasis of the oral cavity, vaginal candidiasis), fungal infections; infrequently - vaginitis; rarely - colitis, caused by the use of antibiotics (including pseudomembranous colitis).

Violations of the blood and lymphatic system: often - anemia; infrequently - leukopenia, neutropenia, thrombocytopenia, eosinophilia; rarely - pancytopenia; frequency unknown - myelosuppression, sideroblastic anemia.

Immune system disorders: frequency is unknown - anaphylaxis.

Disorders from the metabolism and nutrition: infrequently - hyponatremia; frequency is unknown - lactic acidosis.

Disorders of the psyche: often - insomnia.

Disturbances from the nervous system: often - headache, perversion of taste ("metallic taste" in the mouth), dizziness; infrequently - convulsions, hypesthesia, paresthesia; frequency is unknown - serotonin syndrome, peripheral neuropathy.

Disorders from the side of the organ of vision: infrequently - blurred vision; rarely - the appearance of visual field defects; frequency unknown - neuropathy of the optic nerve, optic neuritis, loss of vision, changes in visual acuity, change in color vision.

Hearing disorders and labyrinthine disturbances: infrequent - ringing in the ears.

Disorders from the cardiovascular system: often - increased blood pressure; infrequently - arrhythmia (tachycardia), transient ischemic attack, phlebitis, thrombophlebitis.

Disorders from the gastrointestinal tract: often - diarrhea, nausea, vomiting, localized or diffuse pain in the abdomen, constipation, indigestion; infrequently - pancreatitis, gastritis, bloating, dry mouth, glossitis, loose stools, stomatitis, discoloration of the tongue mucosa and other disorders of the language; rarely - a superficial change in the color of the enamel of the teeth.

Disorders from the liver and bile ducts: often - changes in the results of functional liver tests, increased activity of "liver" enzymes (including alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase (AFP)); infrequently, an increase in the concentration of total bilirubin.

Disturbances from the skin and subcutaneous tissues: often - a rash, itching; infrequently - dermatitis, excessive sweating, urticaria; frequency unknown - bullous skin lesions (such as Stevens-Johnson syndrome, toxic epidermal necrolysis), angioedema, alopecia.

Disorders from the kidneys and urinary tract: often - increased blood urea concentration; infrequently - renal insufficiency, increase in the concentration of creatinine in the blood plasma, polyuria.

Violations of the genitals and breast: infrequently - violations of the vagina and vulva.

General disorders and disorders at the site of administration: often - fever, localized pain; infrequently - chills, weakness, thirst; pain at the injection site (for solution for infusion).

Laboratory indicators: Increasing the number of neutrophils, eosinophils, reducing hemoglobin, hematocrit or red blood cell number, increasing or decreasing the number of platelets or leukocytes, increasing the activity of lactate dehydrogenase, creatine kinase, lipase, amylase, increasing fasting glucose, reducing total protein, albumin, sodium or calcium, increase or decrease of potassium or hydrocarbonates; infrequent - an increase in the content of sodium or calcium in the blood plasma, a decrease in glucose concentration not fasting, an increase or decrease in blood chlorides, an increase in the number of reticulocytes, a decrease in the number of neutrophils.

The following side effects with linezolid in rare cases were classified as serious: localized abdominal pain, transient ischemic attack, arterial hypertension.

In controlled clinical trials in which linezolid was used for a maximum of 28 days, only 2% of the patients developed anemia. In another study among patients with life-threatening infections, 2.5% (33/1326) of patients who received linezolid less than 28 days, anemia developed, while with linezolid more than 28 days, anemia developed in 12.3% (53/430) patients. The proportion of cases of development of anemia requiring a blood transfusion was 9% among patients receiving linezolid less than 28 days (3/33), and 15% (8/53) in those cases where linezolid used more than 28 days.

Side effects in children do not differ from those in adult patients.

Overdose:

No cases of overdose of linezolid have been reported. Recommended symptomatic treatment (including the need to maintain the speed of glomerular filtration). There is no data on the acceleration of deducing linezolid in peritoneal dialysis or hemoperfusion.

Interaction:

Drugs metabolized by the cytochrome P450 system

It is established that cytochrome P450 isoenzymes do not participate in the metabolism of linezolid in vitro. Linezolid does not inhibit and does not potentiate the activity of clinically important isoenzymes of cytochrome P450 (1A2, 2C9, 2C19, 2D6, 2E1, 3A4). Thus, no CYP450-induced interaction is expected when taking linezolid. With simultaneous application of linezolid and (S) - warfarin, which is largely metabolized by the isoenzyme CYP2C9, the pharmacokinetic characteristics of warfarin do not change. Such drugs as warfarin and phenytoin, which are the substrates of the isoenzyme CYP2C9, can be used simultaneously with linezolid without dose adjustment.

Inhibitors of monoamine oxidase

Linezolid is a non-selective reversible inhibitor of monoamine oxidase, therefore, in some patients receiving linezolid, there may be a moderate reversible strengthening of the pressor action pseudoephedrine and phenylpropanolamine. In this regard, it is recommended to reduce the initial doses of the following groups of drugs: adrenomimetics (for example, pseudoephedrine, phenylpropanolamine, epinephrine, norepinephrine, dobutamine), dopaminomimetics (for example, dopamine) and subsequently to carry out the dose selection by titration.

In studies, there was no development of serotonin syndrome in patients who received linezolid together with serotonergic drugs. However, there were several reports about the development of serotonin syndrome during treatment with linezolid and antidepressants - selective serotonin reuptake inhibitors.

When used simultaneously with gentamicin and aztreonam there was no change in the pharmacokinetics of linezolid.

Rifampicin C caused a decrease in C_mOh and AUC linezolid on average by 21% and 32%, respectively.

Special instructions:

In an open study among critically ill patients with intravascular catheter-related infections were observed excess mortality in patients treated with linezolid, Compared with patients who received vancomycin / dicloxacillin / oxacillin [78/363 (21.5%) vs. 58/363 (16.0%)]. The main factor influencing mortality was the gram-positive pathogen of infection at the initial stage. The mortality rate was similar among patients who had infections caused by Gram-positive microorganisms only, but was significantly higher in the linezolid group when detected, and other microorganisms, or could not be detected at an early stage.The greatest imbalance was noted during treatment and within 7 days after the end of antibiotic therapy. In many patients of the linezolid group, Gram-negative microorganisms were detected during the study, and patients died from Gram-negative infections or polymicrobial infections. Thus, in the case of complicated infections of the skin and soft tissues in patients with known or possible co-infection caused by gram-negative microorganisms, linezolid It should be used only in the absence of alternative treatment options. In these cases, additional use of drugs acting on gram-negative microflora is shown simultaneously.

In some patients taking linezolid, reversible myelosuppression may develop (with anemia, thrombocytopenia, leukopenia and pancytopenia), depending on the duration of therapy. The risk of developing this condition in elderly patients is also increased. Thrombocytopenia occurred more often in patients with severe renal failure, regardless of the patient's hemodialysis.In connection with this, during the treatment it is necessary to monitor blood levels in patients with an increased risk of bleeding, myelosuppression in the anamnesis, and also with simultaneous use of drugs that reduce hemoglobin or platelet count and / or their functional properties, with severe renal failure, and also in patients taking linezolid more than 2 weeks. Linezolid in such patients can only be used if it is possible to carefully monitor the level of hemoglobin, the number of leukocytes and platelets. If during treatment linezolid develops marked myelosuppression, treatment should be stopped, except when continuing treatment is absolutely necessary. In this case, intensive monitoring of blood counts and appropriate treatment are required. In addition, it is recommended that a blood test (including determination of hemoglobin level, platelet count and leukocyte count (with the calculation of the leukocyte count)) be performed weekly in patients receiving linezolid, regardless of the initial blood test.A higher incidence of severe anemia was observed in patients who received linezolid longer than the maximum recommended duration of treatment - 28 days. Such patients often required a blood transfusion.

Cases of sideroblastic anemia were registered in the post-marketing period. In most cases, the duration of linezolid therapy exceeded 28 days. Most patients after cancellation of linezolid completely or partially recovered as a result of specific treatment of anemia or without treatment.

In patients taking antibacterial drugs, including linezolid, should take into account the risk of developing pseudomembranous colitis of varying severity. About cases of diarrhea associated with Clostridium difficile, reported in connection with the use of almost all antibacterial drugs, including linezolid. The severity of diarrhea can range from mild to severe forms. Treatment with antibacterial drugs disrupts the normal intestinal microflora, which leads to excessive growth Clostridium difficile. Clostridium difficile produces toxins A and B, which lead to the development of diarrhea associated with Clostridium difficile. Excessive amount of toxins produced by strains Clostridium difficile, may cause an increase in mortality among patients, since such infections can be resistant to antimicrobial therapy, and may require a colonectomy. Do not use drugs that inhibit the intestinal motility. The possibility of developing diarrhea associated with Clostridium difficile, should be considered in all patients with diarrhea that followed the use of antibiotics. Careful medical supervision for 2 months is necessary for patients who have had diarrhea associated with Clostridium difficile after the introduction of antibacterial drugs.

When symptoms of impaired visual function appear, such as changes in visual acuity, changes in color perception, blurred vision, visual field defects, it is recommended that you urgently consult an ophthalmologist for advice. Monitor visual function in all patients taking linezolid for a long time (more than 28 days), as well as for all patients with newly appeared symptoms of visual disturbances, regardless of the duration of therapy.

In the case of peripheral neuropathy and optic nerve neuropathy, the risk / benefit ratio of linezolid therapy in these patients should be assessed. The risk of developing neuropathy is higher if linezolid is used in patients who are currently or recently received antimycobacterial drugs for the treatment of tuberculosis.

The development of lactic acidosis was reported in connection with the use of linezolid. Patients who experience repeated nausea or vomiting with linezolid, abdominal pain, unexplained acidosis, or a decrease in the concentration of bicarbonate anions, require close monitoring by the physician.

Linezolid inhibits the synthesis of the mitochondrial protein. As a result of this depression, side effects such as lactic acidosis, anemia and neuropathy (peripheral or optic nerve) can be observed. These effects are observed more often when the drug is used for longer than 28 days.

Cramping was reported in patients taking linezolid, and in most cases in the history there was an indication of convulsions or the presence of risk factors for their development.Patients need to collect a detailed history of previous episodes of seizures.

If the drug is to be used in combination with selective serotonin reuptake inhibitors, patients should be constantly monitored to identify signs and symptoms of serotonin syndrome, such as cognitive impairment, hyperpyrexia, hyperreflexia and impaired coordination of movements. If these symptoms appear, you should cancel one or both of the drugs taken. When discontinuing the use of a serotonergic drug, symptoms of the withdrawal syndrome may be observed.

There have been reports of reversible surface changes in tooth enamel staining with linezolid. These changes in staining were removed by professional dental cleaning.

There were reported cases of symptomatic hypoglycemia in patients with diabetes mellitus who received linezolid simultaneously with insulin or hypoglycemic drugs. Although a causal relationship between the use of linezolid and the development of hypoglycemia has not been established, patients with diabetes should be warned about the possibility of developing hypoglycemia.In case of hypoglycaemia, correction of insulin dose / hypoglycemic drugs or cancellation of linezolid is necessary. Patients should be advised not to take large amounts of food containing tyramine (such as red wine, old cheese, some alcoholic drinks, smoked meat).

Clinical studies that studied the effect of linezolid on the normal microflora of the human body were not carried out. The use of antibacterial drugs can sometimes lead to an increased growth of microorganisms that are not susceptible to it. In clinical studies, it was shown that approximately 3% of patients receiving recommended doses of linezolid developed candidiasis associated with taking antibiotics. If superinfection occurs with the use of linezolid, appropriate medical measures should be taken.

Clinical researches

The safety and efficacy of linezolid for more than 28 days have not been established.

In controlled clinical trials, patients with "diabetic foot" syndrome, bedsores or ischemic impairment, severe burns or gangrenous lesions did not participate.Thus, the experience of using linezolid in the therapy of these conditions is limited.

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

During the treatment with linezolid, it is not recommended to drive vehicles, special equipment or engage in activities involving an increased risk and activities requiring increased concentration of attention and speed of psychomotor reactions due to the possibility of developing dizziness or symptoms of visual impairment.

Form release / dosage:

Film-coated tablets, 300 mg.

Packaging:

Primary packaging

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10, 14, 20, 24, 30, 50, 60 or 100 tablets in a jar of low-pressure polyethylene with a lid that is pulled with the control of the first opening. Free space is filled with cotton wool. On cans are labeled with paper label or from polymer materials, self-adhesive.

Secondary packaging

By 1, 2, 3, 5, 6 or 10 contour mesh packages together with the instruction for use are placed in a cardboard pack.

On 1 bank together with the instruction on application place in a pack from a cardboard.

Storage conditions:

In the original packaging of the manufacturer, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003984

Date of registration:29.11.2016

Expiration Date:29.11.2021

The owner of the registration certificate:FARMASINTEZ, JSC (Irkutsk) FARMASINTEZ, JSC (Irkutsk) Russia

Manufacturer: & nbsp

FARMASINTEZ, JSC (Irkutsk) Russia

Representation: & nbspPharmasynthesis, JSCPharmasynthesis, JSC

Information update date: & nbsp03.08.2017

Illustrated instructions

Instructions

Amisolide (Amizolid)