Levomycetin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LEVOMYCETIN (LAEVOMYCETIN)

Composition:

Active substance: 1 vial contains 0.5 g or 1.0 g of sterile sodium chloramphenicol succinate, calculated as chloramphenicol.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: white powder or white with a yellowish tinge. Hygroscopic.

Pharmacotherapeutic group.

Antibacterial agents for systemic use. Phenicol derivatives.

ATC Code J01B A01.

Pharmacological Properties

Pharmacodynamics

A broad-spectrum antibiotic. Active against many Gram-positive bacteria (staphylococci, streptococci, pneumococci, enterococci) and Gram-negative bacteria: Escherichia coli, Haemophilus influenzae, Salmonella, Shigella, Klebsiella, Serratia, Yersinia, Proteus, Neisseria gonorrhoeae, Neisseria meningitidis, anaerobes, rickettsiae, spirochetes, chlamydia, and some large viruses (causative agents of trachoma, psittacosis, lymphogranuloma venereum, etc.); acts on bacterial strains resistant to penicillin, streptomycin, and sulfonamides. Weakly active against acid-resistant bacteria, Pseudomonas aeruginosa, Clostridium species, and protozoa. Bacteriostatic at usual doses. Inhibits peptidyl transferase and disrupts protein synthesis in bacterial cells.

Pharmacokinetics

After intramuscular and intravenous administration, high drug concentrations in blood plasma are rapidly achieved (within 5–10 minutes after intravenous, and within 30–45 minutes after intramuscular administration). Maximum plasma concentration is reached within 1 hour and remains at effective levels in blood plasma for 8–12 hours. A substantial portion (60–80%) binds to plasma albumin. The drug readily penetrates into organs and body fluids, crosses the blood-brain barrier, placental barrier, and is excreted into breast milk.

The drug is primarily excreted by the kidneys in the form of inactive metabolites, and partially via bile.

Clinical characteristics.

Indications.

Treatment of infections caused by microorganisms sensitive to chloramphenicol (typhoid fever, paratyphoid, generalized forms of salmonellosis, dysentery, brucellosis, tularemia, meningitis, typhus fever, and other rickettsioses, trachoma). Infectious processes caused by pathogens sensitive to levomycetin in cases where other chemotherapeutic agents are ineffective or their use is impossible.

Contraindications.

Hypersensitivity to chloramphenicol or other amphenicols; bone marrow suppression; blood disorders; skin diseases (psoriasis, eczema, fungal infections); severe impairment of liver and/or kidney function; glucose-6-phosphate dehydrogenase deficiency; porphyria.

Levomycetin should not be prescribed for acute respiratory diseases, tonsillitis, or for the prevention of bacterial infections.

Interaction with other medicinal products and other types of interactions.

Prolonged use of levomycetin, which is a liver enzyme inhibitor, in the preoperative period or during surgery may reduce plasma clearance and prolong the action of alfentanil.

Chloramphenicol inhibits the cytochrome P450 enzyme system. Therefore, when used concomitantly with antiepileptic drugs (phenobarbital, phenytoin) and indirect anticoagulants (dicoumarol, warfarin), metabolism of these drugs is reduced, excretion is slowed, their plasma concentrations increase, and their toxicity is enhanced.

When levomycetin is used concomitantly with tolbutamide (butamide) and chlorpropamide, their hypoglycemic effect may be potentiated (due to inhibition of hepatic metabolism and increased concentrations), requiring dose adjustment.

Phenobarbital, rifampicin, rifabutin decrease chloramphenicol plasma concentration by accelerating its hepatic metabolism.

When used concomitantly with paracetamol, a prolonged elimination half-life of chloramphenicol may be observed.

Phenytoin. When used concomitantly, both decreased and increased plasma concentrations of chloramphenicol may be observed.

Cyclosporine. When used concomitantly with chloramphenicol, an increase in cyclosporine plasma levels may occur; therefore, monitoring of cyclosporine concentration is required.

Cyclophosphamide. Concomitant use prolongs the elimination half-life of cyclophosphamide from 7.5 to 11.5 hours.

Tacrolimus. When used concomitantly with chloramphenicol, an increase in tacrolimus plasma levels may occur. The dose of tacrolimus should be adjusted when used together.

Levomycetin reduces the antibacterial effect of penicillins and cephalosporins.

Macrolides (erythromycin, oleandomycin, clindamycin), lincosamides (lincomycin), polyene antibiotics (nystatin, levorin). When chloramphenicol is used concomitantly with these agents, mutual reduction in antimicrobial activity occurs because chloramphenicol may displace these drugs from binding sites or interfere with their binding to the 50S subunit of bacterial ribosomes. Therefore, simultaneous use should be avoided.

Cycloserine. Concomitant use enhances the neurotoxicity of chloramphenicol.

Mediticines that suppress hematopoiesis (sulfonamides, cytostatics, cimetidine, ristomycin) or radiation therapy, when used concomitantly with chloramphenicol, may intensify their suppressive effects on bone marrow and increase the severity of such manifestations.

When used concomitantly with vitamin B12, iron preparations, folic acid, levomycetin may counteract the stimulation of hematopoiesis by vitamin B12, thereby reducing the efficacy of these agents.

Prolonged concomitant use of levomycetin and estrogen-containing oral contraceptives may lead to reduced contraceptive reliability and increased frequency of breakthrough bleeding.

Ethanol. Concomitant intake of ethanol may result in a disulfiram-like reaction (skin flushing, tachycardia, nausea, vomiting, reflex coughing, seizures).

Special precautions for use.

The drug should be used only under medical supervision.

Due to the possibility of developing severe hematopoietic organ damage resulting from the drug's toxic effects, peripheral blood counts should be monitored during treatment, and liver and kidney function should be closely observed.

If leukopenia, thrombocytopenia, anemia, or other pathological blood changes occur, chloramphenicol should be discontinued immediately. Although regular monitoring of peripheral blood composition during chloramphenicol therapy may detect early hematological changes (leukopenia, reticulocytopenia, or granulocytopenia) before they become irreversible, this does not exclude the possibility of developing aplastic anemia due to bone marrow depression. Aplastic anemia, thrombocytopenia, and granulocytopenia typically manifest after completion of treatment. Therefore, symptoms such as pallor, sore throat, elevated body temperature, bleeding, or weakness appearing several weeks or months after discontinuation of the drug require immediate medical attention. Prolonged use of chloramphenicol may increase the risk of hemorrhage, which may result from either bone marrow suppression or inhibition of normal intestinal flora leading to reduced vitamin K synthesis.

In patients with impaired liver or kidney function, serum levels of chloramphenicol may increase, and the risk of toxic reactions to the drug may be higher; therefore, dosage adjustments are necessary. Periodic measurement of drug concentration in the blood, along with monitoring of liver and kidney function, is advisable.

Clinical experience with chloramphenicol has not revealed differences in therapeutic efficacy among patients of different age groups. However, due to age-related differences in liver and kidney function, cardiovascular status, presence of comorbid conditions, and concomitant medication use, dosage for elderly patients should be determined cautiously, usually starting at the lower end of the recommended dosage range. Antibacterial therapy may disrupt the normal flora of the large intestine and promote overgrowth of Clostridium difficile, whose toxins are the primary cause of pseudomembranous colitis. Pseudomembranous colitis may develop either during treatment or up to 2 months after completion of antibacterial therapy. Cases of pseudomembranous colitis, ranging from mild to life-threatening, have been reported with nearly all antibacterial agents, including chloramphenicol. Therefore, it is essential to confirm the diagnosis in patients presenting with diarrhea following antibacterial therapy.

Without appropriate treatment, toxic megacolon, peritonitis, and shock may develop. It should be noted that colitis is most likely to occur in severely ill or debilitated patients, particularly the elderly.

Antibacterial therapy may lead to overgrowth of resistant microorganisms, including fungi. If infections caused by resistant organisms develop during treatment, appropriate measures should be taken.

Blood count monitoring is required during treatment. Any evidence of adverse effects on blood components is an indication for immediate discontinuation of the drug.

In patients previously treated with cytostatic agents or radiation therapy, the potential risks and expected benefits of chloramphenicol therapy should be carefully evaluated due to the increased risk of severe adverse effects.

Chloramphenicol should not be used to treat mild infections or for prophylactic purposes, nor for any infections for which less toxic antibiotics are available. Repeated courses and prolonged treatment should also be avoided.

Use with caution in patients with cardiovascular disorders or a predisposition to allergic reactions.

Chloramphenicol has been associated with acute attacks of porphyria; therefore, its use in patients with porphyria is considered dangerous.

Each gram of sodium chloramphenicol succinate contains 2.264 mmol of sodium, which should be taken into account when administering the drug to patients on a sodium-restricted diet.

Concomitant ethanol intake may lead to a disulfiram-like reaction (skin flushing, tachycardia, nausea, vomiting, reflex coughing, seizures).

Chloramphenicol may affect the development of immune response and should not be used during active immunization.

Treatment should not extend beyond the time necessary to achieve therapeutic benefit without risking complications or disease relapse.

Rapid intravenous administration of chloramphenicol may cause an intense bitter taste in the mouth.

Use during pregnancy or breastfeeding.

The use of chloramphenicol is contraindicated during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

The drug should be used with caution in individuals who drive vehicles or operate machinery due to the risk of potential adverse reactions affecting the nervous system.

Method of Administration and Dosage

The dose and concentration of the drug should be used according to the severity of the infection.

Children. Chloramphenicol should be administered intramuscularly in a daily dose: for children under 1 year of age – 25–30 mg/kg body weight; for children from 1 year of age – 50 mg/kg body weight, divided into two doses given at 12-hour intervals.

Adults. Chloramphenicol should be administered intramuscularly or intravenously. Prepare solutions immediately before use.

For intramuscular administration, dissolve the contents of the vial (0.5 g or 1 g) in 2–3 mL of sterile water for injections and administer deep into the muscle. As a solvent for intramuscular administration, 0.25% or 0.5% novocaine solution may be used.

For intravenous bolus injection, dissolve a single dose of the drug in 10 mL of sterile water for injections or in 5% or 40% glucose solution and administer intravenously slowly over 3–5 minutes. For patients with diabetes mellitus, dissolve the drug in 0.9% sodium chloride solution.

The daily dose of the drug for adults in systemic infections ranges from 1 to 3 g; administer 0.5–1.0 g 2–3 times daily at 8–12 hour intervals. If necessary, the daily dose may be increased up to 4 g.

In ophthalmology, the drug is used for parabulbar injections and instillations. For injections, administer 0.2–0.3 mL of a 20% solution 1–2 times daily; for instillations, instill 1–2 drops of a 5% solution into the conjunctival sac 3–5 times daily. Dissolve the drug in sterile water for injections or in sodium chloride solution. The aqueous 5% solution for instillations should be stored for no more than 2 days.

Duration of treatment – 5–15 days.

Children.

Use in children is permitted provided the dosage specified in the section "Method of Administration and Dosage" is strictly followed. Should be prescribed with caution and only if no alternative therapy is available.

Overdose.

Severe complications affecting the hematopoietic system, such as hemolytic anemia, thrombocytopenia, and leukopenia, are usually associated with prolonged use of high doses of the drug (more than 3 g per day) and may manifest as pallor, sore throat and elevated body temperature, bleeding and hemorrhages, fatigue or weakness, as well as vomiting and diarrhea.

Symptoms of overdose include those of the "gray syndrome" (cardiovascular syndrome in infants), which occurs in relative overdose (caused by accumulation of chloramphenicol due to immaturity of liver enzymes and its direct toxic effect on the myocardium) – bluish-gray skin color, low body temperature, abdominal distension, vomiting, irregular breathing, decreased neurological responses, cardiovascular insufficiency, circulatory collapse, acidosis, myocardial conduction depression, coma, and fatal outcome. The "gray syndrome" may also occur in patients with impaired liver or kidney function and is a consequence of drug accumulation. The "gray syndrome" occurs when plasma chloramphenicol concentration exceeds 50 µg/mL.

Treatment: discontinue the drug, gastric lavage, use of enterosorbents, symptomatic therapy. In severe cases – symptomatic therapy, hemosorption.

Adverse Reactions

The most severe adverse reactions are: aplastic anemia, bone marrow suppression, and "gray syndrome".

Possible adverse reactions affecting the following organs and systems:

Neurological disorders: psychomotor disturbances, depression, delirium, confusion, peripheral neuritis, optic neuritis (including ophthalmoplegia), visual and auditory hallucinations, decreased visual and hearing acuity, taste disturbances, headache, encephalopathy.

Gastrointestinal tract: dyspepsia, abdominal distension, dry mouth, nausea, vomiting, diarrhea, dermatitis (including perianal dermatitis), suppression of intestinal microflora, dysbiosis, enterocolitis, stomatitis, glossitis.

Hepatobiliary system: liver function disturbances.

Hematopoietic system: bone marrow suppression, reticulocytopenia, decreased hemoglobin levels, anemia, leukopenia, granulocytopenia, thrombocytopenia, erythrocytopenia, pancytopenia; rarely – aplastic anemia, hypoplastic anemia, agranulocytosis, cytoplasmic vacuolization of early erythrocytic forms.

Immune system: hypersensitivity reactions, including dermatoses, pruritus, skin rashes, fever, angioedema, urticaria, anaphylaxis.

Other: possible development of superinfection, including fungal infections, hyperthermia, bacteriolysis reaction (Jarisch-Herxheimer reaction), collapse (in children).

When Levomycetin is used as eye drops, local allergic reactions may occur.

Shelf life. 5 years.

Storage conditions. Store in original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Incompatibility. Do not use solvents not specified in the section "Administration and dosage". Levomycetin must not be mixed in the same syringe with B-group vitamins or ascorbic acid. Levomycetin is incompatible in solutions with sodium ampicillin, gentamicin sulfate, kanamycin sulfate, and hydrocortisone.

Packaging. 0.5 g or 1 g in a vial.

Prescription category. Prescription only.

Manufacturer. JSC "Kievmedpreparat".

Manufacturer's location and address of operations.

Ukraine, 01032, Kyiv, Saksaganskogo St., 139.

INSTRUCTION

on medical use of medicinal product

LEVOMYCETIN

(LAEVOMYCETIN)

Composition:

Active substance: 1 vial contains sterile sodium chloramphenicol succinate equivalent to chloramphenicol 0.5 g or 1.0 g.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: white or white with a yellowish tint hygroscopic powder.

Pharmacotherapeutic group.
Antimicrobial agents for systemic use. Phenicol antibiotics.
ATC code J01BA01.

Pharmacological properties.

Pharmacodynamics.

A broad-spectrum antibiotic. Effective against many Gram-positive (staphylococci, streptococci, pneumococci, enterococci) and Gram-negative bacteria: Escherichia coli, Haemophilus influenzae, Salmonella, Shigella, Klebsiella, Serratia, Yersinia, Proteus, Neisseria gonorrhoeae, Neisseria meningitidis, anaerobes, rickettsiae, spirochetes, chlamydiae, and some large viruses (causative agents of trachoma, psittacosis, lymphogranuloma venereum, etc.); active against strains resistant to penicillin, streptomycin, and sulfonamides; weakly active against acid-resistant bacteria, Pseudomonas aeruginosa, Clostridia, and protozoa. Bacteriostatic at usual doses. Inhibits peptidyl transferase and disrupts protein synthesis in bacterial cells.

Pharmacokinetics.

After intramuscular and intravenous administration, high plasma concentrations are rapidly achieved (within 5–10 minutes after intravenous, 30–45 minutes after intramuscular administration). Maximum blood concentration is reached within 1 hour and remains at effective levels in plasma for 8–12 hours. A significant portion (60–80%) binds to plasma albumins. Easily penetrates organs and body fluids, crosses the blood-brain barrier, placenta, and enters breast milk.

Excreted mainly by kidneys as inactive metabolites, partially with bile.

Clinical characteristics.

Indications.

Treatment of infections caused by chloramphenicol-sensitive microorganisms (typhoid fever, paratyphoid, generalized forms of salmonellosis, dysentery, brucellosis, tularemia, meningitis, typhus, and other rickettsioses, trachoma). Infectious processes caused by pathogens sensitive to levomycetin when other chemotherapeutic agents are ineffective or contraindicated.

Contraindications.

Hypersensitivity to chloramphenicol or other phenicols, bone marrow suppression, blood disorders; skin diseases (psoriasis, eczema, fungal infections); severe liver and/or kidney function impairment; glucose-6-phosphate dehydrogenase deficiency; porphyria.

Levomycetin should not be prescribed for acute respiratory infections, tonsillitis, or for bacterial infection prophylaxis.

Interaction with other medicinal products and other types of interactions.

Prolonged use of levomycetin, a liver enzyme inhibitor, in the preoperative period or during surgery may reduce alfentanil plasma clearance and prolong its action.

Chloramphenicol inhibits the cytochrome P450 enzyme system; therefore, when used concomitantly with antiepileptic drugs (phenobarbital, phenytoin), indirect anticoagulants (dicoumarol, warfarin), metabolism of these drugs is reduced, excretion is delayed, their plasma concentration and toxicity increase.

When used concomitantly with tolbutamide (butamide) and chlorpropamide, their hypoglycemic effect may be enhanced (due to inhibition of hepatic metabolism and increased concentration), requiring dose adjustment.

Phenobarbital, rifampicin, rifabutin reduce chloramphenicol plasma concentration by accelerating its hepatic metabolism.

When used concomitantly with paracetamol, prolonged elimination half-life of chloramphenicol may be observed.

Phenytoin. Concurrent use may result in either decreased or increased chloramphenicol plasma concentration.

Cyclosporine. Concurrent use with chloramphenicol may increase cyclosporine plasma levels; cyclosporine concentration monitoring is required.

Cyclophosphamide. Concurrent use prolongs cyclophosphamide elimination half-life from 7.5 to 11.5 hours.

Tacrolimus. Concurrent use with chloramphenicol may increase tacrolimus plasma levels. Tacrolimus dosage should be adjusted.

Levomycetin reduces the antibacterial effect of penicillins and cephalosporins.

Macrolides (erythromycin, oleandomycin, clindamycin), lincosamides (lincomycin), polyene antibiotics (nystatin, levorin). Concurrent use with chloramphenicol results in mutual reduction of antimicrobial activity, as chloramphenicol may displace these drugs from binding sites or prevent their binding to the 50S subunit of bacterial ribosomes. Therefore, their simultaneous use should be avoided.

Cycloserine. Concurrent use enhances chloramphenicol neurotoxicity.

Meditations suppressing hematopoiesis (sulfonamides, cytostatics, cimetidine, ristomycin) or radiation therapy, when used concurrently with chloramphenicol, may enhance bone marrow suppression and severity of its manifestations.

When used concomitantly with vitamin B12, iron preparations, folic acid, levomycetin may counteract vitamin B12-stimulated hemopoiesis, reducing the efficacy of these agents.

Prolonged concurrent use of levomycetin and estrogen-containing oral contraceptives may reduce contraceptive reliability and increase breakthrough bleeding frequency.

Ethanol. Concurrent ethanol intake may cause a disulfiram-like reaction (skin hyperemia, tachycardia, nausea, vomiting, reflex cough, seizures).

Special precautions.

The drug should be used only under medical supervision.

Due to the risk of severe hematopoietic system damage from the drug's toxic effects, peripheral blood counts should be monitored during treatment, along with liver and kidney function.

If leukopenia, thrombocytopenia, anemia, or other blood abnormalities occur, levomycetin should be discontinued immediately. Although regular monitoring of peripheral blood counts during chloramphenicol treatment may detect early hematological changes (leukopenia, reticulocytopenia, or granulocytopenia) before they become irreversible, it does not exclude the possibility of aplastic anemia due to bone marrow depression. Aplastic anemia, thrombocytopenia, and granulocytopenia usually manifest after treatment cessation. Therefore, symptoms such as skin pallor, sore throat, elevated body temperature, bleeding, or weakness (if occurring several weeks or months after drug discontinuation) require urgent medical attention. Prolonged chloramphenicol use may increase bleeding tendency, due to both bone marrow suppression and suppression of normal intestinal flora, leading to inhibition of vitamin K synthesis.

In patients with impaired liver or kidney function, levomycetin serum levels may increase, and the risk of toxic reactions may be higher; therefore, dosage should be adjusted accordingly. Periodic determination of drug concentration in blood, along with liver and kidney function tests, is advisable.

Clinical experience with levomycetin has not revealed differences in treatment efficacy among patients of different age groups. However, considering age-related differences in kidney, liver, and cardiovascular system function, comorbidities, and concomitant medications, dosage for elderly patients should be determined cautiously, usually starting at the lower end of the dosing range. Antibacterial treatment may disrupt normal colonic flora and promote excessive growth of Clostridium difficile, whose toxins are the main cause of pseudomembranous colitis. Pseudomembranous colitis may occur during or up to 2 months after antibacterial therapy. Cases of pseudomembranous colitis, ranging from mild to life-threatening, have been reported with nearly all antibacterial agents, including chloramphenicol. Therefore, accurate diagnosis is essential in patients with diarrhea after antibacterial treatment.

Without appropriate treatment, toxic megacolon, peritonitis, and shock may develop. Colitis is most likely in severely ill elderly patients and immunocompromised individuals.

Antibacterial treatment may lead to overgrowth of non-susceptible microorganisms, particularly fungi. If infections caused by non-susceptible organisms develop during treatment, appropriate measures should be taken.

Blood count monitoring is required during drug use. Any evidence of harmful effects on blood elements is an indication for immediate discontinuation of therapy.

In patients previously treated with cytostatic agents or radiation therapy, potential risks and expected benefits of levomycetin treatment should be carefully evaluated due to the risk of severe adverse effects.

Chloramphenicol should not be used for mild infections, prophylaxis, or when less toxic antibiotics are available. Repeated courses and prolonged treatment should be avoided.

Use with caution in patients with cardiovascular diseases and predisposition to allergic reactions.

Chloramphenicol use has been associated with acute porphyria attacks; therefore, its use in porphyria patients is considered unsafe.

Each gram of sodium chloramphenicol succinate contains 2.264 mmol of sodium, which should be considered when prescribing to patients on sodium-restricted diets.

Concurrent ethanol intake may cause a disulfiram-like reaction (skin hyperemia, tachycardia, nausea, vomiting, reflex cough, seizures).

Chloramphenicol may affect immune response development; it should not be administered during active immunization.

Treatment should not exceed the duration necessary to achieve positive outcomes without risk of complications or disease recurrence.

Rapid intravenous injection of chloramphenicol may cause an intense bitter taste in the mouth.

Use during pregnancy or breastfeeding.

Levomycetin use is contraindicated during pregnancy or breastfeeding.

Ability to affect reaction rate when driving or operating machinery.

The drug should be used cautiously by individuals driving or operating machinery due to the risk of possible adverse neurological reactions.

Administration and dosage.

The administered dose and concentration depend on infection severity.

Children. Levomycetin should be administered intramuscularly at a daily dose: for children under 1 year – 25–30 mg/kg body weight, from 1 year – 50 mg/kg body weight, divided into two doses 12 hours apart.

Adults. Levomycetin should be administered intramuscularly or intravenously. Prepare solutions ex tempore.

For intramuscular injection, dissolve the vial contents (0.5 g or 1.0 g) in 2–3 ml of sterile water for injections and inject deeply into muscle. As a solvent for intramuscular administration, 0.25% or 0.5% novocaine solution may be used.

For intravenous bolus injection, dissolve a single dose in 10 ml of sterile water for injections or in 5% or 40% glucose solution and administer slowly over 3–5 minutes. For diabetic patients, dissolve the drug in 0.9% sodium chloride solution.

The daily dose for adults with systemic infections is 1–3 g; administer 0.5–1.0 g 2–3 times daily at 8–12 hour intervals; if necessary, daily dose may be increased to 4 g.

In ophthalmology, the drug is used for periocular injections and instillations. For injections, administer 0.2–0.3 ml of 20% solution 1–2 times daily; for instillations, instill 5% solution (1–2 drops) into the conjunctival sac 3–5 times daily. Dissolve the drug in sterile water for injections or sodium chloride solution.

The aqueous 5% solution for instillations should be stored no longer than 2 days.

Duration of use – 5–15 days.

Children.

Use in children is permitted provided the dosing instructions in the "Administration and dosage" section are followed. Should be prescribed cautiously and only when alternative therapies are unavailable.

Overdose.

Severe hematopoietic system complications such as hemolytic anemia, thrombocytopenia, leukopenia, usually associated with prolonged use of high doses (more than 3 g daily), may manifest as skin pallor, sore throat, elevated body temperature, bleeding and hemorrhages, fatigue or weakness, as well as vomiting and diarrhea.

Symptoms of overdose include "gray syndrome" (cardiovascular syndrome in young children), caused by relative overdose (due to levomycetin accumulation resulting from immature liver enzymes and its direct toxic effect on myocardium) – bluish-gray skin color, hypothermia, abdominal distension, vomiting, irregular breathing, decreased neurological responses, cardiovascular failure, circulatory collapse, acidosis, myocardial conduction depression, coma, and fatal outcome. "Gray syndrome" may also occur in patients with impaired liver and kidney function due to drug accumulation. "Gray syndrome" occurs at plasma chloramphenicol concentrations exceeding 50 μg/ml.

Treatment: discontinue the drug, gastric lavage, use of enterosorbents, symptomatic therapy. In severe cases – symptomatic therapy, hemoadsorption.

Adverse reactions.

The most severe adverse reactions are: aplastic anemia, bone marrow suppression, and "gray syndrome".

Possible adverse reactions affecting the following organs and systems:

Neurological disorders: psychomotor disturbances, depression, delirium, confusion, peripheral neuritis, optic neuritis (including ophthalmoplegia), visual and auditory hallucinations, decreased visual and hearing acuity, taste disturbances, headache, encephalopathy.

Gastrointestinal tract: dyspepsia, abdominal distension, dry mouth, nausea, vomiting, diarrhea, dermatitis (including perianal dermatitis), suppression of intestinal microflora, dysbiosis, enterocolitis, stomatitis, glossitis.

Hepatobiliary system: liver function disturbances.

Hematopoietic system: bone marrow suppression, reticulocytopenia, decreased hemoglobin levels, anemia, leukopenia, granulocytopenia, thrombocytopenia, erythrocytopenia, pancytopenia; rarely – aplastic anemia, hypoplastic anemia, agranulocytosis, cytoplasmic vacuolization of early erythrocytic forms.

Immune system: hypersensitivity reactions, including dermatoses, pruritus, skin rashes, fever, angioedema, urticaria, anaphylaxis.

Other: possible development of superinfection, including fungal infections, hyperthermia, bacteriolysis reaction (Jarisch-Herxheimer reaction), collapse (in children).

When Levomycetin is used as eye drops, local allergic reactions may occur.

Shelf life. 5 years.

Storage conditions. Store in original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Incompatibility. Do not use solvents not specified in the section "Administration and dosage". Levomycetin must not be mixed in the same syringe with B-group vitamins or ascorbic acid. Levomycetin is incompatible in solutions with sodium ampicillin, gentamicin sulfate, kanamycin sulfate, and hydrocortisone.

Packaging. 0.5 g or 1 g in a vial.

Prescription category. Prescription only.

Manufacturer. JSC "Kievmedpreparat".

Manufacturer's location and address of operations.

Ukraine, 01032, Kyiv, Saksaganskogo St., 139.