Instructions Levomycetin tablets 0.5 g blister No. 10
Composition
active ingredient: chloramphenicol (chloramphenicol);
1 tablet contains chloramphenicol (chloramphenicol) 500 mg (0.5 g);
Excipients: potato starch; calcium stearate.
Dosage form
Pills.
Main physicochemical properties: tablets of white or white with a slightly yellowish tint, with a flat surface, beveled edges and a score.
Pharmacotherapeutic group
Antibacterials for systemic use. Amphenicols. Chloramphenicol. ATX code J01B A01.
Pharmacological properties
Pharmacodynamics
Levomycetin is a bacteriostatic antibiotic with a broad spectrum of action. The action is associated with a violation of the process of protein synthesis in the microbial cell at the stage of amino acid transfer from t-RNA to ribosomes. Effective against many gram-positive and gram-negative bacteria: Escherichia coli, Shigella flexneri spp., Shigella boydii spp., Shigella sonnei spp., Salmonella spp., (including Salmonella typhi), effective against Streptococcus spp. (including Streptococcus pneumoniae), Neisseria gonorrhoeae, Neisseria meningitidis, a number of strains of Proteus spp., some strains of Pseudomonas aeruginosa; active against Ricketsia spp., Treponema spp., Chlamydia spp. (including Chlamydia trachomatis), pathogens of purulent infections, typhoid fever, dysentery, meningococcal infection, Brucella, Rickettsia, Chlamydia, spirochetes. Inactive against Mycobacterium tuberculosis, pathogenic protozoa and fungi. Active against strains of bacteria resistant to penicillin, tetracyclines, sulfonamides. Resistance of microorganisms develops slowly. The drug is inactive against acid-fast bacteria, Pseudomonas aeruginosa, clostridia and protozoa.
The mechanism of action is due to inhibition of protein synthesis in the cells of microorganisms. In therapeutic concentrations, it exhibits a bacteriostatic effect. Resistance of microorganisms to the drug develops slowly and, as a rule, cross-resistance to other chemotherapeutic agents does not occur. Due to its high toxicity, Levomycetin can be used to treat severe infections in which less toxic antibacterial agents are ineffective or contraindicated.
Pharmacokinetics
Quickly and almost completely absorbed from the digestive tract. The maximum concentration in blood plasma is reached after 2-3 hours. Therapeutic concentration in blood is maintained for 4-5 hours. Bioavailability after oral administration is 80%. It penetrates well into organs, tissues and body fluids, penetrates through the blood-brain barrier (BBB), placenta, and breast milk. 50-60% of chloramphenicol binds to plasma proteins. The highest concentrations of chloramphenicol are observed in the liver and kidneys. Up to 30% of the administered dose is observed in bile. The maximum concentration in cerebrospinal fluid is observed after 4-5 hours after a single oral administration. Biotransformed in the liver, 90% binds to inactive glucuronide. Chloramphenicol palmitate is hydrolyzed to a free state in the digestive tract before absorption begins. Chloramphenicol sodium succinate is hydrolyzed to the free state in blood plasma, liver, lungs and kidneys. In fetuses and premature infants, the liver is not sufficiently developed to bind Levomycetin, which leads to the accumulation of toxic concentrations of the active form of the drug and can lead to the development of "gray syndrome". In the intestine, under the action of intestinal bacteria, hydrolysis of Levomycetin occurs with the formation of inactive metabolites.
It is excreted mainly in the urine (mainly in the form of inactive metabolites), partially in the bile (up to 30% of the dose taken) and feces.
The half-life in adults with normal renal and hepatic function is 1.5-3.5 hours, in impaired renal function - 3-4 hours, in severe hepatic impairment - 4.6-11 hours.
Indication
Infectious-inflammatory diseases caused by microorganisms sensitive to the drug: typhoid fever, paratyphoid fever, yersiniosis, brucellosis, shigellosis, salmonellosis, tularemia, rickettsiosis, chlamydia, purulent peritonitis, bacterial meningitis, biliary tract infections.
The drug is indicated in cases of ineffectiveness of other antimicrobial agents due to the possibility of developing severe side effects.
Contraindication
Increased individual sensitivity (allergy) to chloramphenicol (chloramphenicol), thiamphenicol, azidamphenicol and other components of the drug; blood diseases, including inhibition of hematopoiesis; severe liver and/or kidney dysfunction; deficiency of the enzyme glucose-6-phosphate dehydrogenase; skin diseases (psoriasis, eczema, fungal diseases); porphyria.
Levomycetin should not be prescribed for acute respiratory diseases, angina, or for the prevention of bacterial infection.
Interaction with other medicinal products and other types of interactions
Drugs that suppress hematopoiesis (cytostatics, carbamazepine, phenylbutazone, penicillamine, some antipsychotics, including clozapine, procainamide, reverse transcriptase inhibitors, propylthiouracil, sulfonamides, cimetidine, ristomycin), radiotherapy: their suppressive effect on the bone marrow may be enhanced. Therefore, such a combination should be avoided.
Hypoglycemic drugs (e.g., tolbutamide (butamide), chlorpropamide): their hypoglycemic effect may be enhanced (due to inhibition of the metabolism of these drugs in the liver and an increase in their concentration), which requires dose adjustment.
Phenobarbital, rifampicin, rifabutin: decrease in the concentration of chloramphenicol in the blood plasma by accelerating its metabolism in the liver.
Phenytoin: both a decrease and an increase in the concentration of chloramphenicol in the blood plasma are possible.
Inhibition of the cytochrome P450 enzyme system by chloramphenicol may impair the hepatic metabolism of phenobarbital, phenytoin, dicoumarin, warfarin, and other drugs metabolized by this oxidase system, leading to delayed elimination and increased blood concentrations and toxicity of these drugs.
Paracetamol: possible increase in the toxicity of chloramphenicol, as the half-life is prolonged and its concentration in the blood plasma increases.
Calcineurin inhibitors (cyclosporine, tacrolimus): their plasma levels may increase. Plasma concentrations of these drugs should be monitored; their doses may need to be adjusted when used with chloramphenicol.
Cyclophosphamide: prolongation of the half-life of cyclophosphamide from 7.5 to 11.5 hours.
Cycloserine: potentiation of chloramphenicol neurotoxicity.
Estrogen-containing oral contraceptives: may reduce contraceptive reliability and increase the frequency of breakthrough bleeding. In this regard, it is recommended to use non-hormonal methods of contraception during treatment with chloramphenicol.
Penicillin, cephalosporins, macrolides (erythromycin, oleandomycin), lincosamides (clindamycin, lincomycin), polyene antibiotics (nystatin, levorin): mutual weakening of antimicrobial action, since chloramphenicol can displace these drugs from the bound state or prevent their binding to the 50S subunit of bacterial ribosomes, therefore, simultaneous use should be avoided.
Vitamin B12, iron preparations, folic acid: possible counteraction of the stimulation of hematopoiesis by vitamin B12, reduction in the effectiveness of these drugs.
Ethanol: development of a disulfiram-like reaction (skin hyperemia, tachycardia, nausea, vomiting, reflex cough, convulsions).
Application features
Given the possibility of developing severe lesions of the hematopoietic organs as a result of the toxic effects of the drug, during treatment, the composition of peripheral blood should be monitored, and the condition of the liver and kidneys should be monitored.
If leukopenia, thrombocytopenia, anemia or other pathological changes in the blood appear, Levomycetin should be immediately discontinued. Although constant monitoring of the peripheral blood composition during treatment with chloramphenicol can detect early changes in the blood system (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 usually occur after the end of treatment. Therefore, symptoms such as pale skin, sore throat and fever, unusual bleeding, weakness (even if they occur several weeks or months after drug withdrawal) require urgent medical attention.
In patients who have previously been treated with cytostatic drugs or radiation therapy, the potential risks and expected benefits of chloramphenicol treatment should be weighed against the possibility of severe side effects. Chloramphenicol should be avoided in combination with other drugs that may cause bone marrow suppression. To increase the safety of treatment, plasma chloramphenicol concentrations should be monitored, if possible. The therapeutic range is 5-15 μg/ml.
The use of antibacterial drugs may lead to overgrowth of non-susceptible microorganisms, including fungi, and the development of superinfection, which requires appropriate measures.
Antibacterial therapy disrupts the normal flora of the large intestine and may result in overgrowth of Clostridium difficile, the toxins of which are the main cause of pseudomembranous colitis. Pseudomembranous colitis can occur either immediately during treatment or within 2 months after the end of antibacterial therapy. Cases of pseudomembranous colitis, ranging from mild to life-threatening, have been reported with nearly all antibacterial agents, including chloramphenicol. The possibility of this diagnosis should be considered in all patients who develop diarrhea during or after antibiotic therapy.
Clinical experience has not revealed differences in the response to chloramphenicol treatment in patients of different age categories. However, taking into account the age-related characteristics of the functions of the kidneys, liver, cardiovascular system, the presence of concomitant diseases, the use of other drugs, it is necessary to determine the dose of the drug for elderly patients with caution, starting, as a rule, from the lower end of the dosage range.
In patients with impaired liver and/or kidney function, serum chloramphenicol levels may be increased and the risk of toxic reactions may be higher, so the dosage should be adjusted accordingly. It is advisable to periodically determine the concentration of the drug in the blood and check liver and kidney function.
Chloramphenicol should be prescribed with caution to patients with a tendency to allergic reactions and cardiovascular diseases.
Chloramphenicol may also interfere with the development of post-vaccination immunity, so it should not be used during active immunization.
Simultaneous intake of ethanol leads to the development of a disulfiram-like reaction (skin hyperemia, tachycardia, nausea, vomiting, reflex cough, convulsions).
Uncontrolled prescription of chloramphenicol and its use for mild forms of infectious processes, for acute respiratory diseases or as a prophylactic agent to prevent bacterial infections, especially in pediatric practice, is unacceptable.
Repeated courses of chloramphenicol treatment should be avoided. Treatment should not last longer than necessary to obtain positive results without the risk of complications or relapse of the disease.
Ability to influence reaction speed when driving vehicles or other mechanisms
Until the patient's individual reaction to the drug is determined, one should refrain from driving or operating other mechanisms, given that nervous system disorders may occur during treatment with Levomycetin.
Use during pregnancy or breastfeeding
The safety of the drug for pregnant women has not been established, therefore the drug is contraindicated during pregnancy.
Chloramphenicol passes into breast milk, so breastfeeding should be discontinued during treatment with the drug.
Method of administration and doses
Levomycetin should be taken orally 30 minutes before meals; in case of nausea or vomiting, 1 hour after meals.
The dosage regimen is set by the doctor individually depending on the severity of the disease and the patient's condition.
Adults are prescribed 250-500 mg 3-4 times a day. The daily dose is 2 g. In especially severe forms of infections (typhoid fever) in a hospital setting, the dose may be increased to 4 g per day (maximum daily dose for adults) under strict control of blood counts and liver and kidney function.
Children aged 3 to 8 years should be prescribed a single dose of 125 mg, children over 8 years old - 250 mg. The frequency of administration is 3-4 times a day. If it is necessary to use a dose of 125 mg, tablets with a lower content of the active substance should be taken.
The course of treatment is usually 7-10 days. If necessary and subject to satisfactory tolerance and no changes in the composition of peripheral blood, the course of treatment may be extended to 2 weeks.
Children
Levomycetin in this dosage form should not be used in children under 3 years of age.
For the treatment of children aged 3 years and older, Levomycetin should be prescribed with extreme caution and only in the absence of alternative therapy.
Given the content of the active substance in the tablet, the drug can be used in children aged 8 and over.
Overdose
Symptoms: Severe hematopoietic complications are usually associated with prolonged use of large doses (more than 3 g per day) - pale skin, sore throat and fever, unusual bleeding and bruising, unusual fatigue or weakness. Blood levels of chloramphenicol exceeding 25 μg/ml are considered toxic.
Other adverse reactions typical of chloramphenicol may also develop (see section "Adverse reactions").
Particularly dangerous is the "gray syndrome", which is observed mainly in newborns (born from mothers who were given chloramphenicol during childbirth or in whom chloramphenicol therapy was started in the first 48 hours of life), but in case of overdose it is also possible in older children or in particularly sensitive people (abdominal bloating, vomiting, respiratory distress with severe metabolic acidosis, bluish-gray skin color, decreased body temperature, decreased nervous reactions, inhibition of myocardial conduction, cardiovascular failure, circulatory collapse, coma and death).
"Gray syndrome" can also be observed due to drug cumulation in relative overdose (accumulation of chloramphenicol due to immaturity of liver enzymes and its direct toxic effect on the myocardium) in patients with impaired liver and kidney function. "Gray syndrome" manifests itself when the concentration of chloramphenicol in the blood plasma exceeds 50 μg/ml.
Treatment. Drug withdrawal, gastric lavage, administration of enterosorbents (including activated charcoal), saline laxative, high cleansing enema, symptomatic therapy. In severe cases, hemosorption.
Adverse reactions
The most serious adverse reactions are aplastic anemia, bone marrow depression, and "gray syndrome."
Immune system: hypersensitivity reactions, including fever, itching, skin rashes (including macular and vesicular), dermatoses, anaphylactic reactions, including urticaria, angioedema. There have been reports of the development of Jarisch-Herxheimer reactions (bacteriolysis reactions) during the therapy of typhoid fever (more relevant to parenteral forms of chloramphenicol).
From the side of the blood and lymphatic system: toxic effects on the hematopoietic system and bone marrow depression (reticulocytopenia, thrombocytopenia, granulocytopenia, pancytopenia, erythrocytopenia, decreased hemoglobin level in the blood, anemia), rarely in severe cases, the development of hypoplastic anemia, aplastic anemia, thrombocytopenic purpura, agranulocytosis, leukopenia, cytoplasmic vacuolization of early erythrocyte forms is possible.
On the part of the digestive tract: dyspeptic phenomena (bloating, nausea, vomiting), the likelihood of which is reduced when taking the drug 1 hour after a meal, diarrhea, dry mouth, stomatitis, glossitis, irritation of the mucous membranes of the mouth and pharynx, suppression of intestinal microflora, dysbacteriosis, enterocolitis.
Hepatobiliary system: liver dysfunction.
From the nervous system: headache, encephalopathy, psychomotor disorders, moderate depression, confusion, delirium. Prolonged use of large doses of the drug can lead to impaired taste, decreased hearing and vision, the development of visual and auditory hallucinations, optic and peripheral neuritis (including paralysis of the eyeballs). If these symptoms occur, the drug should be discontinued immediately.
Other: possible development of superinfection, including fungal, dermatitis (including perianal dermatitis), hyperthermia, collapse (in children). Cases of paroxysmal nocturnal hemoglobinuria have been reported.
Expiration date
5 years.
Storage conditions
In the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in strips or blisters.
Vacation category
According to the recipe.
Producer
PJSC "Monpharm".
Location of the manufacturer and its business address
Ukraine, 19100, Cherkasy region, Monastyryshche, Zavodska st., 8.
