контрактне виробництво
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Levomycetin
Release form
Tablets
For children
From 8 years old
For pregnant women
contraindicated
For nursing mothers
contraindicated
For drivers
contraindicated
Storage temperature
to 25 °C
INSTRUCTION
storage
active ingredient: Levomycetin (chloramphenicol); 1 tablet contains levomycetin (chloramphenicol) 500 mg (0.5 g); auxiliary substances: potato starch; calcium stearate
Medicinal form
Tablets. The main physicochemical properties: tablets are white or white with a slightly yellowish tint, with a flat surface, beveled edges and a line.
Pharmacotherapeutic group
Antibacterial agents for systemic use. Amphenicol. Chloramphenicol. ATX code J01B A01.
Pharmacological properties
Pharmacodynamics. Levomycetin is a broad-spectrum bacteriostatic antibiotic. The action is associated with the disruption of the protein synthesis process in the microbial cell at the stage of transfer of t-RNA amino acids 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), acts on Streptococcus spp. (including on Streptococcus pneumoniae), Neisseria gonorrhoeae, Neisseria meningitidis, a number of strains of Proteus spp., on some strains of Pseudomonas aeruginosa; active against Ricketsia spp., Treponema spp., Chlamydia spp. (including Chlamydia trachomatis), causative agents of purulent infections, typhoid, dysentery, meningococcal infection, brucella, rickettsia, chlamydia, spirochetes. Does not work on Mycobacterium tuberculosis, pathogenic protozoa and fungi. Active against strains of bacteria resistant to penicillin, tetracyclines, and sulfonamides. Resistance of microorganisms develops slowly. The drug is weakly active against acid-resistant 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 has a bacteriostatic effect. The resistance of microorganisms to the drug develops slowly and, as a rule, there is no cross-resistance to other chemotherapeutic agents. Due to its high toxicity, Levomycetin can be used to treat severe infections in which less toxic antibacterial agents are ineffective or contraindicated. Pharmacokinetics. It is quickly and almost completely absorbed from the digestive tract. The maximum concentration in blood plasma is reached after 2-3 hours. The therapeutic concentration in the blood is maintained for 4-5 hours. Bioavailability after oral administration is 80%. It penetrates well into the organs, tissues and fluids of the body, penetrates through the blood-brain barrier (HEB), the placenta, and into breast milk. 50-60% of chloramphenicol binds to blood plasma proteins. The highest concentrations of Levomycetin are observed in the liver and kidneys. Up to 30% of the administered dose is observed in the bile. The maximum concentration in the cerebrospinal fluid is observed 4-5 hours after a single oral administration. It is biotransformed in the liver, 90% binds to inactive glucuronide. Chloramphenicol palmitate is hydrolyzed to the free state in the digestive tract before absorption. Chloramphenicol sodium succinate is hydrolyzed to a free state in blood plasma, liver, lungs and kidneys. In fetuses and premature babies, 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 intestines, under the action of intestinal bacteria, chloramphenicol is hydrolyzed with the formation of inactive metabolites. Excreted mainly with urine (mainly in the form of inactive metabolites), partly - with bile (up to 30% of the dose taken) and feces. The elimination half-life in adults with normal kidney and liver function is 1.5-3.5 hours, in impaired kidney function - 3-4 hours, in severe liver impairment - 4.6-11 hours.
Indication
Infectious-inflammatory diseases caused by microorganisms sensitive to the drug: typhoid, paratyphoid, 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 pronounced side effects.
Contraindication
• Increased individual sensitivity (allergy) to chloramphenicol (chloramphenicol), thiamphenicol, azidamphenicol and other components of the drug; • blood diseases, including hematopoiesis suppression; • pronounced liver and/or kidney function disorders; • glucose-6-phosphate dehydrogenase enzyme deficiency; • skin diseases (psoriasis, eczema, fungal diseases); • porphyria. Levomycetin should not be prescribed for acute respiratory diseases, angina, and also for the prevention of bacterial infection.
Interaction with other medicinal products and other forms of interaction
Alfetanil: Long-term use of chloramphenicol, which is a liver enzyme inhibitor, preoperatively or during surgery may decrease the plasma clearance of alfetanil and prolong its duration of action. Drugs that inhibit hematopoiesis (cytostatics, carbamazepine, phenylbutazone, penicillamine, some antipsychotics, including clozapine, procainamide, reverse transcriptase inhibitors, propylthiouracil, sulfonamides, cimetidine, ristomycin), radiation therapy: possible strengthening of their suppressive effect on the bone marrow . Therefore, such a combination should be avoided. Hypoglycemic drugs (for example, tolbutamide (butamide), chlorpropamide): it is possible to increase their hypoglycemic effect (due to inhibition of the metabolism of these drugs in the liver and an increase in their concentration), which requires dose correction. Phenobarbital, rifampicin, rifabutin: reducing 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. Suppression of the cytochrome P450 enzyme system by chloramphenicol can weaken the hepatic metabolism of phenobarbital, phenytoin, dicoumarin, warfarin and other drugs metabolized by this oxidase system, which leads to a delay in elimination and an increase in their concentration in the blood and the toxicity of these drugs. Paracetamol: increased toxicity of chloramphenicol is possible, as the half-life is prolonged and its concentration in the blood plasma increases. Calcineurin inhibitors (cyclosporine, tacrolimus): possible increase in their levels in blood plasma. Plasma concentrations of these drugs should be monitored; correction of their doses is necessary when used with chloramphenicol. Cyclophosphamide: prolongation of the half-life of cyclophosphamide from 7.5 to 11.5 hours. Cycloserine: enhancing the neurotoxicity of chloramphenicol. Estrogen-containing oral contraceptives: a possible decrease in the reliability of contraception and an increase in 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 the antimicrobial effect, since chloramphenicol can displace these drugs from the bound state or prevent their binding to 50S subunit of bacterial ribosomes, so simultaneous use should be avoided. Vitamin B12, iron preparations, folic acid: it is possible to counteract the stimulation of hematopoiesis by vitamin B12, reducing the effectiveness of these preparations. Ethanol: development of a disulfiram-like reaction (skin hyperemia, tachycardia, nausea, vomiting, reflex cough, convulsions).
Features of use
In view of the possibility of developing serious lesions of hematopoietic organs as a result of the toxic effect of the drug, the composition of peripheral blood should be monitored during the treatment, and the condition of the liver and kidneys should be monitored. If leukopenia, thrombocytopenia, anemia or other pathological blood changes occur, Levomycetin should be discontinued immediately. Although continuous monitoring of the composition of peripheral blood during treatment with chloramphenicol may 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 high fever, unusual bleeding, weakness (even if they occur several weeks or months after drug withdrawal) require immediate assistance. In patients previously treated with cytostatic drugs or radiation therapy, the potential risks and expected benefits of treatment with chloramphenicol should be weighed against the possibility of severe side effects. The use of chloramphenicol with other drugs that can cause suppression of bone marrow function should be avoided. To increase the safety of treatment, if possible, monitor the plasma concentration of chloramphenicol. The therapeutic range is 5-15 μg/ml. The use of antibacterial drugs can lead to the overgrowth of non-susceptible microorganisms, in particular fungi, and the development of superinfection, which requires taking appropriate measures. Treatment with antibacterial drugs leads to disruption of the normal flora of the large intestine and can cause overgrowth of Clostridium difficile, whose toxins are the main cause of pseudomembranous colitis. Pseudomembranous colitis can occur both immediately during the administration of the drug and within 2 months after the end of antibacterial therapy. Mild to life-threatening pseudomembranous colitis has been reported with almost all antibacterial agents, including chloramphenicol. The possibility of this diagnosis should be considered in all patients who develop diarrhea during or after the use of antibiotics. In the absence of the necessary treatment, toxic megacolon, peritonitis, and shock may develop. It should be taken into account that the development of colitis is most likely in severe diseases in elderly patients, as well as in weakened patients. Clinical experience has not revealed differences in the response to treatment with chloramphenicol in patients of different age categories. However, taking into account the age-related features 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 carefully, starting, as a rule, from the lower limit of the dosage range. In patients with impaired liver and/or kidney function, an increase in the level of chloramphenicol in blood serum is possible and the risk of developing 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, check the functions of the liver and kidneys. Chloramphenicol should be prescribed with caution to patients with a tendency to allergic reactions, with cardiovascular diseases. Chloramphenicol can 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 in mild forms of infectious processes, in acute respiratory diseases or as a prophylactic to prevent bacterial infections, especially in pediatric practice, is unacceptable. Repeated courses of treatment with chloramphenicol should be avoided. Treatment should last no longer than necessary to obtain positive results without the risk of developing complications or disease recurrence. Use during pregnancy or breastfeeding. The safety of using the drug by pregnant women has not been established, therefore the drug is contraindicated during pregnancy. Chloramphenicol penetrates into breast milk, so breastfeeding should be stopped during treatment with the drug. The ability to influence the speed of reaction when driving vehicles or other mechanisms. Until the patient's individual reaction to the drug is clarified, one should refrain from driving a motor vehicle or working with other mechanisms, given that during treatment with Levomycetin, disturbances from the nervous system may be observed than is necessary to obtain positive results without the risk of complications or relapse of the disease. Use during pregnancy or breastfeeding. The safety of using the drug by pregnant women has not been established, therefore the drug is contraindicated during pregnancy. Chloramphenicol penetrates into breast milk, so breastfeeding should be stopped during treatment with the drug. The ability to influence the speed of reaction when driving vehicles or other mechanisms. Until the patient's individual reaction to the drug is clarified, one should refrain from driving a motor vehicle or working with other mechanisms, given that during treatment with Levomycetin, disturbances from the nervous system may be observed than is necessary to obtain positive results without the risk of complications or relapse of the disease. Use during pregnancy or breastfeeding. The safety of using the drug by pregnant women has not been established, therefore the drug is contraindicated during pregnancy. Chloramphenicol penetrates into breast milk, so breastfeeding should be stopped during treatment with the drug. The ability to influence the speed of reaction when driving vehicles or other mechanisms. Until the patient's individual reaction to the drug is clarified, one should refrain from driving a motor vehicle or working with other mechanisms, given that during treatment with Levomycetin, disturbances from the nervous system may be observed
Methods of application
Levomycetin should be taken orally 30 minutes before meals; in case of nausea, vomiting - 1 hour after eating. 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 case of particularly severe forms of infection (typhoid), in hospital conditions, the dose may be increased to 4 g per day (maximum daily dose for adults) under strict control of the blood condition and liver and kidney function. Children aged 3 to 8 years should be prescribed a single dose of 125 mg, children aged 8 years and older - 250 mg. Frequency of reception - 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 under the condition of satisfactory transfer, in the absence of changes in the composition of peripheral blood, it is possible to extend the course of treatment up to 2 weeks. Children. Levomycetin in this dosage form should not be used by children under 3 years of age. Levomycetin should be prescribed with extreme caution and only in the absence of alternative therapy for the treatment of children aged 3 years and older. Taking into account the content of the active substance in the tablet, it is possible to use the drug for children aged 8 years and older.
Overdose
Symptoms Serious complications from the hematopoietic system are usually associated with long-term use of large doses (more than 3 g per day) - pale skin, sore throat and fever, unusual bleeding and hemorrhages, unusual fatigue or weakness. Blood levels of chloramphenicol above 25 µg/ml are considered toxic. It is also possible to develop other side reactions characteristic of chloramphenicol (see the section "Side reactions"). Particularly dangerous is the "gray syndrome", which is observed mainly in newborns (who were born to mothers who used 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 especially sensitive people (abdominal bloating, vomiting, respiratory distress with severe metabolic acidosis, blue-gray skin color, decreased body temperature, decreased nervous responses, inhibition of myocardial conduction, cardiovascular failure, circulatory collapse, coma and fatal outcome). "Gray syndrome" can also be observed as a result of drug cumulation in case of relative overdose (accumulation of chloramphenicol due to the immaturity of liver enzymes and its direct toxic effect on the myocardium) in patients with impaired liver and kidney function. "Gray syndrome" is manifested when the concentration of chloramphenicol in the blood plasma exceeds 50 μg/ml. Treatment. Cancellation of the drug, gastric lavage, appointment of enterosorbents (including activated carbon), saline laxative, high cleansing enema, appointment of symptomatic therapy. In severe cases - hemosorption.
Side effects
The most severe adverse reactions are aplastic anemia, bone marrow depression, and gray syndrome. From the side of the immune system: hypersensitivity reactions, including fever, itching, skin rashes (including macular and vesicular), dermatoses, anaphylaxis reactions, including urticaria, angioedema. There have been reports of the development of Yaris-Herxheimer reactions (bacteriolysis reactions) during typhoid therapy (more relevant to parenteral forms of chloramphenicol). From the side of the blood and lymphatic system: toxic effects on the hematopoietic system and depression of the bone marrow (reticulocytopenia, thrombocytopenia, granulocytopenia, pancytopenia, erythrocytopenia, a decrease in the level of hemoglobin in the blood, anemia), rarely, in severe cases, the development of hypoplastic anemia, aplastic anemia, thrombocytopenic purpura is possible , agranulocytosis, leukopenia, cytoplasmic vacuolization of early erythrocyte forms. On the part of the digestive tract: dyspeptic symptoms (abdominal bloating, nausea, vomiting), the probability of development of which decreases when taking the drug 1 hour after a meal, diarrhea, dry mouth, stomatitis, glossitis, irritation of the mucous membranes of the mouth and throat, inhibition of intestinal microflora, dysbiosis, enterocolitis. From the side of the hepatobiliary system: impaired liver function. From the side of the nervous system: headache, encephalopathy, psychomotor disorders, moderate depression, confusion, delirium. Long-term use of large doses of the drug can lead to impaired sense of taste, decreased hearing and vision, development of visual and auditory hallucinations, optic and peripheral neuritis (including paralysis of the eyeballs). If these symptoms occur, you should immediately stop taking the drug. Others: 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 higher than 25 ºС. Keep out of the reach of children.
Packaging
10 tablets in a strip; 1 strip in a paper envelope; 10 tablets in a strip; 2 or 10 strips in a cardboard pack; 10 tablets in a blister; 1, or 2, or 10 blisters in a cardboard pack; 10 tablets in strips or in blisters.
Leave category
By prescription
Producer
Monfarm PJSC.
Address
Ukraine, 19161, Cherkasy region, Uman district, village Avramivka, str. Zavodska, 8.