Instructions Levomycetin-Darnitsa tablets 500 mg No. 10
Composition
active ingredient: chloramphenicol;
1 tablet contains chloramphenicol (chloramphenicol) 500 mg;
excipients: potato starch, hydroxypropyl cellulose, stearic acid.
Dosage form
Pills.
Main physicochemical properties: tablets of white or white with a slightly yellowish tint, flat-cylindrical shape, with a score and a bevel. The presence of grayish or yellowish inclusions is allowed.
Pharmacotherapeutic group
Antibacterials for systemic use. Amphenicols. Chloramphenicol. ATX code J01B A01.
Pharmacological properties
Pharmacodynamics
Levomycetin (chloramphenicol) 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 transfer of amino acids from tRNA 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 has 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 is used to treat severe infections in which less toxic antibacterial agents are ineffective or contraindicated.
Pharmacokinetics
Quickly and almost completely absorbed from the digestive system. 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, 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 of chloramphenicol is observed in bile. It penetrates well through the blood-brain barrier: 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 system before absorption begins. Chloramphenicol sodium succinate is hydrolyzed to the free state in the blood plasma, liver, lungs and kidneys. In fetuses and premature infants, the liver is not sufficiently developed to bind chloramphenicol, 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, chloramphenicol is hydrolyzed to form 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 administered dose) and feces.
The half-life in adults with normal renal and hepatic function is 1.5–3.5 hours, in renal impairment – 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 pronounced side effects.
Contraindication
Increased individual sensitivity (allergy) to chloramphenicol, other amphenicols and/or 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
Chloramphenicol inhibits the cytochrome P450 enzyme system, therefore, when used simultaneously with antiepileptic drugs (phenobarbital, phenytoin), indirect anticoagulants (dicoumarin, warfarin) and other drugs metabolized by this oxidase system, there is a weakening of the metabolism of these drugs, a slowing of excretion, an increase in their concentration in blood plasma and an increase in their toxicity.
Oral hypoglycemic drugs (chlorpropamide, tolbutamide) - when used with chloramphenicol, an increase in the effect of oral hypoglycemic drugs is noted (due to inhibition of metabolism in the liver and an increase in their concentration in blood plasma), which requires dose adjustment.
Phenobarbital, rifampicin, rifabutin - reduce the concentration of chloramphenicol in the blood plasma by accelerating its metabolism in the liver.
Paracetamol - with simultaneous use, a prolongation of the half-life of chloramphenicol may be observed.
Phenytoin - with simultaneous use, both a decrease and an increase in the concentration of chloramphenicol in the blood plasma may be observed.
Cyclosporine - when used simultaneously with chloramphenicol, an increase in cyclosporine plasma levels may be observed. When using these drugs simultaneously, it is necessary to monitor cyclosporine concentrations.
Cyclophosphamide – concomitant use prolongs the half-life of cyclophosphamide from 7.5 to 11.5 hours.
Tacrolimus - when used simultaneously with chloramphenicol, an increase in tacrolimus plasma levels may occur. The dose of tacrolimus should be adjusted when used simultaneously.
Levomycetin reduces the antibacterial effect of penicillins and cephalosporins.
Macrolides (erythromycin, oleandomycin), lincosamides (clindamycin, lincomycin), polyene antibiotics (nystatin, levorin) - with simultaneous use of chloramphenicol with these drugs, a mutual weakening of the effect is noted due to the fact that chloramphenicol can displace these drugs from the bound state or prevent their binding to the 50S subunit of bacterial ribosomes. Therefore, their simultaneous use should be avoided.
Cycloserine – simultaneous use enhances the neurotoxicity of chloramphenicol.
Drugs that suppress hematopoiesis (sulfonamides, carbamazepine, phenylbutazone, penicillamine, some antipsychotics, including clozapine, procainamide, reverse transcriptase inhibitors, propylthiouracil, cytostatics, cimetidine, ristomycin), radiotherapy - simultaneous use increases the risk of bone marrow suppression and the severity of its manifestations. Therefore, their combined use should be avoided.
Estrogen-containing oral contraceptives - long-term concomitant use may lead to reduced contraceptive reliability and an increased incidence of breakthrough bleeding. In this regard, it is recommended to use non-hormonal methods of contraception during treatment with chloramphenicol.
Iron, folic acid, cyanocobalamin preparations - chloramphenicol may reduce the effectiveness of these medications.
Ethanol - with simultaneous use of ethanol, a disulfiram-like reaction may develop (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 therapy it is necessary to monitor the composition of peripheral blood, monitor the condition of the liver and kidneys.
If leukopenia, thrombocytopenia, anemia or other pathological changes in the blood appear, the drug should be discontinued immediately. Although constant monitoring of the peripheral blood composition 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 aplastic anemia due to the development of 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 (if they appear several weeks or months after discontinuation of the drug) require urgent care.
Treatment with antibacterial drugs leads to a disruption of the normal flora of the large intestine and can cause overgrowth of Clostridium difficile, toxins of which are the main cause of pseudomembranous colitis. Pseudomembranous colitis occurs both during the use of the drug and within 2 months after the end of antibacterial therapy. Cases of pseudomembranous colitis, ranging from mild to life-threatening, have been reported with the use of almost all antibacterial drugs, including chloramphenicol. Therefore, it is important to clarify the diagnosis in patients with diarrhea after the use of antibacterial drugs. In the absence of appropriate treatment, toxic megacolon, peritonitis, shock may develop. It should be borne in mind that the development of colitis is most likely in severe diseases in elderly patients, as well as in debilitated patients.
The use of antibacterial drugs may result in overgrowth of nonsusceptible organisms, particularly fungi. If infections caused by nonsusceptible organisms develop during treatment, appropriate measures should be taken.
In patients with impaired liver or kidney function, increased serum levels of chloramphenicol may occur and the risk of toxic reactions to this drug may be higher, so the dosage should be adjusted accordingly. It is advisable to periodically determine the concentration of the drug in the blood by checking liver and kidney function.
Clinical experience has not revealed any differences in the responses to treatment with chloramphenicol between patients of different age categories. However, given the age-related characteristics of the functions of the kidneys, liver, cardiovascular system, the presence of concomitant diseases, the use of other medications, 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.
Levomycetin should be prescribed with caution to patients with a tendency to allergic reactions.
Simultaneous use of ethanol leads to the development of a disulfiram-like reaction (skin hyperemia, tachycardia, nausea, vomiting, reflex cough, convulsions).
Uncontrolled administration of Levomycetin-Darnitsa 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.
Chloramphenicol administration may provoke acute attacks of porphyria. The drug is dangerous for use in patients with porphyria.
Chloramphenicol may affect the development of the immune response and should not be administered during active immunization.
Repeated courses of treatment with chloramphenicol should be avoided; therapy should last no longer than necessary to obtain positive results without the risk of complications or recurrence of the disease.
Use with caution in cardiovascular diseases.
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 therapy with chloramphenicol.
Use during pregnancy or breastfeeding
The use of chloramphenicol is contraindicated during pregnancy. Breastfeeding should be discontinued during treatment with the drug.
Method of administration and doses
Take orally 30 minutes before eating; in case of nausea or vomiting, 1 hour after eating.
The dosage regimen should be established individually depending on the severity of the disease and the patient's condition.
Adults should take 250–500 mg 3–4 times a day. Daily dose – 2000 mg. In especially severe cases, the drug can be used orally in a dose of up to 4000 mg (maximum daily dose for adults) per day under strict control of blood count and liver and kidney function. The daily dose should be divided into 3–4 doses.
Children aged 3 to 8 years should be prescribed a single dose of 125 mg, children aged 8 and over should be prescribed 250 mg. The frequency of administration is 3–4 times a day.
The course of treatment with the drug is 7–10 days. According to indications, provided that it is well tolerated and there are no changes in the composition of peripheral blood, the course of treatment may be extended to 2 weeks.
Children
Use for children aged 3 years and over.
For the treatment of children aged 3 years and older, the drug should be prescribed with extreme caution and only in the absence of alternative therapy.
Overdose
Symptoms: Severe hematopoietic complications are usually associated with prolonged use of large doses of the drug (more than 3 g per day) - pale skin, sore throat and fever, bleeding and hemorrhages, fatigue or weakness. Blood levels of chloramphenicol exceeding 25 μg / ml are considered toxic.
Particularly dangerous is the "gray syndrome", which is observed mainly in newborns (whose mothers 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 especially sensitive people (abdominal bloating, vomiting, respiratory distress with severe metabolic acidosis, bluish-gray skin color, decreased body temperature, irregular breathing, decreased nervous reactions, inhibition of myocardial conduction, cardiovascular failure, circulatory collapse, coma and death).
"Gray syndrome" can also occur due to drug accumulation 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" occurs when the concentration of chloramphenicol in the blood plasma exceeds 50 μg/ml.
Treatment. Drug withdrawal and symptomatic therapy, gastric lavage, enterosorbents (including activated charcoal), saline laxative, high cleansing enema. In severe cases, hemosorption.
Adverse reactions
The most severe adverse reactions are: aplastic anemia, bone marrow suppression, and "gray syndrome."
The development of adverse reactions from the following organs and systems is also observed:
On the part of the gastrointestinal tract: dyspepsia, bloating, nausea, vomiting (the likelihood of development is reduced when used 1 hour after a meal), diarrhea, irritation of the mucous membrane of the oral cavity and pharynx, dry mouth, suppression of intestinal microflora, dysbacteriosis, enterocolitis, stomatitis, glossitis.
Liver and biliary tract disorders: liver dysfunction.
Nervous system: psychomotor disorders, moderate depression, confusion, headache, encephalopathy, delirium. Prolonged use of high doses of the drug can lead to taste disturbance, decreased hearing and vision acuity, 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.
From the side of the blood and lymphatic system: toxic effect on the hematopoietic system, bone marrow suppression, reticulocytopenia, decreased hemoglobin level in the blood, anemia, leukopenia, granulocytopenia, thrombocytopenia, erythrocytopenia, pancytopenia; rarely - aplastic anemia, thrombocytopenic purpura, hypoplastic anemia, agranulocytosis, cytoplasmic vacuolization of early erythrocyte forms.
Skin and subcutaneous tissue disorders: allergic reactions, including fever, skin rashes (including macular and vesicular), dermatoses; anaphylactic reactions, including urticaria, angioedema, facial edema, angioedema, skin itching, hyperemia.
General disorders: possible development of superinfection, including fungal, dermatitis (including perianal dermatitis), hyperthermia, collapse (in children).
There have been reports of the development of Jarisch-Herxheimer reactions (bacteriolysis reaction) during the treatment of typhoid fever (more relevant to parenteral forms of chloramphenicol).
Cases of paroxysmal nocturnal hemoglobinuria have been reported.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. It allows for continued monitoring of the benefit-risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions via the national reporting system.
Expiration date
5 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in contour blister packs.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and its business address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
