Pharmacological properties
Pharmacodynamics. Broad-spectrum antibiotic. Effective against many gram-positive (staphylococci, streptococci, pneumococci, enterococci) and gram-negative bacteria: Escherichia coli and Haemophilus influenzae, Salmonella, Shigella, Klebsiella, Serratia, Yersinia, Proteus, gonococci, meningococci, anaerobes, rickettsia, spirochetes, chlamydia, as well as pathogens of trachoma, psittacosis, inguinal lymphogranulomatosis; active against strains of bacteria resistant to penicillin, streptomycin, sulfonamides; weakly active against acid-fast bacteria, Pseudomonas aeruginosa, clostridia and protozoa.
In normal doses, it has a bacteriostatic effect. It inhibits peptidyltransferase and disrupts protein synthesis in the bacterial cell.
Pharmacokinetics. With i / m and i / v administration, a high concentration of the drug in the blood plasma is quickly achieved (5-10 min after i / v, 30-45 min after i / m administration). C max in the blood is achieved after 1 h and is maintained at effective concentrations in the blood plasma for 8-12 h. A significant part (60-80%) binds to blood plasma albumin. Easily penetrates into organs and body fluids, through the blood-brain barrier, through the placenta, into breast milk.
It is excreted mainly by the kidneys in the form of inactive metabolites, partially with bile.
Quickly and almost completely absorbed in the gastrointestinal tract. Bioavailability when taken orally is 80%. Time to reach C max - 1-3 hours. Therapeutic concentration is maintained for 4-5 hours after taking the drug. 45-50% binds to proteins. Penetrates well into body fluids and tissues, penetrates through the placenta and into breast milk. The highest concentrations of chloramphenicol are observed in the liver and kidneys. Up to 30% of the administered dose is noted in bile. Penetrates well through the blood-brain barrier: C max in cerebrospinal fluid is reached 4-5 hours after a single oral dose. Metabolized 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 chloramphenicol, which leads to the accumulation of toxic concentrations of the active form of the drug and can cause the development of gray syndrome. The drug is excreted mainly in the urine (mainly in the form of inactive metabolites), partially in the feces (1-3%).
T ½ in adults with normal renal and hepatic function is 1.5-3.5 hours, with impaired renal function - 3-4 hours, with severe impaired hepatic function - 4.6-11 hours.
Indication
Levomycetin, powder for injection. Treatment of infections caused by microorganisms sensitive to chloramphenicol (typhoid fever, paratyphoid fever, generalized forms of salmonellosis, dysentery, brucellosis, tularemia, meningitis, typhus and other rickettsioses, trachoma). Infectious processes caused by pathogens sensitive to levomycetin, in case of ineffectiveness of other chemotherapeutic drugs or when their use is impossible.
Levomycetin, tablets. 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, given the possibility of developing pronounced side effects.
Application
Levomycetin, injections. The dose administered and the concentration of the drug used depend on the severity of the infection.
Children. Levomycetin should be administered intramuscularly in a daily dose: for children under 1 year of age - 25-30 mg/kg of body weight, from 1 year of age - 50 mg/kg, divided into two doses with an interval of 12 hours.
Adults. Levomycetin should be administered intramuscularly or intravenously. The drug solutions should be prepared ex tempore.
For intramuscular administration, the contents of the vial (0.5 or 1 g) are diluted in 2-3 ml of sterile water for injection and injected deeply intramuscularly. 0.25% or 0.5% novocaine solution can be used as a solvent for intramuscular administration.
For intravenous injection, a single dose of the drug is dissolved in 10 ml of sterile water for injection or in 5% or 40% glucose solution and administered intravenously slowly over 3-5 minutes. For patients with diabetes, the drug is dissolved in 0.9% sodium chloride solution.
The daily dose of the drug for adults with common infections is from 1 to 3 g; 0.5-1 g is administered 2-3 times a day with an interval of 8-12 hours; if necessary, the daily dose is increased to 4 g.
In ophthalmology, the drug is used for parabulbar injections and instillations. For parabulbar injections, 0.2-0.3 ml of a 20% solution is administered 1-2 times a day; for instillations, 1-2 drops of 5% solution are instilled into the conjunctival sac (the drug is dissolved in sterile water for injection or in 0.9% sodium chloride solution) 3-5 times a day. Aqueous 5% solution for instillations is stored for no more than 2 days. Duration of use - 5-15 days.
Levomycetin tablets. Levomycetin is prescribed orally 30 minutes before meals (in case of nausea and vomiting - 1 hour after meals).
Adults are prescribed 250-500 mg 3-4 times a day; daily dose - 2 g. In especially severe cases (typhoid fever, etc.) Levomycetin is prescribed in a dose of up to 4 g/day (maximum daily dose for adults) under strict control of blood parameters and liver and kidney function; the daily dose is divided into 3-4 doses.
The course of treatment with Levomycetin is 7-10 days. According to indications, provided that it is well tolerated and there are no changes in blood parameters, the course of treatment may be extended to 2 weeks.
Contraindication
Hypersensitivity to chloramphenicol, other amphenicols, inhibition of hematopoiesis, blood diseases; skin diseases (psoriasis, eczema, fungal lesions); severe liver and/or kidney dysfunction; deficiency of the enzyme glucose-6-phosphate dehydrogenase; porphyria.
Levomycetin should not be prescribed for acute respiratory diseases, angina, as well as for the prevention of bacterial infection. For the drug in tablet form - children's age up to 3 years.
Side effects
The most serious adverse reactions are aplastic anemia, bone marrow suppression, and gray syndrome.
Adverse reactions from the following organs and systems are possible.
Neurological disorders: psychomotor disorders, depression, delirium, confusion, peripheral neuritis, optic neuritis (including paralysis of the eyeballs), visual and auditory hallucinations, decreased visual and hearing acuity, taste disturbances, headache, encephalopathy.
Gastrointestinal tract: dyspepsia, bloating, dry mouth, nausea, vomiting, diarrhea, dermatitis (including perianal dermatitis), suppression of intestinal microflora, dysbacteriosis, enterocolitis, stomatitis, glossitis.
Hepatobiliary system: liver dysfunction.
From the side of the hematopoietic system: bone marrow suppression, reticulocytopenia, decreased hemoglobin level in the blood, anemia, leukopenia, granulocytopenia, thrombocytopenia, erythrocytopenia, pancytopenia; rarely - aplastic anemia, hypoplastic anemia, agranulocytosis, cytoplasmic vacuolization of early erythrocyte forms.
Immune system: hypersensitivity reactions, including dermatoses, itching, skin rash, fever, angioedema, urticaria, anaphylaxis.
Others: possible development of superinfection, including fungal, hyperthermia, bacteriolysis reaction (Jarish-Herxheimer reaction), collapse (in children).
When using Levomycetin in the form of eye drops, local allergic reactions are possible.
Special instructions
The drug should be used only under the supervision of a doctor.
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, as well as the condition of the liver and kidneys.
If leukopenia, thrombocytopenia, anemia or other pathological changes in the blood appear, chloramphenicol should be immediately discontinued. Although constant monitoring of the composition of peripheral blood 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 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, bleeding, weakness (if they appear several weeks or months after drug withdrawal) require urgent care. Long-term use of chloramphenicol can lead to an increased tendency to bleeding, which can be caused by both bone marrow suppression and suppression of normal intestinal microflora, which leads to inhibition of vitamin K synthesis.
In patients with impaired liver or kidney function, increased plasma 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, checking liver and kidney function.
Clinical experience with chloramphenicol has not revealed any differences in the effectiveness of therapy in patients of different age categories. However, given the age-related characteristics of the kidney, liver, cardiovascular system, the presence of concomitant diseases, and 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. Treatment with antibacterial drugs leads to a disruption of the normal flora of the large intestine and can cause excessive growth of Clostridium difficile, toxins of which are the main cause of pseudomembranous colitis. Pseudomembranous colitis can occur both directly during the drug intake and within 2 months after the end of antibacterial therapy. Cases of pseudomembranous colitis from mild to life-threatening conditions 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 taking antibacterial drugs.
In the absence of necessary treatment, toxic megacolon, peritonitis, and shock may develop. It should be borne in mind that the development of colitis is most likely in severe diseases in the elderly, as well as in weakened patients.
When using the drug, it is necessary to monitor the blood picture. Data on any harmful effects on blood elements are an indication for immediate discontinuation of drug therapy.
In patients who have previously been treated with cytostatic drugs or radiation therapy, the potential risks and expected benefits of treatment with chloramphenicol should be assessed, taking into account the possibility of developing severe side effects.
Chloramphenicol should not be used for the treatment of mild infections or for prophylaxis, or for any infections for which less toxic antibiotics are available. Repeated courses and prolonged therapy should be avoided.
Use with caution in case of cardiovascular diseases and tendency to allergic reactions.
The use of chloramphenicol has been associated with acute attacks of porphyria, so the use of chloramphenicol for patients with porphyria is considered unsafe.
Each gram of chloramphenicol sodium succinate contains 2.264 mmol of sodium, which should be taken into account when using the drug in patients on a sodium-controlled diet.
Simultaneous intake of ethanol leads to the development of a disulfiram-like reaction (skin hyperemia, tachycardia, nausea, vomiting, reflex cough, convulsions).
Chloramphenicol may affect the development of the immune response and should not be administered during active immunization.
Treatment should last no longer than necessary to obtain positive results without the risk of complications or recurrence of the disease.
In the case of rapid intravenous administration of chloramphenicol, the development of an intense bitter taste in the mouth is possible.
Use during pregnancy and breastfeeding. The use of the drug chloramphenicol is contraindicated during pregnancy and breastfeeding.
Children. The drug in the form of injections is allowed to be used in children, provided that the dosage specified in the USE section is observed. Prescribe with caution and only in the absence of alternative therapy. The drug in the form of tablets is not used in children under 3 years of age.
Ability to influence the reaction rate when driving vehicles or working with other mechanisms. The drug should be used with caution in persons who drive vehicles or work with other mechanisms due to the risk of developing possible adverse reactions from the nervous system.
Interactions
Prolonged use of chloramphenicol, which is an inhibitor of liver enzymes, in the preoperative period or during surgery may reduce the clearance and increase the duration of action of alfetanil.
Chloramphenicol inhibits the cytochrome P450 enzyme system, therefore, when used simultaneously with antiepileptic drugs (phenobarbital, phenytoin), indirect anticoagulants (dicumarol, warfarin), there is a weakening of the metabolism of these drugs, a slowdown in excretion, an increase in their concentration in blood plasma and their toxicity.
With simultaneous use of Levomycetin with tolbutamide and chlorpropamide, their hypoglycemic effect may increase (due to inhibition of metabolism in the liver and an increase in their concentration), which requires dose adjustment.
Phenobarbital, rifampicin, rifabutin reduce the concentration of chloramphenicol in the blood plasma by accelerating its metabolism in the liver.
When used simultaneously with paracetamol, prolongation of T½ of chloramphenicol is possible.
Phenytoin. With simultaneous use, both a decrease and an increase in the concentration of chloramphenicol in the blood plasma are possible.
Cyclosporine. With simultaneous use with chloramphenicol, an increase in the level of cyclosporine in the blood plasma is possible; it is necessary to monitor the concentration of cyclosporine.
Cyclophosphamide. Concomitant use prolongs T½ of cyclophosphamide from 7.5 to 11.5 hours.
Tacrolimus: Concomitant use with chloramphenicol may increase the plasma levels of tacrolimus. The dose of tacrolimus should be adjusted when used concomitantly.
Levomycetin reduces the antibacterial effect of penicillins and cephalosporins.
Macrolides (erythromycin, oleandomycin, clindamycin), lincosamides (lincomycin), polyene antibiotics (nystatin, levorin). With the simultaneous use of chloramphenicol with these drugs, a mutual weakening of the antimicrobial 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: Concomitant use enhances the neurotoxicity of chloramphenicol.
Drugs that suppress hematopoiesis (sulfonamides, cytostatics, cimetidine, ristomycin) or radiation therapy when used simultaneously with chloramphenicol may enhance their inhibitory effect on the bone marrow and the severity of its manifestations.
When used simultaneously with vitamin B12, iron preparations, folic acid, chloramphenicol may counteract the stimulation of hematopoiesis by vitamin B12, reducing the effectiveness of these drugs.
Long-term simultaneous use of chloramphenicol and estrogen-containing oral contraceptives may lead to a decrease in the reliability of contraception and an increase in the frequency of breakthrough bleeding.
Ethanol. With simultaneous use of ethanol, a disulfiram-like reaction may develop (skin hyperemia, tachycardia, nausea, vomiting, reflex cough, convulsions).
Severe complications from the hematopoietic system, such as hemolytic anemia, thrombocytopenia, leukopenia, are usually associated with the use of the drug in high doses (3 g/day) for a long time and may manifest as pale skin, sore throat and fever, bleeding and hemorrhages, fatigue or weakness, as well as vomiting and diarrhea.
Symptoms of overdose are symptoms of gray syndrome (cardiovascular syndrome in young children), with relative overdose (the cause of development is the accumulation of chloramphenicol, which is due to the immaturity of liver enzymes, and its direct toxic effect on the myocardium) - bluish-gray skin color, low body temperature, bloating, vomiting, irregular breathing, decreased nervous reactions, cardiovascular failure, circulatory collapse, acidosis, inhibition of myocardial conduction, coma and death. Gray syndrome is also possible in patients with impaired liver and kidney function and is a consequence of drug accumulation. Gray syndrome manifests itself at a concentration of chloramphenicol in the blood plasma of 50 μg / ml.
Treatment: drug withdrawal, gastric lavage, use of enterosorbents, symptomatic therapy. In severe cases - symptomatic therapy, hemosorption.
Storage conditions
In the original packaging at a temperature not exceeding 25 °C.
