Levomycetinum - Darnitsa

General characteristics. Structure:

Active ingredient: chloramphenicol;

1 tablet contains: chloramphenicol (levomycetinum) of 250 mg or 500 mg;

excipients: potato starch, hydroxypropyl cellulose, stearic acid.

Pharmacological properties:

Pharmacodynamics. Chloramphenicol is an antibiotic with a broad spectrum of activity concerning gram-positive and gram-negative bacteria, and also some other microorganisms. It is effective concerning strains of the bacteria steady against penicillin, tetracyclines, streptocides. Effect of drug is connected with disturbance of process of synthesis of protein in a microbic cell at a stage of transfer of amino acids t-RNK on ribosomes. Chloramphenicol has mainly bacteriostatic action on pathogenic microorganisms though it can be bactericidal concerning some microorganisms, including Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae, at higher concentration.

Activity range. Chloramphenicol is active against many species of bacteria.

Gram-positive microorganisms, including Bacillus anthracis, Corynebacterium diphtheriae and anaerobe bacterias, such as Peptococcus and Peptostreptococcus spp, usually are sensitive to chloramphenicol. However gram-positive cocci, including such, as staphylococcus of Staphylococcus epidermidis and some strains of Staphylococcus aureus and streptococci for example, Str. pneumoniae, Str. pyogenes and viridans, Methicillinum - resistant staphylococcus and Enterococcus faecalis usually were steady against chloramphenicol.

Gram-negative cocci, such as Neisseria meningitidis and N. gonorrhoeae are, as a rule, very sensitive to drug, as well as Haemophilus influenzae and some other gram-negative bacteria, including Bordetella pertussis, Brucella abortus, Campylobacter spp, Legionella pneumophila, Pasteurella and Vibrio spp.

Enterobacteriaceae differ on the sensitivity, many strains found the acquired resistance, however Escherichia coli and strains of Klebsiella spp, Proteus mirabilis, Salmonella, Shigella and Yersinia spp. are sensitive to chloramphenicol.

Many strains of Enterobacter, indole - positive Proteus and Serratia spp. are steady, or at best are moderately sensitive to chloramphenicol. Pseudomonas aeruginosa steadily is steady though Burkholderia (before Pseudomonas) spp. can be sensitive. Some gram-negative anaerobe bacterias (Bacteroides fragilis, Veillonella and Fusobacterium spp.) are sensitive or moderately sensitive to drug.

Other microorganisms, sensitive to chloramphenicol: Actinomyces spp, Leptospira spp, spirochetes.

Such microorganisms as Treponema pallidum, Chlamydiaceae, Mycoplasma spp, and Rickettsia spp. Nocardia spp. are steady against effect of drug.

Chloramphenicol is inefficient concerning mushrooms, protozoa and viruses.

Stability of microorganisms develops slowly.

Pharmacokinetics. Chloramphenicol at intake is easily acquired. Concentration in blood of 10 mkg/ml or can be reached approximately in 1 or 2 hours after a single dose inside in a dose of 1 g more, and concentration in blood            about 18,5 mkg/ml was defined after reception of several doses by 1 g of drug. Chloramphenicol palmitate at intake is hydrolyzed before absorption in a digestive tract to chloramphenicol and sodium of succinate; newborns and babies can have incomplete such hydrolysis, promoting non-constant pharmacokinetics of drug in this age group. Chloramphenicol easily gets into fabrics and liquids of a body, gets to cerebrospinal fluid, creating concentration about 50% from existing in blood (even in lack of an inflammation of a meninx), it diffuses through a placenta, gets to breast milk and to water and vitreous liquid of eyes. Approximately to 60% of the accepted dose of drug contacts proteins of a blood plasma. The elimination half-life of chloramphenicol is ranging from 1,5 till 4 o'clock; the elimination half-life is longer at patients with a heavy liver failure, and also much bigger at newborns. The renal failure has rather small influence on an elimination half-life of active ingredient of drug thanks to his intensive metabolism, but can lead to accumulation of inactive metabolites. Chloramphenicol is removed generally with urine, but only 5-10% of a peroral dose – in not changed look; the rest is inactivated in a liver, generally by conjugation with glucuronic acid. About 3% are allocated in bile. However the most part is absorbed also only about 1%, generally in an inactive form, allocated with a stake. Absorption, metabolism and removal of chloramphenicol are subject to considerable interpersonal variations, especially at babies and children that does necessary monitoring of concentration in a blood plasma for definition of pharmacokinetics at this patient.

Pharmaceutical characteristics.

Main physical and chemical properties: tablets of color, white or white with slightly yellowish shade, a ploskotsilindrichesky form, with risky and a facet.

Indications to use:

Treatment of heavy mephitic gangrenes (brain abscess) and infections of an abdominal cavity (purulent peritonitis, infections of biliary tract, infections of urinary tract) where activators often is Bacteroides fragilis.

Treatment of a meningococcal infection, bacterial meningitis as empirically and when it is known that activators are sensitive microorganisms, such as Haemophilus influenzae.

Chloramphenicol is shown also at treatment of clamidiosis, brucellosis, rickettsial infections, such as a sapropyra, ерлихиоз, trachoma and spotty fever of the Rocky Mountains.

Serious gastrointestinal infections belong to bacterial infections at which treatment chloramphenicol can be applied as an alternative to other medicines (including the caused Salmonella enteritis, Yersinia enteritis, Shigella spp.), the typhoid, paratyphus, a purulent wound fever, an inguinal lymphogranuloma, heavy infections caused by Haemophilus influenzae, a tularemia (especially at suspicion of meningitis).

Chloramphenicol is widely applied to treatment of purulent otitis.

Route of administration and doses:

Levomitsetin-Darnitsa apply inside in 30 minutes prior to food.

Adults accept drug on 250-500 mg 3-4 times a day. A daily dose – 2000 mg. In especially hard cases Levomitsetin-Darnitsa it is possible to apply in a dose up to 4000 mg (the maximum daily dose to adults) in days under strict control of a condition of blood and function of a liver and kidneys. The daily dose is distributed on 3-4 receptions.

The single dose of drug for children from 3 to 8 years makes 10 mg/kg of body weight, for children 8 years – on 250 mg are more senior. Frequency rate of reception – 3-4 times a day.

The course of treatment of Levomitsetinom-Darnitsa makes 7-10 days. According to indications on condition of good tolerance and lack of changes in the hemopoietic system extension of a course of treatment up to 2 weeks is possible.

Features of use:

Use during pregnancy or feeding by a breast.

Use of chloramphenicol is contraindicated during pregnancy. During treatment it is necessary to stop feeding by a breast.

Children.

Drug in this dosage form is used for treatment of children aged 3 years are more senior.

Drug should be used only under observation of the doctor.

Chloramphenicol can lead to serious oppression of function of marrow which can cause development of an agranulocytosis, Werlhof's disease or aplastic anemia. These effects from the hemopoietic system are, as a rule, connected with a high dose, prolonged use or repeated courses, but they can arise at use of rather low doses. Patients cannot appoint chloramphenicol with already existing oppression of function of marrow or a dyscrasia of blood. It is necessary to avoid use of chloramphenicol with other medicines which can cause oppression of function of marrow.

For increase in safety of treatment it is necessary if it is possible, to carry out by drug monitoring of its concentration in blood serum. Therapeutic range makes 5-15 mkg/ml. Monitoring is especially necessary for patients with liver diseases, and also to patients of advanced age, patients with a disease of kidneys and to the persons receiving other drugs with which chloramphenicol can interact.

At use it is necessary to carry out control of a picture of blood. Data on any harmful effects on elements of blood is the instruction to immediately stop therapy by drug.

Cytostatics or radiation therapy also development of toxic reactions in the form of oppression of marrow, an abnormal liver function can lead the previous treatment to accumulation of chloramphenicol in an organism.

Patients should appoint the reduced doses with a liver failure. Excessive concentration of chloramphenicol in a blood plasma can also arise after use of a usual dose for patients with a heavy renal failure: it is necessary to reduce a dose of drug or to increase an interval between receptions.

Chloramphenicol cannot be applied at treatment of slight infections or for the purpose of prevention, and also at any infections to which less toxic antibiotics are available. Also it is necessary to avoid repeated courses and prolongation of treatment.

With care to apply at cardiovascular diseases and tendency to allergic reactions. Use of chloramphenicol leads to increase in frequency of microbic infections of an oral cavity, delay of processes of healing and bleeding of gums that can be manifestation of a miyelotoksichnost. Dental interventions should be completed whenever possible prior to treatment by drug.

Purpose of chloramphenicol can provoke a bad attack of a porphyria. Drug is to patients, dangerous to use, with a porphyria.

Chloramphenicol can influence development of an immune response, it is impossible to appoint it when carrying out active immunization.

Ability to influence speed of response at control of motor transport or work with other mechanisms.

With care persons whose activity requires special attention and speed of psychomotor reactions should use drug.

Side effects:

The heaviest side reactions are: aplastic anemia, oppression of activity of marrow and "a gray syndrome".

Also development of side reactions from the following bodies and systems is observed.

Neurologic disturbances: psychomotor frustration, depression, delirium, confusion of consciousness, peripheral neuritis, optic neuritis, visual and auditory hallucinations, decrease in visual acuity and hearing, disturbance of feeling of taste, headache, encephalopathy.

Gastrointestinal frustration: dyspepsia, abdominal distention, nausea, vomiting (the probability of development decreases at reception in 1 hour after food, diarrhea, irritation of a mucous membrane of an oral cavity and pharynx, dermatitis (including perianal dermatitis), intestinal microflora oppression, dysbacteriosis, a coloenteritis, stomatitis, a glossitis.

From gepatobiliarny system: abnormal liver function.

From bodies of a hemopoiesis: oppression of marrow, a reticulocytopenia, reduction of level of hemoglobin in blood, anemia, a leukopenia, a granulocytopenia, thrombocytopenia, an erythrocytopenia, a pancytopenia, is rare – aplastic anemia, hypoplastic anemia, an agranulocytosis, cytoplasmatic vacuolation of early erythrocyte forms.

Allergic reactions: skin rash, fever, Quincke's disease, small tortoiseshell, anaphylaxis.

Others: a hyperthermia, a consecutive fungal infection, reaction to a bacteriolysis (Yarisha-Geksgeymer's reaction), a collapse (at children).

Interaction with other medicines:

Chloramphenicol suppresses fermental system of P450 cytochrome therefore at its simultaneous use with antiepileptic drugs (phenobarbital, Phenytoinum), indirect anticoagulants (Dicumarinum, warfarin) note weakening of metabolism of these drugs, delay of a conclusion, increase in their concentration in a blood plasma and increase in their toxicity.

Peroral hypoglycemic drugs (Chlorproramidum, Tolbutamidum. At use with chloramphenicol strengthening of effect of peroral hypoglycemic drugs is noted (due to oppression of metabolism in a liver and increases in their concentration in a blood plasma).

Phenobarbital, rifampicin, рифабутин – reduce concentration of chloramphenicol in a blood plasma by acceleration of his metabolism in a liver.

At simultaneous use with paracetamol lengthening of an elimination half-life of chloramphenicol can be observed.

Phenytoinum. At simultaneous use both decrease, and increase in concentration of chloramphenicol in a blood plasma can be observed.

Cyclosporine – at simultaneous use with chloramphenicol can be observed increase in level of cyclosporine in plasma. At simultaneous use of these drugs it is necessary to carry out monitoring of concentration of cyclosporine.

Cyclophosphamide – simultaneous use extends a cyclophosphamide elimination half-life from 7,5 to 11,5 o'clock.

Takrolimus – at simultaneous use with chloramphenicol can be observed increase in level of a takrolimus in plasma. At simultaneous use the dose of a takrolimus needs to be adjusted.

Levomycetinum reduces antibacterial effect of penicillin and cephalosporins.

Macroleads (erythromycin, Oleandomycinum, clindamycin), linkozamida (lincomycin), half-yen antibiotics (nystatin, levorinum) – at simultaneous use of chloramphenicol with these drugs mutual weakening of action is noted because chloramphenicol can force out these drugs from the connected state or interfere with their linkng with subunit 50S of bacterial ribosomes.

Cycloserinum – simultaneous use strengthens a chloramphenicol neurotoxicity.

The medicines suppressing a hemopoiesis (streptocides, cytostatics, Cimetidinum, Ristomycinum) – simultaneous use can increase risk of oppression of activity of marrow and weight of its manifestations.

Estrogensoderzhashchy oral contraceptives, iron preparations, folic acid, cyanocobalamine – chloramphenicol can reduce efficiency of these drugs.

Ethanol – at a concomitant use of ethanol development of disulfiramopodobny reaction is possible (a hyperemia of integuments, tachycardia, nausea, vomiting, reflex cough, spasms).

Contraindications:

Hypersensitivity to chloramphenicol, other amfenikol and/or other components of drug; blood diseases, hemopoiesis oppression; skin diseases (psoriasis, eczema, fungal infections); pregnancy and period of feeding by a breast; acute respiratory diseases, quinsy; the expressed abnormal liver functions and/or kidneys; deficit of enzyme glyukozo-6-fosfatdegidrogenazy; porphyria.

Unacceptably uncontrolled use of Levomitsetin-Darnits and its use with the preventive purpose at easy forms of infectious processes, especially to children.

Overdose:

Symptoms of overdose are "a gray syndrome" (a cardiovascular syndrome at children of early age), at relative overdose (the accumulation of levomycetinum caused by immaturity of enzymes of a liver and its direct toxic action on a myocardium is the reason of development) – bluish-gray skin color, the lowered body temperature, spasmodic breath, decrease in nervous reactions, cardiovascular insufficiency, a circulator collapse, acidosis, oppression of myocardial conductivity, a lump and a lethal outcome. "The gray syndrome" can be also observed at patients with an abnormal liver function and kidneys and is a consequence of cumulation of drug. "The gray syndrome" is shown at concentration of chloramphenicol in a blood plasma higher than 50 mkg/ml.

Treatment. Gastric lavage, reception of salt laxative, absorbent carbon, high cleansing enema. In hard cases – symptomatic therapy, hemosorption.

Storage conditions:

Period of validity. 5 years. To store in original packaging at a temperature not above 25 °C in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging, on the 2nd blister strip packagings in a pack, on 10 tablets in blister strip packagings.