Composition, form of production and packaging
Lyophilizate for the preparation of a solution for infusions in the form of almost white (with a pink or light brown hue) powder.
1 f.
vancomycin (in the form of hydrochloride) 500 mg
Auxiliary substances: hydrochloric acid or sodium hydroxide (up to pH 3.2-3.3), nitrogen, water d / u.
Vials (1) - packs of cardboard.
Lyophilizate for the preparation of a solution for infusions in the form of almost white (with a pink or light brown hue) powder.
1 f.
vancomycin (in the form of hydrochloride) 1 g
Auxiliary substances: hydrochloric acid or sodium hydroxide (up to pH 3.2-3.3), nitrogen, water d / u.
Vials (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
The product description was approved by the manufacturer for the 2009 print edition.
PHARMACHOLOGIC EFFECT
Vancomycin is a tricyclic glycopeptide antibiotic isolated from Amycolatopsis orientalis . The bactericidal action of vancomycin is manifested by inhibition of the cell wall biosynthesis. In addition, vancomycin can alter the permeability of the bacterial cell membrane and alter the synthesis of RNA. Cross-resistance between vancomycin and antibiotics of other classes is absent.
In vitro, vancomycin is active against Gram-positive microorganisms, including: Staphylococcus aureus and Staphylococcus epidermidis (including heterogeneous methicillin-resistant strains), Streptococcus pyogenes . Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus agalactiae, viridance group, Streptococcus bovis and enterococci (eg Enterococcus faecalis); Clostridium difficile (eg, toxigenic strains taking part in the development of pseudomembranous enterocolitis) and diphtheria. Other microorganisms that are sensitive to vancomycin in vitro include Listeria monocytogenes, genera of bacteria Lactobacillus, Actinomyces, Clostridium and Bacillus.
In vitro, some isolated strains of enterococci and staphylococcus are resistant to vancomycin. The combination of vancomycin and aminoglycosides acts synergistically in vitro for many strains of Staphylococcus aureus, streptococci not belonging to entero group D, enterococci and bacteria of the Streptococcus group (group of viridance).
Vancomycin is inactive in vitro against gram-negative microorganisms, mycobacteria and fungi.
PHARMACOKINETICS
In individuals with normal renal function, repeated iv administration of 1 g of vancomycin (15 mg / kg) (infusion over 60 min) created average plasma concentrations of about 63 mg / L immediately after completion of the infusion; 2 hours after infusions, average plasma concentrations were about 23 mg / L, and 11 hours after infusions - about 8 mg / L. Multiple infusions of 500 mg administered over 30 minutes created average plasma concentrations of about 49 mg / L after infusions; 2 hours after the infusions, the average plasma concentrations were about 19 mg / L, and after 6 hours, about 10 mg / L. Concentrations in plasma under repeated administration are similar to plasma concentrations for a single administration.
The average T 1/2 vancomycin from plasma is 4-6 hours in patients with normal renal function. About 75% of the administered dose of vancomycin is excreted in the urine by glomerular filtration in the first 24 hours. The average plasma clearance is about 0.058 l / kg / h, and the average renal clearance is about 0.048 l / kg / h. Renal clearance of vancomycin is quite constant and ensures its elimination by 70-80%. V d ranges from 0.3 to 0.43 l / kg. The drug is practically not metabolized. As shown by ultrafiltration, with a concentration of vancomycin in the serum from 10 mg / l to 100 mg / l, 55% of vancomycin is found in the protein-bound state.
After intravenous administration, vancomycin hydrochloride is found in pleural, pericardial, ascitic, synovial fluids and atrial auricle tissue, as well as in urine and peritoneal fluid in concentrations that inhibit the growth of microorganisms. Vancomycin slowly penetrates into the cerebrospinal fluid. When meningitis occurs, penetration of the drug into the cerebrospinal fluid. Vancomycin penetrates the placental barrier and into breast milk.
Impaired renal function slows the excretion of vancomycin. In patients with missing kidneys, the mean T 1/2 is 7.5 days. The total systemic and renal clearance of vancomycin can be reduced in elderly patients as a result of natural slowing of glomerular filtration.
INDICATIONS
- endocarditis;
Vancomycin is effective both in monotherapy and in combination with aminoglycosides for the treatment of endocarditis caused by Streptococcus viridaus or S. bovis. With endocarditis caused by enterococci (for example, E. faecalis), Vancomycin is effective only in combination with aminoglycosides.
There is evidence that vancomycin is effective in treating diphtheria endocarditis. Vancomycin is successfully used in combination with rifampicin, aminoglycosides or both antibiotics for early endocarditis caused by S. epidermidis or diphtheroids, after valve replacement.
In some cases, vancomycin is indicated for the prevention of endocarditis.
- sepsis;
- infections of bones and joints;
- infections of the lower parts of the respiratory tract;
- skin and soft tissue infections;
Vancomycin can also be used for infections caused by gram-positive microorganisms in cases of: allergies to penicillin; intolerance or non-response to treatment with other antibiotics, including penicillins or cephalosporins; infections caused by microorganisms sensitive to vancomycin, but resistant to other antimicrobial agents.
- pseudomembranous colitis (as a solution for oral administration).
DOSING MODE
With the introduction of vancomycin, the recommended concentration is not more than 5 mg / ml and the injection rate is not more than 10 mg / min. In patients who are shown to limit fluid intake, a concentration of up to 10 mg / ml and a rate of administration not exceeding 10 mg / min can be used. However, in the case of such concentrations, the incidence of side effects associated with infusion increases.
Adults:
The dose for patients with normal renal function is 2 g IV (500 mg every 6 hours or 1 g every 12 h). Each dose should be administered at a rate of not more than 10 mg / min and for at least 60 minutes. Age and obesity in the patient may require a change in the usual dose based on the determination of the concentration of vancomycin in the serum.
Children:
The usual dose is 10 mg / kg and is administered iv every 6 hours. Each dose should be administered for at least 60 minutes.
Children of early age and newborns:
For the newborn, the initial dose should be 15 mg / kg, and then 10 mg / kg every 12 hours during the first week of their life. Starting from the second week of life - every 8 hours until reaching the age of one month. Each dose should be administered for at least 60 minutes.
Patients with impaired renal function and elderly patients :
Patients with impaired renal function need to individually select the dose. To select a dose of vancomycin for this group of patients, serum creatinine levels can be used. In elderly patients, vancomycin has a lower clearance and a greater volume of distribution. In this group, the selection of a dose is expediently based on the concentrations of vancomycin in the serum. In premature infants and in elderly patients, as a result of reduced renal function, a significant dose reduction may be required. The concentration of vancomycin in the serum should be monitored regularly. The table below shows the doses of vancomycin depending on the creatinine clearance.
Table of doses of vancomycin for patients with impaired renal function
Creatinine clearance (ml / min) Vancomycin Dose (mg) / 24 h
100 1.545
90 1.390
80 1.235
70 1.080
60,925
50,770
40,620
30,465
20 310
10 155
This table can not be used to determine the dose of the drug in anuria. Such patients should be given an initial dose of 15 mg / kg body weight to quickly create therapeutic concentrations of the drug in the serum. The dose required to maintain a stable concentration of the drug is 1.9 mg / kg / 24 hours. Patients with severe renal insufficiency are advised to administer maintenance doses of 250-1000 mg once every few days (with KK 10-50 ml / min - 1 g every 3 -7 days, less than 10 ml / min - 1 g every 7-14 days). With anuria, a dose of 1 g is recommended every 7-10 days.
Instructions for preparing a solution for intravenous administration
Solution for injection is prepared immediately before the administration of the drug. For this, a necessary volume of water for injections is added to the vial of dry, sterile powder of vancomycin in order to obtain a solution with a concentration of 50 mg / ml. Further dilution of the prepared solution is required.
Prepared solutions of vancomycin before administration are subject to further dilution to a concentration of not more than 5 mg / ml. The required dose diluted in the above way vancomycin should be administered by fractional IV infusion for at least 60 minutes. As solvents, a 5% solution of dextrose for injection or a 0.9% solution of sodium chloride for injection can be used. Before injection, the prepared parenteral solution should be visually inspected, if possible, for mechanical impurities and discoloration.
SIDE EFFECT
The body as a whole: anaphnlactoid reactions.
Cardiovascular system: cardiac arrest; tides; reduction of blood pressure, shock (these symptoms are mainly associated with rapid infusion of the drug).
Gastrointestinal tract: nausea; pseudomembranous colitis.
Blood system: agranulocytosis; eosinophilia; neutropenia; thrombocytopenia.
Influence at kidney: interstitial nephritis; change in functional renal tests; impaired renal function.
Skin: exfoliative dermatitis; hypersensitivity reactions; benign (IgA) vesicular dermatosis; itching dermatosis; rash; syndrome of "red man"; Stevens-Johnson syndrome; toxic epidermal necrolysis; hives; vasculitis.
Organs of the senses: vertigo, ringing in the ears, ototoxic effects. A number of patients who received vancomycin had an ototoxic effect. It can be transient or permanent. It is reported that the majority of such cases were observed among patients who received excessive doses of vancomycin, with a history of hearing loss, or in patients receiving simultaneous treatment with other drugs with the possible development of ototoxicity, for example, aminoglycosides.
Others: chills; drug fever; necrosis of tissues at injection sites; pain in the injection site; thrombophlebitis.
During or soon after too rapid infusion of vancomycin, patients may develop anaphylactoid reactions. Rapid injection of the drug can also cause "red person" syndrome, redness of the upper body or pain and spasm of the muscles of the chest and back. After discontinuation of the infusion, these reactions usually take place within 20 minutes, but sometimes can last up to several hours.
CONTRAINDICATIONS
- Pregnancy (I trimester);
- lactation period;
- neuritis of the auditory nerve;
- kidney failure;
hypersensitivity to vancomycin.
Use with caution in case of hearing impairment (including anamnesis), during pregnancy (II and III trimester).
PREGNANCY AND LACTATION
Application in the II-III trimester of pregnancy is possible only for life indications.
APPLICATION FOR FUNCTIONS OF THE LIVER
Vancomycin should be used with caution in patients with renal insufficiency (it is desirable to determine the concentrations of vancomycin in the serum of patients with renal insufficiency in patients older than 60 years), since high concentrations of the drug remaining in the blood for a long time may increase the risk of toxic effects of the drug (maximum concentrations should not be more than 40 Ојg / ml, and the minimum - 10 Ојg / ml, concentrations above 80 Ојg / ml are considered toxic). For patients with renal insufficiency, doses of vancomycin should be selected individually.
APPLICATION FOR CHILDREN
The usual dose is 10 mg / kg and is administered iv every 6 hours. Each dose should be administered for at least 60 minutes.
For the newborn, the initial dose should be 15 mg / kg, and then 10 mg / kg every 12 hours during the first week of their life. Starting from the second week of life - every 8 hours until reaching the age of one month. Each dose should be administered for at least 60 minutes
APPLICATION IN ELDERLY PATIENTS
In elderly patients, vancomycin has a lower clearance and a greater volume of distribution. In this group, the selection of a dose is expediently based on the concentrations of vancomycin in the serum. In elderly patients, as a result of reduced renal function, a significant dose reduction may be required.
SPECIAL INSTRUCTIONS
When appointing newborns, monitoring of serum concentration is desirable.
Rapid administration (eg, within a few minutes) of vancomycin may be accompanied by a marked decrease in blood pressure and in rare cases, cardiac arrest. Vancomycin should be administered as a diluted solution for at least 60 minutes to avoid adverse reactions associated with infusion.
Vancomycin should be administered with caution to patients with an allergy to teicoplanin, t.p. cases of cross-allergy have been reported.
Patients receiving vancomycin IV should periodically undergo a blood test and control kidney function.
Vancomycin should be used with caution in patients with renal insufficiency (it is desirable to determine the concentrations of vancomycin in the serum of patients with renal insufficiency in patients older than 60 years), since high concentrations of the drug remaining in the blood for a long time may increase the risk of toxic effects of the drug (maximum concentrations should not be more than 40 Ојg / ml, and the minimum - 10 Ојg / ml, concentrations above 80 Ојg / ml are considered toxic). For patients with renal insufficiency, doses of vancomycin should be selected individually.
Vancomycin is an "irritant" agent and therefore the diffusion of the dissolved drug through the vascular wall can cause necrosis of adjacent tissues. There may be thrombophlebitis, although the likelihood of their development can be reduced by slow administration of dilute solutions (2.5-5 g / l) and alternation of injection sites.
OVERDOSE
Symptoms: increased severity of side effects.
Treatment. Corrective therapy aimed at maintaining glomerular filtration. Vancomycin is poorly removed during dialysis. There is evidence that hemofiltration and hemoperfusion through polysulfone ion exchange resin leads to an increase in vancomycin clearance.
DRUG INTERACTION
With simultaneous iv administration of vancomycin and anesthetics, erythema, redness of the skin and anaphylactoid reactions were noted, a risk of lowering blood pressure or developing a neuromuscular blockade is possible. The administration of vancomycin in the form of a 60-minute infusion prior to administration of an anesthetic may reduce the likelihood of these reactions occurring.
With simultaneous and / or sequential systemic or topical application of other potentially ototoxic and / or nephrotoxic drugs (aminoglycosides, amphotericin B, ASA or other salicylates, bacitracin, capreomycin, carmustine, paromomycin, cyclosporine, loop diuretics, polymyxin B, cisplatin, ethacrynic acid ) requires careful monitoring of the possible development of these symptoms.
Kolestyramin reduces activity.
Antihistamines, meclosin, phenothiazines, thioxanthenes can mask the symptoms of the ototoxic action of vancomycin (tinnitus, vertigo).
The solution of vancomycin has a low pH, which can cause physical or chemical instability when mixed with other solutions. Avoid mixing with alkaline solutions.
Solutions of Vancomycin and beta-lactam antibiotics are physically incompatible when mixed. The probability of precipitation increases with increasing concentration of vancomycin. It is necessary to adequately rinse the intravenous system between the applications of these antibiotics. In addition, it is recommended to reduce the concentration of Vancomycin to 5 mg / ml or less.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. Store in a dark place at a temperature of 15 В° -25 В° C. Keep out of the reach of children. Shelf life - 3 years.
