Vancomycin J - instructions for use, dose, side effects, contraindications

Pharmacodynamics:The antibiotic of the tricyclic glycopeptide group, isolated from Amycolatopsis orientalis, is effective against many Gram-positive microorganisms.
The bactericidal action of vancomycin is manifested by inhibition of the cell wall biosynthesis. Besides, vancomycin can change the permeability of the bacterial cell membrane and 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, Staphylococcus epidermidis (including heterogeneous methicillin-resistant strains), Streptococcus pyogenes, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus agalactiae, Streptococcus bovis, Streptococcus spp . group viridians, Clostridium difficile (including toxigenic strains taking part in the development of pseudomembranous colitis) and Corynebacterium spp .. Bacteriostatic acts on Enterococcus spp. (including Enterococcus faecalis and Enterococcus faecium (most strains of E. faecium have an intermediate sensitivity to vancomycin)). Optimum action - at pH 8, with a decrease in pH to 6, the effect is dramatically reduced.Actively acts only on microorganisms, which are in the stage of reproduction. To other microorganisms that are sensitive to vancomycin in vitro, include Listeria monocytogenes, Lactobacillus spp., Actinomyces spp., Clostridium spp., Bacillus spp.
In vitro, some isolated strains of enterococci and staphylococcus are resistant to vancomycin. The combination of vancomycin and aminoglycosides exhibits synergism in vitro for many strains of Staphylococcus aureus, Streptococcus spp. (not belonging to entero group D), Enterococcus spp., Streptococcus spp. group of viridians.
Vancomycin is inactive in vitro against gram-negative microorganisms, mycobacteria, viruses, protozoa and fungi.

Pharmacokinetics:Suction
Multiple intravenous administration (iv) 1 g of vancomycin (15 mg / kg, infusion over 60 min) creates average plasma concentrations of about 63 mg / l immediately after the infusion is complete. Two hours after the infusion, the average plasma concentrations were about 23 mg / L, and after 11h, about 8 mg / L.
Multiple infusions of 500 mg (infusion over 30 min) created average plasma concentrations of about 49 mg / L after infusions. Two hours after the infusion, the average plasma concentrations were about 19 mg / L, and after 6 hours, about 10 mg / L. Concentrations of vancomycin in plasma with repeated administration are similar to plasma concentrations for a single administration.
Distribution
The volume of distribution varies from 0.3 to 0.43 l / kg. 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 iv introduction vancomycin is found in pleural, pericardial, ascitic, synovial fluids and atrial auricle tissue, as well as in urine and in peritoneal fluid in concentrations that inhibit the growth of microorganisms. When meningitis occurs, the penetration of the drug into the cerebrospinal fluid at therapeutic concentrations is noted. The brain penetrates well only with inflammation of the meninges. Vancomycin penetrates the placental barrier and is excreted in breast milk.
Metabolism and excretion
Vancomycin is practically not metabolized. The mean half-life (T_1/2) vancomycin from plasma in patients with normal renal function is 4-6 hours. About 75% of the dose of vancomycin is excreted by the kidneys due to glomerular filtration in the first 24 hours. In small amounts can be excreted with bile. In small amounts, it is excreted in hemodialysis or peritoneal dialysis.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%.
Pharmacokinetics in special clinical cases
Impaired renal function slows the excretion of vancomycin. In patients with anuria, the mean T_1/2 is 7.5 days. In applying inwardly it has no systemic action, acts topically to sensitive microflora in the gastrointestinal tract (Staphylococcus aureus, Clostridium difficile). The total systemic and renal clearance of vancomycin can be reduced in elderly patients as a result of natural slowing of glomerular filtration.

Indications:Vancomycin It is used for serious or severe infections caused by sensitive microorganisms, including Staphylococcus spp. (Penitsillinazaobrazuyuschie and including methicillin-resistant strains), Streptococcus spp., (Including strains resistant to penicillin) with an allergic reaction to penicillin, in case of intolerance to other antimicrobial.
Endocarditis
endocarditis caused by Streptococcus viridans, Streptococcus bovis (monotherapy, combined with aminoglycoside therapy); endocarditis caused by enterococci (incl.Eterococcus faecalis; as a combination therapy with aminoglycosides for treatment); early endocarditis caused by Staphylococcus epidermidis, Corynebacterium spp. after valve replacement (in combination with rifampicin, aminoglycosides / both antibiotics); prevention of bacterial endocarditis in patients with resistance to penicillin and heart valve diseases (regardless of their etiology) before surgical interventions in the oral cavity, tonsillectomy, removal of adenoids, before catheterization of the bladder, cystoscopy, surgery on the rectum or large intestine (monotherapy or combination with aminoglycosides).

sepsis;
infection of bones and joints (including osteomyelitis);
infections of the central nervous system (including meningitis);
infections of the lower respiratory tract (including community acquired and nosocomial pneumonia, lung abscess and pleural empyema);
infections of the skin and soft tissues;

For oral administration:

pseudomembranous colitis caused by Clostridium difficile;
Enterocolitis caused by Staphylococcus aureus.

Contraindications:

increased sensitivity to vancomycin;
neuritis of the auditory nerve.

Carefully:Hearing impairment (including anamnesis), renal failure, pregnancy (I, II and III trimester), patients with allergies to teicoplanin (the possibility of cross-allergy).

Pregnancy and lactation:The use of the drug in pregnancy - only for life indications, if the intended benefit for the mother exceeds the potential risk to the fetus.
The use of the drug in the period of breastfeeding is contraindicated.

Dosing and Administration:Vancomycin is not intended for intramuscular and bolus injections, it is used intravenously infusion.
With iv administration of vancomycin, the recommended concentration is not more than 5 mg / ml and the injection rate is not more than 10 mg / min.
Adults the drug should be administered at 2 g IV every day (500 mg every 6 h / 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. The maximum single dose is 1000 mg, the maximum daily dose is 2000 mg.
Children over 1 month the drug should be administered at 10 mg / kg IV every 6 hours. Each dose should be administered for at least 60 minutes.
For newborns the initial dose is 15 mg / kg, then 10 mg / kg every 12 hours during the first week of 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. When appointing newborns, control over serum concentration is desirable.
The maximum single dose for children is 15 mg / kg of body weight, the daily dose for a child should not be higher than the daily dose for an adult (2 g).
In patients with obesity, the drug is used in usual doses.
Patients with impaired renal function need to individually select the dose. For the purpose of selecting a dose of vancomycin for this group of patients, creatinine clearance (CK) of serum can be used.

Table of doses of vancomycin for patients with impaired renal function
Creatinine clearance ml / min	Dose of vancomycin mg / 24 h
100	1545
90	1390
80	1235
70	1080
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. For anuria, it is recommended to administer 1 g every 7-10 days.
Correction by increasing the intervals between administrations
In patients with severe renal failure, it is advisable to adjust the dose by increasing the intervals between the administrations: with KK 10-50 ml / min - 1 g every 3-7 days,with KK <10 ml / min - 1 g every 7-14 days.
Preterm infants and elderly patients as a result of decreased renal function may require a significant dose reduction.
Preparation of a solution for intravenous administration
The solution is prepared by adding 10 ml of water for injection to 500 mg and 20 ml to 1000 mg to give a concentration of 50 mg / ml. Before use, the drug solution is diluted in a minimum of 100 ml (solutions containing 500 mg of vancomycin) or in 200 ml (solutions containing 1 g of vancomycin) 5% dextrose solution or 0.9% sodium chloride solution. Before injection, the prepared parenteral solution should be visually inspected for mechanical impurities and discoloration.
The concentration of vancomycin in the prepared solutions should not exceed 5 mg / ml.
Stability of solutions.
Solutions prepared on the basis of the following infusion liquids can be stored in the refrigerator (at 2-8 ^aboutC) for 96 hours:

5% dextrose injection and 0.9% sodium chloride injection;
Ringer's injectable lactate;
Ringer's injection of lactate and a 5% injection of dextrose.

Preparation of solution for oral administration
Vancomycin can be used orally to treat pseudomembranous colitis caused by Clostridium difficile, due to the use of antibiotics, as well as for the treatment of staphylococcal enterocolitis. Intravenous administration of the drug has no advantages for the treatment of these diseases.
The drug should be used in the following doses: adults 0.5 - 2 g 3-4 times / day, children 0.04 g / kg 3-4 times / day. The total daily dose should not exceed 2 g. The appropriate dose is prepared in 30 ml of water and given to the patient to drink or injected through the probe. To improve the taste of the solution, ordinary food syrups can be added to it. Duration of treatment is from 7 to 10 days.
Vancomycin is ineffective when taken orally in case of other types of infections.

Side effects:From the cardiovascular system: heart failure, "hot flashes" of blood; reduction in blood pressure, shock (symptoms are mainly associated with rapid infusion of the drug), vasculitis, thrombophlebitis.
From the digestive system: nausea, pseudomembranous colitis.
On the part of the hematopoiesis system: agranulocytosis, eosinophilia, neutropenia, thrombocytopenia.
From the urinary system: interstitial nephritis, changes in functional renal tests, impaired renal function.
From the sense organs: vertigo, ringing in the ears, ototoxic effects (transient / persistent). In most cases, ototoxic effects were observed in patients who received excessive vancomycin doses, with a history of hearing loss, or in patients receiving concomitant treatment with other drugs with the possible development of ototoxicity, for example, aminoglycosides.
Dermatological reactions: exfoliative dermatitis, rash.
Allergic reactions: urticaria, anaphylactoid reactions (associated with rapid drug infusion), hypersensitivity reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, itchy dermatosis, benign pemphigus dermatosis, diffuse exfoliative erythroderma (red man syndrome - reddening of the upper body, pain and spasm muscles of the chest and back, after stopping the infusion the reactions usually last for 20 minutes, but sometimes can last up to several hours)
Other: drug fever, phlebitis at the injection site, necrosis at the injection site, dyspnea, stridor, pain at the injection sites; drug rash, accompanied by eosinophilia and systemic manifestations (DRESS syndrome), increased activity of "liver" transaminases, pancytopenia, anemia, and leukopenia.

Overdose:Symptoms: increased severity of dose-dependent side effects.
Treatment: symptomatic therapy aimed at maintaining glomerular filtration. Vancomycin poorly removed during dialysis. There is evidence that hemofiltration and hemoperfusion through polysulfone ion exchange resin leads to an increase in vancomycin clearance.

Interaction:With the simultaneous use of vancomycin with local anesthetics in children, erythema, redness of the skin and anaphylactoid reactions were noted, in adults - violation of intracardiac conduction.
When used simultaneously with common anesthetics and vecuronium bromide, the frequency of side effects increases (risk of lowering blood pressure, development of neuromuscular blockade). The introduction of vancomycin at least 60 minutes before the administration of anesthetic can reduce the likelihood of these reactions.
With simultaneous, and / or sequential application of other potentially ototoxic and / or nephrotoxic drugs (aminoglycosides, amphotericin B, acetylsalicylic acid or other salicylates, bacitracin, bumetanide, capreomycin, carmustine, paromomycin, ciclosporin, "loop" diuretics, polymyxin AT, cisplatin, ethacrynic acid) requires careful monitoring of the possible development of these symptoms.
Kolestyramin lowers the effectiveness of vancomycin (if ingested). Antihistamines, meclozine, 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 pharmaceutically incompatible when mixed. The probability of precipitation increases with increasing concentration of vancomycin. It is necessary to thoroughly wash the system for intravenous administration between the use of these antibiotics.In addition, it is recommended to reduce the concentration of vancomycin to 5 mg / ml or less.

Special instructions:The rapid introduction of vancomycin (within a few minutes) 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 rapid infusion.
Patients receiving vancomycin in / in, should periodically carry out a blood test and monitor kidney function.
When prescribing the drug to newborn children (especially premature infants), control over the concentration of vancomycin in the serum is desirable.
Vancomycin is used for serious or severe infections caused by sensitive microorganisms, including Staphylococcus spp. (including penicillinase-forming and methicillin-resistant strains), Streptococcus spp. (including strains resistant to penicillin) with an allergic reaction to penicillin, intolerance to other antimicrobial drugs.
Vancomycin should be used with caution in patients with renal insufficiency (determine the concentration of vancomycin in the serum with renal failure in patients older than 60 years), since high,long-term concentrations of the drug in the blood can increase the risk of toxic effects of the drug (maximum concentrations of vancomycin in the blood serum (C max) should not exceed 40 mcg / ml, and minimal - 10 mcg / ml, concentration> 80 mcg / ml is considered toxic).
For patients with renal failure, doses of vancomycin should be selected individually.
When prescribing the drug, thrombophlebitis can be observed; the likelihood of their development can be reduced by the slow introduction of dilute solutions (2.5-5 g / l) and the alternation of injection sites.

Effect on the ability to drive transp. cf. and fur:During the period of treatment with the drug, the ability to concentrate attention can be reduced, which should be taken into account when driving vehicles or performing work that requires a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Lyophilizate for the preparation of a solution for infusions of 500 mg and 1000 mg.

Packaging:For 500 mg and 1000 mg of active ingredient in bottles of clear glass, sealed with a cork made of bromobutyl rubber, coated with an aluminum ring (possibly a plastic cap).
Solvent: water for injection (RU No. LP-002377 dated February 18, 2014) of 10.0 ml per ampoule of colorless neutral glass or low-density polyethylene.
For a dosage of 500 mg:
1 bottle with the drug and 1 ampoule with or without solvent, together with instructions for use in a cardboard pack; 5 vials and 5 ampoules with or without solvent on the plastic pallet, 1 or 2 pallets together with instructions for use in a cardboard box.
For a dosage of 1000 mg:
1 bottle with the drug and 2 ampoules with or without solvent, together with instructions for use in a cardboard pack; 5 vials and 10 ampoules with or without solvent on a plastic pallet, 1 or 2 pallets together with instructions for use in a cardboard box.
For hospitals: 25, 50 and 100 vials, together with the appropriate number of ampoules with a solvent (for dosage of 500 mg - 25, 50 or 100 ampoules, for a dosage of 1000 mg - 50, 100 or 200 ampoules) or without a solvent and instructions for use in a box cardboard.

Storage conditions:In dry, dark place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002058

Date of registration:25.04.2013 / 07.08.2015

Expiration Date:25.04.2018

The owner of the registration certificate:JODAS EKSPOIM, LLC JODAS EKSPOIM, LLC Russia

Manufacturer: & nbsp

JODAS EXPOIM, Pvt. Ltd. India

Representation: & nbspJodas Expoim, Open CompanyJodas Expoim, Open Company

Information update date: & nbsp22.01.2017

Illustrated instructions

Instructions

Vancomycin J (Vancomycin-Jd)