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

Vancomycin is a tricyclic glycopeptide antibiotic isolated from Amycolatopsis orientalis. The bactericidal action of vancomycin is carried out by inhibiting the biosynthesis of the cell wall of microorganisms. Besides, vancomycin can change 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 usually exhibits activity against gram-positive microorganisms, such as Staphylococcus aureus and Staphylococcus epidermidis (including heterogeneous methicillin-resistant strains), Streptococcus pyogenes, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus agalactiae, Streptococcus spp. groups viridians. Streptococcus bovis and enterococci (for example. Enterococcus faecalis, Clostridium difficile (eg, toxigenic strains taking part in the development of pseudomembranous enterocolitis) and Corynebacterium spp. To other microorganisms sensitive to vancomycin in vitro, relate Listeria monocytogenes, microorganisms of the genus Lactobacillus, Actinomyces, Clostridium and Bacillus.

There is evidence that in vitro some isolated strains of enterococci and staphylococci manifest resistance to vancomycin.

The combination of vancomycin and aminoglycosides exhibits synergism in vitro for many strains Staphylococcus aureus, Streptococcus spp. (not belonging to the entero group D), Enterococcus spp., Streptococcus spp. groups viridians.

Vancomycin is inactive in vitro against gram-negative microorganisms of mycobacteria, viruses, protozoa and fungi.

When applied orally does not have a systemic effect, acts locally on the sensitive microflora in the gastrointestinal tract (Staphylococcus aureus, Clostridium difficile).

Pharmacokinetics:

Suction

After oral administration vancomycin absorbed in minimum quantities. Absorption of the drug is slightly higher with inflammation of the intestinal mucosa. In patients with inflammation of the intestinal mucosa, the maximum concentration of the drug in the blood plasma after taking 0.5 g every 6 hours varies from 2.4 mg / l to 3.0 mg / l.

After intravenous administration (iv) of vancomycin in a dose of 0.5 g to patients with normal renal function, the highest concentration of the drug in the blood plasma is observed immediately after the administration of the drug (33 mg / l), 1 hour after administration, it decreases to 7.3 mg / l.

After intravenous administration of vancomycin in a dose of 1.0 g the concentration of the drug in the blood plasma is doubled; immediately after the administration, it is from 20 μg / ml to 50 μg / ml; 12 hours after the infusion the concentration of vancomycin varies from 5 μg / ml to 10 μg / ml.

Mean plasma concentrations after intravenous infusion of 0.5 g of vancomycin for 60 min were approximately 33 mg / L at the end of the infusion; after 1 h about -7.3 mg / l and after 4 hours about 5.7 mg / l.

Concentrations of the drug in blood plasma with repeated administration of the drug are similar to those for a single administration.

Distribution

The volume of distribution ranges from 0.2 l / kg to 1.25 l / kg.

The volume distribution in newborns and children is similar and slightly less than in adults, and is 0.53-0.82 l / kg. As shown by ultrafiltration, at a serum concentration of 10 mg / l to 100 mg / l, vancomycin binding to plasma proteins is 30-55%. After iv introduction vancomycin is found in many tissues of the body (kidneys, liver, lungs, heart, vascular walls, abscess walls, atrial auricle tissue) and body fluids (pleural, pericardial, ascitic, peritoneal, synovial), as well as in urine in concentrations inhibiting the growth of sensitive microorganisms . Vancomycin slowly penetrates into the cerebrospinal fluid, however, the penetration rate through the blood-brain barrier directly increases proportionally 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 average half-life (T1 / 2) of 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. It can be excreted in small amounts 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 T1 / 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:

For intravenous infusion

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; with intolerance or lack of response to treatment with other antibacterial drugs, including penicillins or cephalosporins; in infections caused by microorganisms sensitive to vancomycin, but resistant to other antimicrobial agents.

Endocarditis:

- caused by Streptococcus viridans or Streptococcus bovis (as monotherapy or in combination with aminoglycosides);

- caused by enterococci, for example, Enterococcus faecalis (only in combination with aminoglycosides);

- early endocarditis caused by Staphylococcus epidermidis after valve replacement (in combination with rifampicin, aminoglycosides or both);

- prevention of endocarditis in patients with hypersensitivity reactions to antibacterial drugs of the penicillin series.

Infectious-inflammatory diseases caused by vancomycin-susceptible pathogens:

- sepsis;

- infections of the central nervous system (meningitis);

- infection of bones and joints (including osteomyelitis);

- infections of the lower respiratory tract (pneumonia, lung abscess);

- infections of the skin and soft tissues.

For oral administration

- pseudomembranous colitis caused by Clostridium difficile;

- enterocolitis caused by Staphylococcus aureus.

Contraindications:

- Hypersensitivity to vancomycin.

- Neuritis of the auditory nerve.

Carefully:

Hearing impairment (including history), kidney failure, pregnancy (I, II and III trimester), patients with allergies to teicoplanin (the possibility of a cross-allergic reaction).

Pregnancy and lactation:

The use of the drug during pregnancy is possible only by "vital" 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:

For IV infusion and ingestion.

A drug Vancomycin is introduced only in / in the drip!

A drug Vancomycin can not be administered intramuscularly or iv bolus (jet)!

With iv introduction, the recommended concentration of vancomycin is not more than 5 mg / ml, the rate of administration is not more than 10 mg / min.

Adults the drug should be administered iv in 2.0 g per day (0.5 g every 6 hours or 1.0 g every 12 hours).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 1.0 g, the maximum daily dose is 2.0 g.

Children over 1 month. the drug should be administered iv in a dose of 10 mg / kg 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 1st week of life. Starting from the 2nd week of life - every 8 hours until reaching the age of 1 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 newborns is 15 mg / kg of body weight, the daily dose for a child should not exceed the daily dose for an adult (2.0 g). Patients obese the drug is given in usual doses.

Patients with impaired renal function it is necessary to select a dose individually. To select a dose of vancomycin for this group of patients, creatinine clearance (CK) can be used.

Doses of vancomycin for patients with impaired function of the nights

CK, ml / min	Vancomycin dose, mg / day
100	1545
90	1390
80	1235
70	1080
60	925
50	770
40	620
30	465
20	310
10	155

These calculations can not be used to determine the dose of the drug in anuria. To such patients vancomycin should be given in an initial dose of 15 mg / kg body weight to quickly create therapeutic concentrations of the drug in the blood serum. The dose required to maintain a stable drug concentration is 1.9 mg / kg / day. With anuria vancomycin it is recommended to inject 1.0 g every 7-10 days.

Correction of dose 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: for KK 10-50 ml / min - 1.0 g every 3-7 days, with KK <10 ml / min - 1.0 g every 7-14 days. Preterm infants and elderly patients as a result of decreased renal function may require a significant reduction in dose.

Rules for the preparation of a solution for intravenous administration

Solution for infusion is prepared immediately before the administration of the drug. For this purpose, a necessary volume of water for injections is added to the vial of a dry, sterile lyophilizate of vancomycin. To obtain a solution with a concentration of 50 mg / ml, 0.5 g of vancomycin is diluted in 10 ml of water for injection or 1.0 g of vancomycin is diluted in 20 ml of water for injection.

The solution prepared in this way can be stored at room temperature (up to 25 ° C) for 24 hours or in a refrigerator at a temperature of 2 ° C to 8 ° C for 96 hours.

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 of the drug diluted in the above manner should be administered by fractional intravenous infusions for at least 60 minutes. As solvents, a 5% solution of dextrose (glucose) for injection or 0.9% solution of sodium chloride for injection can be used: for 0.5 g - 100 ml, for 1.0 g - 200 ml.

Before the infusion, the prepared parenteral solution should, if possible, be visually inspected for mechanical impurities and discoloration.

Preparation of solution for oral administration and its use

For the treatment of pseudomembranous colitis caused by Clostridium difficile due to the use of antibiotics, as well as for the treatment of staphylococcal enterocolitis drug Vancomycin designate inside. The recommended dose of 0.5 g is diluted in 30 ml of water.

A diluted solution may be administered for drinking or administered to a patient through a probe. Food syrup can be used to improve the taste of a solution for oral administration.

Adults appoint 0.5-2.0 g, divided into 3-4 doses, children - in a daily dose of 40 mg / kg, 3-4 times a day. The maximum daily dose should not exceed 2.0 g. The duration of treatment is 7-10 days.

In / in the introduction of vancomycin has no advantages for the treatment of these diseases. Vancomycin It is not effective for ingestion in case of other types of infections.

Side effects:

Disturbances from the organs of the blood and lymphatic system: leukopenia, reversible neutropenia, transient thrombocytopenia, agranulocytosis, eosinophilia, pancreatomy, anemia.

Immune system disorders: anaphylactic reactions.

Heart Disease: cardiac arrest.

Vascular disorders: lowering blood pressure, shock, vasculitis.

Disorders from the gastrointestinal tract: nausea, pseudomembranous colitis.

Disturbances from the liver and bile ducts: increased activity of "liver" transaminases.

Disturbances on the part of the organ of sight: transient, prolonged (up to 10 h) lacrimation.

Hearing disorders and labyrinthine disorders: transient or permanent hearing loss, hearing loss, vertigo, tinnitus.

Disturbances from the respiratory system, chest and mediastinal organs: shortness of breath, respiratory noises.

Disturbances from the skin and subcutaneous tissues: rash, itching, urticaria, exfoliative dermatitis, benign (IgA) bladder dermatosis, itching dermatosis, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis; drug rash, accompanied by eosinophilia and systemic manifestations (DRESS-syndrome).

Disorders from the kidneys and urinary tract: renal failure, manifested by an increase in the concentration of creatinine and urea nitrogen in the blood serum, interstitial nephritis, acute renal failure.

General disorders and disorders at the site of administration: phlebitis, hyperemia of the upper half of the trunk and face, spasm of the muscles of the chest and back, chills, drug fever, pain at the injection site, tissue necrosis at the site of injection.

During or soon after too rapid infusion of vancomycin, patients may develop anaphylactoid reactions (lowering blood pressure, including shock and cardiac arrest, respiratory noises, shortness of breath, skin rash, itching). Rapid administration of the drug can also cause the syndrome of "red man" (chills, fever, heart palpitations, hyperemia of the upper body and face, spasm of the muscles of the chest and back).After cessation of the infusion, these reactions usually take place within 20 minutes, but sometimes can last up to several hours.

In a number of patients who received vancomycin, symptoms of ototoxicity were observed. They can be transitory and have a permanent character. In most cases, such reactions were observed in patients with deafness and renal insufficiency in the history who received high doses of vancomycin, or in patients who received simultaneous treatment with other drugs that cause ototoxicity, for example, aminoglycosides.

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 and anesthetics there were erythema and anaphylactoid reactions (including lowering blood pressure, rash, hives, and itching).The administration of vancomycin in the form of a 60-minute infusion prior to the induction of anesthesia may reduce the likelihood of these reactions occurring. If vancomycin injected during or immediately after surgery, while simultaneously applying muscle relaxants (eg, suxamethonium iodide), then their effects (neuromuscular blockade) can be strengthened and prolonged.

With simultaneous and / or sequential systemic or topical application of other potentially ototoxic and / or nephrotoxic drugs (aminoglycosides, amphotericin B, acetylsalicylic acid or other salicylates, bacitracin, capreomycin, carmustine, paromomycin, ciclosporin, loop diuretics, polymyxin AT, cisplatin, ethacrynic acid) requires careful monitoring of the possible development of ototoxicity symptoms (tinnitus, dizziness and hearing loss) and nephrotoxicity (increased levels of creatinine and urea blood, hematuria, proteinuria, rash, eosinophilia and eosinophiluria.

Kolestyramine reduces the effectiveness of vancomycin (for oral administration).

Antihistamines, meclozine, phenothiazines, thioxanthenes can mask the symptoms of ototoxic action of vancomycin (tinnitus, dizziness and hearing loss).

Incompatibility. 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 thoroughly wash the infusion system between the procedures for the administration of these antibacterial drugs. In addition, it is recommended to reduce the concentration of vancomycin to 5 mg / ml or less.

Special instructions: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.

In some patients with inflammatory diseases of the intestinal mucosa, significant systemic absorption is possible upon admissionvancomycin orally, so there is a risk of developing adverse reactions associated with oral administration of vancomycin.

Because of potential ototoxicity and nephrotoxicity vancomycin should be used with caution in patients with renal insufficiency (it is recommended to monitor the concentration of vancomycin in the blood plasma), since at high, persistent concentrations of the drug in the blood may increase the risk of toxic effects of the drug. The maximum concentration should not exceed 40 μg / ml, the minimum concentration should be 10 μg / ml, concentrations above 80 μg / ml are considered toxic. For patients with renal failure, doses of vancomycin should be individually determined. Patients receiving vancomycin it is necessary to periodically carry out a blood test and monitor kidney function (general urine analysis, creatinine and urea nitrogen).

Vancomycin should be administered with caution to allergic patients teicoplanincases of cross-allergy have been reported. Vancomycin is an irritant, so the diffusion of the dissolved drug through the vascular wall can cause necrosis of adjacent tissues.There were thrombophlebitis, although the likelihood of their development can be reduced by slow administration of dilute solutions (with a concentration of 2.5-5.0 mg / ml) and alternating injection site.

Long-term use of vancomycin can lead to the emergence of resistant strains of bacteria and the development of superinfection.

In rare cases, the development of pseudomembranous colitis associated with Clostridium difficile, in patients who received vancomycin intravenously.

Vancomycin is poorly absorbed after oral administration, therefore it can be administered orally only for the treatment of staphylococcal enterocolitis and pseudomembranous colitis caused by Clostridium difficile.

Pediatric Use

When appointing newborns (including premature), it is recommended to control the concentration of vancomycin in the blood plasma.

Effect on the ability to drive transp. cf. and fur:

Special studies of the influence of vancomycin on the ability to drive vehicles and control mechanisms have not been carried out.

During treatment, cognitive impairment may be felt. Patients should be informed of possible dizziness associated with a drop in blood pressure.It should be recommended that they take care when driving vehicles or performing work that requires a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Lyophilisate for solution for infusion and oral administration 0.5 g and 1.0 g.

Packaging:

By 0.5 g or 1.0 g of the drug in terms of the base in flasks of colorless glass, hermetically sealed with rubber stoppers and crimped caps aluminum, or combined.

On 1 bottle together with the instruction on application place in a pack from a cardboard.

For 5 or 10 bottles with instructions for use are placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004138

Date of registration:13.02.2017

Expiration Date:13.02.2022

The owner of the registration certificate:TECHNOLOGY OF DRUGS, LTD. TECHNOLOGY OF DRUGS, LTD. Russia

Manufacturer: & nbsp

R-PHARM, JSC Russia

Representation: & nbspR-PHARM, JSC R-PHARM, JSC Russia

Information update date: & nbsp22.03.2017

Illustrated instructions

Instructions

Vancomycin (Vancomycin)