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

Vancomycin is a chromatographically purified tricyclic glycopeptide antibiotic isolated from Amycolatopsis orientalis. 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 alter the synthesis of RNA. Cross-resistance between vancomycin and antibiotics of other classes is absent.

In vitro Vancomycin usually shows activity 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, group viridance, Streptococcus bovis and enterococci (for example, Enterococcus faecalis), Clostridium difficile (eg, toxigenic strains taking part in the development of pseudomembranous enterocolitis) and diphtheria. To other microorganisms that are sensitive to vancomycin in vitro relate Listeria monocytogenes, bacterial genera 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 aminoglycoside is synergistic in vitro for many strains Staphylococcus aureus, streptococci groups D, not belonging to enterococci, enterococci and bacteria of the group Streptococcus (group of viridance).

Vancomycin is inactive in vitro against gram-negative bacilli, mycobacteria and fungi.

Pharmacokinetics:

In persons with normal renal function, repeated intravenous administration of 1 g of vancomycin (15 mg / kg) (infusion over 60 minutes) creates average plasma concentrations of about 63 mg / L immediately after completion of the infusion; 2 hours after the infusion the average plasma concentrations are about 23 mg / l, and 11 hours after the infusion - about 8 mg / l. Multiple infusions of 500 mg administered over 30 minutes create average plasma concentrations of about 49 mg / L after the infusion is complete; 2 hours after the infusion the average plasma concentrations are 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 half-life of 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%. The volume of distribution varies 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 in peritoneal fluid at concentrations inhibiting the growth of microorganisms. Vancomycin slowly penetrates into the cerebrospinal fluid. When meningitis, the drug penetrates 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 average half-life 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

Vancocin® is effective both in monotherapy and in combination with aminoglycosides for the treatment of endocarditis caused by Streptococcus viridans or S. bovis. With endocarditis caused by enterococci (for example, E. faecalis), vancocin is effective only in combination with aminoglycosides.

There is evidence that Vancocin® is effective in treating diphtheria endocarditis. Vancocin® 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, Vancocin® is indicated for the prevention of endocarditis.

- Sepsis

- Infections of bones and joints

- Infections of the lower respiratory tract

- Infections of the skin and soft tissues

Vancomycin can also be used for infections caused by Gram-positive microorganisms in cases of penicillin allergy, intolerance or lack of response to treatment with other antibiotics, including penicillins or cephalosporins, and infections caused by microorganisms sensitive to vancomycin but resistant to other antimicrobial drugs.

- Pseudomembranous colitis is like a solution for ingestion (see section "Method of administration and dose").

Contraindications:

- Established hypersensitivity to vancomycin.

- Heuryt of the auditory nerve.

Carefully:

In case of hearing impairment (including anamnesis), renal failure, as well as in patients with allergy to teicoplanincases of cross-allergy have been reported.

Pregnancy and lactation:

The safety of vancomycin in human use during pregnancy has not been investigated. Evaluation of the results of experimental animal studies did not reveal a direct or indirect negative effect of vancomycin on the embryo or fetus, the course of pregnancy, and peri- and postnatal development.

Vancomycin should be given to pregnant women only if the expected benefit to the mother exceeds the potential risk to the fetus.

If you need to take the drug during breastfeeding, you should stop feeding for the duration of treatment with the drug.

Dosing and Administration:

Intravenously infuzionalno.

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 intravenously (500 mg every 6 hours or 1 g every 12 hours). Each dose should be administered at a rate of not more than 10 mg / min or 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 intravenously every 6 hours. Each dose should be administered for at least 60 minutes.

Young children and newborns

For newborns, 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. The drug should be administered for at least 60 minutes. The dosing regimen for vancomycin in neonates is shown in the following table.

Recommendations for dosing of vancomycin in newborns

VNSB^a	Chronological age	Serum Creatinine	Dose
(Weeks)	(Days)	Concentration (mg / dL)^b	(mg / kg)
<30	≤7	-------^at	15 every 24 hours
	>7	<1,2	10 every 12 hours
30-36	≤14	-------^at	10 every 12 hours
	>14	≤0,6	10 every 8 hours
		0,7 - 1,2	10 every 12 hours
>36	≤7	-------^at	10 every 12 hours
	>7	≤0,6	10 every 8 hours
		0,7 -1,2	10 every 12 hours

^a VNSB = age from the moment of the onset of pregnancy (the age of intrauterine development plus the chronological age).

^b If the serum creatinine concentration is> 1.2 mg / dl, an initial dose of 15 mg / kg every 24 hours is used.

^at To determine the dose for these patients, do not use the serum creatinine concentration, since this indicator in this case is not informative or because of the lack of information. In such patients, it is advisable to carefully monitor the concentration of vancomycin in the serum.

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 ground clearance and a larger 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, as can be expected. The concentration of vancomycin in the serum should be monitored regularly. In the table below, doses of vancomycin are indicated depending on the creatinine clearance.

Table of doses of vancomycin for patients
with impaired renal function
Creatinine clearance ml / min	Dose of vancomycin mg / 24 hours
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 drug concentration is 1.9 mg / kg / 24 hours. Patients with severe renal failure should be administered maintenance doses of 250-1000 mg once every few days. With anuria, a dose of 1 g is recommended every 7-10 days.

Preparation for introduction

Preparation of a solution for intravenous administration

Solution for injection is prepared immediately before the administration of the drug. To do 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.REQUIRED FURTHER DILUTION of the prepared solution. 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 vancomycin diluted in the above manner should be administered by fractional intravenous infusions 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 administration, the prepared solution should be visually checked for mechanical impurities and discoloration.

Preparation of solution for oral administration

Vancomycin can be used orally to treat pseudomembranous colitis caused by FROM. difficile, due to the use of antibiotics, as well as for the treatment of staphylococcal enterocolitis. Intravenous administration of vancomycin does not have advantages for the treatment of these diseases. Vancomycin It is not effective for ingestion in case of other types of infections. The appropriate dose can be prepared in 30 ml of water and allow the patient to drink it or enter through a probe. To improve the taste of the solution, ordinary food syrups can be added to it.

Side effects:

Organism as a whole: anaphylactoid reaction, a rash accompanied by eosinophilia and systemic manifestations.

Heart Disease: heart failure, blood flushes, lowering blood pressure (BP), shock (these symptoms are mainly associated with rapid infusion of the drug).

Infringements from digestive system: nausea, pseudomembranous colitis, increase in concentration hepatic transaminases.

Violations of the blood and lymphatic systems: agranulocytosis, eosinophilia, neutropenia, thrombocytopenia, pancytopenia, anemia, and leukopenia.

Disorders from the kidneys and urinary tract: interstitial nephritis, changes in the indices of functional renal tests, impaired renal function.

Disturbances from the skin and subcutaneous tissues: exfoliative dermatitis, benign (IgA) blistering dermatosis, itching dermatosis, rash, "Red man" syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, hives, vasculitis.

Impaired sensory organs: ototoxic effects.

In a number of patients who received vancomycin, such symptoms of ototoxicity as tinnitus, dizziness and hearing loss were observed. They can be transitory or of a permanent nature. The majority of such cases were observed in patients receiving 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, tissue necrosis at the injection site, pain at the site of infections, thrombophlebitis.

During or shortly after too rapid infusion of vancomycin in patients may develop anaphylactoid reactions. Rapid introduction of the drug may also cause a syndrome "Red Man", reddening of the upper body or chest pain and spasm of the muscles and the back. After discontinuation of the infusion, these reactions usually take place within 20 minutes, but sometimes can last up to several hours.

Overdose:

Treatment: Corrective 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 simultaneous intravenous administration of vancomycin and anesthetics, erythema, histamine-like reddening 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, 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 symptoms of ototoxicity (tinnitus, dizziness and hearing loss) and nephrotoxicity (increased levels of creatinine and urea blood, hematuria, proteinuria, rash, eosinophilia and eosinophiluria).

Kolestyramin reduces activity.

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 Vancocine 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 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.

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.

Hematology and kidney function monitoring. Patients receiving vancomycin intravenously, a blood test and kidney function monitoring should be performed periodically.

Renal failure. Vancomycin should be used with caution in patients with renal insufficiency, since high,long-term concentrations of the drug in the blood can increase the risk of toxic effects of the drug. For patients with renal insufficiency, doses of vancomycin should be selected individually.

Local Reactions. Vancomycin has an irritating effect, and therefore getting the drug into the tissue adjacent to the vessel can cause them to necrosis. There may be thrombophlebitis, although the likelihood of their development can be reduced by slow administration of solutions with a low concentration (2.5-5 g / l) and alternation of injection sites.

Form release / dosage:Lyophilizate for solution for infusion, 500 mg.

Packaging:

In a vial of neutral transparent glass (type I), sealed with a rubber stopper under an aluminum roll.

One bottle together with the instruction for use is placed in a pack of cardboard.

Storage conditions:

Store at a temperature of 15-25 ° C.

Prepared drug solution: Store in the refrigerator at a temperature of 2-8 ° C for no more than 14 days.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N014757 / 01

Date of registration:17.03.2008

Expiration Date:Unlimited

Date of cancellation:2016-10-03

The owner of the registration certificate:Eli Lilly East SAEli Lilly East SA Switzerland

Manufacturer: & nbsp

VIANEX, S.A. Greece

Representation: & nbspELI LILLY EAST SA ELI LILLY EAST SA Switzerland

Information update date: & nbsp22.01.2017

Illustrated instructions

Instructions

Vancocin® (Vancocin®)