Edicyin - instructions for use, doses, side effects, contraindications

Vancomycin is a tricyclic glycopeptide antibiotic isolated from Amycolatopsis orientalis. Bactericidal action vancomycin is manifested in the ability to inhibit the biosynthesis of the bacterial cell wall, is able to change the permeability of the bacterial cell membrane and alter the synthesis of RNA.

Vancomycin blocks the synthesis of the bacterial cell wall in a region different from that of penicillins and cephalosporins (does not compete with them for binding sites), firmly linking to D-alanyl-D-alanine residues of peptidoglycan subunits (located on the outer surface of the cytoplasmic membrane), the main component of the cell wall, which leads to cell lysis.

Vancomycin is a bactericidal preparation for many gram-positive bacteria and a bacteriostatic drug for Enterococcus spp. Bactericidal effect on Enterococcus spp. is achieved by the combined use of vancomycin and aminoglycosides.

Cross-resistance between vancomycin and antibiotics of other classes is absent.

Vancomycin is active against Gram-positive microorganisms: Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus epidermidis (including their heterogeneous methicillin-resistant strains), Streptococcus spp. (Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus agalactiae and others, including penicillin-resistant strains), Enterococcus spp. (at t.h. Enterococcus faecalis), Clostridium spp., Propionibacterium acnes, Actinomyces spp., some strains Lactobacillus spp., Rhodococcus spp., Corynebacterium spp., Listeria monocytogenes.

In vitro some isolated strains Enterococcus spp. and Staphylococcus spp. may exhibit resistance to vancomycin.

In combination with gentamycin, tobramycin, rifampicin, imipenem, synergy is observed with respect to Staphylococcus aureus. In some cases, with the combination of vancomycin and rifampicin, antagonism of action against strains Staphylococcus spp., this combination of drugs shows a synergistic effect also on certain strains Streptococcus spp.

Vancomycin is not active in vitro in a relationship gram-negative microorganisms, mycobacteria and mushrooms.

The optimum action is when pH 8, with a decrease pH up to 6 the effect is sharply reduced.

The development of resistance of staphylococci during the treatment is very rare. The MIC (minimum inhibitory concentration) for most antibiotic-sensitive microorganisms is less than 5 μg / ml, the MIC value for vancomycin-resistant strains Staphylococcus aureus reaches 10-20 mg / l.

When used internally has minimal systemic effect, acts locally on the sensitive microflora in the gastrointestinal tract (GIT) (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 500 mg every 6 hours varies between 2.4 and 3 mg / l.

After intravenous administration of vancomycin in a dose of 500 mg 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), an hour after administration, it drops to 7.3 mg / l.

After intravenous administration of vancomycin in a dose of 1 g, the concentration of the drug in the blood plasma is doubled; immediately after administration, it ranges from 20 to 50 mg / ml; 12 hours after the infusion the concentration of vancomycin varies from 5 to 10 μg / ml.

Mean plasma concentrations after IV infusion of 500 mg of vancomycin for 60 minutes 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 in blood plasma with repeated administration are similar to those in blood plasma with a single administration.

Distribution

The volume of distribution varies from 0.2 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, with 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 auricles) and body fluids (pleural, pericardial, ascitic, peritoneal, synovial fluids), as well as in urine in growth inhibitory concentrations 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

Vancomycin is practically not metabolized.

Excretion

The half-life (T_1/2) vancomycin from plasma is an average of 4-6 hours (3-9 hours) in adult patients with normal renal function; preterm infants - 9.8 hours; in newborns - 6.7 hours; in children aged 4 months - 4 hours; in children aged 3 years - 2.4 h; in children aged 7 years, 2.2 hours. 80-90% of the administered dose of vancomycin is excreted by the kidneys due to glomerular filtration in the first 24 hours in unchanged form.

In small amounts (less than 5%) can be excreted with bile. In small amounts, it is excreted in hemodialysis or peritoneal dialysis. In adults, the total clearance of vancomycin is 0.7-3.1 ml / s. In children, the clearance of vancomycin is higher and reaches the maximum values at the age of 3.9 years (about 3 ml / s).

Pharmacokinetics in special clinical cases

Impaired renal function slows the excretion of vancomycin, therefore, such patients require a dose adjustment. In patients with a deleted or missing kidney, the average 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:

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 antibiotics, 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 antibiotics);

- prevention of endocarditis in patients with hypersensitivity reactions to penicillin antibiotics.

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.

Vancomycin is also used as a solution for oral administration to treat:

- pseudomembranous colitis caused by Clostridium difficile;

- enterocolitis, caused by Staphylococcus aureus.

Contraindications:

- Increased individual sensitivity to vancomycin;

- neuritis of the auditory nerve;

- I trimester of pregnancy and lactation (breastfeeding).

Carefully:

The drug should be prescribed to patients with impaired hearing (including in history) and kidney failure, patients with allergies to teicoplanin (the possibility of cross-allergy), in the II and III trimesters of pregnancy.

Pregnancy and lactation:

The drug is contraindicated in the first trimester of pregnancy. Application in the II and III trimesters of pregnancy is possible only for "vital" indications in the case when the expected benefit of therapy for the mother exceeds the potential risk to the fetus.

If it is necessary to use the drug during lactation, breastfeeding should be stopped for the duration of the drug treatment.

Dosing and Administration:

Preparation Edicyin® is administered only intravenously drip!

Preparation Edicyin^® can not be administered intramuscularly or intravenously bolus (jet)!

Adults and children over 12 years of age: with normal renal function, the drug is prescribed in a daily dose of 2 g IV (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 and for at least 60 minutes. Age, 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 from 1 month to 12 years: the recommended dose is 40 mg / kg body weight per day, divided into individual administrations (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, followed by 10 mg / kg every 12 hours during the first week of life. Beginning from the second week of life - every 8 hours before reaching age 1 month. Each dose should be administered for at least 60 minutes, constant monitoring of the concentration of vancomycin in the serum is required.

The concentration of the prepared vancomycin solution should not exceed 2,5-5 mg / ml.

The maximum daily dose for a child should not exceed the daily dose for an adult (2 g).

Patients with impaired renal function it is necessary to individually select the dose. Selection of a dose of vancomycin for this group of patients can be carried out under the control of serum creatinine. Correction can be carried out by increasing the intervals between administrations, or by reducing the single dose of the drug.

Correction by increasing the intervals between administrations

Creatinine clearance (ml / min)	Vancomycin Dose	Interval between doses
>80	500 mg or 1 g	12h
80-50	1 g	24 h
50-10	1 g	3-7 days
<10 (anuria)	1 g	7-14 days

Have elderly patients clearance of vancomycin below, the volume of distribution is greater. In this category of patients, it is advisable to select the dose based on the concentrations of vancomycin in the serum.

Have premature infants and elderly patients in cLigament with impaired renal function may require a significant dose reduction. The concentration of vancomycin in the blood plasma should be monitored regularly. The table below shows the doses of vancomycin depending on the QC.

Single dose adjustment

Creatinine clearance kk (ml / min)	Dose of vancomycin (mg / day)
100	1545
90	1390
80	1235
70	1080
60	925
50	770
40	620
30	465
20	310
10	155

When anuria this table can not be used to determine the dose of the drug. For anuria, the drug should be given at an initial dose of 15 mg / kg body weight to quickly create therapeutic concentrations of vancomycin in the serum. The dose necessary to maintain a stable drug concentration is 1.9 mg / kg / day.

Patients with severe renal insufficiency it is advisable to administer maintenance doses of 250 to 1000 mg once every few days: with KK 10-50 ml / min - 1 g every 3-7 days, with QC < 10 ml / min - 1 g every 7-14 days. When anuria a dose of 1 g is recommended 7-10 days.

When only the concentration of creatinine (CC) in the blood serum is known, the following formula can be used to calculate the creatinine clearance:

For men: (body weight (kg)) x (140 - age (years))/72 x KK in serum (mg / 100 ml)

For women: the result is multiplied by 0.85.

Patients on hemodialysis: initial dose (when used (high - flux membrane) is 20-25 μg / kg. Supportive doses should be administered based on the residual plasma concentration of the drug (the dose is adjusted to maintain a residual drug concentration of approximately 15-20 μg / ml).

Vancomycin is effectively removed during hemodialysis using high - flux membranes (such as polysulfone). When using membranes with normal permeability (low - flux membranes) vancomycin is displayed poorly.

Patients with hepatic insufficiency no dose adjustment is required.

Rules for the preparation of 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 the vancomycin with a dry, sterile lyophilizate to obtain a solution with a concentration of 50 mg / ml: 500 mg of vancomycin is diluted in 10 ml of water for injection, 1 g of vancomycin in 20 ml.

The solution so prepared can be stored at room temperature 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 vancomycin diluted in the above manner should be administered by fractional IV infusion for at least 60 minutes. As solvents, 5% solution of dextrose (glucose) for injection or 0.9% solution of sodium chloride for injection: for 500 mg - 100 ml, for 1 g - 200 ml.

Before injection, the prepared solution for parenteral administration should be checked visually, if possible, 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, Edicyin® is administered orally. The recommended dose of 500 mg 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 500 mg - 2 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 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 is ineffective when taken orally in case of other types of infections.

Side effects:

According to the World Health Organization (WHO), undesirable effects are classified according to their frequency of development as follows: very often (≥1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, < 1/100), rarely (≥1 / 10000, <1/1000) and very rarely (<1/10000); frequency is unknown (the frequency of occurrence of phenomena can not be determined on the basis of available data).

The most frequent adverse reactions associated with too rapid intravenous administration of vancomycin were phlebitis and post-fusion reactions.

During rapid infusion of the drug or immediately after it, postinfusion reactions may occur. After cessation of the infusion, these reactions usually take place within 20 minutes -2 hours.

From the sense organs:

often: ototoxicity - temporary or persistent hearing loss, vertigo (ototoxicity was mainly described in patients who received high doses of vancomycin or in patients who received simultaneous treatment with other drugs with possible development of ototoxicity, as well as in patients with severe hearing impairment or renal function);

rarely: noise in the ears, dizziness.

From the urinary system:

often: renal failure, primarily manifested by an increase in plasma concentrations of creatinine or urea nitrogen;

rarely: interstitial nephritis, acute renal failure.

Gastrointestinal-intestinal tract:

often: nausea;

rarely: pseudomembranous colitis.

On the part of the organs of hematopoiesis:

often: neutropenia;

rarely: thrombocytopenia, agranulocytosis, eosinophilia.

From the immune system:

rarely: Anaphylactic reactions (decreased blood pressure, bronchospasm, shortness of breath, skin rash, itching), hypersensitivity reactions.

From the cardiovascular system:

often: lowering of arterial pressure, thrombophlebitis;

rarely: vasculitis;

rarely: heart failure.

From the respiratory system:

often: shortness of breath, stridor.

From the skin:

often: exanthema, inflammation of the mucous membranes, itching, red man syndrome, associated with the release of histamine (chills, fever, heart palpitations, hyperemia of the upper body and face, spasm of the muscles of the chest and back), urticaria;

rarely: exfoliative dermatitis, Stevens-Johnson syndrome, Lyell syndrome, and linear dermatosis.

Other:

rarely: fever, chills;

frequency unknown: phlebitis, pain and irritation at the injection site, tissue necrosis at the injection site.

Overdose:

Symptoms: intensification of the expression of dose-dependent side effects from the urinary and sensory systems.

Treatment: there is no specific antidote. It is recommended to cancel the drug or reduce the dose. Conducted symptomatic therapy, aimed at maintaining glomerular filtration. It is recommended to administer the liquid and monitor the plasma concentrations of vancomycin.

Vancomycin is poorly removed by dialysis.There is evidence that hemofiltration and hemoperfusion through polysulfone ion exchange resin lead to an increase in vancomycin clearance.

Interaction:

With simultaneous intravenous administration of vancomycin and anesthetics may appear erythematous rashes, hyperemia of the skin of the face, anaphylactoid reactions, there is a risk of lowering blood pressure or the development of neuromuscular blockade. The introduction 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 consistent systemic or local application of other potentially ototoxic and / or nephrotoxic drugs (aminoglycosides, amphotericin B, aminosalicylic acid or other salicylates, bacitracin, capreomycin, carmustine, paromomycin, ciclosporin, "loop" diuretics, polymyxin AT, cisplatin, ethacrynic acid) requires careful monitoring of the possible development of these symptoms.

Kolestyramine reduces the activity of vancomycin (if ingested). Antihistamines, meclozine, phenothiazines, thioxanthenes can mask the symptoms of ototoxic action of vancomycin (tinnitus, vertigo).

Pharmaceutical interaction

Vancomycin solution is low pH, which can cause physical or chemical instability when mixed with other solutions. Avoid mixing with alkaline solutions.

It is not recommended to mix or simultaneously use a solution of vancomycin with chloramphenicol, glucocorticoids, methicillin, aminophylline, cephalosporins and phenobarbital.

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 IV in the system between the applications of these antibiotics. In addition, it is recommended to reduce the concentration of vancomycin solution to 5 mg / ml or less.

Special instructions:

Use only in a hospital!

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.

Carefully should be applied vancomycin in patients with renal insufficiency (it is recommended to control the concentrations of vancomycin in blood plasma in renal failure in patients older than 60 years), since at high concentrations of the drug remaining in the blood for a long time, the risk of toxic effects of the drug may increase; 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.

Vancomycin should be administered with caution to allergic patients teicoplanin, t. cases of cross-allergy have been reported.

With prolonged use of vancomycin, an audiogram, a control of the peripheral blood picture, kidney function (general urine analysis, creatinine and urea nitrogen) is necessary.

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 introduction of dilute solutions (with a concentration of 2.5-5 mg / ml) and alternation of injection sites.

Pediatric Use

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

Special precautions for the destruction of unused medicinal product

There is no need for special precautions when destroying an unused Edicyin® preparation.

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

The influence of vancomycin on the management of vehicles and the employment of other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions have not been studied.

Form release / dosage:

Lyophilizate for solution for infusion, 0.5 g and 1.0 g.

Packaging:

By 0.5 g or 1 g of active substance into vials of colorless glass (hydrolytic glass, corresponding to class I according to Eur.F.), closed with rubber stoppers and crimped with aluminum caps with plastic caps.

1 bottle together with instructions for medical use placed in a cardboard box.

For 10 vials together with the instruction for use are placed in a cardboard box with a cardboard holder.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N010233

Date of registration:13.08.2010

The owner of the registration certificate: Lek dd Lek dd Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp12.12.2015

Illustrated instructions

Instructions

Edicyin® (Edicin®)