Vancomycin lyophilized powder for solution for infusion 500 mg vial No. 1

Instructions Vancomycin lyophilized powder for solution for infusion 500 mg vial No. 1

Composition

active ingredient: vancomycin;

1 vial contains vancomycin hydrochloride equivalent to 500 mg or 1000 mg of vancomycin;

Excipients: sodium hydroxide, hydrochloric acid, water for injections.

Dosage form

Lyophilisate for solution for infusion.

Main physicochemical properties:

Lyophilized powder or mass from white to yellow-brown.

Pharmacotherapeutic group

Antimicrobial agents for systemic use. Glycopeptide antibiotics.

ATX code J01X A01.

Pharmacological properties

Pharmacodynamics

Vancomycin is a tricyclic glycopeptide antibiotic obtained from Amycolatopsis orientalis, effective against many gram-positive microorganisms. The bactericidal action of vancomycin is to inhibit bacterial cell wall synthesis by inhibiting glycopeptide polymerization and selectively inhibiting bacterial RNA synthesis. There is no cross-resistance between vancomycin and other antibiotics. Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi.

The combination of vancomycin and an aminoglycoside acts synergistically in vitro against many strains of Staphylococcus aureus, Streptococcus bovis, enterococci, and viridans streptococci.

Vancomycin has been shown to be effective against most strains of the following microorganisms, both in vitro and in clinical infections, as described in the section "Method of administration and dosage".

Aerobic Gram-positive microorganisms

Diphtheroids Enterococci (e.g., Enterococcus faecalis) Staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis (including heterogeneous methicillin-resistant strains) Streptococcus bovis Viridans group streptococci

The following in vitro data are available, but their clinical significance is unknown.

Vancomycin has demonstrated in vitro MICs (minimum inhibitory concentrations) of 1 μg/mL or less against most (≥ 90%) of the following strains of streptococci and MICs of 4 μg/mL or less against most (≥ 90%) of the other listed organisms; however, the safety and efficacy of vancomycin in the treatment of clinical infections caused by these organisms have not been established in adequate and well-controlled clinical trials.

Aerobic Gram-positive microorganisms

Listeria monocytogenes

Streptococcus pyogenes

Streptococcus pneumoniae (including penicillin-resistant strains)

Streptococcus agalactiae

Anaerobic Gram-positive microorganisms

Actinomyces species

Lactobacillus species

Pharmacokinetics

Vancomycin is poorly absorbed after oral administration.

In patients with normal renal function, multiple intravenous administration of 1 g vancomycin (15 mg/kg), administered over 60 minutes, produces mean plasma concentrations of approximately 63 μg/mL immediately after the end of the infusion, 23 μg/mL 2 hours after the infusion, and 8 μg/mL 11 hours after the end of the infusion. Multiple administration of 500 mg, administered over 30 minutes, produces mean plasma concentrations of approximately 49 μg/mL at the end of the infusion, 19 μg/mL 2 hours after the infusion, and 10 μg/mL 6 hours after the infusion. Plasma concentrations during multiple administration are similar to those after a single dose.

The mean plasma half-life of vancomycin is 4 to 6 hours in patients with normal renal function. In the first 24 hours, approximately 75% of the administered vancomycin dose is excreted in the urine by glomerular filtration. The mean plasma clearance is approximately 0.058 L/kg/h, and the mean renal clearance is approximately 0.048 L/kg/h. Renal dysfunction slows the elimination of vancomycin. In patients with a removed kidney, the mean half-life is 7.5 days. The distribution coefficient is 0.3 to 0.43 L/kg. There is no apparent metabolism of the drug. Approximately 60% of an intraperitoneal dose of vancomycin administered during peritoneal dialysis is absorbed systemically within 6 hours. Serum concentrations of about 10 μg/mL are achieved after intraperitoneal injection of 30 mg/kg vancomycin.

However, the safety and efficacy of intraperitoneal administration of vancomycin have not been established in adequate and well-controlled studies (see section "Special warnings and precautions for use").

The total systemic and renal clearance of vancomycin may be reduced in the elderly.

Approximately 55% of administered vancomycin is bound to plasma proteins at serum vancomycin concentrations of 10 to 100 μg/mL. After intravenous administration of vancomycin, inhibitory concentrations are present in pleural, pericardial, ascitic, and synovial fluids; in urine; in peritoneal dialysis fluid; and in atrial appendage tissue. Vancomycin does not readily diffuse across normal meninges into the cerebrospinal fluid; however, when the meninges are inflamed, penetration into the cerebrospinal fluid occurs.

Indication

- For the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (β-lactam-resistant) staphylococci.

- For the treatment of infections caused by vancomycin-sensitive microorganisms resistant to other antimicrobial drugs.

- For the treatment of staphylococcal endocarditis caused by S. viridans or S. bovis. For endocarditis caused by enterococci (e.g. E. faecalis), vancomycin is effective only in combination with aminoglycosides.

- For the treatment of diphtheria endocarditis.

- For the treatment of early prosthetic valve endocarditis caused by S. epidermidis or diphtheriae, in combination with rifampin, an aminoglycoside, or both.

- For the treatment of other infections caused by staphylococci, including septicemia, bone infections, lower respiratory tract infections, skin and skin structure infections.

- For the treatment of localized purulent staphylococcal infections as an adjunct to appropriate surgical measures.

- For the treatment of antibiotic-associated pseudomembranous colitis caused by Clostridium difficile (oral use).

Contraindication

Hypersensitivity to vancomycin or to any other component of the drug.

Interaction with other medicinal products and other types of interactions

Concomitant use of vancomycin and anesthetics has been associated with erythema, histamine-like hyperemia (see section "Special warnings and precautions for use") and anaphylactoid reactions (see section "Adverse reactions").

Monitoring of renal function is recommended in patients receiving concomitant or sequential vancomycin and other potentially neurotoxic and/or nephrotoxic systemic or topical agents such as amphotericin B, aminoglycosides, bacitracin, polymyxin B, colistin, viomycin or cisplatin (see section 4.4). Due to synergistic effects with gentamicin, the maximum dose of vancomycin should be limited to 500 mg every 8 hours.

When vancomycin is administered during or immediately after surgery, the effects of muscle relaxants, such as succinylcholine, may be increased or prolonged. Vancomycin should not be mixed with aminophylline or fluorouracil, as vancomycin may be significantly reduced over time. The combination of vancomycin with aminoglycosides has been shown to be synergistic in vitro against Staphylococcus aureus, non-enterococcal group D streptococci, enterococci, and Streptococcus species (various species). Drugs that reduce intestinal motility are contraindicated in pseudomembranous colitis. Cholestyramine reduces the effectiveness of vancomycin.

Concomitant use of vancomycin and piperacillin/tazobactam may result in acute renal failure.

Application features

Infusion site reactions.

Rapid bolus administration (e.g. over a few minutes) may be associated with excessive hypotension, including shock and, rarely, cardiac arrest. Therefore, the patient's blood pressure should be monitored during administration to reduce the risk of hypotensive reactions.

Vancomycin should only be used intravenously due to the risk of soft tissue necrosis.

Vancomycin hydrochloride for injection should be administered as a diluted solution over a period of at least 60 minutes to prevent infusion reactions. Discontinuation of the infusion usually results in rapid resolution of these reactions. Reactions related to the rate of drug administration may occur at any concentration and rate of administration and resolve after completion of drug administration.

Nephrotoxicity.

Vancomycin should be used with caution in patients with renal insufficiency, including anuria, as the potential for toxic effects is much greater with prolonged maintenance of high blood concentrations of the drug. The risk of toxicity increases with high blood concentrations of the drug or with prolonged therapy.

Regular monitoring of vancomycin blood concentrations is indicated when using high doses of the drug and during prolonged use, in particular in patients with impaired renal function or hearing impairment, as well as with concomitant use of nephrotoxic substances (in particular piperacillin/tazobactam) (see sections “Method of administration and dosage” and “Interaction with other medicinal products”).

Systemic exposure to vancomycin can lead to the development of acute kidney injury (AKI). The risk of AKI increases with increasing systemic exposure/serum concentration of the drug. Monitoring of renal function is necessary in all patients, especially in patients with pre-existing renal impairment, patients with concomitant diseases that predispose to the development of renal failure, as well as in patients taking concomitant nephrotoxic drugs.

Ototoxicity.

Vancomycin dosage should be adjusted for patients with renal dysfunction (see section "Method of administration and dosage").

Severe skin adverse reactions.

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, which may be fatal, have occurred in patients treated with vancomycin (see section 4.8). Reported cutaneous symptoms include skin rash, mucosal lesions and blisters. The majority of these reactions occurred within a few days to 8 weeks of starting vancomycin.

When prescribing vancomycin, patients should be informed of the symptoms of dangerous skin reactions. If such reactions are suspected or symptoms occur, vancomycin should be discontinued immediately and alternative treatment should be considered. If a patient has a history of serious skin reactions to vancomycin, vancomycin should never be prescribed again.

Clostridioides difficile-associated diarrhea (CDAD)

Clostridioides difficile-associated diarrhea has been reported with nearly all antibacterial agents, including vancomycin. This diarrhea can range in severity from mild diarrhea to fatal colitis. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections may be refractory to antimicrobial therapy and may require colectomy. The possibility of CDAD should be considered in all patients who present with diarrhea following antibiotic use. Because CDAD has been reported to occur within two months of antibiotic administration, the patient's medical history should be carefully reviewed.

If CDAD is suspected or confirmed, ongoing use of antibiotics not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte monitoring, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be considered as appropriate for the clinical presentation of the patient.

Eye disorders

Vancomycin is not intended for intracameral or intravitreal use.

Hemorrhagic occlusive retinal vasculitis

Hemorrhagic occlusive retinal vasculitis, including irreversible vision loss, has occurred in patients receiving vancomycin during or after cataract surgery by the intracameral or intravitreal route. The safety and efficacy of vancomycin by the intracameral or intravitreal route of administration have not been established. Vancomycin is not indicated for the prophylaxis of endophthalmitis.

Clinically significant serum concentrations have been observed in some patients treated for active pseudomembranous colitis caused by C. difficile after multiple oral doses of vancomycin.

Prolonged use of vancomycin may result in overgrowth of nonsusceptible organisms. Close patient monitoring is essential. If superinfection develops during therapy, appropriate measures should be taken.

In rare cases, pseudomembranous colitis due to C. difficile has been reported in patients receiving intravenous vancomycin.

Serial tests of auditory function may be useful to minimize the risk of ototoxicity.

Reversible neutropenia has been reported in patients receiving vancomycin (see section 4.8). White blood cell counts should be monitored periodically in patients receiving prolonged vancomycin therapy and in patients receiving concomitant medications that may cause neutropenia.

Vancomycin is a tissue irritant and should therefore only be administered intravenously. Pain, tenderness and tissue necrosis may occur with intramuscular administration or hemorrhage. Thrombophlebitis may occur, the frequency and severity of which can be minimized by administering the diluted solution (2.5–5 g/L) slowly and by rotating the injection site.

The incidence of infusion-related complications (including hypotension, flushing, flushing, urticaria, and pruritus) increases with concomitant administration of anesthetics, therefore it is recommended that anesthesia be initiated after completion of a slow (60 min) vancomycin infusion.

The safety and efficacy of vancomycin by intrathecal (intralumbar or intraventricular) routes of administration have not been established.

There have been reports of cases where the administration of sterile vancomycin intraperitoneally during continuous ambulatory peritoneal dialysis (CAPD) has resulted in a chemical peritonitis syndrome. The syndrome was characterized by the appearance of opaque dialysate, which may be accompanied by varying degrees of abdominal pain and fever. This syndrome is transient and resolves after discontinuation of intraperitoneal vancomycin.

Prescribing vancomycin in the absence of a proven or reasonably suspected bacterial infection or for prophylaxis is unlikely to benefit the patient and instead increases the risk of the proliferation of drug-resistant bacteria.

In children, confirmation of desired serum vancomycin concentrations would be appropriate. Concomitant use of vancomycin and anesthetic agents has been associated with erythema and histamine-like hyperemia in children.

Elderly patients.

The natural decline in glomerular filtration rate with age may result in increased serum vancomycin concentrations if dosage is not adjusted. Vancomycin dosage should be adjusted for elderly patients.

Liver function should be monitored because liver disease may be exacerbated by vancomycin therapy with elevations in bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and, occasionally, lactate dehydrogenase and gamma-glutamyltransferase.

Vancomycin should be used with caution in patients with allergic reactions to teicoplanin, as cases of cross-allergic reactions have been described. In some patients with inflammatory diseases of the intestinal mucosa, significant systemic absorption is possible when vancomycin is taken orally. Therefore, there is a risk of developing adverse reactions associated with parenteral use of vancomycin. Vancomycin should be used with particular caution in premature infants due to the immaturity of their renal system, which may result in an increase in serum concentrations of vancomycin.

It is recommended to monitor the concentration of vancomycin in the serum of premature newborns and infants.

Burn patients have been shown to have a higher overall clearance of vancomycin and therefore require more frequent and increased doses. Individualized vancomycin dosing and close monitoring are recommended in these patients.

Information for patients

Patients should be advised that antibacterial drugs, including vancomycin hydrochloride for injection, should be used only to treat bacterial infections. These drugs will not treat viral infections (such as the common cold). If vancomycin is prescribed to treat a bacterial infection, patients should be advised that although they will usually feel better at the beginning of the course of treatment, they should continue to take the drug exactly as prescribed. Skipping doses or not completing the full course of therapy may result in decreased effectiveness of the treatment and an increased likelihood of bacteria developing resistance that will no longer respond to vancomycin hydrochloride for injection or other antibacterial drugs in the future.

Diarrhea caused by antibiotics usually goes away after the antibiotics are stopped. Sometimes, after starting antibiotic treatment, patients may experience watery, bloody stools (accompanied by stomach cramps, with or without fever), even two or more months after the last dose of the antibiotic. If this occurs, the patient should contact their doctor immediately.

Use during pregnancy or breastfeeding

Pregnancy

Animal reproductive studies have not been conducted with vancomycin. It is unknown whether vancomycin can affect reproductive capacity.

A controlled clinical trial evaluated the potential ototoxic and nephrotoxic effects of vancomycin on infants when administered to pregnant women for the treatment of serious staphylococcal infections associated with intravenous drug abuse. Vancomycin was detected in cord blood. No sensorineural hearing loss or nephrotoxicity related to vancomycin was noted. One infant whose mother had taken vancomycin in the third trimester experienced conductive hearing loss that was not attributed to vancomycin exposure. Because the number of patients treated in this study was limited and vancomycin was administered only in the second and third trimesters, it is unknown whether vancomycin causes fetal harm. Vancomycin should be prescribed during pregnancy only for vital indications, when the expected benefit to the mother outweighs the risk to the fetus, and it is necessary to monitor the concentration of vancomycin in the blood serum.

Breastfeeding period

The drug passes into breast milk. Caution should be exercised during breastfeeding. Due to the possible occurrence of adverse reactions, a decision should be made to discontinue vancomycin or discontinue breastfeeding, depending on the need for its use for the mother.

Ability to influence reaction speed when driving vehicles or other mechanisms

During the period of use of the drug, the ability to concentrate may decrease, which should be taken into account when driving a car or performing work that requires increased attention.

Method of administration and doses

Reactions to the administration of the drug may depend on both the concentration of the solution and the rate of its administration. For the treatment of adults, it is recommended that the concentration during administration does not exceed 5 mg/ml and the rate of administration does not exceed 10 mg/min. In individual patients who need to limit the amount of fluid administered, the drug can be administered with a concentration of up to 10 mg/ml, but the rate of administration should not exceed 10 mg/min. Infusion rates of 10 mg/min or less are associated with a lower incidence of infusion-related adverse events (see section "Adverse reactions"). However, infusion-related adverse reactions can occur at any infusion rate or concentration.

The duration of treatment depends on the therapeutic indications for which the drug is used.

Patients with normal renal function

The usual daily dose for intravenous administration is 2 g, administered as 500 mg every 6 hours or 1 g every 12 hours. Each dose should be administered at a rate not exceeding 10 mg/min or over a period of at least 60 minutes, whichever is longer. Other patient-related factors, such as age or obesity, may require modification of the usual daily intravenous dose.

Children

The usual dose of vancomycin is 10 mg/kg body weight every 6 hours. The solution should be administered over at least 60 minutes. Close monitoring may be warranted in these patients.

vancomycin serum concentrations.

Newborns

The maximum daily dose may be reduced.

Newborns up to 7 days old: the initial dose is 15 mg / kg body weight, then 10 mg / kg body weight every 12 hours.

Neonates aged 7 days to 1 month: Initial dose is 15 mg/kg body weight, followed by 10 mg/kg body weight every 8 hours. One dose should be administered over 60 minutes.

Premature infants: Vancomycin clearance is reduced in premature infants, so increased dosing intervals may be necessary. Dosage reduction may be necessary due to decreased renal function. Close monitoring of vancomycin serum concentrations is recommended in these patients.

Patients with renal impairment and elderly patients

Dosage adjustment is necessary for patients with impaired renal function. A greater dose reduction than expected may be required for premature infants and the elderly due to poorer renal function.

Measurement of vancomycin serum concentrations may be useful in optimizing therapy, especially in critically ill patients with renal impairment. Serum vancomycin concentrations can be determined by microbiological assays, radioimmunoassays, fluorescence polarization immunoassays, fluorescence immunoassays, or high-performance liquid chromatography.

If creatinine clearance can be measured or accurately estimated, the dosage for most patients with renal insufficiency can be calculated using the table below. The daily dose of vancomycin in mg is approximately 15 times the glomerular filtration rate in ml/min. Dosage should be adjusted according to creatinine clearance according to Table 1.

Table 1

The initial dose of the drug should be 15 mg / kg of body weight, including for patients with mild and moderate renal insufficiency.

The table does not apply to the treatment of patients with one functioning kidney. In such cases, an initial dose of vancomycin of 15 mg / kg body weight should be administered until therapeutic serum concentrations are achieved. The maintenance dose is 1.9 mg / kg / day. For patients with significant renal insufficiency, it is recommended to prescribe 250 - 1000 mg of the drug 1 time per day with a break of several days. In case of anuria, a dose of 1000 mg every 7 - 10 days is recommended.

When the serum creatinine concentration is known, the following formula should be used to determine creatinine clearance (taking into account the patient's gender, weight, and age). However, creatinine clearance should be measured to obtain an accurate figure.

Women: 0.85 × the value obtained from the formula above.

The safety and efficacy of vancomycin administered by intrathecal (intralumbar or intraventricular) routes have not been established. The recommended method of administration of vancomycin is intermittent infusion.

Intravenous use

For use, reconstitute the contents of the vial of vancomycin hydrochloride for injection with sterile water for injection to a vancomycin concentration of 50 mg/mL (see Table 2).

Table 2

Store the reconstituted solution at 2 – 8 °C for 96 hours.

The reconstituted solution requires further dilution: to a solution containing 500 mg in 10 ml, add 100 ml of one of the following infusion solvents, and to a solution containing 1000 mg in 20 ml, add 200 ml of one of the following infusion solvents. The required dose, thus diluted, should be administered by intermittent intravenous infusion over a period of at least 60 minutes.

From a microbiological point of view, it is preferable to administer the solution immediately after dilution. The final concentration of the resulting vancomycin solution should not exceed 5 mg/ml.

Compatibility with intravenous fluids

The reconstituted vancomycin solution can be diluted with the following infusion solvents:

- 5% glucose solution for injection;

- 5% glucose solution for injection and 0.9% sodium chloride solution for injection;

- lactated Ringer's solution for injection;

- Ringer's lactate solution for injection and 5% glucose solution for injection;

- 0.9% sodium chloride solution for injection.

Before using the diluted solution, make sure that the solution is clear, colorless and free of mechanical inclusions.

The drug should be administered continuously intravenously by drip for 60 minutes.

Vancomycin solution has a low pH and may cause chemical or physical instability of other compounds when mixed.

Vancomycin and beta-lactam antibiotic solutions have been shown to be physically incompatible. The likelihood of precipitation increases with increasing vancomycin concentration. It is recommended that intravenous lines be thoroughly flushed between administrations of these antibiotics. It is also recommended that vancomycin solutions be diluted to a concentration of 5 mg/mL or less.

Although intravitreal injection is not an approved route of administration of vancomycin, cases of precipitation have been reported following intravitreal administration of vancomycin and ceftazidime for the treatment of endophthalmitis using different syringes and needles. The precipitates gradually resolved with complete vitreous clearance within two months and improvement in visual acuity.

Oral use

Vancomycin is poorly absorbed after oral administration, so it should only be given this way for the treatment of pseudomembranous colitis caused by Clostridium difficile. Vancomycin is not effective when given orally for the treatment of other types of infections.

Adults: The usual daily dose is 500 mg to 2000 mg, divided into 3-4 doses, for 7-10 days. The maximum daily dose should not exceed 2 g.

Children: The usual daily dose is 40 mg/kg body weight, divided into 3-4 doses, for 7-10 days. The maximum daily dose should not exceed 2 g.

The solution for oral administration is prepared by adding about 30 ml of water to the contents of a 500 mg vial of vancomycin. To improve the taste, sweet syrup with flavorings can be added to the solution.

The resulting solution can be administered orally or administered through a nasal probe.

Children.

The medicine can be used in children from birth.

Overdose

Symptoms: Overdose is characterized by increased severity of side effects.

Treatment: Treatment aimed at maintaining adequate glomerular filtration is recommended.

Vancomycin is poorly removed by dialysis.

Hemofiltration and hemoperfusion using polysulfone resin have been shown to increase vancomycin clearance. The median lethal dose when administered intravenously is 319 mg/kg in rats and 400 mg/kg in mice.

When treating an overdose, the possibility of overdose of several drugs, the interaction between them, and the peculiarities of the kinetics of the drugs in a particular patient should be taken into account.

Adverse reactions

During or immediately after rapid administration of the drug, anaphylactic reactions (hypotension, shortness of breath, dyspnea, urticaria or itching) and cardiac disorders (heart failure, up to cardiac arrest) may occur in isolated cases. Rapid administration of the drug may also cause flushing of the upper body or pain or spasms of the chest and back muscles. These reactions usually disappear within 20 minutes, but may occur within several hours. Such reactions almost never occur with slow administration of the drug over 60 minutes.

Blood and lymphatic system disorders: reversible neutropenia (usually starting 1 week or later after starting vancomycin therapy or after receiving a total dose of more than 25 g), agranulocytosis, thrombocytopenia, eosinophilia.

From the respiratory system: dyspnea, shortness of breath.

Gastrointestinal: nausea, vomiting, diarrhea, abdominal pain, pseudomembranous colitis, symptoms of which may appear both during and after treatment.

Cases of chemical peritonitis have been reported following intraperitoneal administration of the drug (see section "Special warnings and precautions for use").

Skin and subcutaneous tissue disorders: pruritus, urticaria, exanthema, Stevens-Johnson syndrome, exfoliative dermatitis, IgA-bullous dermatitis, toxic epidermal necrolysis (very rare).

During treatment with vancomycin, patients have experienced severe skin adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis (very rare), drug-induced skin reaction with eosinophilia and systemic manifestations, which can be fatal (see section "Special warnings and precautions for use").

From the organs of hearing and balance: noise or ringing in the ears, decreased hearing acuity, vertigo. Ototoxic effects were observed most often when using the drug in high doses or when administered simultaneously with other drugs that have an ototoxic effect, as well as with reduced kidney function or hearing damage.

Immune system disorders: anaphylactoid reaction (infusion-related reaction), hypersensitivity reactions, anaphylactoid shock (infusion-related reaction).

Laboratory test results: increased serum creatinine, increased serum urea, increased levels of AST, ALT, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transpeptidase, bilirubin, leucine aminopeptidase.

Nervous system: dizziness, paresthesia.

Urinary system: interstitial nephritis*, azotemia, acute renal failure.

*Possible deterioration of renal function (usually accompanied by an increase in serum creatinine or serum urea nitrogen), mainly after the use of high doses of the drug. Interstitial nephritis occurs rarely. In most cases, such adverse reactions are observed in patients who took aminoglycosides concomitantly with vancomycin or had a history of renal dysfunction. When vancomycin treatment was discontinued, azotemia resolved in almost all patients.

General disorders and administration site conditions: drug fever, chills, injection site changes including pain, inflammation, irritation, tissue necrosis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), lacrimation, inflammation of the mucous membranes.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after the registration of a medicinal product is an important procedure. It allows for continued monitoring of the benefit/risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions through the national pharmacovigilance system.

Expiration date

2 years.

Storage conditions

Store in the original packaging, protected from light, at a temperature not exceeding 25 °C.

Keep out of reach of children.

Store the reconstituted solution at 2 – 8 °C for 96 hours.

Incompatibility

It has been shown that mixtures of vancomycin solutions and beta-lactam antibiotics