Vancomycin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT VANCOMYCIN (VANCOMYCIN)

Composition:

Active substance: vancomycin;

One vial contains vancomycin (as vancomycin hydrochloride) 500 mg or 1000 mg;

Excipients: hydrochloric acid diluted, sodium hydroxide.

Pharmaceutical form. Powder for solution for infusion.

Main physicochemical properties: white or almost white (with a pinkish or light brownish tint) lyophilized mass.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Glycopeptide antibiotics.

ATX code J01X A01.

Pharmacological Properties

Pharmacodynamics

Vancomycin is a tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis (previously known as Nocardia orientalis).

The bactericidal action of vancomycin is primarily due to inhibition of bacterial cell wall biosynthesis. In addition, vancomycin affects bacterial cell membrane permeability and 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.

Synergy

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

Vancomycin has been shown to be active in vitro and in clinical infections against most strains of the following microorganisms (see section "Dosage and Administration"):

Aerobic Gram-Positive Microorganisms

Corynebacteria.

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 susceptibility data are available, but their clinical significance is unknown.

Vancomycin demonstrates in vitro minimum inhibitory concentrations (MICs) of ≤1 µg/mL against most (≥90%) strains of the streptococci listed below, and MICs of ≤4 µg/mL against most (≥90%) strains of the other microorganisms listed below. However, the safety and efficacy of vancomycin in treating clinical infections caused by these microorganisms have not been established by 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, repeated intravenous infusions of 1 g vancomycin (15 mg/kg) administered over 60 minutes result in a mean plasma concentration of approximately 63 µg/mL immediately after the end of infusion, approximately 23 µg/mL at 2 hours after infusion, and approximately 8 µg/mL at 11 hours after the end of infusion. Repeated infusions of 500 mg administered over 30 minutes result in a mean plasma concentration of approximately 49 µg/mL immediately after the end of infusion, approximately 19 µg/mL at 2 hours after infusion, and approximately 10 µg/mL at 6 hours after the end of infusion. Plasma concentrations during repeated dosing are approximately equivalent to those observed after single-dose administration.

The mean elimination half-life of vancomycin in plasma in individuals with normal renal function is 4 to 6 hours. Within the first 24 hours, approximately 75% of the administered dose of vancomycin is excreted in urine by glomerular filtration. Mean plasma clearance is approximately 0.058 L/kg/h, and mean renal clearance is approximately 0.048 L/kg/h. Impaired renal function leads to delayed elimination of vancomycin. In patients without kidneys (anephric), the mean elimination half-life of vancomycin is 7.5 days. The volume of distribution is 0.3–0.43 L/kg. No significant metabolism of vancomycin has been observed. Approximately 60% of a dose of vancomycin administered intraperitoneally during a peritoneal dialysis session is systemically absorbed within 6 hours. A serum concentration of approximately 10 µg/mL is achieved after intraperitoneal administration of 30 mg/kg vancomycin. However, the safety and efficacy of intraperitoneal administration of vancomycin have not been established by adequate and well-controlled clinical trials (see section "Special Warnings and Precautions for Use").

In elderly individuals, total systemic and renal clearance of vancomycin may be reduced. Vancomycin is approximately 55% bound to serum proteins, as determined by ultrafiltration at serum concentrations ranging from 10 to 100 µg/mL. After intravenous administration, inhibitory concentrations of vancomycin are achieved in pleural, pericardial, ascitic, and synovial fluids, in urine, in fluid obtained from peritoneal dialysis, and in atrial appendage tissue. Vancomycin poorly diffuses across intact meninges into cerebrospinal fluid; however, in the presence of meningeal inflammation, the drug penetrates into cerebrospinal fluid.

Clinical Characteristics

Indications

• For the treatment of serious or severe infections caused by methicillin-resistant (β-lactam-resistant) staphylococcal strains susceptible to vancomycin. Vancomycin is indicated for initial therapy when methicillin-resistant staphylococci are suspected; however, after susceptibility data become available, therapy should be adjusted accordingly.
• For treatment of patients with penicillin allergy, including cases where other agents, particularly penicillins or cephalosporins, have not been effective.
• For treatment of infections caused by microorganisms susceptible to vancomycin but resistant to other antimicrobial agents.
• For treatment of staphylococcal endocarditis.
• For treatment of other staphylococcal infections, including septicemia, bone infections, lower respiratory tract infections, and skin and skin structure infections.
• For treatment of localized purulent staphylococcal infections as an adjunct to appropriate surgical interventions.
• For endocarditis caused by S. viridans or S. bovis, vancomycin is effective either alone or in combination with aminoglycosides.
• For endocarditis caused by enterococci (e.g., E. faecalis), vancomycin is effective only in combination with aminoglycosides.
• For treatment of diphtheroid endocarditis.
• For treatment of early prosthetic valve endocarditis caused by S. epidermidis or diphtheroids, in combination with rifampin, an aminoglycoside, or both.
• For treatment of antibiotic-associated pseudomembranous colitis caused by Clostridium difficile, as well as staphylococcal enterocolitis (oral administration). Vancomycin is not effective for these conditions when administered parenterally. Vancomycin is not effective for other types of infections when administered orally.

Specimens should be obtained for bacteriological cultures in order to isolate and identify causative pathogens and determine their susceptibility to vancomycin.

To reduce the development of antimicrobial resistance, the drug should be used only for treatment or prophylaxis of infections caused by susceptible bacteria. When bacteriological culture and susceptibility test results are available, they should be taken into account when selecting or modifying antibacterial therapy. In the absence of such data, local epidemiological information and patterns of susceptibility should be considered when empirically selecting therapy.

Contraindications. Vancomycin hydrochloride for infusion is contraindicated in patients with hypersensitivity to this antibiotic.

Interaction with other medicinal products and other forms of interaction

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

Renal function monitoring is recommended in patients who are receiving vancomycin concomitantly or sequentially with other potentially neurotoxic or nephrotoxic medicinal products administered systemically or locally, such as amphotericin B, aminoglycosides, bacitracin, polymyxin B, colistin, viomycin, and cisplatin.

Special precautions for use

Warnings

Infusion reactions

Rapid bolus administration (e.g., over several minutes) may be associated with excessive arterial hypotension, including shock and, rarely, cardiac arrest.

Vancomycin hydrochloride should be administered as a diluted solution over not less than 60 minutes to avoid infusion-related reactions. Discontinuation of the infusion usually results in rapid resolution of these reactions.

Nephrotoxicity

Systemic exposure to vancomycin may lead to acute kidney injury (AKI). The risk of AKI increases with higher systemic exposure / serum concentrations of vancomycin. Renal function should be monitored in all patients, particularly in those with pre-existing renal impairment, patients with concomitant conditions predisposing to renal failure, and patients receiving concomitant nephrotoxic drugs.

Ototoxicity

Ototoxicity has been observed in patients receiving vancomycin hydrochloride. Transient or permanent ototoxicity occurred in most patients who received excessive doses, already had hearing impairment, or received concomitant ototoxic drugs (e.g., aminoglycosides). Vancomycin should be used with caution in patients with renal insufficiency due to the significantly increased risk of toxicity at high blood concentrations over prolonged periods.

Dosage of vancomycin hydrochloride should be adjusted in patients with renal dysfunction (see below "Precautions" and "Dosage and administration").

Serious skin reactions

During treatment with vancomycin, serious skin adverse reactions have been observed in patients, such as toxic epidermal necrolysis (TEN), Stevens–Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear IgA bullous dermatosis (LABD). Skin signs or symptoms reported include skin rash, mucosal lesions, and blisters. Vancomycin hydrochloride should be discontinued immediately at the first sign or symptom of TEN, SJS, DRESS, AGEP, or LABD.

Clostridioides difficile-associated diarrhea (CDAD)

Diarrhea associated with Clostridioides difficile (CDAD), ranging in severity from mild diarrhea to fatal colitis, has been reported during therapy with nearly all antibacterial agents, including vancomycin hydrochloride. 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. Hyper-toxin-producing strains of C. difficile can cause increased morbidity and mortality, as these infections may be refractory to antimicrobial therapy and may require colectomy. CDAD should be suspected in all patients who develop diarrhea following antibiotic use. Careful medical history is important, as CDAD has been reported to occur up to two months after antibiotic treatment.

If CDAD is suspected or confirmed, ongoing antibiotic treatment not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, treatment with an antibiotic effective against C. difficile, and surgical evaluation should be undertaken if clinically indicated.

Hemorrhagic occlusive retinal vasculitis

Hemorrhagic occlusive retinal vasculitis, including irreversible vision loss, has occurred in patients after intracameral or intravitreal administration of vancomycin during or following cataract surgery. The safety and efficacy of vancomycin administered intracamerally or intravitreally have not been established by adequate and well-controlled studies. Vancomycin is not indicated for the prevention of endophthalmitis.

Precautions

In some patients treated for C. difficile-induced pseudomembranous colitis, clinically significant serum concentrations of vancomycin have been observed after several oral doses.

Prolonged use of vancomycin hydrochloride may result in the overgrowth of non-susceptible microorganisms. Close patient monitoring is required. If superinfection occurs during therapy, appropriate measures should be taken. Rare cases of pseudomembranous colitis caused by C. difficile have been reported in patients receiving intravenous vancomycin hydrochloride.

To minimize the risk of ototoxicity, periodic monitoring of auditory function may be useful.

Cases of reversible neutropenia have been reported in patients receiving vancomycin hydrochloride (see section "Adverse reactions"). In patients planned for prolonged vancomycin hydrochloride therapy or those receiving concomitant drugs that may cause neutropenia, periodic monitoring of white blood cell counts is recommended.

Vancomycin hydrochloride is irritating to tissues and should be administered via a safe intravenous route. Intramuscular injection or accidental extravasation may cause pain, tenderness, and necrosis. Thrombophlebitis may occur; its frequency and severity can be minimized by slow infusion of a diluted solution (2.5–5 g/L) and by rotating venous access sites.

Reports indicate that the incidence of infusion-related adverse events (including arterial hypotension, flushing, erythema, urticaria, and pruritus) increases with concomitant administration of anesthetics. Infusion-related adverse events can be minimized by administering vancomycin as a 60-minute infusion prior to the initiation of anesthetic administration. The safety and efficacy of vancomycin administered intrathecally (intralumbar or intraventricular) or intraperitoneally have not been established by adequate and well-controlled studies.

Reports indicate that intraperitoneal administration of sterile vancomycin during continuous ambulatory peritoneal dialysis (CAPD) has led to the development of chemical peritonitis syndrome. The severity of this syndrome ranges from cloudy dialysate alone to cloudy dialysate accompanied by abdominal pain of varying intensity and fever. Chemical peritonitis syndrome appears to resolve rapidly after discontinuation of intraperitoneal vancomycin administration.

Prescribing vancomycin hydrochloride in the absence of confirmed or strongly suspected bacterial infection, or for prophylaxis, is unlikely to benefit the patient and instead increases the risk of development of drug-resistant bacteria.

Children

In children, it may be advisable to confirm desired serum vancomycin concentrations. Concomitant use of vancomycin and anesthetics has been associated with erythema and histamine-like flushing in children.

Use in elderly patients

Age-related natural decline in glomerular filtration rate may lead to elevated serum vancomycin concentrations if dosage is not adjusted. Dosage regimens of vancomycin should be adjusted in elderly patients (see "Dosage and administration").

Information for patients

Serious skin reactions

Patients should be informed about the signs and symptoms of serious skin reactions. Patients must discontinue vancomycin hydrochloride and seek immediate medical attention at the first sign or symptom of skin rash, mucosal lesions, or blisters (see above "Warnings").

Patients should be aware that antibacterial agents, including vancomycin hydrochloride, should be used only for the treatment of bacterial infections. These agents do not treat viral infections (e.g., the common cold). If the medication is prescribed for a bacterial infection, patients should be informed that, although they may feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may reduce the effectiveness of the treatment and increase the likelihood of bacterial resistance, rendering vancomycin hydrochloride or other antibacterial agents ineffective in future infections.

Antibiotic-associated diarrhea usually resolves after discontinuation of the antibiotic. However, sometimes patients may develop watery stools with blood (accompanied by abdominal cramps, possibly with fever) during or even two months or more after completing antibiotic therapy. If this occurs, patients should contact their physician immediately.

Use during pregnancy or breastfeeding

Pregnancy

Studies on the effect of vancomycin on reproductive function in animals have not been conducted. It is unknown whether vancomycin may affect fertility. In a controlled clinical study, potential ototoxic and nephrotoxic effects of vancomycin on newborns were evaluated after administration to pregnant women for the treatment of serious staphylococcal infections arising as complications of intravenous drug abuse. Vancomycin was detected in umbilical cord blood. No vancomycin-induced sensorineural hearing loss or nephrotoxicity was observed. In one infant whose mother received vancomycin during the third trimester of pregnancy, conductive hearing loss developed, which was not related to vancomycin use. Because the number of patients treated with vancomycin in this study was limited and vancomycin was administered only during the second and third trimesters of pregnancy, it is unknown whether vancomycin may harm the fetus. Vancomycin should be administered to pregnant women only if clearly needed.

Breastfeeding period

Vancomycin hydrochloride is excreted in breast milk. Vancomycin hydrochloride should be administered to nursing women with caution. Due to the potential for adverse effects, the decision to discontinue breastfeeding or to discontinue the drug should be made by considering the importance of the drug therapy to the mother.

Fertility

Although long-term animal studies to evaluate carcinogenic potential have not been conducted, results of standard laboratory tests indicate the absence of mutagenic potential of vancomycin hydrochloride. Specific studies on the effect on fertility have not been conducted.

Ability to affect reaction speed when driving or operating machinery. No data available.

Administration and Dosage

Infusion-related adverse reactions are associated with both the concentration and the rate of vancomycin administration. For adults, it is recommended to administer the drug at a concentration of no more than 5 mg/mL and at a rate not exceeding 10 mg/min (see also age-dependent recommendations below). For certain patients requiring fluid restriction, concentrations up to 10 mg/mL may be used; however, the use of such higher concentrations correspondingly increases the risk of infusion-related adverse reactions. An infusion rate of 10 mg/min or less is associated with a lower incidence of infusion-related adverse reactions (see section "Adverse Reactions"). Nevertheless, these adverse reactions may occur at any infusion rate or concentration.

Patients with Normal Renal Function

Adults. The usual daily dose for intravenous administration is 2 g: 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. Factors such as patient age or obesity may necessitate modification of the usual daily intravenous dose.

Children. The usual dose of vancomycin for intravenous administration is 10 mg/kg every 6 hours. Each dose should be administered over a period of at least 60 minutes. These patients may require careful monitoring of serum vancomycin concentrations.

Neonates. For infants up to 1 month of age, the total daily dose of vancomycin for intravenous administration may be lower. For neonates, an initial dose of 15 mg/kg is recommended, followed by 10 mg/kg every 12 hours during the first week of life and every 8 hours thereafter until they reach 1 month of age. Each dose should be administered over 60 minutes.

Preterm infants. In preterm neonates, vancomycin clearance is lower the lower the postconceptional age. Therefore, longer dosing intervals may be required for preterm neonates. Careful monitoring of serum vancomycin concentrations is recommended in these patients.

Patients with Impaired Renal Function and Elderly Patients

Dosage adjustment is required for patients with impaired renal function. Preterm neonates and elderly patients may require greater dosage reductions than expected due to reduced renal function.

Monitoring of serum vancomycin concentrations helps optimize therapy, especially in critically ill patients with impaired renal function. Serum vancomycin concentrations can be determined using microbiological assay, radioimmunoassay, fluorescence polarization immunoassay, fluorescence immunoassay, or high-performance liquid chromatography.

If creatinine clearance can be accurately measured or calculated, dosing for most patients with impaired renal function can be determined using the table below. The daily dose of vancomycin in mg is approximately 15 times the glomerular filtration rate in mL/min (see Table 1).

Table 1

Vancomycin Dosing for Patients with Impaired Renal Function

Creatinine clearance, 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

The initial dose should be at least 15 mg/kg, even for patients with mild or moderate renal function impairment.

Table 1 does not apply to patients with a single functioning kidney. For such patients, an initial dose of 15 mg/kg body weight should be administered to rapidly achieve therapeutic serum concentrations. The dose required to maintain steady-state concentration is 1.9 mg/kg/day. For patients with severe renal impairment, it may be more convenient to administer maintenance doses of 250 to 1000 mg once daily with several-day intervals, rather than daily administration of the drug. In anuria, a dose of 1000 mg every 7–10 days is recommended.

If only the serum creatinine level is known, the formula provided below (taking into account the patient's gender, body weight, and age) can be used to calculate creatinine clearance. The calculated creatinine clearance (mL/min) is only an approximate estimate. Creatinine clearance should be measured accurately.

Men	Body weight (kg) × (140 – age (years)) 72 × serum creatinine concentration (mg/dL)
Women	0.85 × value calculated by the formula above

Serum creatinine levels should be determined under conditions of stable renal function. Otherwise, the calculated creatinine clearance value may be inaccurate. The calculated creatinine clearance is higher than the actual clearance in patients with the following conditions: (1) those characterized by impaired renal function, such as shock, severe heart failure, or oliguria; (2) those in which the normal ratio between muscle mass and total body weight is altered, for example, in patients with obesity, liver disease, edema, or ascites; (3) those associated with cachexia, malnutrition, or immobility.

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

The recommended method of vancomycin administration is intermittent infusion.

Intravenous administration

Compatibility with other medicinal products and intravenous fluids

Diluents that are physically and chemically compatible (with 4 g/L vancomycin hydrochloride):

• 5% dextrose injection;
• 5% dextrose injection and 0.9% sodium chloride injection;
• lactated Ringer's injection;
• 5% dextrose and lactated Ringer's injection;
• 0.9% sodium chloride injection.

Standard professional practice requires that prepared mixtures be administered as soon as possible after preparation.

Vancomycin solution has a low pH value and may cause physical instability of other compounds.

Preparation of solution and stability

Before administration, dissolve the contents of the vancomycin hydrochloride vial for infusion with sterile water for injection to a vancomycin concentration of 50 mg/mL (see Table 2).

Table 2

Vancomycin content in the vial	Solvent volume
500 mg	10 ml
1000 mg	20 ml

After reconstitution, the vial can be stored in the refrigerator for 14 days without significant loss of drug activity.

Reconstituted vancomycin solution (500 mg / 10 mL) must be further diluted in at least 100 mL of an appropriate infusion solution. For a 1000 mg dose (20 mL), at least 200 mL of an appropriate infusion solution must be used. The desired dose, so diluted, should be administered by intermittent intravenous infusion over at least 60 minutes.

Compatibility with intravenous fluids

Solutions diluted with 5% dextrose injection or 0.9% sodium chloride injection may be stored in the refrigerator for 14 days without significant loss of drug activity. Solutions diluted with the following infusion fluids may be stored in the refrigerator for 96 hours:

• 5% dextrose injection and 0.9% sodium chloride injection;
• lactated Ringer's injection;
• lactated Ringer's and 5% dextrose injection.

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

Vancomycin solutions have been shown to be physically incompatible with beta-lactam antibiotics. The probability of precipitation increases with increasing vancomycin concentration. It is recommended to thoroughly flush intravenous administration systems between the administration of these antibiotics. It is also recommended to dilute vancomycin solutions to a concentration of 5 mg/mL or less.

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

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Oral administration

Vancomycin is administered orally for the treatment of antibiotic-associated pseudomembranous colitis caused by C. difficile. For other types of infections, oral administration of vancomycin is not effective.

Adults. The usual daily dose for adults is 500 mg to 2 g given in 3 or 4 divided doses over 7–10 days. The total daily dose should not exceed 2 g.

Children. The total daily dose for children is 40 mg/kg body weight given in 3 or 4 divided doses over 7–10 days. The total daily dose should not exceed 2 g.

The appropriate dose may be diluted in 30 mL of water and administered orally. To improve taste during oral administration, flavored syrups may be added to the solution. The diluted solution may also be administered via a nasogastric tube.

Children. The drug may be used in children from birth.

Overdose

Supportive therapy is recommended, including maintenance of glomerular filtration. Vancomycin is poorly removed by dialysis. Hemofiltration and hemoperfusion using polysulfone resin have been reported to enhance vancomycin clearance. The average lethal dose following intravenous administration in animals is 319 mg/kg in rats and 400 mg/kg in mice.

When treating overdose, consider the possibility of multiple drug overdoses, interactions between drugs, and the specific pharmacokinetics of the drugs in the individual patient.

Side effects

Infusion-related reactions

During or shortly after rapid infusion of vancomycin hydrochloride, patients may develop anaphylactoid reactions, including arterial hypotension, wheezing, dyspnea, urticaria, or pruritus. Rapid infusion may also cause upper body flushing ("red neck") or pain and muscle spasm in the chest and back. These reactions usually resolve within 20 minutes but may last for several hours. Such events are uncommon when vancomycin hydrochloride for infusion is administered by slow infusion over 60 minutes. In studies involving healthy volunteers, infusion-related adverse events were not observed when vancomycin hydrochloride for infusion was administered at a rate of 10 mg/min or less.

Nephrotoxicity

Systemic exposure to vancomycin may lead to the development of AKI. The risk of AKI increases with higher systemic exposure / serum drug concentrations. Additional risk factors for AKI in patients receiving vancomycin therapy include concomitant use of nephrotoxic drugs, pre-existing renal impairment, and comorbid conditions predisposing to renal dysfunction. Cases of interstitial nephritis have also been reported in patients receiving vancomycin.

Gastrointestinal tract

Symptoms of pseudomembranous colitis may occur during or after antibiotic therapy (see section "Special precautions").

Ototoxicity

Hearing loss has been reported in several dozen patients receiving vancomycin. Most of these patients had pre-existing renal impairment or hearing loss, or were concurrently receiving treatment with an ototoxic agent. Vertigo, dizziness, and tinnitus have been reported rarely.

Hematopoiesis

Reversible neutropenia has been observed in many patients, usually occurring one week or more after initiation of vancomycin therapy or after receiving a total dose exceeding 25 g of the drug. Neutropenia appears to resolve rapidly after discontinuation of vancomycin. Thrombocytopenia has occasionally been observed. Reversible agranulocytosis (granulocyte count <500/mm³) has been reported rarely, although a causal relationship with vancomycin use has not been established.

Phlebitis

Inflammation at the injection site has been reported.

Other

Anaphylaxis, drug fever, nausea, chills, eosinophilia, rash including exfoliative dermatitis, Stevens-Johnson syndrome (see section "Special precautions"), and vasculitis associated with vancomycin use have been reported.

Cases of chemical peritonitis have been documented following intraperitoneal administration of the drug (see section "Special precautions").

Post-marketing experience

The following adverse reactions have been identified during post-approval use of vancomycin. It is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Disorders of the skin and subcutaneous tissue: severe dermatological reactions such as toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear IgA bullous dermatosis (LABD) (see section "Special precautions").

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after drug registration is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua

Shelf life. 2 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Incompatibilities

Solutions of vancomycin and beta-lactam antibiotics have been shown to be physically incompatible. The likelihood of precipitation increases with higher vancomycin concentrations. It is recommended to thoroughly flush intravenous administration systems between administration of these antibiotics. It is also recommended to dilute vancomycin solutions to a concentration of 5 mg/mL or less.

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

This medicinal product should not be mixed with other medicinal products except those specified in the section "Dosage and administration".

Packaging. 500 mg or 1000 mg powder for infusion solution in a vial; 10 vials in a blister pack, 1 blister pack per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and location of its business activities. 139 Saksaganskogo Street, Kyiv, 01032, Ukraine.