Instructions Vancomycin-Pharmex lyophilized powder for solution for infusion 1000 mg vial No. 1
Composition
active ingredient: vancomycin;
1 vial contains vancomycin hydrochloride equivalent to vancomycin 500 mg or 1000 mg;
excipients: sodium hydroxide/dilute hydrochloric acid (possible presence due to the need for pH correction).
Dosage form
Lyophilisate for solution for infusion.
Main physicochemical properties: lyophilized porous mass or powder from almost white to light brown in color in vials. A pinkish tint is allowed.
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. Cross-resistance between vancomycin and other antibiotics does not occur.
Vancomycin is particularly effective against: staphylococci, including Staphylococcus aureus and S. eridermidis (including methicillin-resistant strains); streptococci, including Streptococcus pyogenes, S. agalactiae, Enterococcus faecalis (mainly Streptococcus faecalis), S. bovis, hemolytic streptococci groups, Streptococcus pneumoniae (including penicillin-resistant strains); Clostridium difficile (including toxigenic strains - causative agents of pseudomembranous enterocolitis); diphtheriae.
Vancomycin is susceptible in vitro to Listeria monocytogenes, Lactobacillus species, Actinomyces species, Clostridium species, and Bacillus species. It is inactive in vitro against Gram-negative bacteria, fungi, and mycobacteria.
Pharmacokinetics.
After intravenous administration of 1 g of vancomycin, the concentration in blood plasma after 2 hours is 23 mg/l and 8 mg/l - 11 hours after the end of the administration. Almost 55% of the administered vancomycin binds to plasma proteins. After intravenous administration, the concentration of the drug that inhibits microorganisms is found in pleural, pericardial, ascitic and synovial fluids, in urine, peritoneal dialysis fluid, and in atrial tissues. Despite poor penetration through the pia mater under normal conditions, in the presence of inflammation, vancomycin penetrates well into the cerebrospinal fluid. The metabolism of this drug is insignificant. The half-life of the drug is on average 4-6 hours. In the first 24 hours, about 75% of the administered dose of vancomycin is excreted in the urine by glomerular filtration. In patients with impaired renal function, the elimination of vancomycin is slowed. For example, in patients with a removed kidney, the half-life is 7.5 days.
Indication
Treatment of infections caused by gram-positive microorganisms that are sensitive to the drug, including in patients with a history of allergy to penicillins and cephalosporins:
endocarditis;
sepsis;
osteomyelitis;
infections of the central nervous system;
lower respiratory tract infections (pneumonia);
skin and soft tissue infections;
pseudomembranous colitis (for oral use).
Prevention of endocarditis in patients with hypersensitivity to penicillin antibiotics. Prevention of infections after surgical procedures in the oral cavity and ENT organs.
Contraindication
Hypersensitivity to vancomycin or to any other component of the drug.
Interaction with other medicinal products and other types of interactions
When vancomycin is administered simultaneously or sequentially with other drugs with neurotoxic and/or nephrotoxic effects, in particular gentamicin, ethacrynic acid, amphotericin B, streptomycin, neomycin, kanamycin, amikacin, tobramycin, viomycin, bacitracin, polymyxin B, colistin and cisplatin, the nephrotoxic and/or ototoxic effects of vancomycin may be enhanced.
There is a risk of acute renal failure when vancomycin is used with concomitant piperacillin/tazobactam therapy (see section 4.4).
Due to synergistic effects with gentamicin, the maximum dose of vancomycin should be limited to 500 mg every 8 hours.
Concomitant administration of vancomycin and anesthetic agents increases the risk of hypotension and may cause erythema, histamine-like flushing, and anaphylactoid reactions.
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 the properties of vancomycin may be significantly weakened over time.
The combination of vancomycin with aminoglycosides acts synergistically in vitro against Staphylococcus aureus, non-enterococcal group D streptococci, enterococci, and Streptococcus species (various species).
Medications that reduce intestinal peristalsis are contraindicated in pseudomembranous colitis.
Cholestyramine reduces the effectiveness of vancomycin.
Application features
Rapid administration of the drug in the form of a bolus injection (within a few minutes) can cause significant arterial hypotension, including shock, occasionally with cardiac arrest, therefore, to reduce the risk of developing hypotensive reactions, the patient's blood pressure should be monitored during administration of the drug.
Vancomycin should only be used intravenously due to the risk of soft tissue necrosis.
To prevent adverse reactions, vancomycin solution should be administered over at least 60 minutes. The risk of thrombophlebitis can be reduced by slow administration of diluted solution (2.5-5 mg/ml) and by changing the injection site.
It should be noted that adverse reactions related to the rate of drug administration may occur at any concentration and rate of drug administration and disappear after completion of drug administration.
It should be used with caution in elderly patients, patients with hearing impairment, or during concomitant use of other ototoxic drugs such as aminoglycosides.
During long-term treatment with vancomycin, blood, urine, and kidney function should be periodically monitored.
Liver function should be monitored continuously, as liver disease may be exacerbated by vancomycin therapy with elevations in bilirubin, AST, ALT, alkaline phosphatase, and, occasionally, elevations in lactate dehydrogenase and gamma-glutamyltransferase.
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 the vancomycin infusion.
Vancomycin should be used with caution in patients with allergic reactions to teicoplanin, as cases of cross-allergic reactions have been described.
Some patients with inflammatory bowel disease may experience significant systemic absorption of oral vancomycin, and are therefore at risk of adverse reactions associated with parenteral vancomycin administration.
Vancomycin should be used with extreme caution in premature infants due to the immaturity of the renal system, which may result in increased serum concentrations of vancomycin.
It is recommended to monitor the serum concentration of vancomycin in premature newborns and infants.
There is a risk of ototoxic effects when treating with vancomycin, so the drug should be used with caution in patients with hearing impairment or during concomitant use of other ototoxic drugs, such as aminoglycosides.
Prolonged use of vancomycin may lead to the development of resistant microorganisms and fungi. Careful monitoring of the patient is of great importance. If superinfection (secondary infection on the background of an ongoing infectious disease) occurs during therapy, appropriate measures should be taken.
There have been reports of cases of pseudomembranous colitis caused by Clostridium difficile in patients receiving intravenous vancomycin.
Burn patients have been reported to have higher total clearance of vancomycin and therefore require more frequent administration with increased doses. Individualized dosing and close monitoring are recommended when using vancomycin in these patients.
Severe cutaneous adverse reactions: Severe cutaneous adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis, which can be life-threatening or fatal, have been reported in association with vancomycin treatment.
Most of these reactions occurred within a few days and up to eight weeks after starting vancomycin therapy. Patients should be advised of signs and symptoms and monitored closely for skin reactions when vancomycin is prescribed. If signs and symptoms suggestive of these reactions occur, vancomycin should be discontinued immediately and alternative therapy should be considered. If a patient develops a severe skin adverse reaction to vancomycin, vancomycin therapy should not be restarted at any time.
Eye disorders: Vancomycin is not approved for intracameral or intravitreal use, including prophylaxis of endophthalmitis. Hemorrhagic occlusive retinal vasculitis, including permanent vision loss, has been reported following intracameral or intravitreal administration of vancomycin during or after cataract surgery.
Nephrotoxicity. Vancomycin should be used with caution in patients with renal insufficiency, including anuria, as there is a possibility of toxic effects. The risk of toxicity increases with increased vancomycin blood concentrations or prolonged therapy. Regular monitoring of vancomycin blood levels is indicated during high-dose therapy and prolonged use, especially in patients with impaired renal function or with impaired auditory potential, as well as with concomitant use of nephrotoxic or ototoxic substances, respectively (see section "Interaction with other drugs").
Use during pregnancy or breastfeeding
There are no data on the safety of the drug during pregnancy. The use of vancomycin in the first trimester of pregnancy is contraindicated. The appointment of vancomycin in the second and third trimesters of pregnancy is possible only for vital indications, when the expected benefit to the mother outweighs the risk to the fetus, while it is necessary to monitor the concentration of vancomycin in the blood serum.
The drug penetrates into breast milk, so if necessary, its use should be discontinued breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
During treatment with 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
Vancomycin should be administered intravenously for the treatment of life-threatening infections. Vancomycin should never be administered as a bolus injection or intramuscularly due to pain and possible necrosis at the injection site.
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. For 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. A high concentration of the administered drug increases the risk of adverse reactions.
The duration of treatment depends on the therapeutic indications for which the drug is used.
Intravenous administration of the drug.
Dissolve the contents of the 500 mg vial in 10 ml or the contents of the 1 g vial in 20 ml of water for injections.
After dilution, the drug solution in vials remains stable for 24 hours at 25°C or for 96 hours in a refrigerator at a temperature of +2°C to +8°C.
Further dilution is required: to a solution containing 500 mg or 1 g of vancomycin, at least 100 ml or 200 ml of 0.9% sodium chloride solution for injection or 5% glucose solution for injection, respectively, should be added. The resulting solution remains stable for 48 hours in a refrigerator at +2 °C to +8 °C or for 24 hours at 25 °C.
From a microbiological point of view, it is advisable to administer the solution immediately after dilution.
The final concentration of the resulting vancomycin solution should not exceed 5 mg/ml.
Aqueous vancomycin solution can also be diluted with the following infusion solvents:
lactated Ringer's solution,
lactated Ringer's solution and 5% glucose solution,
Ringer's acetate solution.
Vancomycin solutions prepared using the above solvents can be stored in a refrigerator at a temperature of +2 °C to +8 °C for 96 hours.
Before using the diluted solution, make sure that there is no precipitate or discoloration.
The drug should be administered continuously intravenously by drip for 60 minutes.
Patients with normal renal function.
Adults: 500 mg every 6 hours or 1000 mg every 12 hours. The solution should be administered intravenously by infusion over at least 60 minutes. The maximum single dose is 1000 mg, the maximum daily dose is 2 g.
Children.
Newborns up to 7 days old: the initial dose is 15 mg/kg body weight, followed by 10 mg/kg body weight every 12 hours.
Newborns aged 7 days to 1 month: the initial dose is 15 mg/kg body weight, followed by 10 mg/kg body weight every 8 hours.
Children 1 month of age and older: The usual dose of vancomycin is 10 mg/kg body weight every 6 hours.
The maximum single dose for children is 15 mg/kg of body weight, the maximum daily dose is 2 g.
The concentration of the prepared vancomycin solution for children should not exceed 2.5-5 mg/ml. The solution should be administered over at least 60 minutes.
Elderly patients: Dose reduction may be required due to age-related decline in renal function.
Overweight patients: Adjustment of the standard daily dose may be required.
Patients with hepatic insufficiency: no daily dose adjustment is required.
Patients with renal dysfunction.
Dosage should be adjusted according to creatinine clearance according to the table below.
When the serum creatinine concentration is known, the following formula (taking into account the patient's gender, body weight and age) should be used to determine creatinine clearance.
The estimated creatinine clearance (ml/min) is only determined, and the exact creatinine clearance should be measured.
| Men: | Body weight (kg) x (140 – age (years)) |
| 72 x serum creatinine concentration (mg/dL) |
Women: 0.85 x the value obtained from the formula above.
| 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 |
In anuria, 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 once a day with a break of several days.
Dosage regimen during hemodialysis
For patients on dialysis, the loading dose is 1000 mg, the maintenance dose is 1000 mg of the drug every 7-10 days. When using polysulfone membranes for hemodialysis, an increase in the maintenance dose of vancomycin is necessary.
Serum creatinine should be a constant indicator of renal function. Otherwise, creatinine clearance values obtained are invalid. Monitoring of vancomycin serum concentrations is recommended in cases where the risk of toxicity exceeds these values: 2 hours after infusion of 1 g of the drug, the peak concentration is 20-50 mg/l, and the minimum concentration before the next dose is 5-10 mg/l. In cases where these values are exceeded, a dosage review is recommended.
Intravenous administration
Vancomycin is poorly absorbed after oral administration, so it can only be administered this way for the treatment of pseudomembranous colitis caused by Clostridium difficile.
The solution for oral administration is prepared by adding 30 ml of water to the contents of the 500 mg vancomycin vial. The resulting solution can be administered orally or administered through a nasal probe. To improve the taste, sweet syrup with flavorings can be added to the solution.
Adults: The usual daily dose is 500-1000 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.
Children.
The drug can be used in children immediately after birth.
Overdose
Overdose is characterized by increased severity of side effects.
Treatment aimed at maintaining adequate glomerular filtration is recommended. Vancomycin is poorly dialysable. Excess vancomycin should be removed by hemofiltration and hemodialysis using polysulfone membranes.
Specific antidote is unknown.
Side effects
During or immediately after rapid administration of the drug, in isolated cases, anaphylactic reactions (hypotension, shortness of breath, dyspnea, urticaria or itching) and cardiac disorders (heart failure, up to cardiac arrest) may occur. Rapid administration of the drug may also cause a rush of blood to 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 practically do not occur with slow administration of the drug over 60 minutes.
Blood and lymphatic system disorders: neutropenia*, agranulocytosis, thrombocytopenia, eosinophilia.
*Reversible neutropenia is possible. It usually begins 1 week or later after initiation of vancomycin therapy or after receiving a total dose of 25 g or more.
Cardiovascular system: heart failure, hypotension, phlebitis, vasculitis, cardiac arrest (these reactions are mainly associated with rapid infusion of the drug).
From the respiratory system: dyspnea, shortness of breath.
Gastrointestinal: nausea, vomiting, diarrhea, abdominal pain, pseudomembranous colitis.
Skin and subcutaneous tissue disorders: pruritus, urticaria, exanthema, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis.
From the organs of hearing and balance: noise or ringing in the ears, decreased hearing acuity, vertigo.
Ototoxic effects were observed most often when the drug was used in high doses or when administered simultaneously with other drugs that have an ototoxic effect, as well as in cases of reduced kidney function or hearing impairment.
Immune system disorders: anaphylactoid reaction (infusion-related reaction), hypersensitivity reactions, anaphylactoid shock (infusion-related reaction).
Infections and infestations: pseudomembranous colitis.
Laboratory results: increased serum creatinine, increased serum urea, increased levels of AST, ALT, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transpeptidase, bilirubin, leucine aminopeptidase.
Musculoskeletal system: muscle spasms (infusion-related reaction).
Nervous system: dizziness, paresthesia.
Urinary system: interstitial nephritis*, azotemia, acute renal failure.
General disorders and administration site conditions: drug fever, chills, injection site changes including pain, inflammation, irritation, tissue necrosis, chest and back muscle pain and spasms, growth of resistant bacteria and fungi, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), lacrimation, inflammation of the mucous membranes, flushing of the upper body and face.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Incompatibility
Vancomycin solution (prepared by dissolving the powder in sterile water for injection and further diluting with 0.9% sodium chloride solution or 5% glucose solution) has a low pH value, which may cause physical or chemical instability when mixed with other components. Vancomycin solutions should not be mixed with other solutions except those with which compatibility has been demonstrated.
The simultaneous use and mixing of vancomycin solutions with chloramphenicol, corticosteroids, methicillin, heparin, aminophylline, cephalosporin antibiotics, and phenobarbital is not recommended.
Packaging
500 or 1000 mg in a glass vial, 1 vial in a contour blister pack, 1 contour blister pack in a pack.
Vacation category
According to the recipe.
Producer
LLC "PHARMEX GROUP".
Address
Ukraine, 08301, Kyiv region, Boryspil city, Shevchenko st., building 100.
