Vancocin^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Eli Lilly Vostok, S.A. (Switzerland)

Manufactured By

Vianex, S.A. (Greece)

ATC Code

J01XA01 (Vancomycin)

Active Substance

Vancomycin (Rec.INN registered by WHO)

Dosage Form

Vancocin®

Lyophilizate for preparation of solution for infusion 500 mg: fl. 1 pc.

Dosage Form, Packaging, and Composition

Lyophilizate for preparation of solution for infusion white or almost white in color.

Glass bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antibiotic of the glycopeptide group

Pharmacotherapeutic Group

Antibiotic-glycopeptide

Pharmacological Action

Vancomycin is a chromatographically purified tricyclic glycopeptide antibiotic isolated from Amycolatopsis orientalis.

The bactericidal action of vancomycin results from the inhibition of cell wall biosynthesis. Furthermore, Vancomycin may alter the permeability of the bacterial cell membrane and alter RNA synthesis. Cross-resistance between vancomycin and antibiotics of other classes is absent.

In vitro, Vancomycin is usually active against gram-positive microorganisms, including: Staphylococcus aureus and Staphylococcus epidermidis (including heterogeneous methicillin-resistant strains), Streptococcus pyogenes, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus agalactiae, the viridans group, Streptococcus bovis, and enterococci (e.g., Enterococcus faecalis); Clostridium difficile (e.g., toxigenic strains involved in the development of pseudomembranous enterocolitis) and diphtheroids. Other microorganisms susceptible to vancomycin in vitro include Listeria monocytogenes, bacteria of the genera Lactobacillus, Actinomyces, Clostridium, and Bacillus.

There is evidence that in vitro, some isolated strains of enterococci and staphylococci exhibit resistance to vancomycin.

The combination of vancomycin and an aminoglycoside exhibits synergism in vitro against many strains of Staphylococcus aureus, non-enterococcal group D streptococci, enterococci, and bacteria of the Streptococcus group (viridans group).

Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, and fungi.

Pharmacokinetics

In individuals with normal renal function, multiple intravenous administrations of 1 g of vancomycin (15 mg/kg) (infusion over 60 minutes) produce mean plasma concentrations of about 63 mg/l immediately after the end of the infusion; 2 hours after the infusion, mean plasma concentrations are about 23 mg/l, and 11 hours after the infusion – about 8 mg/l.

Multiple infusions of 500 mg administered over 30 minutes produce mean plasma concentrations of about 49 mg/l after the end of the infusion; 2 hours after the infusion, mean plasma concentrations are about 19 mg/l, and 6 hours later – about 10 mg/l. Plasma concentrations with multiple administrations are similar to plasma concentrations with a single administration. The plasma T_1/2 of vancomycin is 4-6 hours in patients with normal renal function.

About 75% of the administered dose of vancomycin is excreted in the urine via glomerular filtration within the first 24 hours. The mean plasma clearance is about 0.058 L/kg/h, and the mean renal clearance is about 0.048 L/kg/h. The renal clearance of vancomycin is quite constant and accounts for 70-80% of its elimination.

V_d ranges from 0.3 to 0.43 L/kg. The drug is practically not metabolized. As ultrafiltration has shown, at vancomycin serum concentrations from 10 mg/L to 100 mg/L, 55% of vancomycin is found in a protein-bound state. After intravenous administration, vancomycin hydrochloride is found in pleural, pericardial, ascitic, synovial fluids, and in atrial appendage tissue, as well as in urine and peritoneal fluid at concentrations that inhibit microbial growth. Vancomycin slowly penetrates into the cerebrospinal fluid. In meningitis, the drug penetrates into the cerebrospinal fluid. Vancomycin crosses the placental barrier and into breast milk.

Impaired renal function slows the elimination of vancomycin. In patients with absent kidneys, the mean T_1/2 is 7.5 days. The total systemic and renal clearance of vancomycin may be reduced in elderly patients due to the natural slowing of glomerular filtration.

Indications

• Endocarditis. Vancocin^® is effective both as monotherapy and in combination with aminoglycosides for the treatment of endocarditis caused by Streptococcus viridans or Streptococcus bovis. In endocarditis caused by enterococci (e.g., E. faecalis), vancomycin is effective only in combination with aminoglycosides.

There is evidence that Vancocin^® is effective in the treatment of diphtheroid endocarditis. Vancocin^® has been successfully used in combination with rifampicin, aminoglycosides, or both antibiotics for early endocarditis due to Staphylococcus epidermidis or Corynebacterium species following valve prosthesis. In certain cases, Vancocin^® is indicated for the prophylaxis of endocarditis.

• Sepsis;
• Bone and joint infections;
• Lower respiratory tract infections;
• Skin and soft tissue infections;
• Pseudomembranous colitis (as an oral solution).

Vancomycin may also be used for infections caused by gram-positive microorganisms in cases of penicillin allergy, intolerance, or lack of response to treatment with other antibiotics, including penicillins or cephalosporins, as well as infections caused by microorganisms susceptible to vancomycin but resistant to other antimicrobial drugs.

ICD codes

Dosage Regimen

Intravenous infusion.

When administering vancomycin, the recommended concentration is no more than 5 mg/ml and the infusion rate is no more than 10 mg/min. In patients requiring fluid restriction, a concentration of up to 10 mg/ml and an infusion rate not exceeding 10 mg/min may be used. However, with such concentrations, the likelihood of infusion-related adverse events increases.

Adults

The dose for patients with normal renal function is 2 g IV (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. The patient’s age and the presence of obesity may require adjustment of the usual dose based on the determination of vancomycin serum concentrations.

Children

The usual dose is 10 mg/kg administered IV every 6 hours. Each dose should be administered over at least 60 minutes.

Infants and Neonates

For neonates, the initial dose should be 15 mg/kg, then 10 mg/kg every 12 hours during their first week of life. Starting from the second week of life – every 8 hours until reaching the age of 1 month. The drug should be administered over at least 60 minutes. The vancomycin dosing regimen in neonates is given in the following table.

Vancomycin dosing recommendations for neonates

^a – PMA = postmenstrual age (gestational age plus chronological age).

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

^c – serum creatinine concentration is not used to determine the dose for these patients because this parameter is not informative in this case or due to lack of information.

In such patients, careful monitoring of vancomycin serum concentrations is advisable.

Patients with impaired renal function require individualized dose adjustment. The serum creatinine level can be used to select the vancomycin dose for this group of patients.

In elderly patients, Vancomycin has lower clearance and a larger volume of distribution. In this group, dose selection should be based on vancomycin serum concentrations.

In premature infants and elderly patients, a significant dose reduction may be required due to reduced renal function than might be expected. Vancomycin serum concentrations should be monitored regularly. The table below shows vancomycin doses depending on creatinine clearance.

Table of vancomycin doses for patients with impaired renal function

This table cannot be used to determine the drug dose in anuria. Such patients should be prescribed an initial dose of 15 mg/kg of body weight to rapidly achieve therapeutic serum concentrations of the drug. The dose required to maintain a stable drug concentration is 1.9 mg/kg/24 h. In patients with severe renal failure, it is advisable to administer maintenance doses of 250-1000 mg once every few days. In anuria, a dose of 1 g every 7-10 days is recommended.

Preparation of solution for intravenous administration

The injection solution is prepared immediately before administration of the drug. To do this, the required volume of Water for Injections is added to the vial with the dry, sterile vancomycin powder to obtain a solution with a concentration of 50 mg/ml; further dilution of the prepared solution is required. Prepared vancomycin solutions must be further diluted to a concentration not exceeding 5 mg/ml before administration. The required dose of vancomycin diluted as described above should be administered by fractional intravenous infusions over at least 60 minutes. 5% Dextrose injection or 0.9% Sodium Chloride injection can be used as solvents. Before administration, the prepared solution should be visually inspected for mechanical impurities and color change.

Preparation of oral solution

Vancomycin can be used orally for the treatment of pseudomembranous colitis caused by C. difficile due to antibiotic use, as well as for the treatment of staphylococcal enterocolitis. Intravenous administration of vancomycin has no advantages for the treatment of these conditions. Vancomycin is not effective when taken orally for other types of infections. The appropriate dose can be prepared in 30 ml of water and given to the patient to drink or administered through a tube. To improve the taste of the solution, common food syrups can be added to it.

Adverse Reactions

Allergic reactions anaphylactoid reaction, hypersensitivity reactions.

Cardiovascular system: cardiac arrest, flushing, decreased blood pressure, shock (these symptoms are mainly associated with rapid infusion of the drug).

Digestive system: nausea, pseudomembranous colitis.

Hematopoietic system: agranulocytosis, eosinophilia, neutropenia, thrombocytopenia.

Urinary system: interstitial nephritis, changes in renal function tests, impaired renal function.

Skin and subcutaneous tissue: exfoliative dermatitis, benign (IgA) bullous dermatosis, pruritic dermatosis, rash, Red Man Syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, vasculitis.

Special senses: ototoxic effects. In a number of patients receiving Vancomycin, symptoms of ototoxicity such as tinnitus, dizziness, and hearing loss have been observed. These may be transient or permanent. Most such cases were observed in patients receiving excessive doses of vancomycin, with a history of hearing loss, or in patients receiving concurrent treatment with other drugs with potential ototoxicity, such as aminoglycosides.

Other: chills, drug fever, tissue necrosis at injection sites, pain at injection sites, thrombophlebitis.

During or shortly after too rapid infusion of vancomycin, patients may develop anaphylactoid reactions. Rapid administration of the drug can also cause Red Man Syndrome (reddening of the upper body or pain and muscle spasm in the chest and back). After stopping the infusion, these reactions usually resolve within 20 minutes, but can sometimes last for several hours.

Contraindications

• Acoustic neuritis;
• Established hypersensitivity to vancomycin.

With caution: in cases of hearing impairment (including history), renal failure, and in patients allergic to teicoplanin, as cases of cross-allergy have been reported.

Use in Pregnancy and Lactation

The safety of vancomycin in humans during pregnancy has not been studied.

Evaluation of the results of experimental studies in animals did not reveal a direct or indirect adverse effect of vancomycin on the embryo or fetus, pregnancy, or peri- and postnatal development. Vancomycin should be prescribed to pregnant women only if the expected benefit to the mother outweighs the potential risk to the fetus.

If it is necessary to take the drug during breastfeeding, breastfeeding should be discontinued for the duration of treatment with the drug.

Use in Renal Impairment

With caution: in renal failure.

Pediatric Use

The usual dose is 10 mg/kg administered IV every 6 hours. Each dose should be administered over at least 60 minutes.

Geriatric Use

In elderly patients, Vancomycin has lower clearance and a larger volume of distribution. In this group, dose selection should be based on vancomycin serum concentrations.

Special Precautions

Rapid administration (e.g., over a few minutes) of vancomycin may be accompanied by a pronounced decrease in blood pressure and, in rare cases, cardiac arrest. Vancomycin should be administered as a diluted solution over at least 60 minutes to avoid infusion-related adverse reactions.

Patients receiving Vancomycin IV should periodically have blood tests and renal function monitoring.

Vancomycin should be used with caution in patients with renal failure, as high, persistently prolonged blood concentrations of the drug may increase the risk of toxic effects. For patients with renal failure, vancomycin doses should be individualized.

Vancomycin has an irritant effect, and therefore, if the drug enters the tissues adjacent to the vessel, it can cause tissue necrosis. Thrombophlebitis may be observed, although the likelihood of its development can be reduced by slow administration of solutions with low concentration (2.5-5 g/L) and rotation of the injection site.

Overdose

Treatment corrective therapy aimed at maintaining glomerular filtration. Vancomycin is poorly removed by dialysis. There is evidence that hemofiltration and hemoperfusion through polysulfonate ion-exchange resin leads to an increase in vancomycin clearance.

Drug Interactions

With simultaneous intravenous administration of vancomycin and anesthetics, erythema, histamine-like skin flushing, and anaphylactoid reactions have been noted; there is a risk of decreased blood pressure or the development of neuromuscular blockade. Administration of vancomycin as a 60-minute infusion before anesthetic administration may reduce the likelihood of these reactions.

When other potentially ototoxic and/or nephrotoxic drugs (aminoglycosides, amphotericin B, acetylsalicylic acid or other salicylates, bacitracin, capreomycin, carmustine, paromomycin, cyclosporine, loop diuretics, polymyxin B, cisplatin, ethacrynic acid) are used simultaneously and/or sequentially, either systemically or topically, careful monitoring for the possible development of symptoms of ototoxicity (tinnitus, dizziness, and hearing loss) and nephrotoxicity (increased blood creatinine and urea levels, hematuria, proteinuria, rash, eosinophilia, and eosinophiluria) is required.

Cholestyramine reduces the activity.

Antihistamines, meclizine, phenothiazines, and thioxanthenes may mask the symptoms of the ototoxic effect of vancomycin (tinnitus, dizziness, and hearing loss).

Incompatibility

The vancomycin solution has a low pH, which may cause physical or chemical instability when mixed with other solutions.

Mixing with alkaline solutions should be avoided.

Vancomycin and beta-lactam antibiotic solutions are physically incompatible when mixed. The likelihood of precipitation increases with higher vancomycin concentrations. The IV line must be thoroughly flushed between administrations of these antibiotics. Furthermore, it is recommended to reduce the vancomycin concentration to 5 mg/ml or less.

Storage Conditions

List B. Store at a temperature of 15°-25°C (59°-77°F).

Prepared solution of the drug: store refrigerated at a temperature of 2°-8°C (36°-46°F) for no more than 14 days.

Keep out of reach of children.

Shelf Life

The shelf life is 2 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.