Vancorus, powder and oral intake 1 g

Pharmacodynamics

Vancomycin is a tricyclic glycopeptide antibiotic, produced by Amycolatopsisorientalis, acts bactericidally on most microorganisms (on Enterococcus spp. – bacteriostatically). It blocks the synthesis of the bacterial cell wall at a site different from that of penicillins and cephalosporins (it does not compete with them for binding sites), firmly binding to the D-alanyl-D-alanine part of the cell wall precursor, which leads to cell lysis.

Active against Gram-positive microorganisms, including: Staphylococcusaureus andStaphylococcusepidermidis(including heterogeneous methicillin-resistant strains),Streptococcusspp.,Enterococcusspp. (including Enterococcus faecalis), Clostridium spp. (including Clostridium difficile). Listeria monocytogenes, bacterial genera Lactobacillus spp., Actinomyces spp., Bacillus spp. are sensitive to vancomycin in vitro.

The maximum effect is at pH 8, at lowering pH to 6 the effect sharply decreases.

It is active only against microorganisms in the reproduction stage.

Resistant to almost all Gram-negative bacteria, Mycobacterium spp., fungi, viruses, protozoa. It does not have cross-resistance with other antibiotics.

When administered orally it has no systemic action, it acts locally on sensitive microflora in the gastrointestinal tract (Staphylococcus aureus, Clostridium difficile).

Pharmacokinetics

The maximum concentration (Cmax) after intravenous infusion of 500 mg is 49 µg/ml after 30 minutes and 20 µg/ml after 1-2 hours; after an intravenous infusion of 1 g – 63 mcg/ml after 60 minutes and 23-30 mcg/ml after 1-2 hours. The binding to plasma proteins is 55%.

Therapeutic concentrations are determined in ascitic, synovial, pleural, pericardial and peritoneal fluids, urine, atrial auricle tissue. It does not penetrate through the intact blood-brain barrier (with meningitis it is detected in cerebrospinal fluid in therapeutic concentrations).

Vancomycin penetrates through the placenta. It is excreted with breast milk.

Half-life (T1/2) in normal renal function: adults – about 6 hours (4-11 hours), newborns – 6-10 hours, infants – 4 hours, older children – 2-3 hours; T1/2 in chronic renal failure (oliguria or anuria) in adults – 6-10 days. Cumulation is possible when administered repeatedly. 75-90% of the drug is excreted by the kidneys by passive filtration in the first 24 hours. In patients with one kidney it is excreted slowly and the excretion mechanism is unknown.

In small and moderate amounts vancomycin may be excreted with bile. It is excreted in small amounts by hemodialysis or peritoneal dialysis. It is poorly adsorbed by ingestion and usually does not penetrate into the systemic bloodstream. Detectable plasma concentrations of vancomycin may be observed in isolated cases with repeated oral administration in patients with acute pseudomembranous colitis caused by C. difficile.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to vancomycin:

In oral solution: pseudomembranous colitis caused by Clostridium difficile; enterocolitis caused by Staphylococcus aureus.

Active ingredient

Composition

1 vial of lyophilizate for preparation of solution for infusion contains:

the active ingredient:

vancomycin (in hydrochloride form) 1 g.

How to take, the dosage

Vancomycin is administered as a slow intravenous infusion at a rate of no more than 10 mg/minute for at least 60 minutes. The concentration of prepared vancomycin solution should not exceed 5 mg/ml.

In adults, 0.5 g or 7.5 mg/kg every 6 hours or 1 g or 15 mg/kg every 12 hours.

In children: to newborns up to 7 days of life the initial dose is 15 mg/kg of body weight, then 10 mg/kg every 12 hours; starting from the second week of life – 10 mg/kg every 8 hours; to children from 1 month and older – 10 mg/kg every 6 hours.

Patients with impaired renal excretory function require correction of dosage regimen with regard to creatinine clearance (CK) values.
Correction can be done by increasing the intervals between injections or by reducing the single dose of the drug:

Correction by increasing the intervals between injections:

Creatinine clearance (ml/min)

/td>

Vancomycin dose

Interval between injections

over 80

1 g

12 h

80-50

1 g

1-3 days

50-10

1 g

3-7 days

less than 10

1 g

7-14 days

Correction of the single dose:

Creatinine clearance (ml/min)

Vancomycin dose (mg/day)

100

1545

90

1390

80

1235

70

1080

60

925

50

Interaction

In concomitant intravenous administration of vancomycin and local anesthetics erythematous rashes and facial skin hyperemia may appear, in adults – intracardiac conduction disorders.

When other potentially ototoxic and/or nephrotoxic drugs (aminoglycosides, amphotericin B, aminosalicylic acid or other salicylates, capreomycin, carmustine, cyclosporine, “loop” diuretics, including etacrynic acid, etacrynic acid and other salicylates) are used simultaneously and/or sequentially systemically or topically.including etacrynic acid, polymyxin B, cisplatin) requires close monitoring of the possible development of these symptoms.

Colestiramine reduces the activity of vancomycin when taken orally.

Antihistamines, meclosine, phenothiazines, thioxanthenes may mask the symptoms of ototoxic effects of vancomycin (tinnitus, vertigo).

Pharmaceutical interactions

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 increasing vancomycin concentration. The intravenous system should be adequately flushed between applications of these antibiotics. In addition, it is recommended that vancomycin concentrations be reduced to 5 mg/ml or less.

Special Instructions

The drug is intended for hospital use only.

When the drug is used in infants and premature infants, plasma vancomycin concentrations should be monitored regularly.

The drug should be administered by infusion slowly (at least 60 minutes). Rapid administration (e.g., within a few minutes) of vancomycin may be accompanied by a marked decrease in BP and, in rare cases, by cardiac arrest.

The incidence and severity of thrombophlebitis can be reduced by proper dilution of the initial solution and by alternating the injection sites.

Long-term use of vancomycin requires audiogram, monitoring of peripheral blood count, renal function (total urinalysis, blood creatinine and urea nitrogen values).

It is desirable to determine vancomycin serum concentrations in renal failure in patients over 60 years because high, long-term vancomycin concentrations in the blood may increase the risk of toxic effects of the drug (maximum concentrations should not exceed 40 mcg/ml and minimum – 10 mcg/ml, concentrations over 80 mcg/ml are considered toxic). For patients with renal insufficiency, vancomycin doses should be adjusted individually.

Contraindications

Side effects

Postinfusion reactions (due to rapid administration): anaphylactoid reactions (BP decrease, cardiac arrest, bronchospasm, dyspnea, skin rash, itching); “red man” syndrome associated with histamine release (chills, fever, palpitations, hyperemia of the upper torso and face, spasm of the chest and back muscles).

Urinary system disorders: nephrotoxicity (up to development of renal failure) more often in combination with aminoglycosides or when administered for more than 3 weeks in high concentrations, manifested by increased concentration of creatinine and urea nitrogen in blood; interstitial nephritis.

Digestive system disorders: nausea, pseudomembranous colitis.

Sensory system disorders: ototoxicity – decreased hearing, vertigo, tinnitus.

Hematopoietic organs: reversible neutropenia, transient thrombocytopenia, agranulocytosis.

Allergic reactions: fever, chills, eosinophilia, rash (including exfoliative dermatitis), erythema malignant exudative (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome), vasculitis.

Local reactions (if infusion rules are violated): pain and tissue necrosis at the injection sites, phlebitis.

Overdose

Symptoms: increased severity of side effects on the urinary system and sensory organs.

Treatment: symptomatic therapy is carried out. Fluid administration and control of plasma concentrations of vancomycin are recommended. Hemofiltration is more effective than hemodialysis for rapid removal of excess vancomycin from the body.

Pregnancy use

In pregnancy (II-III trimester), Vancorus is prescribed only if the estimated benefit to the mother outweighs the potential risk to the fetus.

Vancomycin is excreted with the breast milk. Breastfeeding should be stopped while taking the drug.

Similarities