Ванкомабол®

General characteristics. Structure:

Active ingredient: 500 mg or 1000 mg of Vancomycinum a hydrochloride (in terms of Vancomycinum).
 
Antibiotik-glikopeptid, effective concerning gram-positive microorganisms: stafilokokk (including the penitsillinazoobrazuyushy / forming enzyme a penicillinase destroying penicillin / and metitsillinorezistentny/steady to Methicillinums / strains), streptococci (including strains, resistant to penicillin), korinebakteriya, clostridiums.

Pharmacological properties:

Pharmacodynamics. The antibacterial agent produced by Amycolatopsis (Nocardia) orientalis. Works bakteritsidno. The mechanism of action is caused by blocking of polymerization of glycopeptides of a cell wall that leads to destruction of a microbic cell. Also changes permeability of a cytoplasmic membrane and selectively inhibits synthesis of RNA of bacteria. The target of action of Vancomycinum is other than what penicillin and cephalosporins therefore between Vancomycinum and antibiotics of other groups cross resistance is not observed affect.

It is selectively active concerning gram-positive microorganisms: Staphylococcus aureus, Staphylococcus epidermidis (including the strains steady against Methicillinum/Oxacillinum); the majority of streptococci, including Streptococcus pyogenes, Streptococcus pneumoniae (including the strains steady against penicillin), Streptococcus agalactiae, the green streptococci, Streptococcus bovis; enterococci, including Enterococcus faecalis and Enterococcus faecium (the majority of strains of E.faecium have intermediate sensitivity to Vancomycinum); Corynebacterium spp.; Listeria monocytogenes, Bacillus spp. Clostridium spp., (including toksinprodutsiruyushchy strains of Clostridium difficile causing pseudomembranous colitis); Peptococcus spp., Peptostreptococcus spp. and Actinomyces spp.

Ванкомабол® it is inactive against gram-negative microorganisms (an exception significant activity concerning Flavobacterium meningosepticum makes), mycobacteria, intracellular pathogens, Bacteroides spp. and mushrooms.

The optimum of action is observed at рН 8; at decrease рН to the 6th the antimicrobic effect sharply decreases.

Pharmacokinetics. At patients with normal function of kidneys at once after infusion in a dose of 15 mg/kg lasting about 1 hour of concentration in a blood plasma make 63 mkg/ml, in two hours decrease to 23 mkg/ml, and in 11 hours - to 8 mkg/ml. Distribution volume - 0,39-0,92 l/kg. After concentration Vancomycinum lasting 30 min., intravenous (in/in) introductions of 500 mg, in plasma make 49 mkg/ml; in 1-2 h decrease to 20 mkg/kg. At repeated introductions does not kumulirut. Communication with proteins of plasma of-55%.

Well gets into many bodies and fabrics. Bactericidal concentration more than 4 mg/l are defined in ascitic, synovial, pleural and pericardiac liquids, in urine, auricula atrii fabric.
 
Does not get through the unimpaired blood-brain barrier, but at an inflammation of a meninx it is found in liquor in the therapeutic concentration exceeding 4 mg/l.
 
Gets through a placenta. It is allocated with breast milk.
 
The elimination half-life at normal function of kidneys varies depending on age: adults have about 6 h (4-11 h), newborns have 6-10 h, children about one year have 4 h, children of more advanced age have 2-3 h Т½ at a renal failure and a renal failure increases, reaching at a heavy and terminal renal failure (clearance of creatinine less than 10 ml/min.) 6-10 days.

In an organism it is practically not metabolized. 75-90% of drug are removed by kidneys by glomerular filtering in the first 24 h.
 
In small and moderate amounts it can be removed through intestines. In insignificant quantities it is removed at a hemodialysis or peritoneal dialysis.

Indications to use:

Intravenously:
The medium-weight and heavy infections caused by gram-positive aerobic cocci and gram-positive bacteria, steady against penicillin and cephalosporins, and also heavy gram-positive infections at an allergy to penicillin and cephalosporins:
 
- the infections of the central nervous system caused by stafilokokka and streptococci (especially S. pneumoniae) with multiple resistance; the infections caused by Flavobacterium meningosepticum, including meningitis;
 
- lower respiratory tract infections, including extra hospital and nozokomialny pneumonia, abscess of lungs and empyema of a pleura;
 
- the bacterial endocarditis caused by Streptococcus viridans, Streptococcus bovis; at the endocarditis caused by enterococci (for example Enterococcus faecalis), Vancomycinum is used combinations with aminoglycosides;
 
- infections of bones and joints (including osteomyelitis);
 
- infections of skin and soft tissues;
 
- the sepsis caused by gram-positive microorganisms.
 
Inside:
 
- the coloenteritis caused by S. aureus, including Oxacillinum - resistant strains;
 
- the pseudomembranous colitis caused by Cl.difficile.

Route of administration and doses:

Ванкомабол® it is entered only intravenously kapelno; the recommended concentration of solution for infusions of 5 mg/ml, rate of administering less than 10 ml/min.

Adults: usual doses at adults with normal function of kidneys - on 0,5 g each 6 h, or on 1 g each 12 h. For treatment of bacterial meningitis enter 500-750 mg each 6 hours. The recommended duration of intravenous infusion of a single dose - 60 min.

Dose adjustment of Vankomabola® taking into account values of clearance of creatinine is required from patients with a renal failure.
Dosing of Vankomabola® at patients with a renal failure:
 
The clearance of creatinine more than 80 ml/min. - to 1 g is each 12 hours; 80-50 - To 1 g there are each 1-3 days; 50-10 - To 1 g there are each 3-7 days; to less than 10 - 1 g there are each 7-14 days; the hemodialysis - to 1 g is each 7-10 days.
 
Children from 1 month to 12 years - on 10 mg/kg each 6 hours; the single dose is entered in a look into infusions lasting about 1 hour. The maximum daily dose - no more than 2 g. For treatment of bacterial meningitis the dose is increased to 15 mg/kg which is entered by each 6 hours. Newborn children - on 15 mg/kg, and then 10 mg/kg each 12 h.

For treatment of the coloenteritis caused by S.aureus, and pseudomembranous colitis: adult - 0,125-0,5 g in each 6-8 hours, to children - 40 mg/kg/days (but no more than 2 g), divide the received dose into 3-4 receptions of per os.

Duration of therapy is 7-10 days. The single dose is dissolved approximately in 30 ml of water, the received solution is allowed to drink. For improvement of flavoring properties it is possible to add sugar syrup. Solution can be also entered via the nazogastralny probe.

Cultivation. Lyophilisate is dissolved in water for injections: 500 mg - in 10 ml, 1 g - in 20 ml (concentration of solution makes 50 mg/ml). The received solution is diluted with the following minimum quantities of 0.9% of solution of sodium of chloride or 5% of solution of a dextrose: for 500 mg - 100 ml and for 1000 mg - 200 ml. Ready solution should be entered in the form of slow intravenous infusion lasting about 60 min.

Features of use:

Dynamic control of function of kidneys, including indicators of creatinine and urea nitrogen, the analysis of urine is necessary for reduction of risk of nephrotoxicity at patients with the available renal failures (including at elderly patients), at the patients with a hypovolemia and also who are at the same time accepting other nefrotoksichny drugs (aminoglycosides, polymyxin B, Amphotericinum In, furosemide, antineoplastic drugs).

The risk of ototoxicity is higher in group of patients with initial renal failures and hearing (functional or organic lesion of an inner ear and acoustical nerve) and/or accepting other ototoksichesky drugs. For decrease in risk of ototoxicity, especially at long therapy of Vankomabolom®, periodic control of audiogrammy is necessary.

Vancomycinum has local irritative effect at hit in soft tissues, especially in high concentration. Therefore, it is necessary to observe strictly a technique of intravenous administration and to avoid hit of solution out of a vessel.

From premature newborns control of serumal concentration of Vancomycinum for correction of the modes of dosing sometimes is required.

It is desirable to define concentration of Vancomycinum to blood serum (at a renal failure, at patients 60 years are more senior) for correction of doses and modes of introduction. The maximum concentration should not exceed 40 mkg/ml and minimum - 10 mkg/ml. Concentration over 80 mkg/ml are considered as toxic
 
Ванкомабол® women can appoint during pregnancy only in II and III trimesters.

In need of use of drug in the period of a lactation it is necessary to stop breastfeeding.

Side effects:

Post-infusional reactions: (owing to bystry introduction), connected with massive release of a histamine from mast cells: anaphylactoid reactions (arterial hypotonia, bronchospasm, диспноэ, skin rash, itch), syndrome of "the red person" (tachycardia, hyperemia of an upper half of a trunk and person), fever, crick of muscles of a thorax and back. The specified reactions take place independently in 20 min. or several hours. For prevention of development of post-infusional complications use only slow intravenous infusion of Vankomabola® lasting not less than 1 hour.

Allergic reactions: fever, nausea, a fever, an eosinophilia, rash (including exfoliative dermatitis), a malignant exudative erythema (Stephens-Johnson's syndrome), a vasculitis.

From an urinary system: nephrotoxicity (increase in creatine of blood serum, an urea nitrogen, is very rare - development of a renal failure), it is rare - intersticial nephrite.

From digestive organs: nausea, it is very rare - pseudomembranous colitis.

From sense bodys: ototoxicity - decrease in hearing, вертиго, a ring in ears.

From bodies of a hemopoiesis: a reversible neutropenia (especially at long reception), it is rare - passing thrombocytopenia, an agranulocytosis.
Local reactions: phlebitis, pain in an injection site, at hypodermic or intramuscular introduction - a necrosis of soft tissues.

Interaction with other medicines:

At co-administration with local anesthetics children can have erythematic rashes and a hyperemia of integuments of the person, adults have disturbances of endocardiac conductivity.

The general anesthetics and vekuroniya bromide - risk of a lowering of arterial pressure or development of neuromuscular blockade. Infusion of Vankomabola® is possible at least in 60 min. prior to their introduction.

Co-administration with nefro-and ototoksichny medicines is not recommended (aminoglycosides, Amphotericinum In, p-aminosalicylic acid or other salicylates, bacitracin, буметанид, капреомицин, кармустин, паромомицин, cyclosporine, "loopback" diuretics, polymyxin B, Cisplatinum, Acidum etacrynicum).

Antihistaminic medicines, меклозин, fenotiazina, thioxanthenes can mask symptoms of ototoksichesky action of Vancomycinum (a sonitus, вертиго). Vankomabola® solutions pharmaceutical are incompatible with solutions of other antibiotics.

Contraindications:

Hypersensitivity to Vancomycinum, other glycopeptides, the I trimester of pregnancy, the lactation period, neuritis of an acoustical nerve.

With care appoint at pregnancy (II, the III trimester), at a hearing disorder (including in the anamnesis), a heavy renal failure (dose adjustment is required).

Overdose:

Symptoms: strengthening of expressiveness of by-effects.

Treatment: the supporting and symptomatic therapy directed to maintenance of glomerular filtering. Vancomycinum is badly washed away at a hemodialysis.
 
There are haemo filterings given about efficiency and hemoperfusion with use of polysulfonic ion-exchange resins for decrease in concentration of Vancomycinum in plasma.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

500 mg or 1000 mg of active agent in bottles glass with a capacity of 10 ml and 20 ml. 1 bottle with drug and the application instruction is placed in a pack from a cardboard.