Teicoplanin

TEYKOPLANIN-PHARMEX lyophilisate for solution for injection 200 mg, lyophilisate for solution for injection 400 mg

Instruction manual

For medical use of the drug

Teicoplanin-farmex

(teicoplanin-pharmex)

Structure:

Active substance: teicoplanin;

1 vial contains teicoplanin 200 mg or 400 mg;

excipients: sodium chloride;

solvent - water for injection.

Dosage form.

Lyophilisate for injection.

Basic physical and chemical properties:

• lyophilisate vial: lyophilized porous mass or yellowish powder;
• solvent bottle: clear, colorless liquid.

Pharmacotherapeutic group.

Glycopeptide antibiotics. atx j01x a02.

Pharmacological properties.

Pharmacodynamics

Teicoplanin is a systemic glycopeptide antibiotic, a fermentation product of Actinoplanes teichomyceticus, which has bactericidal activity against aerobic and anaerobic gram-positive bacteria. Teicoplanin inhibits the growth of sensitive microorganisms by interfering with the biosynthesis of cell membranes in places other than the sites of beta-lactam antibiotics.

Antimicrobial spectrum. The boundary concentrations that allow differentiating sensitive strains (S) from strains with moderate sensitivity and strains with moderate sensitivity from resistant strains (R) are as follows: S

The prevalence of acquired resistance to this drug in some types of pathogens may vary depending on geographic region and time. In this regard, it is useful to have information on the local prevalence of resistance, especially in the treatment of severe infections. These data are only general guidelines indicating the likelihood of sensitivity of a particular bacterial strain to this antibiotic.

In vitro tests confirm that teicoplanin is active against the following sensitive gram-positive aerobes: Bacillus, Enterococci, Listeria, Rhodococcus, Staphylococcus aureus, Staphylococcus non-aureus, Streptococcus, Streptococcus pneumonia; Anaerobes: Clostridium, Eubacterium, Peptostreptococcus, Propionibacterium acnes.

Teicoplanin-resistant microorganisms include gram-positive aerobes, such as Actinomyces, Erysipelothrix, Hetherofermentative Lactobacillus, Leuconostoc, Nocardia asteroides, Pediococcus, as well as gram-negative aerobes, such as cocci, bacilli and other microorganisms, such as microorganisms, microorganisms, and microbes.

Teicoplanin does not show cross-resistance with other classes of antibiotics.

Bactericidal synergism was observed in vitro with aminoglycosides against Enterococci and Staphylococci. The combination of teicoplanin and fluoroquinolones usually has an additive, sometimes synergistic effect against Staphylococci.

Pharmacokinetics

Absorption. It is not absorbed after oral administration. The bioavailability after intramuscular injection is 94%.

Distribution (serum concentrations). The nature of the distribution of concentrations in blood serum after intravenous administration is two-phase (first, the fast distribution phase, then the slow distribution phase) with half-periods of about 0.3 and 3 hours, respectively. After the distribution phase, a slow elimination occurs, the half-period of which is 70–100 hours.

Single dose. 5 minutes after intravenous injection, doses of 3 mg / kg or 6 mg / kg in healthy individuals, serum concentrations reach 54.3 and 111.8 mg / l, respectively. Residual serum concentrations 24 hours after the injection are 2.1 and 4.2 mg / L, respectively.

Repeated doses. In the case of administration of teicoplanin by a 30-minute infusion at a dose of 400 mg every 12 hours for 5 days in healthy individuals, the average residual serum concentrations after the first injection are 5.6 ± 0.7 mg / l, and after the second - 9.4 ± 1.5 mg / l. After further injections, serum concentrations stably exceed 10 mg / l after 12 hours.

In the case of administration of the drug to patients with neutropenia on the first day of treatment by intravenous injection at a dose of 400 mg every 12 hours, 24 hours after the second injection, the residual concentration is 10.8 ± 5.7 mg / L.

In healthy individuals, after 3 intramuscular injections of 200 mg every 12 hours, and then another three injections of 200 mg every 24 hours, the residual concentration 24 hours after the last injection is 6.1 mg / L.

Binding to plasma proteins. 90–95% binding to albumin.

Tissue distribution. The apparent volume of distribution at the saturation stage is in the range of 0.6–1.2 l / kg. After injection of teicoplanin labeled with a radioactive isotope, it was found that it quickly penetrates into tissues (especially skin and bone), then reaches high concentrations in the kidneys, trachea, lungs and adrenal glands. Teicoplanin is absorbed by white blood cells and increases their antibacterial activity. Teicoplanin does not penetrate red blood cells, cerebrospinal fluid and adipose tissue. After intravenous administration of a single dose of 400 mg, the following concentrations were observed in the tissues:

spongy layer of bone: 10.8 μg / g and 7.1 μg / g after 0.5 and 24 hours after injection, respectively;

compact bone layer: 6.1 μg / g and 4.9 μg / g after 0.5 and 24 hours after injection, respectively;

synovial fluid with inflammation: the resulting concentrations were 4 and 1.4 mg / l 6 and 24 hours after injection, respectively;

pulmonary tissue: the resulting concentrations were 7.9 and 4.5 μg / g 30 and 60 min after injection, respectively;

pleural fluid: the average maximum concentration - 2.8 mg / l - was achieved 6 hours after administration;

peritoneal fluid: the concentration was 27.9 mg / l 1 hour after administration.

Biotransformation. No teicoplanin metabolites were found. More than 80% of teicoplanin administered is excreted unchanged in the urine after 16 days.

Breeding.

Persons with normal renal function: injected teicoplanin is almost completely excreted in the urine unchanged. The final half-life of the product is 70-100 hours. Patients with renal failure: teicoplanin is eliminated more slowly than in patients with normal renal function. There is a relationship between the final elimination half-life and creatinine clearance.

Elderly: changes in the elimination of teicoplanin reflect only age-related deterioration of renal function.

Clinical characteristics.

Indications.

Infections caused by gram-positive bacteria, including those sensitive or resistant to methicillin, in particular in patients with allergies to beta-lactam antibiotics.

Adults

Treatment:

infections of the skin and soft tissues;

infections of the upper and lower urinary tract with and without complications;

respiratory tract infections;

infections of the ear, throat, nose;

infections of bones and joints;

septicemia;

endocarditis;

peritonitis associated with continuous peritoneal dialysis on an outpatient basis.

Prevention: infectious endocarditis in case of allergy to beta-lactam antibiotics:

in dentistry or in procedures in the upper respiratory tract when general anesthesia is used;

during surgical interventions on the genitourinary and gastrointestinal tract.

Children (except newborns).

Treatment:

infections of the skin and soft tissues;

infections of the upper and lower urinary tract with and without complications;

respiratory tract infections;

infections of the ear, throat, nose;

infections of bones and joints;

septicemia.

Contraindications

Hypersensitivity to teicoplanin. contraindicated for use in newborns. the use of this drug during breastfeeding is not recommended (see section "use during pregnancy or breastfeeding").

Interaction with other drugs and other types of interactions.

Special warnings related to the mismatch of the international normalized ratio (mms): numerous cases of increased anticoagulant activity have been reported in patients receiving oral antibiotic therapy.in case of infection or severe inflammatory process, the elderly age and severe general condition of the patient are risk factors. under such conditions, it is difficult to determine how much the infection itself or its treatment play a role in the imbalance of mms.

Despite this, certain classes of antibiotics have this effect to a greater extent, in particular fluoroquinolones, macrolides, cyclins, cotrimoxazole and some cephalosporins.

Due to the increased risk of adverse reactions, teicoplanin should be used with caution in patients who are simultaneously using nephrotoxic or ototoxic drugs, such as aminoglycosides, amphotericin B, cyclosporine and furosemide.

Features of the application.

It is necessary to adjust the dose for patients with renal failure (see section "method of administration and dose").

A regular detailed blood test should be performed during prolonged treatment and / or treatment with high doses (especially in the first month of therapy) simultaneously with regular monitoring of liver and kidney function.

When using teicoplanin, cases of ototoxicity, toxic effects on the hematopoietic system and cases of hepatotoxicity and nephrotoxicity have been reported. It is necessary to conduct repeated studies of kidney function and hearing, especially in such situations:

with prolonged treatment of patients with renal failure; with the simultaneous and further use of drugs that can have a neurotoxic and / or nephrotoxic effect (aminoglycosides, colistin, amphotericin, cyclosporine, cisplatin, furosemide and ethacrylic acid).

This medicine should be used with caution in patients with hypersensitivity to vancomycin, since cross-sensitivity may occur. However, the presence of a history of "red man syndrome" associated with the use of vancomycin is not a contraindication to the use of teicoplanin.

This medicine contains sodium. The sodium content is less than 1 mmol per dose, that is, in practice, this drug is considered "not containing sodium."

Use during pregnancy or lactation.

Pregnancy. animal studies have not revealed teratogenic effects, and clinical data are insufficient. however, due to the high therapeutic effect of teicoplanin, its use is possible if during pregnancy there is a need for its admission for health reasons (regardless of gestational age). in this case, the auditory function of the newborn should be checked (otoacoustic emission), due to the possible ototoxic effect of teicoplanin.

Lactation. There is no data on the penetration of teicoplanin into breast milk, so breastfeeding during treatment with teicoplanin-farmex is not recommended.

The ability to influence the reaction rate when driving vehicles or other mechanisms.

It is recommended to refrain from driving vehicles or working with machinery because of the risk of dizziness.

Dosage and administration.

When using antibacterial agents, it is necessary to strictly follow the established recommendations.

Prevention

Adults Prevention of infectious endocarditis: 400 mg intravenously during induction anesthesia. Teicoplanin should be combined with aminoglycoside in patients with prosthetic heart valves.

Treatment.

The total duration of treatment depends on the type, severity and individual characteristics of the patients body.

Adults and older people with normal kidney function.

Infections of the respiratory tract, infections of the skin and soft tissues, urinary tract, ear, throat, nose and other moderate infections:

loading dose: standard dose - 400 mg / day (which is usually 6 mg / kg / day) as a single intravenous injection (on the first day);

maintenance therapy: a standard dose of 200 mg / day (which is usually 3 mg / kg / day) as a single intravenous or intramuscular injection per day. Septicemia, infections of bones and joints, endocarditis, severe lung diseases and other serious infections:

loading dose: standard dose - 400 mg (which is usually 6 mg / kg) intravenously, every 12 hours, from the 1st to the 4th day.

maintenance therapy: a standard dose of 400 mg / day (which is usually 6 mg / kg / day) as a single intravenous or intramuscular injection per day.

Achieving the optimal dose helps determine the concentration of the antibiotic in the blood plasma. In the case of a moderate or more severe infection with the administration of loading doses, it is necessary to monitor the residual plasma concentrations to ensure that stable residual plasma concentrations of at least 10 mg / L (determined by high performance liquid chromatography, HPLC) or 15 mg / L (determined by the immunoenzymatic method) are achieved fluorescence polarization, FPIA), as well as during maintenance therapy, to ensure that these concentrations are stable.

With maintenance therapy in the treatment of septicemia and endocarditis, the transition to the intramuscular route of administration depends on the clinical course of the disease.

In some particularly difficult clinical situations, when the minimum inhibitory concentrations (MIC) of teicoplanin are high (4-8 mg / l), taking into account the bacterial load, or when the pharmacokinetics of the drug in the blood serum are difficult to predict (significant burns, intensive care, etc. ), or subject to a low tissue distribution (bone, heart valve), the recommended loading dose is 3-5 injections of 12 mg / kg every 12 hours. If necessary, maintenance doses can be prescribed - up to 12 mg / kg and above.

Achieving the optimal dose helps determine the concentration of the antibiotic in the blood plasma.

When loading doses are taken, residual plasma concentrations must be monitored to ensure stable plasma residual concentrations are achieved between 20–30 mg / L (HPLC) or 30–40 mg / L (FPIA), as well as during maintenance therapy to ensure that these concentrations are stable.

Children (except newborns) with normal renal function.

The dose and duration of treatment depends on the severity of the infection:

loading dose: the first three injections - 10-12 mg / kg every 12 hours; maintenance therapy: 10 mg / kg / day.

For moderate infection (without neutropenia):

loading dose: the first three injections - 10 mg / kg every 12 hours; maintenance therapy: 6 mg / kg / day.

Achieving the optimal dose helps determine the concentration of the antibiotic in the blood plasma.

In the case of a moderate or more severe infection, when receiving loading doses, it is necessary to monitor the residual plasma concentrations to ensure that stable residual plasma concentrations of at least 10 mg / L (HPLC) or 15 mg / L (FPIA) are achieved, as well as during maintenance therapy to ensure that these concentrations are stable.

In some particularly difficult clinical situations, when the MEC of teicoplanin is high (4-8 mg / l), given the bacterial load, or when the pharmacokinetics of the drug in the blood serum are difficult to predict (significant burns, intensive care, etc.), or in conditions low tissue distribution (bone, heart valve) when receiving loading doses, it is necessary to monitor the residual plasma concentration to ensure stable plasma residual concentrations between 20 and 30 mg / L (HPLC) or 30-40 mg / L (FPIA) are achieved, and during maintenance therapy, to ensure that these concentrations are stable.

Adults and elderly patients with renal failure (impaired renal function).

During the first 3 days, it is recommended to adhere to the standard treatment regimen: if creatinine clearance is 40-60 ml / min, the standard dose should be divided in half (enter the initial dose every two days or half the dose daily);

if creatinine clearance is

For patients with reduced renal function and secondary peritonitis, which arose as a result of continuous ambulatory peritoneal dialysis, a dosage regimen of 20 mg of teicoplanin per 1 liter of dialysis fluid and a loading dose of 200 mg intravenously is recommended (for patients with elevated body temperature).

Achieving the optimal dose helps determine the concentration of the antibiotic in the blood plasma. In the case of a moderate or more severe infection, when receiving loading doses, it is necessary to monitor the residual plasma concentrations to ensure that stable residual plasma concentrations of at least 10 mg / L (HPLC) or 15 mg / L (FPIA) are achieved, as well as during maintenance therapy to ensure that these concentrations are stable.

At some particularly severe clinical concentrations, when MIC of teicoplanin is high (4–8 mg / l), given the bacterial load, or when the pharmacokinetics of the drug in the blood serum are difficult to predict (significant burns, intensive care, etc.), or under conditions of low tissue distribution (bones, heart valve), when applying loading doses, it is necessary to monitor residual plasma concentrations to ensure stable plasma residual concentrations between 20 and 30 mg / L (HPLC) or 30–40 mg / L (FPIA) are reached and during P dderzhivayuschego treatment to make sure that these concentrations are stable.

Mode of application. Enter intravenously or intramuscularly. Intravenous administration is carried out for 1 minute or by intravenous infusion for 30 minutes.

Method of preparation of the solution: slowly introduce the entire solvent into the vial, and then gently shake between the palms until the powder is completely dissolved. Avoid the formation of bubbles! If foam occurs, leave the bottle upright until it disappears. Thus prepared isotonic

the solution (pH 7.5) can be stored for no more than 24 hours at a temperature of no higher than 25 ° C or 7 days at a temperature of (5 ± 3) ° C.

The finished solution can be injected or diluted:

• 0.9% sodium chloride solution. After dilution, the drug can be stored for no more than 24 hours at a temperature of no higher than 25 ° C or 7 days at 4 ° C;
• a solution based on sodium lactate (Ringer-lactate, Hartmann). After dilution, the drug can be stored for no more than 24 hours at a temperature of no higher than 25 ° C or 7 days at 4 ° C;
• 5% glucose solution (ready-made solution prepared in this way can be stored for 24 hours at a temperature not exceeding 25 ° C);
• 0.18% solution of sodium chloride and 4% glucose (the solution prepared in this way can be stored for 24 hours at a temperature not exceeding 25 ° C);
• solution for peritoneal dialysis - 1.36% or 3.86% glucose (prepared in this way, the solution can be stored for 28 days at 4 ° C).

Teicoplanin maintains its stability for 48 hours at 37 ° C in the composition of peritoneal dialysis solutions containing insulin or heparin.

Children.

The use of the drug in newborns is contraindicated.

Overdose.

Teicoplanin is not excreted by hemodialysis. overdose treatment should be symptomatic.

Adverse Reactions

Hypersensitivity reactions: rash, urticaria, erythema, pruritus, fever, colds, anaphylactic reactions (angioedema, bronchospasm, anaphylactic shock), exfoliative dermatitis.

On the part of the skin and subcutaneous tissues: severe bullous skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, in exceptional cases, erythema multiforme).

From the liver: a temporary increase in the level of transaminases and / or alkaline phosphatase.

On the part of the blood and lymph: eosinophilia, leukopenia, thrombocytopenia; neutropenia (rarely severe) or agranulocytosis (reversible after discontinuation of treatment), which often develops when receiving high doses and in the first month of therapy.

From the digestive tract: nausea, vomiting, diarrhea.

On the part of the kidneys and urinary tract: a temporary increase in creatinine,

renal failure, which usually occurs in patients with severe infection, the presence of the underlying disease and / or in patients who receive other drugs that can detect nephrotoxic effects.

From the nervous system: dizziness, headache, hearing loss, tinnitus, disorders of the vestibular apparatus, cases of seizures have been reported.

Local reactions: pain, phlebitis, erythema, abscess.

Other: superinfection (increase in the number of insensitive microorganisms). There have also been reports of cases of erythema and hot flashes in the upper body after application of the solution, which appeared without prior use of teicoplanin and did not recur during subsequent use with a decrease in the rate of administration or a decrease in concentration.

Shelf life.

2 years.

Storage conditions.

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

Keep out of the reach of children.

Packaging

200 or 400 mg per vial, 1 vial complete with 1 vial of solvent (water for injection) 3.2 ml in blister packs, 1 blister pack in a pack of cardboard, 15 blister packs in a box of cardboard.

Vacation category.

On prescription.

Manufacturer.

LLC “farmex group”.

The location of the manufacturer.

Ukraine, 08300, Kiev region, Borispol, st. Shevchenko, 100.

All cases of adverse reactions must be reported to the manufacturer:

LLC “Farmeks Group”, Ukraine, 08300, Kiev region, Borispol, st. Shevchenko, 100, tel. +38 (044) 391–19–19, fax: +38 (044) 391–19–18, or through the form on the website: http://www.pharmex.com.ua/kontakty/forma-137-o/