Lendacin - instructions for use, dose, side effects, contraindications

Ceftriaxone is a third generation generic cephalosporin antibiotic actions for parenteral introduction. Bactericidal activity is due to the suppression of bacterial cell wall synthesis. It is characterized by resistance to the action of most β-lactamases of gram-negative and gram-positive microorganisms. It is active against the following microorganisms:

Gram-positive aerobes:

Staphylosobys aireis (methicillin-sensitive), Staphylosobys spp. (coagulase-negative), Streptococcus ruogens (β-hemolytic, group A), Streptococcus agalactiae (β-hemolytic, group B), Streptococcus spp. (β-hemolytic, the groups of neither A, nor B), Streptococcus pheitoniae, Streptococcus spp. groups viridans.

Note: methicillin-resistant Staphylosobys spp. are resistant to cephalosporins, including ceftriaxone. Usually, Enterosobys faeslis, Enterosobys faesiut and Listeria toposytogens are also stable.

Gram-negative aerobes:

Asinetobacter iwoffii, Asinetobacter anitratus (the main manner, A. baumannii) *, Aerotopas hydrophila, Alsaligenes faeslis, Alcaligenes odorans, alkaligen-like bacteria, Inrrelia burgdorferi, Sarposutophaga spp., FROMitaboutbaster diversus (at Tom number of FROM. atalopatisis), FROMitobacter freudii**, Escherichia coli, Enterobacter aeraboutgens*, Enterobacter from1oasai*, Enterobacter spp. (other)*, Naatorhilus ducreyi, Naatorhilus 1Pfluenzae, Naatorhilus raraiPfluenzae, Onfnia alvei, TOlebsiella oohtosa, TOlebsiella pioneeriae**, MorOhlla fromatarrhalis, MorOhlla ozloensis, MorOhlla spp. (other), Morganella thenrganii, Neisseria gonorrhoeae, Neisseria meningitidis, Rasteurella multocida, Plesiotopas shigelloides, Rroteis tirabilis, Rroteis repri*, Rroteis vulgaris*, Rseidotopas fluorescens*, Rseidotopas spp. (other), Rrovidencia rettgeri*, Rrovidencia spp. (other). Salmonella typhi, Salmonella spp. (non-phytophoid), Serratia thatrcessepsis*, Serratia spp. (other)*, Shigel1a SPR., Vibrio spp., Yersinia spp. (at Tom number of Yersinia enterocolitisa).

* Some isolates of these species are resistant to ceftriaxone, mainly due to the formation of β-lactamases, encoded by chromosomes.

** Some isolates of these species are stable due to the formation of a whole series of plasmid-suppressing β-lactamases.

Note. Many strains of the above microorganisms, multidrug-resistant to other antibiotics, such as aminopenicillins and ureidopenicillins, cephalosporins I and II generation, and aminoglycosides, are sensitive to ceftriaxone.

Trthe rhetoricallidiut sensitive iP vitro and in animal experiments. Clinical isolates Rseidotopas aerandgiPosa resistant to ceftriaxone.

Anaerobes: Youteraboutides spp. (bile-sensitive) *, FROMlostridiut spp. (Besides FROMlostridiut difficile), Fusobacteriut spp. (including Fusobacterium lettertum), Gaffkya apayeraboutbisa (previously called Reptosobys), Peptaboutstreptosobys spp.

* Some isolates of these species are resistant to ceftriaxone due to the formation of β-lactamases.

Note. Many strains of β-lactamase-forming Youterio1des spp. (in particular Youterio1des fragilis) are stable. Stable and FROMlostridium difficile.

Pharmacokinetics:

The pharmacokinetics of ceftriaxone is non-linear. All major pharmacokinetic parameters based on total drug concentrations, except for the period elimination half-life, dose dependent. Ceftriaxone is well absorbed when administered intramuscularly and reaches high concentrations in serum. inaccessibility of the drug is 100%. After intravenous bolus administration of ceftriaxone at a dose of 500 mg and 1 g, the mean maximum concentration of ceftriaxone in the blood plasma (C_m_Oh) is approximately 120 mg / L and 200 mg / L, respectively. After intramuscular injection C_m_Ohceftriaxone in the blood plasma is approximately twice less than after intravenous administration of an equivalent dose. FROM_m_Oh after a single intramuscular introduction of ceftriaxone in a dose of 1 g is about 81 mg / l and is achieved 2-3 hours after introduction. The areas under the concentration-time (AUС) after intramuscular and intravenous the introduction is the same.

Distribution

The volume of distribution is 7-12 liters. Ceftriaxone fast penetrates into tissues and liquids

organism (including the lungs, heart, biliary tract / liver, tonsils, middle ear, mucous shell of the nose, bones, spinal, pleural, synovial fluid secret prostate gland). When repeated administration an increase of Cmax by 8-15%; the equilibrium state in most cases is achieved in for 48-72 hours depending on method of administration.

Ceftriaxone penetrates the membranes of the brain, with inflammation shell penetration increases. Cmax of ceftriaxone in cerebrospinal fluid (CSF) y patients with bacterial meningitis is registered in level to 25% of the concentration in plasma in comparison with 2% of concentration in blood plasma patients with non-inflamed shells of the brain. Сmах ceftriaxone in CSF is achieved

approximately 4 to 6 hours after intravenous injection. When meningitis in children, including newborn, ceftriaxone penetrates CSF in inflammation meningeal shells, while its concentration in cerebrospinal fluid of liquid is 17% of concentration in the blood plasma.

Ceftriaxone penetrates through placental barrier and in small quantities falls into the thoracic milk.

Binding to proteins

Ceftriaxone reversibly binds to albumin, and the degree binding decreases with

increase in concentration, for example, with 95% at a concentration of blood plasma less than 100 mg / l to 85% at a concentration of 300 mg / l.

Metabolism

Ceftriaxone is not subject to systemic metabolism, turns into inactive metabolites under the action of intestinal microflora.

Excretion

Total plasma clearance is 10-22 ml / min. Renal clearance - 5-12 ml / min. 50-60% injected ceftriaxone is excreted in an unchanged form by the kidneys, The rest of the amount (40-50%) - from bile.

The half-life (T1 / 2) y healthy volunteers about 8 hours, in newborns in the first 14 days of life and patients of the elderly (over 75 years) T1 / 2 is 2-3 times more. In patients with terminal stage of renal insufficiency T1 / 2 increases up to 14 hours.

Because of the long T1 / 2 concentration ceftriaxone 24 hours after introduction is higher than the minimum inhibitory concentration (MIC) for most microorganisms,

causing various infections. AT connection with this drug can be administered once a day.

In newborn infants, kidneys about 70% of the drug is withdrawn. Hemodialysis is not effective.

In patients with impaired function kidney or liver pharmacokinetic parameters

ceftriaxone vary slightly, only small increase in T1 / 2 (less than twice).

Indications:

Lendacin® is used to treat infections caused by ceftriaxon-sensitive bacteria, including the following:

- infections of the upper and lower respiratory tract (including pneumonia, lung abscess);

- infection in otorhinolaryngology;

- septicemia;

- endocarditis;

- bacterial meningitis;

- infections of the abdominal cavity (peritonitis, inflammatory diseases of the gastrointestinal tract, bile ducts);

- urinary tract infections;

- infections of the genital tract, including gonorrhea and chancroid;

- infection of bones, joints, soft tissues, skin, wound infections;

- Lyme disease (stage II and III);

- febrile neutropenia in patients with malignant neoplasms;

- prevention of postoperative infections.

Contraindications:

- hypersensitivity to ceftriaxone, other cephalosporins, peiitsillinam or other beta-lactam antibiotics;

- premature newborns under the "expected" age of 41 weeks (including the term

intrauterine growth and age);

- Hyperbilirubinemia or jaundice in term infants;

- full-term newborns, who are shown intravenous administration of calcium-containing

Solutions due to the risk of precipitation of the ceftriaxone-calcium salt complex;

- acidosis, hypoalbuminemia in full-term newborns;

- the period of breastfeeding.

Carefully:

With combined renal and hepatic insufficiency, dyskinesia of bile excretory pathologies, cholelithiasis and gastrointestinal (GI) diseases in a history, ulcerative colitis, enteritis or colitis associated with with the use of antibacterial drugs, during pregnancy.

Pregnancy and lactation:

Ceftriaxone penetrates the placental barrier. The safety of the drug during pregnancy has not been studied, therefore, Lendacin11 should be used during pregnancy, especially in the first trimester, only if the expected benefit for the mother exceeds the potential risk to the fetus.

Ceftriaxone is excreted in small amounts in breast milk. Infants who are breastfed may develop sensitization, diarrhea, candidiasis of the oral mucosa. If necessary application of the drug in the period of breastfeeding should resolve the issue of stopping breastfeeding.

Dosing and Administration:

Dosage and method of use are determined on the basis of data on the severity of infection, sensitivity of microorganisms, age and condition of the patient.

The duration of therapy depends on the course of the disease. The administration of Lendacin® should be continued for at least 48 to 72 hours after the temperature is normalized and the eradication of the pathogen is confirmed. Ceftriaxone is administered as a slow intravenous infusion lasting at least 30 minutes.

The course of treatment is usually 4-14 days; with complicated infections, a longer duration of administration may be required. The course of treatment for infections caused by Streptococcus pyogenes, must be at least 10 days.

Meningitis: for bacterial meningitis in infants and young children, treatment starts with a dose of 100 mg / kg (but not more than 4 g) 1 time per day. After identifying the pathogen and determining its sensitivity, the dose can be reduced accordingly. The best results for meningococcal meningitis were achieved with a treatment duration of 4 days, with meningitis caused by Naatorhilus influenzae - 6 days, Streptococcus pheitonia - 7 days.

Lyme disease (stage II and III): the preparation Lendacin® is prescribed in a dose of 50 mg / kg once a day, the daily dose should not exceed 2 g. The duration of treatment is 14 days.

Prevention of postoperative infections: Lendacin® is given once in a dose of 1 to 2 g, depending on the risk of infection, it is recommended to inject 30 to 90 minutes before the operation.

Adults and children over 12 years of age with a body weight> 50 kg: The usual dose is 1 to 2 g of ceftriaxone once a day or divided into two doses (every 24 hours). The maximum daily dose is 4 g (2 g injected as an intravenous infusion for 30 minutes with a 12-hour interval).

Children from 15 days to 12 years with a body weight <50 kg: the recommended dose is 20 to 80 mg / kg once a day, once or divided into two doses.

Newborns (age 0-14 days): the recommended dose is 20-50 mg / kg intravenously as a slow infusion once a day. A dose of more than 50 mg / kg of body weight should be given as an IV infusion for 30 minutes.

Elderly patients: no dose adjustment is required. In patients with impaired renal function There is no need to reduce the dose if the liver function remains normal. When acute renal failure (CC <10 ml / min), the maximum daily dose should not exceed 2 g.

In patients with hepatic dysfunction there is no need to reduce the dose if the kidney function remains normal.

With a combination of severe renal and hepatic insufficiency it is necessary to regularly determine the concentration of ceftriaxone in the blood plasma and, if necessary, adjust the dose.

With hemodialysis or peritoneal dialysis, patients do not need additional administration of the drug after dialysis. It is necessary to monitor the concentration of ceftriaxone in the serum for possible dose adjustment, since the rate of excretion in such patients may be reduced.

In patients with renal-hepatic insufficiency, the daily dose should not exceed 2 g without determining the concentration of the drug in the blood plasma.

Intravenous infusion

2 g of ceftriaxone is dissolved in 40 ml of a corresponding calcium-free infusion solution (0.45% or 0.9% sodium chloride solution, 2.5%, 5% or 10% glucose, 5% levulose, 6% dextran on glucose). The duration of infusion is not less than 30 min.

The prepared ceftriaxone solution is stable for 24 hours if stored at a temperature of no higher than 25 ° C or 48 hours at a temperature of 2-8 ° C.

Side effects:

According to the World Health Organization (WHO)

Undesirable reactions are classified according to their frequency of development as follows: very often (>1/10), often (>1/100, <1/10), infrequently (>1/1000, <1/100), rarely (>1/10000, <1/1000) and very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

Infectious and parasitic diseases: fungal infection of the genitals.

Immune system disorders: fever or chills, anaphylactic or anaphylactoid reactions (eg, bronchospasm).

Disturbances from the skin and subcutaneous tissues: rash, itching, allergic dermatitis, urticaria, edema, exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Violations from the nervous system: headache, dizziness, vertigo, convulsions.

Disturbances from the gastrointestinal tract: abdominal pain, diarrhea, nausea, vomiting, taste disorder, dyspepsia, bloating, stomatitis, pancreatitis, glossitis, pseudomembranous colitis.

Disorders from the liver and bile ducts: cholelithiasis, jaundice, a "sluggish phenomenon" of the gallbladder.

Violations from the blood and lymphatic system: anemia (including hemolytic), leukopenia, lymphopenia, leukocytosis, lymphocytosis, monocytosis, neutropenia, thrombocytosis, oocytopenia granules, eosinophilia, basophilia, thrombocytopenia, increase (decrease) in prothrombin time, increase in thromboplastin time, agranulocytosis.

Laboratory and instrumental data: increased activity of "liver" transaminases and alkaline phosphatase, hyperbilirubinemia, hypercreatininaemia, increased urea concentration, the presence of sediment in the urine, hematuria, glucosuria.

Disorders from the kidneys and urinary tract: oliguria,

vaginitis, nephrolithiasis.

General disorders and disorders at the site of administration: with iv introduction - phlebitis, tenderness, compaction along the vein; with the / m introduction - soreness, sensation of warmth, tightness or condensation at the injection site.

Other: increased sweating, "hot flashes" of blood, allergic pneumonitis, epistaxis, a feeling of palpitations, serum sickness, education precipitates in the lungs.

Overdose:

Symptoms: nausea, vomiting, diarrhea, confusion, convulsions.

Treatment is symptomatic. There is no specific antidote. Hemodialysis or peritoneal dialysis is not effective.

Interaction:

Ceftriaxone solutions should not be mixed with solutions containing other antimicrobial

drugs.

Solvents containing calcium salts (Ringer's or Hartmann's solution), can not be used for preparation of solutions ceftriaxone for an induction and subsequent dilution, due to the formation of a precipitate of the calcium ceftriaxone salt. There was no reported interaction between ceftriaxone and calcium-containing preparations for oral administration or ceftriaxone for intramuscular administration and intravenous or oral calcium-containing preparations. Pharmaceutically incompatible with amsacrine, vancomycin, fluconazole and aminoglycosides.

Probenecid does not affect the excretion of the drug.

With the simultaneous use of ceftriaxone in large doses and "loop" diuretics (for example, furosemide) there was no disturbance of the function of the nights. Simultaneous application with anticoagulants of the indirect actions can increase the effect of antivitamin K and increase the risk of bleeding. Recommended control of international normalized ratio (MNO) and the choice of a dose of anticoagulants of indirect effect during and after treatment with ceftriaxone. With the simultaneous use of ceftriaxone with aminoglycosides it is recommended to monitor concentration of aminoglycosides and kidney function.

Indications that ceftriaxone increases nephrotoxicity aminoglycosides, no. Synergy between ceftriaxone and aminoglycosides is shown for many gram-negative bacteria. Although the increased effectiveness of such combinations is not always predictable, it should be borne in mind in severe, life-threatening infections, such as conditional Rseidotopas aerandgipose.

Use alcohol after administration of ceftriaxone was not accompanied disulfiram-like reaction. Ceftriaxone does not contain N-methylthio-tetrazole group, which can cause intolerance to ethanol and bleeding.

Bacteriostatic antibiotics reduce the bactericidal effect ceftriaxone.

Antagonism with chloramphenicol n vitro.

Ceftriaxone reduces effectiveness oral contraceptiveat, so it is recommended use of additional non-hormonal contraceptive during the period of taking the drug and within 1 month after the end drug administration.

Special instructions:

As with the use of other cephalosporins, anaphylactic reactions, including fatalities, were recorded, even in cases where the patient did not have allergic

reactions in the anamnesis. In case of allergic reactions, the drug should be discontinued and appropriate treatment should be prescribed. As with the use of other cephalosporins, the development of autoimmune hemolytic anemia is possible with drug treatment. Cases of severe hemolytic anemia in adults and children, including fatal cases, have been reported. In case of anemia, therapy with the drug should be discontinued. When the drug was used, cases of diarrhea caused by Clostridium difficile (pseudomembranous colitis), varying degrees of severity: from mild to colitis with fatal outcome, were recorded.It is necessary to carefully collect the anamnesis, since there are cases of diarrhea caused by Clostridium difficile, more than 2 months after antibiotic therapy. In accordance with clinical indications, appropriate treatment should be prescribed (compensation of fluid loss, electrolytes, protein, antibiotic treatment for Clostridium difficile, surgical treatment). When development of pseudomembranous colitis is contraindicated prescribing drugs, inhibiting peristalsis of the intestine. As with other antibacterial drugs, superinfection may develop. When the drug is used, rare cases changes in prothrombin time.

Patients with vitamin K deficiency (impaired synthesis, eating disorders) may need to monitor prothrombin time and prescribe vitamin K (10 mg / week) with an increase in prothrombin time before or during therapy.

In rare cases, gallbladder marked darkening (precipitates the calcium salt of ceftriaxone) by ultrasound (US), which disappear after cessation of treatment.With the development of the symptoms or signs indicating the possible gallbladder disease, or in the presence of ultrasound signs "sludge phenomenon" is recommended to stop administering the drug.

When using the drug, rare cases of pancreatitis, which developed, possibly, as a result of obstruction of the biliary tract, are described. Most patients had risk factors for congestion of the biliary tract (eg, previous drug therapy, severe co-morbidities, fully

parenteral nutrition); However, the starting role of precipitate formation in the biliary tract under the influence of ceftriaxone can not be ruled out. Like other cephalosporins ceftriaxone can displace bilirubin from association with serum albumin. When combined with severe renal and hepatic insufficiency, as well as in patients on hemodialysis, it is necessary to regularly determine concentration of ceftriaxone in blood plasma. With long-term treatment, it is necessary to regularly monitor the picture of peripheral blood, indicators of the functional state of the liver and kidneys.

Cases of fatal reactions as a result of deposition of ceftriaxone-calcium precipitates in the lungs and kidneys of newborns are described.Theoretically, there is a probability of interaction of ceftriaxone with calcium-containing solutions for intravenous administration and in other age groups of patients,

so ceftriaxone should not be mixed with calcium-containing solutions (including

parenteral nutrition), and also be administered simultaneously, including through separate accesses for

infusions at various sites.

Theoretically, based on the calculation of 5 T1 / 2 ceftriaxone interval between the administration of ceftriaxone and

calcium-containing preparations should be not less than 48 hours.

Data on the possible interaction of ceftriaxone with calcium-containing preparations for oral administration, as well as ceftriaxone for intramuscular administration with calcium-containing drugs

(in / in or for oral administration) are absent.

It is necessary to take into account contraindications to lidocaine when it is co-administered with Lendacin® (when using lidocaine as a solvent, the solution can be administered only intramuscularly).

Intramuscular injection of Lendanin® without lidocaine is painful!

Effect on the results of laboratory tests: in the treatment of ceftriaxone may be noted

false positive results of Coombs test, false positive tests for galactosemia, glucose in urine (glucosuria is recommended to be determined only by enzyme method).

Information for patients. observing a diet with a lower sodium content: 1 bottle

Lendacin® 2.0 g contains 166.0 mg (7.2 meq) of sodium.

Effect on the ability to drive transp. cf. and fur:In rare cases, the Lendacin® preparation causes dizziness, so during the treatment with Lendacin®, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Powder for solution for infusion 2 g.

Packaging:

2 g of active substance in a bottle of colorless glass, corked with a rubber stopper and crimped with an aluminum cap with a plastic lid.

For 1, 5 or 10 vials, along with instructions for use in a cardboard pack.

Storage conditions:At a temperature of no higher than 25 ° C, in a place protected from light. Keep out of the reach of children!

Shelf life:

3 years.Do not use the product after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N008670

Date of registration:13.08.2010

Expiration Date:unlimited

The owner of the registration certificate: Lek dd Lek dd Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

SANDOZ, GmbH Austria

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp14.07.2016

Illustrated instructions

Instructions

Lendacin® (Lendacin®)