Project Description

Ceftriaxone 0,5 g or 1,0 g powder

for preparation of solution for injections – Ceftriaxone

international nonproprietary name

Ceftriaxone – Ceftriaxone

Ref

BP-0021

Pharmacotherapeutic group

Antimicrobial agents for systemic application. Beta-lactam antibiotics.Cephalosporins of III generation.

Composition of the preparation

The active substance in one vial:Ceftriaxone in a form of sodium salt (in recalculation on Ceftriaxone) – 0,5 g or 1,0 g

Pharmacological action

Pharmacodynamics

The preparation possesses antibacterial (bactericidal) action. Inhibits synthesis of bacterial cell wall. Acetylates membrane-bound transpeptidases, breaking thus two-dimensional cross-link of peptidoglycan chains, necessary for maintenance of strength and rigidity of bacterial cell well.

Ceftriaxone is resistant against beta-lactamase action, producing by majority of gram-positive and gram-negative bacteria. Has a wide spectrum of action. It is active in relation to gram-positive aerobes –Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus viridans, Streptococcus bovis;gram-negativeaerobesAeromonas spp., Alcaligenes spp., Branchamella catarhales(including and the strains producing beta-lactamases), Citobacter spp., Enterobacter spp.,(some strains are resistant),Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae(including strains producing penicillinase), Haemophilus parainfluenzae, Klebsiella spp., (including Klebsiella pneumonia), Moraxella spp., Morganella morgani, Neisseria gonorrhoeae(including strains producing penicillinase),Neiseria meningitis, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris, Providensia spp., Proteus aeruginisa, Salmonella spp., (including Salmonella typhi), Serratia spp., (including Serratia marcescens), Shigella spp., Vibrio spp., (including Vibrio cholerae), Yersinia spp., (including Yersinia enterocolitica); anaerobes – Bacteroides spp.(including some strains ofBacteroides fragilis), Clostridium spp., (except forClostridium difficile), Fusobacterium spp., (except for Fusobacterium mortiferum, Fusobacterium verium), Peptococcus spp., Peptostreptococcus spp.

The strains ofStaphylococcusspp., resistant to  Ceftriaxone are resistant to Methicillin; and strainsEnterococcus spp.(Enterococcus faecalis),Clostridium difficile, Bacteiodes spp.,producing beta-lactamase.

It is not hydrolyzed by R-plasmid beta-lactamases, and also by the majority of chromosomal penicillinases and cephalosporinases, can affect on multiresistant strains, tolerant to penicillins, cephalosporins of the first generations and aminoglycosides. The acquired resistance of some bacteria strains is caused by beta-lactamases producing, inactivating Ceftriaxone («Ceftriaxonases»).

Pharmakokinetics

It is not absorbed from gastrointestinal tract at intake. After intramuscular introduction it is quickly and fully absorbed, the peak of concentration in blood plasma is revealed in 1,5 hours. The minimal antimicrobial concentration is found within 24 hours and more. The preparation gets well into organs, body fluids (peritoneal, pleural, cerebrospinal, synovial), in osteal and cartilaginous tissues. It passes through placenta and in insignificant quantities gets into breast milk (3-4 %). Stable concentration of the preparation is reached within 4 days.Смахafter i.m introductions is reached in 2-3 hours, after i.v. introduction – in the end of infusion.Смахafter Ceftriaxone i.m introductions in a dose of 0,5 gis 38 mcg/ml, 1 gis 76 mcg/ml; at 0,5 gi.v. introduction is 82 mcg/ml, 1 g is 151 mkg/ml, 2 g is  257 mcg/ml. In adults after introduction of 50 mcg/kg  the concentration in cerebrospinal fluid is in many times over МTD for the most widespread meningitis pathogens. In reversibly binds with albumin (59-83 %).Т1/2is 6-9 hours that allows to apply the preparation 1 time a day.Т1/2in children with meningitis is 4,3-4,6 hours; in patients being on hemodialysis (Cl of creatinine is 0-5 ml/min) is 14,7 hours; at creatinine Cl of 5-15 ml/min – 15,7 hours; at creatinine Cl of 16-30 ml/min – 11,4 hours; at creatinine Cl of 31-60 ml/min – 12,4 hours.

Volume of distribution is 0,12-0,14 l/kg (5,78-13,5 l), in children is 0,3 l/kg, plasma Cl is 0,58-1,45 l/h, renal clearance is 0,32-0,73 l/h.

The newborns, elder persons and patients with liver and kidneysfunction failure Т1/2is considerably extended; and the cumulation is possible. It is eliminated by kidneys (50-60 % of the preparation in not changed form, 40-50 % are excreted together with bile in an intestine), where is further biotransformed in an inactive metabolite. More than 60 % of the preparation is excreted in newborns by kidneys.

Indications 

Infections of the upper and lower parts of respiratory tract (including pneumonia, lungs abscess, empyema of pleura); infections of skin, soft tissues, bones and joints; infections of abdominal cavity organs (peritonitis, inflammatory diseases  of gastrointestinal tract, bile-excreting tract, cholangitis, empyema of gall-bladder); infectious-inflammatory diseases of pelvis minor organs and urinary tract (including pyelitis, pyelonephritis, cystitis, prostatitis, epididymitis); bacterial meningitis and endocarditis, sepsis, Lime disease,shigellosis, salmonellosis, salmonella carriage, typhous fever; the acute and complicated gonorrhea, and other infections transmitted by sexual way (including ulcus venerium and lues); prophylaxis and treatment of infections at surgical interventions.

special indication

For i.v. introduction the preparation is dissolved in sterile water for injections in the ratio of 1:10 (0,5 gof the preparation is dissolved in 5 ml; 1 gof the preparation — in 10 ml sterile water).

For intravenous infusion the preparation is dissolved in a solution, free from ions of calcium. Duration of i.v. infusions can not be more than 15-30 minutes.

For i.m introductions – in 1 % solution of Lidocain (0,5 gof the preparation in 2 ml or 1 g- in 3,5 ml). The received solution cannot be entered intravenously! At intramuscular introduction, it is recommended to introduce no more than 1 gof the preparation in one gluteus.

Freshly prepared solutions of the preparation are stable within 6 hours at room temperature and within 24 hours at 2-8 °С.

special warning

Not established

Dosage and method of administration

I.m (deeply in a muscle), i.v. by an injection duration of 2-4 minutes. For adults and children elder 12 years a daily dose is 1-2 g. Maximal daily dose for adults is 4 g. For newborns in the age under 14 days per 20-50 mg/kg 1 time a day. The maximal daily dose can not be more than 50 mg/kg. To children in the age from 15 days and to 12 years – 20-80 mg/kg 1 time a day. For children with mass of 50 kg and more the preparation is administrated in recommended for adults doses. The doses more than 50 mg/kg of body weight is necessary to administrate in a form of intravenous infusion for 30 minutes. The treatment is necessary to continue within 2-3 days after disappearance of clinical signs of infection. Duration of therapy is from 4 to 14 days; at the complicated infections longer treatment can be required.

For prophylaxis of postoperative complications – in a single dose, 1-2 g(depending on degree of infection danger) for 30-90 min prior to an operation beginning.

At bacterial meningitis – in a dose of 100 mg/kg 1 time a day, (but no more than 4 gin a day). Duration of treatment depends on a pathogen and can be from 4 days forNeiseria meningitisto 10-14 days for sensitive Enterobacteriactae strains.

Infections of skin and soft tissues: to children – 50-75 mg/kg/day once a day or 25-37,5 mg/kg/day each 12 hours (no more than 2 g/day). At serious infections of other localization —  25-37,5 mg/kg/day each 12 hours (no more than 2 g/day). At otitis medis —  in/m 50 mg/kg once a day, no more than 1 gin a day.

At gonorrhea – in/m, single dose of 250 mg.

To patients with function of kidneys failure (Сl  of creatinine < 10 ml/min) the daily dose should not exceed 2 g.

overdosage

At long introduction occurrence of allergic reactions, dyspeptic upset is possible. The specific antidote is not known, the treatment is symptomatic.

safety measures

At simultaneous renal and hepatic failure, in patients on hemodialysis it is necessary to determine concentration of the preparation in plasma on a regular basis. At long-term treatment hematological parameters, parameters of liver and kidneys functional condition should be controlled. The elderly patients and patients with broken health the administration of vitamin K can required.

Restrictions to use:

Is renal-hepatic failure, bleedings and diseases of gastrointestinal tract (nonspecific ulcerative colitis, enteritis or colitis bound to antibacterial preparations use), prematurely born children.

Use during pregnancy and lactation

It is counter-indicative in Ist trimester of pregnancy. For the period of treatment it is necessary to stop breast feeding.

Side effects

Allergic reactions:urticaria, eruption, itch, erythema, fever, edema, eosinophilia, anaphylactic shock, serum sickness, abdominal pain, bronchospasm.

Local reactions:at i.v. introduction — phlebitises, morbidity downstream vein; at i.m introduction painfullness in a place of introduction.

Nervous system: giddiness and headache

Urinary excretion system:oliguria

Digestive system:nausea, vomiting, tasteabnormalities, meteorism, stomatitis, glossitis, diarrhea, dysbacteriosis.

Hemopoiesis organs:anemia, leukopenia, granulocytopenia, thrombocytosis, basophilia, elongation of prothrombin time.

Hemostasis system:hematuria, nasal bleedings, hemolitic anemia

Others: candidomycosis and other superinfections

Laboratory parameters:increase of activity of hepatic transaminases, alkaline phosphatase, hyperbilirubinemia, hypercreatinemia, increase of urea content, glucosuria

Contraindications

Hypersensitivity to Ceftriaxone or to other preparations of cephalosporins’ group, penicillins, carbapens; pregnancy (Ist trimester), hypoalbuminemia, acidosis or the lowered bilirubin binding; jaundice of the newborns.

Interactions with other medicinal preparations

In combination with aminoglycosides posesses synergy action in relation to many gram-negative bacteria. It is incompatible with alcohol (probably reddening of a face, spasm in a stomach and stomach region, nausea, vomiting, a headache, ABP decrease, tachycardia,dyspnea). HПВСand other thrombocytes aggregation inhibitors increase probability of bleeding. At simultaneous application with loop diuretics and other nephrotoxic preparations the risk of nephrotoxic effect development increases. It is incompatible pharmaceutically with other antibiotics solutions.

The form of release

0,5 g or 1,0 g in vials of 10 ml capacity. A vial  together with the instruction on application are placed in a pack.

Packing for hospitals: 40 vials  with corresponding instructions on application in group boxes.