2010/06/24

Azaran

Composition, structure and packing

Powder for solution for injection from white to yellowish-white color.

1 vial. ceftriaxone (in the form of ceftriaxone disodium triseskvigidrata) 1 PM

Clinico-pharmacological group: cephalosporins III generation.

Pharmacological action

Cephalosporin antibiotic III generation of broad-spectrum parenteral administration. Effective bactericidal, inhibiting the synthesis of the bacterial cell wall. Acetylating transpeptidase of membranes, thereby violating the cross-stitching peptidoglikanov necessary to ensure the strength and rigidity of the cell wall. Resistant against β-lactamase produced by most gram-positive and Gram-negative bacteria.

Active on the Gram positive aerobic bacteria: Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus viridans, Streptococcus bovis; aerobic gram-negative bacteria: Aeromonas spp., Alcaligenes spp., Branhamella catarrhalis (including strains forming β-lactamase), Citrobacter spp., Enterobacter spp., (some strains are resistant), Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae (including strains, penicillinase-producing), Haemophilus parainfluenzae, Klebsiella spp. (Including Klebsiella pneumoniae), Moraxella spp., Morganella morganii, Neisseria gonorrhoeae (including strains that are penicillinase-producing), Neisseria meningitidis, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris, Providencia spp., Salmonella spp. (Including Salmonella typhi), Serratia spp. (Including the Serratia marsescens), Shigella spp., Vibrio spp. (Including Vibrio cholerae), Yersinia spp. (Including Yersinia enterocolitica), Pseudomonas aeruginosa (some strains), Gram-negative anaerobic bacteria: Bacteroides spp. (Including some strains of Bacteroides fragilis), Clostridium spp. (Except for Clostridium difficile), Fusobacterium spp. (Except for Fusobacterium mortiferum and Fusobacterium varium), Peptococcus spp., Peptostreptococcus spp.

To the drug resistant methicillin-resistant strains Staphylococcus spp., Strains of Enterococcus spp. (Enterococcus faecalis), Clostridium difficile, many strains of Bacteroides spp. (Producing β-lactamases).

Not hydrolyzed R-plasmid β-lactamases and a majority hromosomooposredovannyh penicillinases and tsefalosporinaz can act on multidrug strains tolerant to penicillins and cephalosporins of the first generations and aminoglycosides. The acquired resistance of some strains due to production β-lactamase, which inactivates ceftriaxone (tseftriaksonazy).

Pharmacokinetics

Absorption and distribution

After a / m ceftriaxone administration is rapidly and completely absorbed into the systemic circulation. Well into the tissues and body fluids: the respiratory tract, bones, joints, urinary tract, skin, subcutaneous tissue and abdominal cavity. When inflammation of meningeal membranes well into the spinal fluid. Bioavailability of ceftriaxone in the i / m administration of 100%. After i / m administration Cmax achieved within 2-3 h, with a / in the introduction - in the end of infusion.

When i / m administration of ceftriaxone at a dose of 500 mg and 1 g of Cmax in plasma was 38 pg / ml and 76 pg / ml, respectively, with a / in a dose of 500 mg, 1 g and 2 g - 82 mg / ml 151 ug / ml and 257 ug / ml, respectively. In adults over 2-24 hours after administration of the drug in a dose of 50 mg / kg concentration in the cerebrospinal fluid is many times greater than the IPC for the most common meningitis pathogens. The equilibrium state is established within 4 days of drug administration.

The reversible binding to plasma proteins (albumin) is 83-95%. Vd is 5.78-13.5 L (0.12-0.14 L / kg) in children - 0.3 l / kg.

Withdrawal

T1 / 2 of 6-9 h. Plasma clearance - 0.58-1.45 l / h, renal clearance - 0.32-0.73 l / h. The In adult patients within 48 h 50-60% of the drug appears kidneys unchanged, 40-50% is excreted in the bile in the intestine, where biotransformiruetsya in an inactive metabolite.

Pharmacokinetics in special clinical situations

In neonates, the kidneys excreted 70% of the drug. In infants and elderly patients (aged 75 years), as well as in patients with impaired renal function and liver T1 / 2 significantly increased.

Patients who are on hemodialysis with QC 0-5 ml / min, T1 / 2 was 14.7 h and QA 5-15 ml / min - 15.7 h and QA 16-30 ml / min - 11.4 h and CC 31 - 60 ml / min - 12.4 hours

In children with meningitis T1 / 2 after i / v administration in a dose of 50-75 mg / kg is 4.3-4.6 h.

Statement

Treatment of infectious-inflammatory diseases caused by susceptible microorganisms:
infections of the upper and lower respiratory tract (including pneumonia, lung abscess, empyema);
infections of skin and soft tissues;
infections of bones and joints;
urinary tract infections (including pyelonephritis);
inflammatory disease of the gastrointestinal tract and biliary tract (including cholangitis, empyema gall bladder);
pelvic infection;
peritonitis;
bacterial meningitis;
bacterial endocarditis;
sepsis
acute and complicated gonorrhea;
Lyme disease;
shigellosis;
salmonellosis.

Prevention and treatment of infectious postoperative complications.

Dosage regimen

The drug is introduced into the / m or / in.

For adults and children over 12 years, the average daily intake is 1-2 g 1 time / day. The maximum daily dose for adults - 4 PM

For infants under 14 days, the dose is 20-50 mg / kg / day. Maximum daily dose of 50 mg / kg.

For children aged 15 days and up to 12 years of daily dose is 20-80 mg / kg. The daily dose of more than 50 mg / kg of body weight should be prescribed in the form of in / infusion.

Duration is typically less than 10 days. The introduction of the drug should continue for 2-3 days after normalization of body temperature and the disappearance of symptoms.

To prevent infections in the postoperative period the drug injected once per 30-90 minutes prior to surgery at a dose of 1-2 g (depending on the degree of risk of infection). Through an operation on the colon and rectum recommend additional injection of the drug from the group of 5-nitroimidazole.

With bacterial meningitis daily dose is 100 mg / kg. The maximum dose - 4 g 1 time / day. Duration of therapy depends on the type of pathogen and can vary from 4 days in meningitis caused by Neisseria meningitidis, to 10-14 days for meningitis caused by susceptible strains of Enterobacteriaceae.

Children with infections of the skin and soft tissue preparation prescribe a daily dose of 50-75 mg / kg of body weight one time per day or 25-37.5 mg / kg every 12 h, but not more than 2 g / day. In severe infections at other sites - at a dose of 25-37.5 mg / kg every 12 h, but not more than 2 g / day. In otitis media introducing drug / m at a dose of 50 mg / kg of body weight, but not more than 1 g. When gonorrhea introducing drug / m once at a dose of 250 mg.

Patients with impaired renal function dosage adjustment is required only for severe renal insufficiency (CC <10 ml / min), in which case the daily dose of ceftriaxone should not exceed 2 years

Terms preparation and administration solution for injection

To prepare the solution for i / m injection of 1 g of the drug is dissolved in 3.5 ml of 1% lidocaine chloride. Enter deeply into a large muscle mass. Do not enter more than 1 g in a single muscle. It should be remembered that lidocaine chloride can not enter into / in.

To prepare the solution for i / v dose of 1 g dissolved in 9.6 ml of sterile water for injection. The solution is injected slowly over 2-4 min.

To prepare the solution for i / v infusion of 2 g of the drug dissolved in 40 ml of a solution containing no Ca (0.9% sodium chloride solution, 0.45% sodium chloride solution and 2.5% dextrose in 5% dextrose, 10% dextrose 6% solution of dextran and 5% solution of dextrose, 6-10% solution of starch). Running in / infusion - at least 30 minutes.

Freshly ceftriaxone solutions are stable for 6 h at ambient temperature and within 24 hours when stored in a refrigerator at a temperature of 2 ° to 8 ° C.

Side effect
From the CNS: headache, dizziness.
From the urinary system: oliguria, Glycosuria, hematuria, hypercreatininemia, elevated levels of urea.
On the part of the digestive system: nausea, vomiting, breach of taste, flatulence, stomatitis, glossitis, diarrhea, pseudomembranous enterocolitis, psevdoholelitiaz (sludge-syndrome), dysbacteriosis, abdominal pain, increase in liver transaminases and of alkaline phosphatase, hyperbilirubinemia.
On the part of the hemopoietic system: anemia, leukopenia, leukocytosis, lymphopenia, neutropenia, granulocytopenia, and thrombocytopenia, thrombocytosis, basophilia, hemolytic anemia.
From the blood coagulation system: nosebleeds, an increase (decrease) in prothrombin time.

Allergic reactions: urticaria, rash, itching, erythema exudative multiforme, fever, edema, eosinophilia, anaphylactic shock, serum sickness, bronchospasm.

Other: superinfection (including candidiasis).

Local reactions: with a / in the introduction - phlebitis, pain along the vein, with a / m introduction - soreness at the injection site.

Contraindications
hypersensitivity to ceftriaxone and other cephalosporins, penicillins and carbapenems.

With care prescribers in violation of the liver and / or kidneys (the probability of cumulation requires monitoring drug concentration in serum), and preterm newborns with hyperbilirubinemia (there is likely to strengthen the side effects) with ulcerative colitis, as well as enteritis or colitis associated with the use of antibacterial drugs.

Pregnancy and lactation

Application Azarana during pregnancy is possible only in cases where the intended benefits to the mother outweighs the potential risk to the fetus (ceftriaxone penetrates through the placenta).

If necessary, use Azarana during lactation should decide on the termination of breastfeeding (ceftriaxone is excreted in breast milk).

Application for violations of liver function

In patients with hepatic impairment T1 / 2 significantly increased.

Application for violations of renal function

Patients with impaired renal function dosage adjustment is required only for severe renal insufficiency (CC <10 ml / min), in which case the daily dose of ceftriaxone should not exceed 2 years

Cautions

The drug is used only in a hospital. At the same time severe renal and hepatic failure in patients on hemodialysis, should regularly determine the concentration of ceftriaxone in blood plasma.

Prolonged treatment is necessary to regularly monitor the picture of peripheral blood parameters of the functional state of the liver and kidneys.

In rare cases, ultrasonography of the gallbladder observed darkening that disappear after discontinuation of the drug (even if this phenomenon is accompanied by pain in the right hypochondrium, continue to recommend the appointment of an antibiotic and symptomatic treatment).

When applying the drug can not use ethanol, because may develop disulfiramopodobnyh effects (flushing, abdominal cramping and in the stomach, nausea, vomiting, headache, lower blood pressure, tachycardia, dyspnea).

Against the background of Azarana elderly and debilitated patients may require vitamin K.

Overdose

Currently, cases of overdosing Azaran not reported. For removing the drug from the body hemodialysis are not effective.

Drug Interactions

Ceftriaxone and aminoglycosides have synergistic against many gram-negative bacteria. When combined with the use of NSAIDs and other antiagregantami increases the likelihood of bleeding.

When applied simultaneously with the "loop" diuretics and other nephrotoxic drugs increases risk of nephrotoxicity.

Pharmaceutical interactions

Pharmaceutical incompatible with solutions containing other antibiotics.

Terms and Conditions of storage

List B. The drug should be stored out of reach of children, dry, dark place at a temperature of 15 ° to 25 ° C. Shelf life - 3 years.