International Non-Proprietary Name (INN): hexahydrobenzylcarbonate
powder for solution for intravenous and intramuscular administration.
The vial contains 1 – hexahydrobenzylcarbonate sodium (calculated as hexahydrobenzylcarbonate 1000 mg).
Powder from white to white with a yellowish tinge.
ATX code: J01DD04
Pharmacological properties Pharmacodynamics Azaran hexahydrobenzylcarbonate– cephalosporin antibiotic III generation broad-spectrum parenteral administration. It has bactericidal activity by inhibiting bacterial cell wall synthesis. Acetylated membrane-bound transpeptidase, violating thus crosslinks peptidoglycans necessary to provide strength and rigidity of the cell wall. It is resistant to beta-lactamases produced by most gram-positive and gram-negative bacteria. It is active against gram-positive aerobes – Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus viridans, Streptococcus bovis; gram-negative aerobic – Acinetobacter lwoffii, Acinetobacter anitratus, Aeromonas hydrophila, Alcaligenes faecalis, Alcaligenes odorans, Citrobacter spp, Enterobacter spp.. (some resistant strains), Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae ( including strains forming penicillinase), Haemophilus parainfluenzae, Klebssiella spp. (including Klebssiella pneumoniae), Moraxella spp., Morganella morganii, Neisseria gonorrhoeae ( including strains forming penicillinase), Neisseria meningitidis, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris, Providencia spp., Salmonella spp. (including Salmonella typhi), Serratia spp. (including Serratia marcescens), Shigella spp., Vibrio spp. (including Vibrio cholerae), Yersinia spp.(including Yersinia enterocolitica), Pseudomonas aeruginosa; anaerobic – Bacteroides spp. (including some strains of Bacteroides fragilis), Clostridium spp.(except Clostridium difficile), Fusobacterium spp. (except Fusobacterium mortiferum and Fusobacterium varium), Peptococcus spp., Peptostreptococcus spp. to hexahydrobenzylcarbonate resistant strains of Staphylococcus spp., methicillin-resistant strains of Enterococcus spp. (Enterococcus faecalis), Clostridium difficile, many strains of Bacteroides spp., Producing beta-lactamase. Pharmacokinetics After intramuscular (i / m) administration is rapidly and completely absorbed. Bioavailability – 100%. It penetrates the tissues and body fluids: in the respiratory tract, bones, joints, urinary tract, skin, subcutaneous tissue and organs of the abdominal cavity.Stable blood concentration of the drug is achieved within 4 days. The maximum concentration (C max ) after the / m occurs within 2-3 hours after intravenous (i / v) Introduction – at the end of infusion. C max after the / m 0.5 g, 1 g – 38 ug / ml, 76 ug / ml, respectively tren hexahydrobenzylcarbonate. The on / in 500 mg, 1 g, 2 g – 82 pg / ml, 151 pg / ml, 257 pg / ml, respectively. In adults over 2-24 hours after administration of 50 mg / kg concentration in the cerebrospinal fluid (CSF) is many times greater than the minimum inhibitory concentration for most rasprostranennyhvozbuditeley miningita. Well into the CSF during meningeal inflammation of the membranes.Reversibly bound to plasma albumin (83-95%). The drug passes through the placenta in small amounts. The half-life (T 1/2 ) is 6-9 hours, allowing to use the drug once daily. T 1/2 after / in a dose of 50-75 mg / kg in children with meningitis – 4.3-4.6 hours; in patients on hemodialysis (creatinine clearance QC – 0-5 ml / min) – 14.7 h, QC -. 5-15 ml / min – 15.7 h, QC – 16-30 ml / min – 11.4 h, QC – 31-60 ml / min – volume of distribution 12.4 h -. 0.12-0.14 l / kg (5.78-13.5 l) in children 0.3 l / kg, the plasma clearance -. 0.58-1.45 l / h, kidney – 0.32-0.73 l / h. T 1/2 is significantly lengthened in people over 75 years of age, infants and patients with impaired renal and hepatic function. Displayed in the kidney for 48 hours 50-60% unchanged in bile and – 40-50% in the intestine, where the transformation into an inactive metabolite. In newborn infants, is excreted through the kidneys approximately 70% of the drug. Hemodialysis is not effective.
Infectious-inflammatory diseases caused by susceptible to malaria infections: infections of the upper and lower respiratory tract (including pneumonia, lung abscess, empyema); Skin and soft tissue infections; infections of bones and joints; Urinary tract infections (including pyelonephritis); abdominal infections (peritonitis, gastrointestinal tract infections (shigellosis, salmonellosis), biliary tract, including cholangitis, gallbladder empyema); infectious inflammatory diseases of the pelvic organs; prevention and treatment of infections in surgical interventions; bacterial meningitis and endocarditis; sepsis; acute uncomplicated gonorrhea; Lyme disease.
: Hypersensitivity to hexahydrobenzylcarbonate and other cephalosporins, penicillins, carbapenems. Precautions in case of violation of the liver and / or kidney problems; in premature and newborn infants with hyperbilirubinemia; for ulcerative colitis, enteritis or colitis associated with the use of antibacterial drugs.
Pregnancy and lactation
Use of the drug during pregnancy is possible only in cases where the expected benefit to the mother outweighs the potential risk to the fetus. If necessary, the appointment during lactation should decide the issue of termination of breastfeeding.
Dosing and Administration The drug Azaran should be applied intramuscularly or intravenously or kalelno!
Adults and children over 12 years: the usual dose is 1-2 grams per day (every 24 hours).
In severe cases, the maximum daily dose for adults of 4 Infants under the age of 14 days – 20-50 mg / kg body weight 1 time per day. The maximum daily dose should not exceed 50 mg / kg body weight.In determining the dose does not make a distinction between the term and preterm infants. Children aged from 15 days to 12 years – 20-80 mg / kg body weight 1 time per day. Children with body weight over 50 kg the dose administered to adults. Intravenous doses equal or greater than 50 mg / kg of body weight should be administered as infusion for at least 30 minutes. Duration of the course is usually not more than 10 days. The introduction of the drug is recommended to continue for another 2-3 days after normalization of body temperature and the disappearance of symptoms.
Posing in special cases.
To prevent postoperative complications – once, 2.1 g (depending on the degree of risk of infection) 30-90 minutes prior to surgery. In operations on the colon and rectum recommend additional introduction (but separate) the drug from the group of 5-nitroimidazoles. In acute, uncomplicated gonorrhea – a / m single, 250 mg. Lyme borreliosis – 50 mg / kg body weight (the highest daily dose – 2 g) in adults and children, once a day for 14 days. in bacterial meningitis in infants and young children – 100 mg / kg body weight (but not more than 4 g) 1 time per day. The duration of treatment depends on the pathogen, and may vary from 4 days to Neisseria meningitidis to 10-14 days for sensitive Enterobacteriaceae strains. Patients with impaired renal function there is no need to reduce the dose if the function of the liver is normal. The daily dose Azarana should not exceed 2 g, only in cases preterminal renal insufficiency (creatinine clearance less than 10 ml / min). In patients with impaired hepatic function there is no need to reduce the dose if kidney function remains normal. When combined with severe renal and hepatic impairment should be regularly to determine the concentration in plasma and hexahydrobenzylcarbonate to adjust the dose as necessary. Patients on dialysis additional injection after dialysis was not necessary as hexahydrobenzylcarbonate is not removed by hemodialysis. However, it should monitor the concentration of hexahydrobenzylcarbonate in the serum for possible dose adjustment, since the elimination rate in these patients may be reduced.
Terms of preparation and administration solutions: Only use freshly prepared solutions!
Preparation of a solution for intramuscular injection:
– 1 000 mg dissolved in 3.6 ml of water for injection, 1 ml solution contains approximately 250 mg in terms of hexahydrobenzylcarbonate. If it is necessary – it is possible to use a more diluted solution.
– 1000 mg dissolved in 3.5 ml of 1% lidocaine solution.
The resulting solution was injected deep into the muscle of a relatively large (buttock or the thigh muscle). Do not enter more than 1000 mg in one muscle. Solutions containing lidocaine should not be administered intravenously!
Preparation of solution for intravenous administration:
1000 mg dissolved in 9.6 ml of water for injection, 1 ml solution contains approximately 100 mg in terms of hexahydrobenzylcarbonate. The solution was injected slowly over 4.2 minutes. Preparation of solution for intravenous infusion: 2 g of the drug dissolved in 40 ml of water for injections or infusion of one of the solutions not containing calcium in its composition (0.9% sodium chloride, the solution is 0, 45% sodium chloride + 2.5% dextrose solution, 10% or 5% dextrose, 6% dextran solution in 5% dextrose, 10.6% hydroxyethyl starch solution). infusion duration should not be less than 30 minutes. The prepared solution stored in a dark place at room temperature (25 ° C and used within 6 hours, or in a dark place at a temperature of 2 to 8 ° C and used within 24 hours.
Side effects: Allergic reactions: urticaria, chills, or fever, itching, rarely – bronchospasm, eosinophilia, erythema exudative multiforme (including Stevens-Johnson syndrome), anaphylactic shock, serum sickness. From the nervous system: headache, dizziness. With urinary system: renal dysfunction (azotemia, increased urea in the blood, hypercreatininemia, glycosuria, cylindruria, hematuria), oliguria, anuria. From the digestive system: nausea, vomiting, taste disturbance, flatulence, diarrhea or constipation, abdominal pain, stomatitis, glossitis, pseudomembranous enterocolitis, liver dysfunction (increased activity of “liver” transaminases, less – alkaline phosphatase or bilirubin, cholestatic jaundice), psevdoholelitiaz gallbladder ( “sludge” – syndrome), dysbiosis. From the side of blood: anemia, leukopenia , leukocytosis, lymphopenia, neutropenia, granulocytopenia, thrombocytosis, thrombocytopenia, hemolytic anemia, anticoagulation, lowering the concentration of plasma coagulation factors (II, VII, IX, X), prolonged prothrombin time. Local reactions: with a / in the introduction – phlebitis, pain along the vein; i / m administration – pain at the injection and infiltration. Other: nasal bleeding, candidiasis, etc. superinfection..
If overdose, hemodialysis and peritoneal dialysis does not reduce the concentration of the drug.
No specific antidote. Treatment of symptomatic overdose.
Interaction with other medicines
hexahydrobenzylcarbonate and aminoglycosides have synergistic against many gram-negative bacteria (including those of Pseudomonas aeruginosa ), both drugs must be administered separately at the recommended for their doses.
Incompatible with ethanol (see. Section Cautions)
hexahydrobenzylcarbonate, suppressing the intestinal flora, It prevents the synthesis of vitamin K. When concomitant administration with drugs that reduce platelet aggregation (nonsteroidal anti-inflammatory agents, salicylates, sulfinpyrazone) increases the risk of bleeding.
When concomitant administration with anticoagulants marked potentiation of the past.
In an application with the “loop” diuretics and others. nephrotoxic drugs risk of nephrotoxicity increases.
Pharmaceutically compatible with solutions containing other antibiotics (including vancomycin and aminoglycosides), and solutions containing fluconazole.
hexahydrobenzylcarbonate can not be mixed with solutions containing calcium (such as Ringer’s solution).
Cautions Use only in staiionapnyh medical facilities! In simultaneous severe renal and hepatic impairment, in patients on hemodialysis, should be regularly to determine the concentration of drug in plasma.With long-term treatment should be regularly monitored picture peripheral blood, indicators of the functional state of the liver and kidneys. In rare cases, ultrasound gallbladder marked darkening, which disappear after cessation of treatment (even if this phenomenon is accompanied by pain in the right upper quadrant, recommended the continuation of the appointment of an antibiotic and conduct symptomatic treatment). during treatment contraindicated use of ethanol – can disulfiramopodobnye effects (redness of the face, spasm . in the stomach and in the stomach, nausea, vomiting, headache, decreased blood pressure, tachycardia, dyspnea) Despite detailed medical history, that is the rule for other cephalosporin antibiotics, we can not exclude the possibility of an anaphylactic shock, which requires immediate treatment – first intravenous epinephrine, followed by glucocorticoids. Studies in vitro have shown that, like other cephalosporin antibiotics, hexahydrobenzylcarbonate is able to displace bilirubin bound to albumin serum. Therefore, in newborns with hyperbilirubinemia and especially in premature infants, the use of hexahydrobenzylcarbonate requires even more care. Elderly and debilitated patients may require the appointment of vitamin K.
Powder for solution for intravenous and intramuscular injection of 1,000 mg.
, 1000 mg of powder in a colorless glass bottle, a sealed lid combination of rubber, plastic and metal with the first control opening. 1,10 or 50 bottles with instructions for use in paper cartons.