Офрамакс

General characteristics. Structure:

Dose of 250 mg:
Active ingredient: sterile цефтриаксон sodium of 299,28 mg, equivalent to a tseftriakson of 250 mg.
Dose of 1000 mg:
Active ingredient: sterile цефтриаксон sodium of 1197,12 mg, equivalent to a tseftriakson of 1000 mg.
Description: crystal powder from  color, white to white with a yellowish shade.

Pharmacological properties:

Pharmacodynamics. Офрамакс® - the tsefalosporinovy antibiotic of the III generation for parenteral use, possesses bactericidal action, synthesis of a cellular membrane oppresses, in vitro suppresses growth of the majority of gram-positive and gram-negative microorganisms. It is steady against action beta лактамазных enzymes (both a penicillinase, and a tsefalosporinaza, produced by the majority of gram-positive and gram-negative bacteria). It is effective concerning the following microorganisms.
Gram-positive
Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus A (Str.pyogenes), Streptococcus V (Steptococcus agalactiae), Streptococcus viridans, Streptococcus bovis. 
Note: Staphylococcus spp., steady against Methicillinum, резистентен and to cephalosporins, including to a tseftriakson. The majority of strains of enterococci (for example, Streptococcus faecalis) are also steady against a tseftriakson.
Gram-negative
Aeromonas spp., Alcaligenes spp., Branhamella catarrhalis, Citrobacter spp., Enterobacter spp. (some strains are steady), Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp. (including Klebsiella pneumoniae), Moraxella spp., Morganella morganii, Neisseria gonorrhoeae,  Neisseria meningitidis, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa (some strains are steady), Salmonella spp. (including Salmonella typhi), Serratia spp. (including Serratia marcescens), Shigella spp., Vibrio spp. (including Vibrio cholerae), Yersinia spp. (including Yersinia enterocolitica)
Note: many strains of the listed microorganisms which in the presence of other antibiotics , for example, of penicillin, cephalosporins of the first generations and aminoglycosides steadily breed are sensitive to a tseftriakson. Treponema pallidum is sensitive to a tseftriakson as in vitro, and in animal experiments. According to clinical data, at primary and secondary syphilis note good efficiency of a tseftriakson. 
Anaerobic pathogens
Bacteroides spp. (including some strains of V. of fragilis), Clostridium spp. (including Cl. difficile), Fusobacterium spp. (except F. mostiferum, F. varium), Peptococcus spp., Peptostreptococcus spp.
Note: some strains of many Bacteroides spp. (for example, V. of fragilis), the developing beta lactamazu, are steady against a tseftriakson. It is necessary to apply the disks containing цефтриаксон as it is shown that in vitro certain strains of pathogens can be steady against classical cephalosporins to definition of sensitivity of microorganisms.

Pharmacokinetics. At parenteral administration цефтриаксон well gets into fabrics and liquids of an organism.
The areas under a curve concentration - time in blood serum at intravenous and intramuscular administration match. It means that bioavailability of a tseftriakson at intramuscular introduction makes 100%. At intravenous administration цефтриаксон quickly diffuses in intersticial liquid where the bactericidal action concerning pathogens, sensitive to it, keeps within 24 hours.
Tseftriakson reversibly contacts albumine, and this binding in inverse proportion to concentration: for example, at concentration of drug in blood serum less than 100 mg/l linkng of a tseftriakson with proteins makes 95%, and at concentration of 300 mg/l - only 85%. Thanks to lower content of albumine in intersticial liquid, concentration of a tseftriakson in it is higher, than in blood serum.
The elimination half-life at healthy adult examinees makes about 8 hours. At newborns up to 8 days and at elderly people 75 years an average elimination half-life approximately twice more are more senior. At adult 50-60% of a tseftriakson 40-50% - also in not changed form with bile are allocated in not changed form with urine, and. Under the influence of an indestinal flora цефтриаксон turns into an inactive metabolite. At newborns about 70% of the entered dose it is allocated with kidneys. At a renal failure or at liver pathology at adults the pharmacokinetics of a tseftriakson almost does not change, the elimination half-life is extended slightly. If function of kidneys is broken, allocation with bile increases and if liver pathology takes place, then allocation of a tseftriakson kidneys amplifies.
Penetration into medullispinal liquid: at newborns and at children at a meninx inflammation цефтриаксон gets into liquor, at the same time in case of bacterial meningitis on average 17% of concentration of drug in blood serum diffuse in medullispinal liquid that is about 4 times more, than at aseptic meningitis. In 24 hours after intravenous administration of a tseftriakson in a dose of 50-100 mg/kg of body weight concentration in medullispinal liquid exceeds 1,4 mg/l. At adult patients with meningitis in 2-25 hours after introduction of a tseftriakson in a dose of 50 mg/kg of body weight concentration of a tseftriakson repeatedly exceeded that minimum oppressing dose which is necessary for suppression of the pathogens which are most often causing meningitis.

Indications to use:

The infections caused by activators, sensitive to Oframaksu®:
• Sepsis, meningitis, infections of an abdominal cavity (peritonitis, inflammatory diseases of digestive tract, biliary tract), infections of bones, joints, connecting fabric, skin, an infection at patients with the lowered immunity, infections of kidneys and urinary tract, respiratory infections (including pneumonia), and also infections of ENT organs, urogenital infections (including gonorrhea).
• Prevention of infections in the postoperative period.

Route of administration and doses:

Офрамакс® it is applied intramusculary and intravenously.
For adults and children 12 years are more senior
 The average daily dose of Oframaks ® makes 1-2 g of 1 times a day or to 0,5-1 g there are each 12 hours.
In hard cases or in cases of the infections caused by moderately sensitive pathogens, the daily dose can be increased to 4 g.
For newborns
 At a one-time daily dosage the following scheme is recommended.
To two-week age: 20-50 mg/kg of body weight a day (the dose of 50 mg/kg of body weight is not recommended to be exceeded in connection with unripe fermental system of newborns).
For babies and children up to 12 years
 The daily dose makes 20-75 mg/kg of body weight.
Children with body weight have 50 kg and it is necessary to adhere to a dosage for adults above.
It is necessary to appoint a dose more than 50 mg/kg of body weight in the form of intravenous infusion, at least, within 30 minutes.
Therapy duration
 Depends on the course of a disease.
Meningitis
 At bacterial meningitis at newborns and at children the initial dose makes 100 mg/kg of body weight once a day (at most 4 g). As soon as the pathogenic microorganism was succeeded to allocate and to define his sensitivity, the dose needs to be reduced respectively. The best results were achieved at the following terms of therapy:
Activator therapy Duration
Neisseria meningitidis is 4 days old
Haemophilus influenzae is 6 days old
Streptococcus pneumoniae is 7 days old
 Sensitive Enterobacteriacease of 10 - 14 days
 Gonorrhea
 For treatment of the gonorrhea caused by the strains both forming, and not forming a penicillinase, the recommended dose makes 250 mg once intramusculary.
Prevention in before - and the postoperative period
 Before the infected or presumably infected surgical interventions for the prevention of postoperative infections, depending on danger of an infection, in 30-90 minutes prior to operation single introduction of Oframaksa® in a dose of 1-2 g is recommended. 
Insufficiency of function of kidneys and liver
 At patients with an impaired renal function, on condition of normal function of a liver to reduce a dose of Oframaksa® there is no need. Only at insufficiency of kidneys in a preterminal stage (the clearance of creatinine is lower than 10 ml/min.) it is necessary that the daily dose of Oframaks ® did not exceed 2 g.
At patients with the broken function of a liver, on condition of preservation of function of kidneys, ® to reduce Oframaks's dose also there is no need.
In cases of simultaneous existence of heavy pathology of a liver and kidneys concentration of a tseftriakson in blood serum needs to be controlled regularly. At the patients subjected to a hemodialysis, the drug dose after holding this procedure should not be changed.
Instruction for preparation of solution and introduction
 Intramuscular introduction
 For intramuscular introduction drug needs to be dissolved in 1% solution of lidocaine  and to enter deeply into a gluteus. It is recommended to enter no more than 1 g of drug into one buttock. Lidocaine solution can never be entered intravenously!

Dosage solvent Volume in ml
250 mg 0,9
 1000 mg 3,6

Intravenous administration
 For an intravenous injection drug is dissolved in sterile water for injections and entered intravenously slowly within 2-4 minutes.

Dosage solvent Volume in ml
250 mg 2,4
 1000 mg 9,6

Intravenous infusion
 Duration of intravenous infusion, at least, 30 minutes. For intravenous infusion of 2 g of powder it is necessary to part approximately in 40 ml of the solution which is not containing calcium, for example: in 0,9% chloride sodium solution, in 5% dextrose solution, in 10% dextrose solution, in 5% fructose solution.

Features of use:

At a simultaneous heavy renal and liver failure it is regularly necessary to define concentration of drug in plasma.
At the patients who are on a hemodialysis it is necessary to watch concentration of a tseftriakson in plasma since at them the speed of its removal can decrease.
At prolonged treatment it is regularly necessary to control a pattern of peripheral blood, indicators of a functional condition of a liver and kidneys.
In rare instances at ultrasonography of a gall bladder blackouts which disappear after cancellation are noted (even if this phenomenon is followed by pains in right hypochondrium, recommend continuation of purpose of an antibiotic and carrying out a symptomatic treatment).
During treatment the ethanol use is contraindicated - disulfiramopodobny effects are possible (face reddening, a spasm in a stomach, nausea, vomiting, a headache, decrease in the ABP, tachycardia, short wind).
Despite detailed collecting the anamnesis that is the rule and for other tsefalosporinovy antibiotics, it is impossible to exclude a possibility of development of an acute anaphylaxis which demands immediate therapy – at first intravenously enter Epinephrinum, then glucocorticosteroids.
 The researches in vitro showed that it is similar to other tsefalosporinovy antibiotics, цефтриаксон is capable to force out the bilirubin connected with blood serum albumine. Therefore with a hyperbilirubinemia and especially at premature newborns Oframaks's use ® demands a bigger care from newborns.
At appointment in the period of a lactation it is necessary to cancel breastfeeding. Purpose of vitamin K can be required by the elderly and weakened patients.

Side effects:

Allergic reactions: a small tortoiseshell, a fever or fever, rash, an itch, it is rare – a bronchospasm, an eosinophilia, an erythema polymorphic exudative (including Stephens-Johnson's syndrome), a serum disease, a Quincke's disease, an acute anaphylaxis.
From the alimentary system: nausea, vomiting, diarrhea or a lock, a meteorism, abdominal pains, taste disturbance, stomatitis, a glossitis, a pseudomembranous coloenteritis, an abnormal liver function (increase in activity of "hepatic" transaminases, is more rare – an alkaline phosphatase or bilirubin, cholestatic jaundice), a pseudo-cholelithiasis of a gall bladder ("sludge" - a syndrome), dysbacteriosis.
From bodies of a hemopoiesis: anemia, leukopenia, leukocytosis, neutropenia, granulocytopenia, lymphopenia, thrombocytosis, thrombocytopenia, hemolitic anemia, hypocoagulation, decrease in concentration of plasma blood-coagulation factors (II, VII, IX, X), lengthening of a prothrombin time.
From an urinary system: a renal failure, (an azotemia, increase in content of urea in blood, a giperkreatininemiya, a glucosuria, a cylindruria, a hamaturia), an oligouriya, an anury.
Local reactions: phlebitis, morbidity on the vein course, morbidity and infiltrate in the place in oil of introduction.
Others: headache, dizziness, nasal bleedings, candidiasis, superinfection.

Interaction with other medicines:

Tseftriakson and aminoglycosides possess a synergism concerning many gram-negative bacteria.
It is incompatible with ethanol.
Non-steroidal anti-inflammatory drugs and other inhibitors of aggregation of thrombocytes increase probability of bleeding.
At simultaneous use with "loopback" diuretics and other nefrotoksichny medicines the risk of development of nephrotoxic action increases.
Pharmaceutical it is incompatible with the solutions containing other antibiotics.

Contraindications:

• Hypersensitivity to cephalosporins, to penicillin and to karbapenema
• First trimester of pregnancy
With care
Hyperbilirubinemia at newborns, premature children, a renal/liver failure, the nonspecific ulcer colitis, enteritis or colitis connected using antibacterial drugs, pregnancy 2-3 trimester, the lactation period.

Overdose:

High concentration of a tseftriakson in plasma cannot be excessive are lowered by means of a hemodialysis or peritoneal dialysis. For treatment of cases of overdose symptomatic measures are recommended.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. Not to freeze. To store in the place, unavailable to children. Period of validity: 3 years.

Issue conditions:

According to the recipe

Packaging:

Офрамакс ® powder for preparation of solution for intravenous and intramuscular administration of 250 mg and 1000 mg in a bottle of 5 ml (for 250 mg) or 15 ml (for 1000 mg) from transparent colourless glass I of type, corked by the rubber bung which is rigidly fitted by the aluminum cap which is closed the broken plastic cover; one bottle with the application instruction in a cardboard pack.