Rotsefin

General characteristics. Structure:

One bottle with powder for preparation of solution for intramuscular introduction contains:
Active agent: цефтриаксон 250 mg, 500 mg, 1 g (in the form of a tseftriakson of disodium salt of 298.3 mg, 596.5 mg, 1.193 g)
Solvent: lidocaine solution of 1%

One bottle with powder for preparation of solution for intravenous administration contains:
Active agent: цефтриаксон 250 mg, 500 mg, 1 g (in the form of a tseftriakson of disodium salt of 298.3 mg, 596.5 mg, 1.193 g)
Solvent: water for injections

One bottle with powder for preparation of solution for infusions contains:
Active agent: цефтриаксон 2 g (in the form of a tseftriakson of disodium salt of 2.386 g)

One bottle with powder for preparation of solution for intravenous and intramuscular administration contains:
Active agent: цефтриаксон 1 g (in the form of a tseftriakson of disodium salt of 1.193 g) /

Pharmacological properties:

Tseftriakson - a parenteral tsefalosporinovy antibiotic of the III generation with the prolonged action. Bactericidal activity of a tseftriakson is caused by suppression of synthesis of cellular membranes. In vitro цефтриаксон possesses a broad spectrum of activity concerning gram-negative and gram-positive microorganisms. It высокоустойчив to the majority of b-laktamaz (as penicillinases, and цефалоспориназ) developed by gram-positive and gram-negative bacteria. Tseftriakson is usually active concerning the following microorganisms:
Gram-positive aerobes

Staphylococcus aureus (metitsillinochuvstvitelny), koagulazo-negative staphylococcus, Streptococcus pyogenes (b-hemolitic, groups A), Streptococcus agalactiae (b-hemolitic, groups B), b-gemoliticheskiye streptococci (groups And, In), Streptococcus viridans, Streptococcus pneumoniae.

Note. Metitsillinoustoychivye Staphylococcus spp. rezistentna to cephalosporins, including to a tseftriakson. As a rule, Enterococcus faecalis, Enterococcus faecium and Listeria monocytogenes are also steady.

Gram-negative aerobes

Acinetobacter lwoffii, Acinetobacter anitratus (mainly, A. baumannii) *, Aeromonas hydrophila, Alcaligenes faecalis, Alcaligenes odorans, alkaligenopodobny bacteria, Borrelia burgdorferi, Capnocytophaga spp., Citrobacter diversus (including S. amalonaticus), Citrobacter freundii *, Escherichia coli, Enterobacter aerogenes *, Enterobacter cloacae *, Enterobacter spp. (other) *, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae **, Moraxella catarrhalis (which was earlier called by Branhamella catarrhalis), Moraxella osloensis, Moraxella spp. (other), Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Plesiomonas shigelloides, Proteus mirabilis, Proteus penneri *, Proteus vulgaris *, Pseudomonas fluorescens *, Pseudomonas spp. (other), Providencia rettgeri *, Providencia spp. (other), Salmonella typhi, Salmonella spp. (netifoidny), Serratia marcescens *, Serratia spp. (other) *, Shigella spp., Vibrio spp., Yersinia enterocolitica, Yersinia spp. (others).

* Some isolates of these types are steady against a tseftriakson, mainly, owing to formation of b-laktamaz coded by chromosomes.

** Some isolates of these types are steady owing to formation of a number of the plazmido-mediated b-laktamaz.

Note. Many strains of the above-stated microorganisms, polyresistant to other antibiotics, such as aminopenicillin and ureidopenicillin, cephalosporins of the first and second generation and aminoglycosides, are sensitive to a tseftriakson. Treponema pallidum is sensitive to a tseftriakson of in vitro and in experiments on animals. Clinical tests show what цефтриаксон has good efficiency concerning primary and secondary syphilis. Behind very small exceptions, clinical P. aeruginosa isolates are steady against a tseftriakson.

Anaerobe bacterias

Bacteroides spp. (zhelchechuvstvitelny) *, Clostridium spp. (except C. difficile), Fusobacterium nucleatum, Fusobacterium spp. (other), Gaffkya anaerobica (which was earlier called by Peptococcus), Peptostreptococcus spp.

* Some isolates of these types are steady against a tseftriakson because of formation of b-laktamaz.

Note. Many strains of b-lactamazoforming Bacteroides spp. (in particular, B. fragilis) are steady. Also Clostridium difficile is steady.

Sensitivity to a tseftriakson can be determined by the disco - a diffusion method or method of serial delution on an agar or broth, using a standard technique, similar to that which is recommended by the National Committee of Clinical Laboratory Standards (NCCLS). NKKLS established the following criteria for evaluation of results of test for a tseftriakson:

	Are sensitive	Are moderately sensitive	Are steady
Method of cultivations Overwhelming concentration, mg/l	= 8	16-32	= 64
Method of disks (a disk from 30 mkg of a tseftriakson) Diameter of a zone of a growth inhibition, mm	= 21	20-14	= 13

For definition it is necessary to take disks with tseftriaksony as in the researches in vitro it is shown that цефтриаксон it is active concerning separate strains which find stability when using the disks intended for all group of cephalosporins.
Instead of the NKKLS standards for definition of sensitivity of microorganisms it is possible to use also other well standardized standards, for example, of the German institute of standardization of DIN (Deutsches Institut fur Normung) and the international recommendations of ICS (International Collaborative Study) allowing to interpret adequately a condition of sensitivity.

Pharmacokinetics. The pharmacokinetics of a tseftriakson has nonlinear character. All key pharmacokinetic parameters based on the general concentration of drug except for an elimination half-life, depend on a dose.

Absorption. The maximum concentration in plasma after single intramuscular introduction of 1 g of drug makes about 81 mg/l and is reached within 2-3 hours after introduction. The areas under a curve "concentration in plasma – time" after intravenous and intramuscular administration are identical. It means that bioavailability of a tseftriakson after intramuscular introduction makes 100%.

Distribution. The volume of distribution of a tseftriakson equals 7-12 l. After introduction in a dose of 1-2 g цефтриаксон well gets into fabrics and liquids of an organism. Within more than 24 hours of its concentration much more exceed the minimum overwhelming concentration for the majority of causative agents of infections more than in 60 fabrics and liquids (including in lungs, heart, bilious ways, a liver, almonds, a middle ear and mucous a nose, bones, and also spinal, pleural and synovial liquids and a secret of a prostate).
After intravenous use цефтриаксон quickly gets into cerebrospinal fluid where bactericidal concentration concerning sensitive microorganisms remain within 24 hours.

Linkng with proteins. Tseftriakson reversibly contacts albumine, and extent of binding decreases with concentration growth, decreasing, for example, from 95% at concentration in plasma less than 100 mg/l to 85% at concentration of 300 mg/l. Thanks to smaller concentration of albumine in an intercellular lymph, the share of a free tseftriakson in it is higher, than in plasma.

Penetration into separate fabrics. Tseftriakson gets through the inflamed meninx at children, including newborns. In 24 hours after intravenous administration of the drug Rotsefin® in doses of 50-100 mg/kg of body weight (to newborns and babies, respectively) concentration of a tseftriakson in cerebrospinal fluid exceed 1.4 mg/l. The maximum concentration in cerebrospinal fluid is reached approximately in 4 hours after intravenous administration and makes, on average, 18 mg/l. At bacterial meningitis average concentration of a tseftriakson in cerebrospinal fluid makes 17% of concentration in plasma, at aseptic meningitis - 4%. At adult patients with meningitis in 2-24 hours, after introduction of a dose of 50 mg/kg of body weight, concentration of a tseftriakson in cerebrospinal fluid many times over surpass the minimum overwhelming concentration for the most widespread causative agents of meningitis.

Tseftriakson passes through a placental barrier and in small concentration gets to breast milk.

Metabolism. Tseftriakson is not exposed to system metabolism, and turns into inactive metabolites under the influence of an indestinal flora.

Removal. The general plasma clearance of a tseftriakson makes 10-22 ml/min. The renal clearance equals 5-12 ml/min. of 50-60% of a tseftriakson 40-50% - in not changed view with bile are removed in not changed view with urine, and. The elimination half-life of a tseftriakson makes about 8 hours at adults.

Pharmacokinetics in special clinical cases. At newborn children through kidneys about 70% of a dose are removed. Babies in the first 8 days have lives, and also at persons 75 years an elimination half-life, on average, in two or three times more, than at adults of young age are more senior.

At patients with a renal failure or a liver the pharmacokinetics of a tseftriakson changes slightly, only small increase in an elimination half-life is noted. If only function of kidneys is broken, removal with bile increases if only function of a liver is broken, removal through kidneys increases.

Indications to use:

The infections caused by activators, sensitive to the drug Rotsefin®: sepsis; meningitis; the disseminated Lyme's disease (early and late stages of a disease); infections of abdominal organs (peritonitis, infections of bilious ways and digestive tract); infections of bones, joints, soft tissues, skin, and also wound fevers; infections at patients with the weakened immunity; infections of kidneys and urinary tract; respiratory infections, especially pneumonia, and infections of ENT organs; infections of generative organs, including gonorrhea.

Perioperatsionny prevention of infections.

Route of administration and doses:

Standard mode of dosing
Adults and children are more senior than 12 years: on 1-2 g once a day (each 24 hours). In hard cases or at infections which causative agents have only moderate sensitivity to a tseftriakson it is possible to increase a daily dose to 4 g.

Duration of treatment depends on the course of a disease. As well as always at an antibioticotherapia, administration of the drug Rotsefin® should be continued the patient within at least 48-72 hours after normalization of temperature and confirmation of an eradikation of the activator.

Combination therapy

In an experiment a synergism between the drug Rotsefin® and aminoglycosides concerning many gram-negative bacteria is shown. In spite of the fact that the increased efficiency of such combinations is not always predictable, it should be meant at heavy, life-threatening infections, such as the caused Pseudomonas aeruginosa. Because of physical incompatibility of a tseftriakson and aminoglycosides they should be entered separately in the doses recommended for them.

Introduction

Use of solutions right after preparation has to be the general rule.
The prepared solutions keep the physical and chemical stability within 6 hours at the room temperature (or within 24 hours at a temperature 2-8oc). Depending on concentration and duration of storage color of solutions can vary from pale yellow to amber. Coloring of solution does not influence efficiency or portability of drug.
For an intramuscular injection of 250 mg or 500 mg of the drug Rotsefin® dissolve in 2 ml, and 1 g - in 3.5 ml of 1% of solution of lidocaine and enter deeply into rather big muscle (buttock). It is recommended to enter no more than 1 g into the same muscle.
The solution containing lidocaine cannot be entered intravenously.
For an intravenous injection dissolve 250 mg or 500 mg of the drug Rotsefin® in 5 ml, and 1 g - in 10 ml of sterile water for injections; enter intravenously slowly within 2-4 minutes.
Intravenous infusion has to last not less than 30 minutes. For preparation of solution part 2 g of the drug Rotsefin® in 40 ml of one of the following infusion solutions which are not containing calcium ions: 0.9% of sodium chloride, 0.45% of sodium chloride + 2.5% of glucose, 5% of glucose, 10% of glucose, 6% of a dextran in 5% solution of glucose, 6-10% of hydroxyethylstarch, waters for injections. Solutions of the drug Rotsefin® cannot be mixed or added to the solutions containing other antimicrobic drugs or other solvents except for listed above, because of possible incompatibility.
It is impossible to use for preparation of solutions of the drug Rotsefin® for intravenous administration and their subsequent cultivation solvents, calciferous, such as Ringer's solution or Hartman's solution, because of possible formation of precipitated calcium superphosphates.
Formation of precipitated calcium superphosphates of calcic salts of a tseftriakson can happen also when mixing the drug Rotsefin® and kaltsiysoderzhashchy solutions when using one venous access. It is impossible to use Rotsefin® along with kaltsiysoderzhashchy solutions for intravenous administration, including with long infusions of kaltsiysoderzhashchy solutions, for example, at parenteral food with use of the Y-connector. For all groups of patients, except newborns, perhaps consecutive administration of the drug Rotsefin® and kaltsiysoderzhashchy solutions at careful washing of infusional systems between injections by compatible liquid (see the section "Interaction with Other Medicines").
Messages on interaction of a tseftriakson and peroral kaltsiysoderzhashchy drugs or interaction of a tseftriakson for intramuscular introduction and kaltsiysoderzhashchy drugs did not arrive (for intravenous or oral administration).

Dosing in special cases

Patients with an abnormal liver function
Patients with an abnormal liver function have no need to reduce a dose on condition of lack of renal failures.

Patients with a renal failure
Patients with a renal failure have no need to reduce a dose on condition of lack of abnormal liver functions. The daily dose of the drug Rotsefin® should not exceed 2 g only in cases of a renal failure with clearance of creatinine less than 10 ml/min.

At a combination of a heavy renal and liver failure it is regularly necessary to define concentration of a tseftriakson in plasma and if necessary to adjust its dose.

The patient who is on dialysis, additional administration of drug after dialysis is not required. It is necessary to control, however, concentration of a tseftriakson in serum regarding possible dose adjustment as removal speed at these patients can decrease.

Patients of advanced and senile age
Usual doses for adults, without amendments on age.

Children
Newborns, babies and children are younger than 12 years
At purpose of the drug Rotsefin®odin of times a day it is recommended to adhere to the following modes of dosing: newborns (up to 14 days) - 20-50 mg/kg of body weight once a day. The daily dose should not exceed 50 mg/kg of body weight. When determining a dose it is not necessary to do distinctions between the full-term and premature children.
Роцефин® it is contraindicated to newborns (? 28 days), which already appoints or supposes intravenous treatment kaltsiysoderzhashchy solutions, including long kaltsiysoderzhashchy infusions, for example, at parenteral food because of risk of formation of precipitated calcium superphosphates of calcic salts of a tseftriakson (see the section "Contraindications").
Newborns, babies and children of younger age (from 15 days to 12 years): 20-80 mg/kg of body weight once a day.
To children with body weight over 50 kg appoint doses for adults.
Intravenous doses or should be entered into 50 mg/kg kapelno above within not less than 30 minutes.

Meningitis
At bacterial meningitis at babies and children of younger age treatment begin with a dose 100 mg/kg (but no more than 4 g) 1 time a day. After identification of the activator and definition of its sensitivity the dose can be reduced respectively. The best results at a spotted fever were achieved lasting treatment of 4 days, at the meningitis caused by Haemophilus influenzae - 6 days, Streptococcus pneumoniae - 7 days.

Lyme's disease
50 mg/kg (the highest daily dose - 2 g) to adults and children once a day within 14 days.

The gonorrhea (caused by penitsillinazoobrazuyushchy and penitsillinazoneobrazuyushchy strains)
Single intramuscular introduction of 250 mg of the drug Rotsefin®.

Prevention of postoperative infections
Depending on degree of infectious risk 1-2 g of the drug Rotsefin® once in 30-90 min. prior to operation are entered. At operations on thick and a rectum well proved simultaneous (but separate, see the section "Route of Administration and Doses") administration of the drug Rotsefin® and one of 5 nitroimidazoles, for example, of an ornidazol.

Features of use:

As well as at use of other cephalosporins, anaphylactic reactions, including from the death, even in cases when the patient had no allergic reactions in the anamnesis were registered.

As well as at use of other cephalosporins, at treatment by the drug Rotsefin® development of autoimmune hemolitic anemia is possible. Cases of heavy hemolitic anemia at adults and children, including from the death are registered. At development in the patient who is on treatment tseftriaksony anemia cannot exclude the diagnosis cephalosporin - the associated anemia and it is necessary to cancel treatment before clarification of the reason.

As well as at use of the majority of other antibacterial drugs, at treatment tseftriaksony cases of development of the diarrhea caused by Clostridium difficile (C. difficile), various weight are registered: from slight diarrhea to colitis from the death. Treatment by antibacterial drugs suppresses normal microflora of a large intestine and provokes growth of C. difficile. In turn, C. difficile forms toxins A and B which are factors of a pathogeny of the diarrhea caused by C. difficile. S.'s strains of difficile which are hyper producing toxins are causative agents of infections with high risk of complications and mortality, owing to their possible resistance to antimicrobic therapy, treatment can demand a colectomy. It is necessary to remember a possibility of development of the diarrhea caused by C. difficile, at all patients with diarrhea is after an antibioticotherapia. Careful collecting the anamnesis since cases of developing of the diarrhea caused by C. difficile later after therapy are noted more than 2 months by antibiotics is necessary.

At suspicion or confirmation of the diarrhea caused by C. difficile cancellation of the current antibioticotherapia difficile which is not directed to S. perhaps will be required. According to clinical indications the corresponding treatment with administration of liquid and electrolytes, proteins, an antibioticotherapia concerning S. difficile, surgical treatment has to be appointed.

As well as at treatment by other antibacterial drugs, superinfections can develop.

At the patients receiving Rotsefin® exceptional cases of change of a prothrombin time are described. Control of a prothrombin time can be required by patients with insufficiency of vitamin K (synthesis disturbance, disturbance of food) during therapy and purpose of vitamin K (10 mg/week) at increase in a prothrombin time prior to the beginning of or during therapy.

After use of a tseftriakson, usually in the doses exceeding standard recommended, at ultrasound examination of a gall bladder shadows which mistakenly took for stones came to light. They represent precipitated calcium superphosphates of calcic salt of a tseftriakson which disappear after end or the termination of therapy by the drug Rotsefin®. Similar changes seldom give any symptomatology, but also in such cases only conservative treatment is recommended. If these phenomena are followed by clinical symptomatology, then the decision on drug withdrawal is left to the discretion of the attending physician.

Despite availability of the intravascular precipitated calcium superphosphates given about education only at newborns at use of a tseftriakson and kaltsiysoderzhashchy infusion solutions or any other kaltsiysoderzhashchy drugs, Rotsefin® should not mix or appoint children and adult patients along with kaltsiysoderzhashchy infusion solutions, even using various venous accesses (see sections of "Contraindication", "Interaction with Other Medicines", "Post-marketing Observation").

At the patients receiving Rotsefin® exceptional cases of the pancreatitis developing perhaps, owing to obstruction of bilious ways are described. Most of these patients had risk factors of stagnation in bilious ways, for example, earlier carried out therapy, a serious illness and completely parenteral food already before. At the same time it is impossible to exclude a starting role, formed under the influence of the drug Rotsefin®, precipitated calcium superphosphates in bilious ways in development of pancreatitis.

Safety and efficiency of the drug Rotsefin® at newborns, babies and children of younger age were defined for the dosages described in the section "Route of Administration and Doses". Researches showed what like other cephalosporins цефтриаксон can force out bilirubin from communication with a seralbumin.

Роцефин® it is impossible to apply at newborns, especially premature which have a risk of development of bilirubinovy encephalopathy (see the section "Contraindications").

At prolonged treatment it is necessary to carry out an integrated analysis of blood regularly.

Influence on driving of vehicles and work with cars and mechanisms
There are no data testimonial of influence of drug on driving of vehicles and work with cars and mechanisms. However it is necessary to remember possible developing of dizziness at therapy by the drug Rotsefin®.

Side effects:

Post-marketing observation
At use of the drug Rotsefin® the following by-effects which, as a rule, disappeared or independently, or after drug withdrawal were observed.

System reactions
Digestive tract (about 2%): not properly executed chair or diarrhea, nausea, vomiting, stomatitis, glossitis, taste disturbance (less than 1%).
Hematologic changes (about 2%): eosinophilia, leukopenia; less often (<1%): granulocytopenia, hemolitic anemia, thrombocytosis, thrombocytopenia, increase in a tromboplastinovy and prothrombin time. Separate cases of an agranulocytosis are described (<500 cells / мкл), and most of them developed after 10 days of treatment and use of a cumulative dose of 20 g and more.
Skin reactions (about 1%): rash, allergic dermatitis, itch, small tortoiseshell, hypostases. Separate cases of heavy side reactions (exudative multiformny erythema (Stephens-Johnson's syndrome), toxic epidermal necrolysis (Lyell's disease)).
Other (are observed seldom): a headache and dizziness, precipitation of calcic salts of a tseftriakson in a gall bladder with the corresponding symptomatology, pancreatitis, increase in activity of liver enzymes (ALT, nuclear heating plant), ShchF, a hyperbilirubinemia, an oliguria, increase in concentration of creatinine of serum, mycoses of generative organs, a vaginitis, temperature increase, a fever, the increased sweating, "inflows", an allergic pneumonitis, a bronchospasm, nasal bleeding, a hamaturia, jaundice, decrease in a prothrombin time, a convulsive attack, heartbeat, a serum disease, and also anaphylactic or anaphylactoid reactions.
Separate fatal cases of formation of precipitated calcium superphosphates in lungs and kidneys by results of an autopsy research at the newborns receiving Rotsefin® and kaltsiysoderzhashchy solutions are described. At the same time one venous access was in some cases used, and formation of precipitated calcium superphosphates was observed directly in system for intravenous administration. At least, one case from the death is also described, at various venous accesses and to various time of administration of the drug Rotsefin® and kaltsiysoderzhashchy solutions. At the same time by results of an autopsy research precipitated calcium superphosphates were not found in this newborn. Similar cases were observed only at newborns (see the section "Special Instructions").
Very exceptional cases of pseudomembranous colitis are described (<0.01%) and in kidneys, mainly, at children 3 years receiving or high daily doses of drug are more senior than disturbances of coagulability of blood, and also formation of concrements (? 80 mg/kg a day), or cumulative doses more than 10 g, and also having accessory factors of risk (liquid consumption restriction, a bed rest, etc.). Formation of concrements in pochkakhmozht to proceed asymptomatically or to be shown clinically, can lead to a renal failure. This undesirable phenomenon has reversible character and disappears after the therapy termination by the drug Rotsefin®.
Local reactions (very seldom): phlebitis after intravenous administration. It can be avoided, administering the drug slowly within 2-4 minutes.
The intramuscular injection without use of lidocaine is painful.

Influence on results of laboratory analyses
In rare instances at treatment by the drug Rotsefin® at patients false positive results of test of Koombs can be noted. As well as other antibiotics, Rotsefin® can yield false positive result of test on a galactosemia. False positive results can be received also when determining glucose in urine by not fermental methods therefore during therapy by the drug Rotsefin® the glucosuria if necessary needs to be determined only by a fermental method.

Interaction with other medicines:

At simultaneous use of high doses of the drug Rotsefin® and "petlevykh" of diuretics (for example, furosemide), renal failures were not observed. Instructions on the fact that Rotsefin® increases nephrotoxicity of aminoglycosides no. Alcohol intake after administration of the drug Rotsefin® was not followed by disulfiramopodobny reaction. Tseftriakson does not support N-methylthiotetracindery group which could cause intolerance of ethanol and bleeding that is inherent in some other cephalosporins. Probenetsid does not influence drug Rotsefin® removal.

Bacteriostatic antibiotics reduce bactericidal effect of a tseftriakson.

In vitro was found antagonism between chloramphenicol and tseftriaksony.

It is impossible to use solvents, calciferous, such as Ringer's solution or Hartman's solution, at preparation of solutions of the drug Rotsefin® for intravenous administration and their subsequent cultivation because of possible formation of precipitated calcium superphosphates.

Formation of precipitated calcium superphosphates of calcic salts of a tseftriakson can happen also when mixing the drug Rotsefin® and kaltsiysoderzhashchy solutions when using one venous access. It is impossible to use Rotsefin® along with kaltsiysoderzhashchy solutions for intravenous administration, including with long infusions of kaltsiysoderzhashchy solutions, for example at parenteral food with use of the Y-connector. For all groups of patients, except newborns, perhaps consecutive administration of the drug Rotsefin® and kaltsiysoderzhashchy solutions at careful washing of infusional systems between injections by compatible liquid. For assessment of interaction of a tseftriakson and calcium two researches in vitro are conducted: one with use of a blood plasma of the adult, another – plasmas of umbilical blood of the newborn. Various combinations of a tseftriakson with initial concentration to 1 mm (the maximum concentration which reaches цефтриаксон in vivo at infusional introduction of 2 g of drug within not less than 30 min.) and calcium with initial concentration to 12 mm (48 mg/dl) were analyzed. Decrease in concentration of a tseftriakson in plasma was observed when using calcium in concentration of 6 mm (24 mg/dl) and above for plasma of the adult and in concentration of 4 mm (16 mg/dl) and above for the newborn's plasma that demonstrates the increased risk of formation of calcic salts of a tseftriakson at newborns (see the sections "Route of Administration and Doses", "Contraindications").

Tseftriakson pharmaceutical is incompatible with amsakriny, Vancomycinum, flukonazoly and aminoglycosides.

Contraindications:

Hypersensitivity to cephalosporins and penicillin.

Hyperbilirubinemia at newborn and premature (the researches in vivo showed what цефтриаксон can force out bilirubin from communication with a seralbumin, increasing risk of development of bilirubinovy encephalopathy in such patients).
Newborns (? 28 days) which already appoints or supposes intravenous treatment kaltsiysoderzhashchy solutions, including long kaltsiysoderzhashchy infusions, for example, at parenteral food, because of risk of formation of precipitated calcium superphosphates of calcic salts of a tseftriakson (see the sections "Route of Administration and Doses" and "Interaction with Other Medicines").

Separate fatal cases of formation of precipitated calcium superphosphates in lungs and kidneys at the newborns receiving Rotsefin® and kaltsiysoderzhashchy solutions are described. At the same time one venous access was in some cases used, and formation of precipitated calcium superphosphates was observed directly in system for intravenous administration, at least, one case from the death at various venous accesses and to various time of administration of the drug Rotsefin® and kaltsiysoderzhashchy solutions is also described. Similar cases were observed only at newborns (see the section "Post-marketing Observation").

With care
Feeding period breast.

Pregnancy and period of feeding by a breast
Pregnancy
Tseftriakson gets through a placental barrier. Safety of use at pregnancy for women is not established. Preclinical trials of reproductibility did not reveal embriotoksichesky, fetotoksichesky, teratogenic effect or other adverse effects of drug on fertility of males and females, process of childbirth, perinatal and post-natal fetation. At pregnancy, especially in the first trimester, it is necessary to appoint only according to strict indications provided that the estimated advantage for mother exceeds potential risk for a fruit.

Feeding period breast
In small concentration цефтриаксон gets to breast milk. At its appointment of the nursing mother it is necessary to be careful.

Overdose:

At overdose the hemodialysis and peritoneal dialysis will not reduce concentration of drug. There is no specific antidote. Overdose treatment - symptomatic.

Storage conditions:

To store at a temperature not above 30 °C in the place protected from light.
To store in the place, unavailable to children.
To store the prepared solution at the room temperature no more than 6 hours or in the refrigerator at 2-8 °C no more than 24 hours.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of solution for intramuscular introduction of 250 mg, 500 mg, 1 g
Set:
On 250 mg, 500 mg or 1 g of a tseftriakson in the glass bottle (glass a hydrolytic class 1 EF) corked by a stopper from butyl rubber, which is pressed out by an aluminum cap and closed by a plastic cover.
On 2 ml (for the drug Роцефин® 250 of mg and 500 mg) or 3.5 ml (for the drug Роцефин® 1 of) solution of lidocaine of 1% in the ampoules made, according to ISO 9187, from glass of a hydrolytic class 1 EF, hermetically soldered. On an ampoule with solvent there is a point of blue color; on an ampoule tip – two rings – blue and green color.
1 bottle with drug together with 1 ampoule of solution of lidocaine of 1% and the application instruction is placed in a cardboard pack.

Powder for preparation of solution for intravenous administration on 250 mg, 500 mg, 1 g the Set:
On 250 mg, 500 mg or 1 g of a tseftriakson in the glass bottle (glass a hydrolytic class 1 EF) corked by a stopper from butyl rubber, which is pressed out by an aluminum cap and closed by a plastic cover.
On 5 ml (for the drug Роцефин® 250 of mg and 500 mg) or 10 ml (for the drug Роцефин® 1 of) waters for injections in the ampoules made, according to ISO 9187, from glass of a hydrolytic class 1 EF, hermetically soldered. On an ampoule there is a point of blue color.
1 bottle with drug together with 1 ampoule of water for injections and the application instruction is placed in a cardboard pack.

Powder for preparation of solution for infusions of 2 g
On 2 g of a tseftriakson in the glass bottle (glass a hydrolytic class 1 EF) corked by a stopper from butyl rubber, which is pressed out by an aluminum cap and closed by a plastic cover.
1 bottle together with the application instruction is placed in a cardboard pack.

Powder for preparation of solution for intravenous and intramuscular administration of 1 g
On 1 g of a tseftriakson in the glass bottle (glass a hydrolytic class 1 EF) corked by a stopper from butyl rubber, which is pressed out by an aluminum cap and closed by a plastic cover.
1 bottle together with the application instruction is placed in a cardboard pack.

For hospitals: on 143 bottles together with the corresponding number of application instructions place in a cardboard box.