Rocephin 1g #1 vial

Rocefin 1g #1 vial

Rocephin Annotation
(ROCEPHINE)
CEFTRIAXONE

chemical name
disodium_(Z)_(6R,7R)_7-[2_(2_amino-1,3_thiazol-4_yl)-2_(methoxyimino)acetamido[_8-oxo_3-](2,5_dihydro_2_methyl-6-oxido_5_oxo-1,2,4- Triazin-3-yl)thiomethyl]-5-thia-1-azabicyclo[4,2,0]-oct_2-carboxylate EBA

Composition and release form
chemical name
Dry substance for preparation of intramuscular injection solution:
5 and 50 pcs. in a vial, in a package. in a set with a solvent
1 fl.
Ceftriaxone. . . . . . . . . . . . . . . 500 mg
1 fl.
Ceftriaxone. . . . . . . . . . . . . . . . . 1 g
Solvent: 1 ampoule of 2 ml and 3.5 ml of 1% lidocaine solution
Dry substance for the preparation of intravenous injection solution:
5 and 50 pcs. in a vial, in a package. in a set with a solvent
1 fl.
Ceftriaxone. . . . . . . . . . . . . . 500 mg
1 fl.
Ceftriaxone. . . . . . . . . . . . . . . . . 1 g
Solvent: 1 ampoule of 5 ml and 10 ml of water for injection
Dry substance for preparation of intramuscular and intravenous injection solution:
Ceftriaxone. . . . . . . . . . . . . . . . . 1 g
without solvent 1 fl
Dry substance for preparation of infusion solution:
5 and 50 pcs. in a vial, in a package.
1 fl.
Ceftriaxone. . . . . . . . . . . . . . . . 2 c

Description
White or white-yellow crystalline powder

Clinical-pharmacological group
An antibiotic of the group of cephalosporins

Pharmacological properties
Rocefin is a long-acting third-generation broad-spectrum cephalosporin antibiotic for parenteral use. The bactericidal effect of ceftriaxone is due to the inhibition of the synthesis of the cell wall of the microbe as a result of the disruption of mucopeptide murein synthesis. In vitro, it has a broad-spectrum activity against gram-positive and gram-negative microorganisms. The drug is resistant to beta-lactamases (produced by most gram-negative and gram-positive bacteria, such as penicillinase and cephalosporinase). Rocefin is active against the following microorganisms in vitro and in clinical practice:
Gram-positive aerobes:
Staphylococcus aureus (susceptible to methicillin), coagulase-negative staphylococci, Streptoccocus pyogenes (-hemolytic, group A), Streptococcus agalactiae (-hemolytic, group B), -hemolytic streptococci (not group A and B), Streptococcus viridans, Streptococcus pneumoniae.
Note: Methicillin-resistant Staphylococcus spp. are resistant to cephalosporins, including rocephin.
Typically, Enterococcus faecalis, Enterococcus faecium, and Listeria monocytogenes are also resistant to rocefin.
Gram-negative aerobes:
Acinetobacter iwoffi, Acinetobacter anitratus (mainly A. baumanii)*, Aeromonas Hydrophila, Alcaligenes faecalis, Alcaligenes odorans, Borrelia burgdorferi, Citrobacter diversus (including C. amalonaticus), Citrobacter freundii*, Escherichia coli, Enterobacter aerogenes*, Enterobacter cloacae* , Enterobacter spp.*, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis (formerly called Branhamella catarralis), Moraxella spp., Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Plesiomonas shigelloides, Proteus mirabiles, Proteus vulgaris*, Proteus penneri*, Pseudomonas fluorescens*, Pseudomonas spp., Providentia rettgeri*, Providentia spp., Salmonella typhi, Salmonella spp.(aratifoiduri), Serratia marcescens*, Serratia spp.*, Shigella spp. ., Vibrio spp., Yersinia enterocolitica, Yersinia spp.

Some of the listed microorganisms that produce beta-lactamase are resistant to Rocefin.
Note: some strains of the microorganisms listed above are polyresistant to other antibiotics, such as: aminopenicillins and ureidopenicillins, I and II generation cephalosporins and aminoglycosides, and are sensitive to Rocefin. Treponema pallidum is susceptible to ceftriaxone both in vitro and in animal studies. Rocefin is characterized by a good effect in case of primary and secondary inflammation.
Anaerobic pathogens:
Bacteroides spp., Clostridium spp., (except C. difficile), Fusobacterium nucleatum, Fusobacterium spp., Gaffkia anaerobica (formerly Peptococcus wodebuli), Peptostreptococcus spp.
Some strains of the listed microorganisms are resistant to Rocefin due to the production of beta-lactamase.
Note: Beta-lactamase-producing Bacteroides spp. Many strains (particularly B. fragilis) are resistant to the drug, as is Clostridium difficile. To determine susceptibility to rocephin, use the standard methods of disk diffusion or serial dilutions on agar and broth provided by the National Committee for Clinical Laboratory Standards. Discs containing ceftriaxone are used for determination. Certain strains of pathogens are resistant to classical rocefin in vitro. Susceptibility tests of causative strains to Rocefin:
Sample on dilution, inhibitory concentration mg/l:
susceptible strain =8;
moderately susceptible strain 16-32;
Resistant strain =64.
Diffusion test (disc containing 30 mcg ceftriaxone) diameter in mm:
susceptible strain =21;
moderately susceptible strain 14-20;
Resistant strain =13.

Pharmacokinetics
All the main pharmacokinetic parameters depending on the total concentration of rocefin (except for the half-life) depend on the dose of the drug.
Absorption: the maximum concentration of rocefin in the blood plasma is observed within 2-3 hours after a single intramuscular injection of 1 g of the drug and is about 81 mg/l. The area of the “concentration-time” curve during intramuscular and intravenous injection of the drug is similar, which indicates that Rocefin’s bioavailability during intramuscular injection is 100%.
Distribution: The volume of distribution of Rocefin is 7-12 L. During intravenous administration, 1-2 g quickly diffuses into tissues and interstitial fluids. During 24 hours, its concentration is many times higher than the minimum inhibitory concentration of infectious agents in the lungs, heart, biliary tract, liver, tonsils, middle ear and nasal mucosa, bones, as well as in cerebrospinal fluid, pleural and synovial fluids, and secretion of the pituitary gland. After intravenous use, rocefin quickly passes through the blood-brain barrier, where the bactericidal effect of the drug against susceptible pathogens is maintained for 24 hours.
Connection with plasma proteins: Rocefin is reversibly bound to albumin and this connection depends on its concentration
It is inversely proportional: e.g. In the case when the concentration of the drug in the blood serum is not less than 100 mg/l, the connection of rocefin with proteins is 95%, and when the concentration of the drug is 300 mg/l – only 85%. Due to the low content of albumin in the interstitial fluid, the concentration of ceftriaxone in it is higher than in the blood serum. Penetration of the drug into the cerebrospinal fluid: Ceftriaxone penetrates into the cerebrospinal fluid during inflammation of the meninges in infants and children. During bacterial meningitis, an average of 17% of the concentration of the drug in the blood serum diffuses into the cerebrospinal fluid, which is about 4 times more than during aseptic meningitis.
24 hours after intravenous infusion of Rocefin at a dose of 50-100 mg/kg body weight, the concentration of the drug in the cerebrospinal fluid exceeds 1.4 mg/l. The maximum concentration is reached approximately 4 hours after intravenous administration and is 18 mg/l. 2-24 hours after administration of rocefin at a dose of 50 mg/kg body weight in adults with meningitis, the concentration of rocefin is many times higher than the minimum dose necessary to inhibit pathogenic microorganisms causing meningitis.

Rocefin crosses the placental barrier and is excreted in small concentrations in breast milk.
Metabolism: Rocefin does not undergo systemic metabolism. Under the influence of intestinal flora, it is transformed into an inactive metabolite.
Excretion: total plasma clearance of rocefin is 10-22 ml/min, and renal clearance is 5-12 ml/min. 50-60% of Rocefin is eliminated unchanged by kidneys, 40-50% with bile. The half-life of Rocefin in adults is about 8 hours.
Approximately 70% of the dose administered to newborns is excreted by the kidneys. In newborns up to 8 days and in patients over 75 years old, the mentioned period is twice as long. In adult patients with liver and kidney failure, the pharmacokinetics of Rocefin is almost unchanged, and the elimination half-life is slightly prolonged. In case of renal dysfunction, the release of the drug increases with the bile, and in case of liver pathology, on the contrary, through the kidneys.

testimonials
Infections caused by pathogenic microorganisms sensitive to Rocefin: sepsis, meningitis, disseminated Lyme borreliosis (early and late stages of the disease), infections of abdominal organs (peritonitis, infections of the gastrointestinal tract, biliary tract), bones, joints, connective tissue, skin, wounds caused by infections. Infections in patients with a weakened immune system. Kidney and urinary tract infections, lower respiratory tract infections (especially pneumonia, bronchitis), otorhinolaryngological infections, genital infections, including uncomplicated gonorrhea and other sexually transmitted infections. Perioperative prophylaxis of infections.

Dosage regimen
Rocephin is injected into a muscle or vein.
For adults and children over 12 years of age, the dose of Rocefin is 1-2 g once (every 24 hours) a day.
In severe cases or infections caused by moderately sensitive pathogenic microbes, it is possible to increase the single daily dose to 4 g. The dose of ceftriaxone in newborns up to 2 weeks old is 20-50 mg/kg per day. (Due to the deficiency of the enzyme system in newborns, it is not allowed to prescribe the drug in a dose higher than 50 mg/kg/weight).
The daily dose for children from 2 months to 12 years of age is 20-80 mg/kg of body weight per day. Children weighing 50 kg and more are prescribed the drug in the same doses as adults. Infusion of the drug into the vein continues for 30 minutes. The duration of treatment depends on the course of the pathological process and the degree of severity of the disease, as well as on the given bacteriological examinations. Basically, it is 4-14 days. In severe infectious diseases, longer therapy is possible. After the disappearance of the symptoms of the disease, in most infectious diseases, treatment continues for at least 48-72 hours.
Combination therapy: Synergism between rocephin and aminoglycosides against many Gram-negative bacteria has been established, although the potentiating effect of such a combination cannot be predicted. This combination should be considered in severe and life-threatening infections (eg caused by Pseudomonas aeruginosa).
Due to their physical incompatibility, Rocefin and aminoglycosides must be administered separately in the recommended doses.
Meningitis: in case of bacterial meningitis in infants and children, the initial dose of the drug is 100 mg/kg of body weight once a day (maximum 4 g). After it is possible to isolate pathogenic microorganisms and determine their sensitivity, it is necessary to reduce the dose accordingly.
Important data can be obtained in the appropriate time frame as a result of the treatment given in the table below.

Duration of treatment causing the disease
Neisseria meningitidis 4 days
Haemophilus influenzae 6 days
Streptococcus pneumoniae 7 days

Lyme borreliosis:
Adults and children are prescribed 50 mg/kg (highest daily dose – 2 g) once a day for 14 days.
Gonorrhea:
The recommended dose for the treatment of gonorrhea caused by both penicillinase-producing and non-penicillinase-producing strains is 250 mg once intramuscularly.
Infected or likely to be infected before surgical intervention, depending on the severity of the infection – 30-90 minutes before surgery, 1-2 g Rocefin is recommended to be administered once.
Liver and kidney failure:
In patients with impaired renal function – under conditions of normal liver function, it is not necessary to reduce the dose of ceftriaxone. In the pre-terminal stage (creatinine clearance is less than 10 ml/min) in renal failure, the daily dose of ceftriaxone should not exceed 2 g.
In patients with impaired liver function – in case of normal kidney function – it is not necessary to reduce the dose of ceftriaxone.
In the case of simultaneous severe pathologies of the liver and kidneys, it is necessary to regularly control the concentration of Rocefin in the blood serum.
In patients on hemodialysis, after the mentioned procedure, it is not necessary to change the dose of the drug.
input
The prepared solution maintains its physical and chemical stability at room temperature for 6 hours, at 2-8ºC for 24 hours. According to the generally accepted rule, it is necessary to immediately introduce the newly prepared solution into the body.
The color of the prepared solution may be yellowish. The color of the solution of the active substance does not affect the medicinal effect of the drug. For painless intramuscular injections, 0.25 g or 0.5 g of the drug is dissolved in 2 ml of 1% lidocaine solution in the following ratio: 1 g of the contents of the vial is dissolved in 3.5 ml of lidocaine solution and injected deep into the buttock. Intravenous administration of lidocaine is not allowed. During intravenous administration, 0.25 g or 0.5 g of the drug is dissolved in 5 ml of sterile water for injection in the following ratio: 1 g of the contents of the vial is dissolved in 10 ml of sterile distilled water and slowly injected into the vein for 2-4 minutes. Duration of intravenous infusion is 30 minutes. For this, 2 g of powder is dissolved in approximately 40 ml of calcium ion-free solution: e.g. 0.9% sodium chloride or 0.45% sodium chloride solution with 2.5% glucose content, 5% or 10% glucose solution, 5% fructose, 6% dextrose solution. No other solvents are used.

Side effects
Systemic side effects: complaints from the gastrointestinal tract (about 2% of patients):
Loose stools or diarrhea, nausea, vomiting, stomatitis and glossitis. Changes in the blood picture (about 2% of patients): eosinophilia, leukopenia, agranulocytopenia, hemolytic anemia, thrombocytopenia. Single cases of agranulocytosis (less than 500 cells in 1 μl) have been described, most of them occurring after 10 days of treatment and when taking the drug in cumulative doses of 20 mg and more. Skin reactions (about 1% of patients): rash, allergic dermatitis, urticaria, swelling. In severe cases, erythema multiforme, Stevens-Johnson syndrome, Lyell’s syndrome or toxic epidermal necrolysis develop.

Miscellaneous: rarely headache, dizziness, increased activity of liver enzymes, precipitation of rocefin calcium salts with relevant symptoms in the gallbladder, oliguria, increased creatinine in the blood serum, mycoses in the genital area, increased temperature, chills, anaphylaxis or anaphylactic reactions. Rarely, the development of pseudomembranous colitis and blood coagulation disorders, as well as the formation of calculi in the kidneys, mainly in children over the age of 3 years, who receive the drug in high daily doses (80 mg/kg per day), or in cumulative doses of 10 mg and more, as well as other additional During risk factors (restriction of fluid intake, bed rest, etc.). The process of formation of concretions in the kidneys is asymptomatic, or sometimes it is clinically manifested by kidney failure. This process is reversible upon discontinuation of Rocefin treatment.
Local side effects (rarely): the development of phlebitis is not excluded when the drug is administered intravenously. This event can be avoided by slow (within 2-4 minutes) administration of the drug.
Intramuscular injection without lidocaine is painful. These side effects generally disappear spontaneously or after stopping treatment with the drug.

Contraindications
increased sensitivity to cephalosporin antibiotics;

Pregnancy and lactation
Rocefin crosses the placental barrier.
The safety of using the drug during pregnancy has not been established to date. However, animal studies did not reveal embryotoxic, fetotoxic, teratogenic effects or any adverse effects on subsequent fertility, parturition, perinatal and postnatal development of the fetus. Embryotoxicity and teratogenic events were not detected in primates.
Rocephin passes into breast milk in small concentrations, so special care should be taken during its use during lactation.

Special instructions
Despite the collection of accurate anamnesis data, which is a necessity in relation to other cephalosporin antibiotics, the possibility of developing anaphylactic shock cannot be excluded.
In patients with increased sensitivity to penicillin, special care should be taken to avoid possible cross-allergic reactions. As during treatment with other antibacterial drugs, it is possible to develop superinfections.
During ultrasound examinations, sometimes, the presence of a shadow is observed in the gallbladder, which indicates the accumulation of sediments, which are precipitates of the calcium salt of Rocefin. These events soon disappear after symptomatic treatment or temporary discontinuation of rocephin treatment. Even the presence of pain syndrome, in such cases, does not require surgical intervention, conservative treatment is sufficient.
In some patients, there have been rare cases of pancreatitis caused by obstruction of the biliary tract during the use of rocephin. It is established that, like other cephalosporin antibiotics, Rocefin displaces albumin bound to the blood serum, therefore Rocefin should be used with extreme caution in infants with hyperbilirubinemia and especially in premature children who are at risk of developing bilirubin-induced encephalopathy.

overdose
In case of overdose, hemodialysis and peritoneal dialysis are ineffective.
There is no specific antidote.
Treatment is symptomatic.

Interaction with other drugs
With high doses of rocefin and the simultaneous use of strong diuretics (for example, furosemide), no impairment of renal function is observed. Rocefin does not increase the nephrotoxicity of aminoglycosides. Drinking alcohol after rocephin administration does not cause disulfiram-like reactions.
Rocefin does not contain the N-methylthiotetrazole group, which causes a reaction to ethanol and bleeding, which essentially characterizes some other cephalosporins. Probenecid does not affect the process of Rocefin’s excretion from the body.
Antagonism between chloramphenicol and rocephin has been established in vitro.

Incompatibility:
Mixing rocefin solution with other infusion solutions containing calcium e.g. It is not recommended to use Hartmann’s and Ringer’s solutions, or its simultaneous introduction into the body with other antibacterial drugs, vancomycin, fluconazole and aminoglycosides. Effects on laboratory indicators: in the course of treatment with rocefin in patients, in rare cases, there are false negative indicators on the Coombs test.
Like other antibiotics, Rocefii gives false-negative results in the galactosemia test. The same indicators are obtained during the determination of glucose in urine, therefore, in the course of Rocefin treatment, the determination of glucosuria, if necessary, is performed only by the enzymatic method.

Storage conditions and term
The drug is stored at a temperature of no more than 25ºC, in a place protected from light. in a place protected from children.
The prepared solution is stored at room temperature for no more than 6 hours or in a refrigerator at 2-8ºC
temperature for no more than 24 hours.
Shelf life – 3 years.
It is issued with a doctor’s prescription
Issuing LLC Hoffman-La Roche,
Switzerland, Basel