Ceftriaxone-Jodhas - instructions for use, dose, side effects, contraindications

The bactericidal activity of ceftriaxone is due to the suppression of the synthesis of cell membranes. The drug is resistant to the action of most beta-lactamases (penicillinase and cephalosporinase) Gram-positive and Gram-negative microorganisms. Ceftriaxone is active against the following microorganisms:

Gram-positive aerobes - Staphylococcus aureus (including strains that form penicillinase), Streptococcus pyogenes (β-hemolytic streptococci of group A), Streptococcus agalactiae (β-hemolytic streptococci of group B), β-hemolytic streptococci (pi A or B groups), Streptococcus viridans. Streptococcus pneumonia.

Note: Methicillin-resistant Staphylococcus spp., resistant to cephalosporins, at Tom number of and to ceftriaxone. Most strains enterococci (eg, Enterococcus faecalis) and Listeria monocytogenes also are stable to ceftriaxone.

Gram-negative aerobes: Acinetobacter Iwoffii, Acinetobacter anitratus * (the main manner, A. baumannii), Aeromonas hydrophila, Alcaligenes spp. (including Alcaligenes faccalis, Alcaligenes odorans), alkaligen-like bacteria, Borrelia burgdorferi, Capnocytophaga spp., Citrobacter diversus (at Tom number of, FROM. amalonaticus), Citrobacter freundii *, Escherichia coli. Enterobacter aerogenes *, Enterobacter cloacae *, Enterobacter spp. (other)*. Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainlluenzae, Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae **, Moraxella catarrhalis, Moraxella osloensis, Moraxella spp.(other), Morganella morganii, Neisseria gonorrhoeae. Neisseria meningitidis, Pasteurella multocida, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris *. Proteus penneri *, Pseudomonas fluorescens *, Pseudomonas spp. (other), Providencia rettgeri *, Providencia spp. (other), Salmonella spp. (non-phytophoid). Salmonella typhi, Serratia spp. (other)*, Serratia marcescens, Shigella spp. Vibrio spp., Yersinia spp. (other),Yersinia enterocolitica.

* Some isolates these species are stable to ceftriaxone, the main manner, due to of education β-lactamase, coded chromosomes.

** Some isolates of these species are stable due to the formation of a number of plasmid-mediated β-lactamases.

Note. Many strains of the above microorganisms, multiresistant to other antibiotics, such as aminopenicillins and ureidopenicillins, first and second generation cephalosporins and aminoglycosides,sensitive to ceftriaxone. Treponema pallidum sensitive to ceftriaxone in vitro and in animal experiments. According to clinical data, in the primary and secondary syphilis, a good efficacy of ceftriaxone is noted. With very few exceptions, clinical isolates P.aeruginosa resistant to ceftriaxone.

Anaerobes: Bacteroides spp. (bile-sensitive) *, Clostridium spp. (with the exception of Clostridium difficile), Fusobacterium spp. (including Fusobacterium nucleatum), Gaffkia anaerobica, Peptostreptococcus spp.

* Some isolates of these species are resistant to ceftriaxone due to the formation of β-lactamases.

Note. Many strains of β-lactamase-forming Bacteroides spp. (for example, in. fragilis) resistant to ceftriaxone. Clostridium difficile also resistant to ceftriaxone.

To determine the sensitivity of microorganisms, discs containing ceftriaxone, since it is shown that in vitro to classical cephalosporins, certain strains of pathogens can be stable.

Pharmacokinetics:

With intramuscular injection ceftriaxone is well absorbed from the injection site and reaches high concentrations in the blood plasma. Bioavailability of the drug is 100%. Ceftriaxone well penetrates into tissues and body fluids (including the lungs,heart, bile ducts, liver, tonsils, middle ear and nasal mucosa, bones, as well as spinal, pleural and synovial fluids and the secretion of the prostate), and reaches concentrations significantly exceeding the minimum inhibitory concentrations (MICs) that are maintained for 24 h.

The average concentration in the plasma is achieved 2-3 hours after the injection. With repeated intramuscular or intravenous administration in doses of 0.5-2.0 g with an interval of 12 to 24 hours, there is accumulation of ceftriaxone in a concentration that is 15% -36% higher than the concentration achieved with a single injection. When administered at a dose of 0.15 to 3.0 g, the elimination half-life is between 5.8 and 8.7 hours; volume of distribution - 7-12 liters; the plasma clearance is 0.58-1.45 l / h, the renal clearance is 0.32-0.73 l / h. Ceftriaxone reversibly binds to blood plasma proteins. From 33% to 67% of the drug is excreted unchanged in the urine, the rest is excreted with bile into the intestine, where it is biotransformed into an inactive metabolite. The maximum concentration (C max) of ceftriaxone after a single intramuscular (IM) dose of 1 g is approximately 81 mg / l, and is achieved (TCmax) 2-3 hours after administration.Cmax after a single intravenous infusion of 1 g and 2 g of the drug is 168 mg / l and 257 mg / l, respectively. The iodine content of the pharmacokinetic concentration-time curve (AUC) for ceftriaxone after IM is the same as after intravenous (iv) equivalent dose administration, indicating 100% bioavailability after IM administration. In neonates, approximately 70% of the administered dose is excreted by the kidneys.

In renal failure or liver disease in adults pharmacokinetics ceftriaxone hardly changes, half-life period is lengthened slightly. If the kidney function is impaired, the secretion with bile increases, and if liver pathology takes place, then the excretion of ceftriaxone by the kidneys increases.

Penetration into the cerebrospinal fluid: in newborns and in children with inflammation of the meninges ceftriaxone penetrates into the cerebrospinal fluid, while in the case of bacterial meningitis, an average of 17% of the concentration of the drug in the plasma diffuses into the cerebrospinal fluid, which is approximately 4 times greater than with aseptic meningitis. 24 hours after intravenous administration of ceftriaxone in a dose of 50-100 mg / kg body weight, concentrations in the cerebrospinal fluid exceed 1.4 mg / l.In adults with meningitis, 2 to 24 hours after a dose of 50 mg / kg body weight, ceftriaxone concentrations in the cerebrospinal fluid are many times greater than the minimal inhibitory concentrations for the most common meningitis pathogens.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to ceftriaxone:

- sepsis,

- meningitis,

- disseminated borreliosis Lyme (early and late stages of the disease),

- infection of the abdominal cavity (peritonitis, infection of the biliary tract and gastrointestinal tract).

- infection of bones, joints, soft tissues, skin, as well as wound infections:

- infection in patients with weakened immunity;

- infections of the kidneys and urinary tract;

- infections of the respiratory tract, especially pneumonia and infection of the ENT organs;

- infections of the genitals, including gonorrhea. Perioperative infection prevention.

Contraindications:

Hypersensitivity to ceftriaxone, other cephalosporins, penicillins, carbapenems.

Hyperbilirubinemia or jaundice in term infants. Acidosis, hypoalbuminemia in full-term newborns.Premature newborns under the "expected" age of 41 weeks (including the term of intrauterine development and age). Newborn babies who are shown intravenous administration of calcium-containing solutions.

Carefully:prescribe the drug for nonspecific ulcerative colitis, with violations of the liver and kidneys, with enteritis and colitis associated with the use of antibacterial drugs.

Pregnancy and lactation:

In pregnancy, especially in the first trimester, should be prescribed only on strict indications, provided that the intended benefit to the mother exceeds the potential risk to the fetus.

If it is necessary to use the drug during lactation, the question of stopping breastfeeding (ceftriaxone excreted in breast milk).

Dosing and Administration:

The drug is administered intramuscularly or intravenously (drip, jet). The content of bacterial endotoxins does not exceed 0.05 EE / mg ceftriaxone.

Standard dosing regimen

Adults and children over 12 years of age: for 1-2 g once a day (every 24 hours). In severe cases or infections, the causative agents of which have only moderate sensitivity to ceftriaxone, the daily dose can be increased to 4 g. Newborns (up to 2 weeks): 20-50 mg / kg body weight once a day. The daily dose should not exceed 50 mg / kg of body weight. When determining the dose, there is no need to distinguish between full and premature babies.

Infants and young children (from 15 days to 12 years): 20-80 mg / kg body weight once a day. The daily dose should not exceed 2 g. Children with a body weight above 50 kg are prescribed doses for adults.

Intravenous doses of 50 mg / kg or higher should be administered drip for at least 30 minutes.

Fellow of the senile age: usual doses for adults, without adjustments for age. Duration of treatment depends on the course of the disease. Usually the duration of treatment is 7-14 days, with a complicated infection, longer treatment may be required; with infection caused by Streptococcus pyogenes - not less than 10 days.

As always with antibiotic therapy, ceftriaxone should be continued for at least 48-72 hours after the temperature is normalized and the eradication of the pathogen is confirmed.

Dosing in special cases

When bacterial meningitis in infants and young children treatment starts with a dose of 100 mg / kg (but not more than 4 g) 1 time per day. After identifying the pathogen and determining its sensitivity, the dose can be reduced accordingly.The best results for meningococcal meningitis (Neisseria mcningitides) were achieved with a duration of treatment of 4 days, with meningitis caused by Haemophilus influenzae - 6 days, Streptococcus pneumoniae -7 days.

Borrelia Lyme: 50 mg / kg (the highest daily dose is 2 g) for adults and children over 12 years of age once a day for 14 days.

Gonorrhea (caused by penicillinase-forming and penicillin-zoned strains): single intramuscular injection of 250 mg of the drug.

Prevention of postoperative infections: depending on the degree of infectious risk, 1-2 g of ceftriaxone is administered once 30-90 minutes before the start of the operation. In operations on the colon and rectum, simultaneous (but separate) administration of ceftriaxone and one of 5-nitroimidazoles, for example, ornidazole, was well established.

In patients with impaired renal function there is no need to reduce the dose, if the function liver remains normal. The daily dose of ceftriaxone should not exceed 2 g only in cases of preterminal renal failure (creatinine clearance less than 10 ml / min). In patients with hepatic dysfunction there is no need to reduce the dose, if the function kidneys remains normal.

When combination of severe renal and hepatic insufficiency should regularly determine the concentration of ceftriaxone in the plasma and, if necessary, adjust its dose.

Patients on dialysis additional introduction of the drug after dialysis is not required. It should, however, control the concentration of ceftriaxone in the serum for possible dose adjustment, since the rate of excretion of the drug in these patients may be reduced.

In the treatment of acute otitis media in children, a single I / m dose of 50 mg / kg (no more than 1 g) is recommended.

Mode of application

For intramuscular injection: The contents of the vial are dissolved as follows:

Contents of the bottle Solvent (water for injection)

1000 mg of 3.6 ml

After preparation, each ml of the solution contains about 250 mg in terms of ceftriaxone.

If necessary, a more dilute solution may be used. As with other intramuscular injections, Ceftriaxone-Jodas is injected into a relatively large muscle; Trial aspiration helps to avoid unintentional insertion into the blood vessel. It is recommended to inject no more than 1000 mg of the drug into one buttock. To reduce pain with intramuscular injection, the drug is recommended to be administered with a 1% solutionlidocaine (intra-annual). When administered, it is preferable to dissolve 1000 mg of the drug in 3.5 ml of a 1% solution of lidocaine. Do not inject lidocaine solution intravenously.

Ceftriaxone retains stability in solution without special storage conditions at room temperature + 25 ° C for 6 hours (amount of solvent up to 3.5 ml) for up to 24 hours (amount of solvent up to 10 ml); at a temperature of 4 - 5 ° C - from 24 hours (the amount of solvent to 3.5 ml) to 7 days (the amount of solvent to 10 ml). Before use, the prepared preparation should be shaken. After preparation the preparation remains active for:

Solvent	Concentration mg / ml	Room temperature, 25 ° С	Storage in the refrigerator, 4 ° С
Water for injections	100,	2 days	10 days
	250, 350	24 hours	3 days
0.9% Sodium chloride	100, 250,350	2 days 24 hours	10 days 3 days
5% dextrose	100, 250, 350	2 days 24 hours	10 days 3 days
Bacteriostatic water + 0.9% benzyl alcohol	100, 250.350	2 days 24 hours	10 days 3 days
1% lidocaine without epinephrine	100, 250. 350	2 days 24 hours	10 days 3 days

For intravenous administration: The contents of the vial are dissolved as follows:

Contents of the bottle Solvent (water for injection)

1000 mg 9.6 ml (10 ml)

At a concentration of 10. 20. 40 mg / ml for intravenous administration, the prepared preparation remains active for:

Solvent	Room temperature, 25 ° С	Storage in the refrigerator, 4 ° С
Water for injections	2 days	10 days
0.9% sodium chloride	2 days	10 days
5% dextrose	2 days	10 days
10% dextrose	2 days	10 days
5% dextrose + 0.9% Sodium chloride *	2 days	-
5% dextrose + 0.45% 11 sodium chloride	2 days	-

* -applicable for solutions with a concentration of 10-40 mg / ml only in PBX bottles.

After preparation, each ml of the solution contains about 100 mg in terms of ceftriaxone. The solution is administered slowly for 2-4 minutes.

For intravenous infusion dissolve 2 g of Ceftriaxone-Jodas in 40 ml of sterile water for injection or one of the calcium-free infusion solutions (0.45% or 0.9% sodium chloride solution, 2.5%, 5% or 10% dextrose solution, 5% fructose solution. 5% levulose solution, 6% dextran solution in dextrose, 6% dextran 70 solution in 5% dextrose solution, 0.45% sodium chloride solution and 2.5% dextrose solution, 5% dextrose + 0.9% sodium chloride. 5% dextrose + 0.45% sodium chloride. Doses of 50 mcg / kg or more should be administered iv in drip. The solution is introduced for 30 minutes.

Solvents containing calcium, such as Ringer's solution or Hartmann's solution, can not be used to prepare solutions of Ceftriaxone-Jodas for intravenous administration and subsequent dilution, due to the possible formation of precipitates.section "Interaction with other drugs").

Side effects:

Allergic reactions: urticaria, chills or fever, rashes, itching, bronchospasm, allergic pneumonitis, eosinophilia, erythema exudative multiforme (incl. Stevens-Johnson syndrome). Serum sickness, anaphylactic shock, angionescurotic edema.

From the digestive system: nausea, vomiting, diarrhea or constipation, flatulence, pseudomembranous colitis, abdominal pain, taste disorder, stomatitis, glossitis, impaired liver function (increased activity of "liver" transaminases, less often - alkaline phosphatase or bilirubin, cholelithiasis, cholestatic jaundice, "sluggish phenomenon "a gallbladder), a dysbacteriosis, a pancreatitis.

From the hematopoiesis: anemia, leukopenia, leukocytosis, neutropenia, granulocytopaediasis, lymphopenia, lymphocytosis, thrombocytosis, thrombocytopenia, hemolytic anemia, hypocoagulation, decrease in plasma clotting factor concentration (II VII, IX .X). prolongation of prothrombin time, reduction of prothrombin time, increase in thromboplastin time, basophilia.

From the genitourinary system: candidiasis of the vagina, vaginitis.

From the urinary system: renal dysfunction (azotemia, increased urea in the blood, hypercreatininaemia, glycosuria, cylindruria), oliguria, anuria, the presence of sediment in the urine.

Local reactions: phlebitis, soreness along the vein, soreness and infiltration at the site of the / m introduction.

Other: increased sweating, "hot flashes" of blood, a feeling of palpitations, a headache. verge. dizziness, nosebleeds. candidiasis, superinfection.

Post-marketing experience: stomatitis, glossitis, oliguria, rash, allergic dermatitis, urticaria, edema, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome.

Severe, in some cases fatal, adverse reactions with the formation of precipitates of ceftriaxone calcium salts in the lungs and kidneys in newborns who received ceftriaxone and calcium-containing solutions. In some cases, the venous accesses and the time of administration of ceftriaxone and calcium-containing solutions were different.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:In case of an overdose, hemodialysis and peritoneal dialysis will not reduce the concentration of the drug. There is no specific antidote. Treatment is symptomatic.

Interaction:

Ceftriaxone, suppressing the intestinal flora, interferes with the synthesis of vitamin K. With simultaneous administration with drugs that reduce platelet aggregation (non-steroidal anti-inflammatory drugs, salicylates, sulfinpyrazone), the risk of bleeding increases.

With a simultaneous appointment with anticoagulants, the effect of the latter is noted.

With the simultaneous administration of large doses of ceftriaxone and loop diuretics (eg, furosemide), renal dysfunction was not observed. Ceftriaxone does not contain N-methylthiotetrazol group, therefore, when interacting with ethanol does not lead to the development of disulfiram-like reactions inherent in some cephalosporins. Probenecid does not affect the excretion of ceftriaxone. Bacteriostatic antibiotics reduce the bactericidal effect of ceftriaxone. Diclofenac stimulates the allocation of bile and reduces the overall clearance in the urine. Antagonism with chloramphenicol in vitro.

Pharmaceutically incompatible with solutions containing calcium (incl.solution of Hartmann and Ringer), as well as with amsacrine, vancomycin, fluconazole, and aminoglycosides.

Solvents containing calcium, such as Ringer's solution or Hartmann's solution, can not be used to prepare solutions of Ceftriaxone-Jodas for intravenous administration and their subsequent dilution due to the possible formation of precipitates.

The formation of precipitates of calcium salts of ceftriaxone can occur also when the preparation of Ceftriaxone-Jodas and calcium-containing solutions are mixed using one venous access. Do not use Ceftriaxone-Jodas concomitantly with calcium-containing solutions for intravenous administration, including long infusions of calcium-containing solutions, for example, with parenteral nutrition using a Y-connector.

For all groups of patients, except for newborns, sequential administration of Ceftriaxone-Jodas and calcium-containing solutions is possible with thorough washing of infusion systems between infusions of a compatible liquid.

There have been no reports on the interaction of ceftriaxone and oral calcium-containing drugs or the interaction of ceftriaxone for intramuscularadministration and calcium-containing drugs (for intravenous or oral administration).

Special instructions:As with the use of other cephalosporins, anaphylactic reactions, including fatalities, were recorded, even in cases where the patient did not have any allergic reactions in the anamnesis. In case of allergic reactions, the drug should be discontinued and appropriate treatment should be prescribed. As with the use of other cephalosporins, the development of autoimmune hemolytic anemia is possible with drug treatment. Cases of severe hemolytic anemia in adults and children, including fatal cases, have been reported. In case of anemia, therapy with the drug should be discontinued. With the use of the drug, cases of the development of diarrhea caused by Clostridium difficile (pseudomembranous colitis), varying degrees of severity: from mild to colitis with fatal outcome. It is necessary to carefully collect the anamnesis, tk. Cases of diarrhea caused by Clostridium difficile occurred more than 2 months after antibiotic therapy. In accordance with clinical indications, appropriate treatment should be prescribed (compensation for loss of fluid, electrolytes, protein,antibiotic therapy for Clostridium difficile, surgical treatment). When the development of pseudomembranous colitis is contraindicated the appointment of drugs that inhibit the intestinal motility. As with other antibacterial drugs, superinfection may develop. When using the drug, rare cases of prothrombin time change are described. Patients with vitamin K deficiency (impaired synthesis, eating disorders) may need to monitor prothrombin time and prescribe vitamin K (10 mg / week) with an increase in prothrombin time before or during therapy. In rare cases, gallbladder marked darkening (precipitates the calcium salt of ceftriaxone) by ultrasound (US), which disappear after cessation of treatment. With the development of the symptoms or signs indicating the possible gallbladder disease, or in the presence of ultrasound signs "sludge phenomenon" is recommended to stop administering the drug. When using the drug, rare cases of pancreatitis, which developed, possibly, as a result of obstruction of the biliary tract, are described.Most patients had risk factors for congestion of the biliary tract (eg, previous drug therapy, severe co-morbidities.

completely parenteral nutrition); However, the starting role of precipitate formation in the biliary tract under the influence of ceftriaxone can not be ruled out. Like other cephalosporins ceftriaxone can displace bilirubin from association with serum albumin. In combination with severe renal and hepatic insufficiency, as well as in patients on hemodialysis, the concentration of ceftriaxone in the blood plasma should be regularly determined. With long-term treatment, it is necessary to regularly monitor the picture of peripheral blood, indicators of the functional state of the liver and kidneys. Cases of fatal reactions as a result of deposition of ceftriaxone-calcium precipitates in the lungs and kidneys of newborns are described. Theoretically there is a probability of interaction of ceftriaxone with calcium-containing solutions for intravenous administration and in other age groups of patients, therefore ceftriaxone not be mixed with calcium-containing solutions (including for parenteral nutrition) and administered simultaneously, including through a separate access for infusion at different sites.Theoretically, based on the calculation of 5 T1 / 2 ceftriaxone, the interval between the administration of ceftriaxone and calcium-containing solutions should be at least 48 hours. Data on the possible interaction of ceftriaxone with calcium-containing preparations for oral administration, as well as ceftriaxone for intramuscular administration with calcium-containing drugs or for oral administration) are not available.

In the treatment of ceftriaxone, false-positive results of the Coombs test, a test for galactosemia, glucose in urine (glycosuria should be determined only by enzyme method).

Effect on the ability to drive transp. cf. and fur:Given the profile of adverse reactions (vertigo, convulsions, dizziness), during the treatment period, care must be taken when driving vehicles, working with mechanisms and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Powder for the preparation of solution for intravenous and intramuscular administration of 1000 mg.

Packaging:

By 1.0 g of the active substance in a vial of clear glass (hydrolytic type I).corked with a stopper made of chlorobutyl rubber, crimped with an aluminum ring with a safety plastic cap.

The solvent is "Water for Injection", corresponding to the requirements of ND No. LP002377- 180214. 10 ml each in a vial of neutral neutral glass or low density polyethylene.

For 1 bottle with the drug and 1 ampoule with a solvent, or without a solvent, along with instructions for use in a cardboard pack.

For hospitals:

10, 25, 48 or 100 vials together with an appropriate number of ampoules with or without solvent and instructions for use in a cardboard box.

Storage conditions:Store in a dry place, protected from light and out of reach of children, at a temperature not exceeding 25 ° C.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-002538

Date of registration:25.12.2011

The owner of the registration certificate:Jodas Expo Pvt.LtdJodas Expo Pvt.Ltd India

Manufacturer: & nbsp

JODAS EXPOIM, Pvt. Ltd. India

Representation: & nbspJodas Expoim, Open CompanyJodas Expoim, Open Company

Information update date: & nbsp15.11.2015

Illustrated instructions

Instructions

Ceftriaxone-Jodhas (Ceftriaxone-Jodas)