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

Cephalosporin antibiotic III generation of a broad spectrum of action for parenteral administration. Bactericidal activity is due to the suppression of bacterial cell wall synthesis. It is characterized by resistance to the action of most beta-lactamases of gram-negative and gram-positive microorganisms. Active against the following microorganisms: gram-positive aerobes -Staphylococcus aureus (including strains producing penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus spp. groups of viridans; Gram-negative aerobes: Acinetobacter calcoaceticus, Borrelia burgdorferi, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (including strains forming penicillinase), Haemophilus parainfluenzae, Klebsiella spp. (incl.Klebsiella pneumoniae), Moraxella catarrhalis, (including penicillinase-producing strains), Morganella morganii, Neisseria gonorrhoeae (including strains forming penicillinase), Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Serratia spp. (including Serratia marcescens); individual strains of Pseudomonas aeruginosa are also sensitive; anaerobes: Bacteroides fragilis), Clostridium spp. (except Clostridium difficile), Peptostreptococcus spp.

Has in vitro activity against most strains of the following microorganisms, although the clinical significance of this is unknown: Citrobacter diversus, Citrobacter freundii, Providencia spp. (including Providencia rettgeri), Salmonella spp., including Salmonella typhi, Shigella spp .; Streptococcus agalactiae, Bacteroides bivius, Bacteroides melaninogenicus. Methicillin-resistant staphylococci are resistant to cephalosporins, incl. to ceftriaxone, many strains of group D streptococcus and enterococci, including Enterococcus faecalis, are also resistant to ceftriaxone.

Pharmacokinetics:Bioavailability - 100%, the time to reach the maximum concentration after the / m introduction - 2-3 hours, after intravenous administration - at the end of the infusion. The maximum concentration after a / m administration of 1 g is 76 μg / ml. The maximum concentration for iv administration of 1 g is 151 μg / ml. In adults, 2-24 hours after administration at a dose of 50 mg / kg, the concentration in the cerebrospinal fluid is many times greater than the minimum inhibitory concentration for the most common meningitis pathogens. Well penetrates into the cerebrospinal fluid with inflammation of the meninges.The connection with plasma proteins is 83-96%. The volume of distribution is 0,12-0,14 l / kg (5,78-13,5 l), in children -0,3 l / kg, the plasma clearance is 0,58-1,45 l / h, the renal - 0.32-0.73 l / h. The elimination half-life after IM is 5.8-8.7 hours, after intravenous administration at a dose of 50-75 mg / kg in children with meningitis - 4.3-4.6 hours; in patients on hemodialysis (creatinine clearance 0-5 ml / min), 14.7 hours, with creatinine clearance of 5-15 ml / min - 15.7 hours, 16-30 ml / min-11.4 h, 31 -60ml / min-12.4h.

It is excreted unchanged - 33-67% by the kidneys; 40-50% - with bile in the intestine, where the inactivation occurs. About 70% of the drug is excreted through the kidneys in newborn infants. Hemodialysis is ineffective.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to ceftriaxone: infections of the abdominal cavity organs (peritonitis, inflammatory diseases of the gastrointestinal tract, bile ducts, including cholangitis, empyema of the gallbladder), infections of the pelvic organs, infections of the upper and lower respiratory tract and ENT organs (including acute and chronic bronchitis, pneumonia, lung abscess, pleural empyema, acute otitis media, epiglottitis), infections of bones and joints, skin and soft tissue (including infected wounds andburns), infections of the maxillofacial area, infections of the urinary tract (complicated and uncomplicated), uncomplicated gonorrhea, incl.caused by microorganisms that release penicillinase, mild chancre and syphilis, bacterial meningitis and endocarditis, bacterial septicemia, Lyme disease, salmonellosis and salmonella-carrying.

Prevention of postoperative infections.

Infectious diseases in persons with weakened immunity.

Contraindications:Hypersensitivity to ceftriaxone (including other cephalosporins, penicillins, carbapenems), hyperbilirubinemia in newborns, newborns, which show intravenous administration of calcium-containing solutions.

Carefully:Premature infants, renal and / or hepatic insufficiency, ulcerative colitis, enteritis or colitis associated with the use of antibacterial drugs.

Pregnancy and lactation:

When pregnancy is possible, if the expected benefit for the mother exceeds the potential harm to the fetus.

The action category for the fetus according to FDA is B.

For the duration of treatment, breastfeeding should be stopped (penetrates into breast milk).

Dosing and Administration:

Intravenous, intramuscular. Do not use calcium-containing solutions to dilute the preparation! In adults, the initial daily dose, depending on the type andthe severity of infection is 1-2 g once a day or divided into 2 divided doses (every 12 hours), the total daily dose should not exceed 4 g. Lyme disease: adults and children - 50 mg / kg (but not more than 2 g) 1 time per day for 14 days.

With uncomplicated gonorrhea - 250 mg intramuscularly once. For the prevention of postoperative complications - once 1 g for 30-60 minutes before the operation. In operations on the colon and rectum, additional administration of a drug from the 5-nitroimidazole group is recommended.

The dose for newborns is 20-50 mg / kg / day. For the treatment of skin and soft tissue infections, the recommended daily intake in children is 50-75 mg / kg, divided into 2 divided doses (every 12 hours). The total daily dose in children should not exceed 2 g. For severe infections of other localization - 25-37.5 mg / kg every 12 hours, not more than 2 g / day. For bacterial meningitis in children, the initial dose is 100 mg / kg (but not more than 4 g) once a day, then 100 mg / kg / day (but not more than 4 g) once a day or divided into 2 doses (every 12 hours). The duration of treatment is 7-14 days.

In the treatment of acute otitis media in children, a single intramuscular injection of 50 mg / kg is recommended (but not more than 1 g). In the treatment of other infections in children, the recommended daily dose is 50-75 mg / kg, divided into 2 divided doses (every 12 hours). The total daily intake for children should not exceed 2 g.

In children with a body weight of 50 kg and above, doses for adults are used. A dose of more than 50 mg / kg body weight should be administered as an intravenous infusion within 30 minutes.

In chronic renal failure (creatinine clearance less than 10 ml / min), the daily dose should not exceed 2 g; patients on hemodialysis do not require an additional dose after a hemodialysis session, however, it is necessary to control the concentration of ceftriaxone in the plasma, since its excretion in such patients can be slowed down (dose adjustment may be required). Treatment with ceftriaxone should continue for at least 2 more days after the disappearance of symptoms and signs of infection. The course of treatment is usually 4-14 days; with complicated infections, a longer duration of administration may be required. The course of treatment for infections caused by Streptococcus pyogenes should be at least 10 days.

In patients with renal-hepatic insufficiency, the daily dose should not exceed 2 g without determining the concentration of the drug in the blood plasma.

Rules for the preparation and administration of solutions: Use only freshly prepared solutions.For intramuscular administration, 1 g of the drug is dissolved in 3.5 ml of a 1% solution of lidocaine. Recommend to enter no more than 1 g in one buttock. For intravenous injection, 1 g is dissolved in 10 ml of water for injection. Enter intravenously slowly (2-4 minutes). For intravenous infusions, dissolve 2 g of - 40 ml of a solution that does not contain Ca2 + (sodium chloride solution isotonic 0.9%, dextrose solution 5%). Doses of 50 mg / kg or more should be administered intravenously drip, for 30 minutes.

Side effects:

Allergic reactions: rash, itching, fever or chills, anaphylaxis, bronchospasm, serum sickness, allergic pneumonitis.

From the nervous system: headache, dizziness, convulsions.

On the part of the digestive system: diarrhea, nausea, vomiting, taste disorder, dyspepsia, bloating, pseudomembranous colitis, abdominal pain, jaundice, "sluggish phenomenon" of the gallbladder, cholelithiasis.

On the part of the organs of hematopoiesis and cardiovascular system: anemia (including hemolytic), leukopenia, lymphopenia, neutropenia, thrombocytopenia, epistaxis, thrombocytosis, eosinophilia, agranulocytosis, basophilia leukocytosis, lymphocytosis, monocytosis, palpitation.

On the part of the genitourinary system: candidiasis of the vagina, vaginitis, glucosuria, hematuria, nephrolithiasis.

Local reactions: with intravenous injection - phlebitis, tenderness, tightening along the veins; intramuscular injection - soreness, sensation of warmth, tightness or condensation at the injection site.

Laboratory indicators: increase (decrease) of prothrombin time, increase in activity of "liver" transaminases and alkaline phosphatase, hyperbilirubinemia, hypercreatininemia, increase in urea concentration, presence of sediment in urine. Other: increased sweating, "hot flashes" of blood.

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

Overdose:

Symptoms:dizziness, paresthesia, headache, convulsions.

Treatment: symptomatic. Hemodialysis and peritoneal dialysis are not effective.

Interaction:

Bacteriostatic antibiotics reduce the bactericidal effect of ceftriaxone. Antagonism with chloramphenicol in vitro.

Pharmaceutically incompatible with calcium-containing solutions (including Hartman and Ringer's solution), as well as with amsacrine, vancomycin, fluconazole, and aminoglycosides. 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.

Special instructions:

In combination with severe renal and hepatic insufficiency, as well as in patients on hemodialysis, it is necessary to regularly determine the concentration of the drug in the plasma.

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. In rare cases with ultrasound of the gallbladder, blackouts (precipitates of the calcium salt of ceftriaxone) are observed, which disappear after the 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 the drug is used, rare cases of pancreatitis have been described, possibly due to biliary obstruction. Most patients had risk factors for congestion of the biliary tract (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. 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.

Cases of fatal reactions as a result of deposition of ceftriaxone-Ca2 + 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 should not be mixed with calcium-containing solutions (including for parenteral nutrition), and also administered simultaneously, incl. through separate accesses for infusions at different sites. Theoretically, based on the calculation of 5 half-lives of 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 oral calcium-containing drugs, as well as ceftriaxone for intramuscular injection with calcium-containing drugs (intravenous and oral) are absent.

In the treatment of ceftriaxone, false-positive results of the Coombs test, a sample for galactosemia, with certain glucose in the urine (glucocooling is recommended to be determined only by the enzyme method).

Studies to evaluate the effect of the drug on the ability to drive vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions have not been conducted.

Effect on the ability to drive transp. cf. and fur:Given the side effects of ceftriaxone on the nervous system (possibly the occurrence of dizziness, seizures) during the treatment period, one should refrain from managing motor transport and complex mechanisms.

Form release / dosage:

Powder for solution for intravenous and intramuscular injection, 1.0 g.

Packaging:

By 1.0 g of active substance in glass vials, hermetically sealed with rubber stoppers, crimped with aluminum caps.

Vials with a drug of 10, 25, 50 pieces are placed in boxes with cardboard partitions with an equal number of instructions for the use of the drug (for hospitals).

1 bottle with the drug and instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-002533

Date of registration:09.08.2011

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Information update date: & nbsp17.11.2015

Illustrated instructions

Instructions

Ceftriaxone (Ceftriaxone)