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-positive and gram-negative microorganisms. It is active against the following microorganisms:

gram-positive aerobes: Staphylococcus aureus (including strains producing penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus spp. groups viridans;

gram-matic aerobes: Acinetobacter calcoaceticus, Borrelia burgdorferi, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (including strains that form penicillinase), Haemophilus par ainfluenzae, Klebsiella s pp. (incl. Klebsiella pneumoniae), Moraxella catarrhalis (including penicillinase-producing strains), Morganella morganii, Neisseria gonorrhoeae (including strains that form penicillinase), Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Serratia spp. (incl. Serratia marcescens); individual strains Pseudomonas aeruginosa are also sensitive; anaerobes: Bacteroides fragilis, Clostridium spp. (Besides Clostridium difficile), Peptostreptococcus spp.

Has activity in vitro in a relationship 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.

Staphylococcus spp., Resistant to methicillin, is resistant to cephalosporins, incl. to ceftriaxone, many strains of streptococcus group D and enterococci, incl. Enterococcus faecalis, also resistant to ceftriaxone.

Pharmacokinetics:

Bioavailability is 100%, the time to reach the maximum concentration (TCmax) after intramuscular (IM) administration is 2-3 hours, after intravenous (IV) administration - at the end of the infusion. The maximum concentration (Cmax) after i / m administration in doses of 0.5 g and 1 g is 38 and 76 μg / ml, respectively.Cmax with iv introduction in doses of 0.5 g, 1 g and 2 g - 82, 151 and 257 μg / ml, respectively. In adults, 2-24 hours after administration at a dose of 50 mg / kg, the concentration in the cerebrospinal fluid (CSF) is many times greater than the minimum inhibitory concentration for the most common meningitis pathogens. It penetrates well into CSF with inflammation of the meninges. The connection with plasma proteins is 83-96%. The volume of distribution - 0,12-0,14 l / kg (5,78-13,5 l), in children - 0,3 l / kg, plasma clearance - 0,58-1,45 l / h, renal - 0.32-0.73 l / h. The half-life period (T1 / 2) after IM was 5.8-8.7 hours after iv injection at a dose of 50-75 mg / kg in children with meningitis - 4.3-4.6 hours; in patients on hemodialysis (creatinine clearance (CK) 0-5 ml / min), 14.7 hours, with KK 5-15 ml / mbn - 15.7 h, 16-30 ml / min -11.4 h, 31-60 ml / min - 12.4 hours.

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 and inflammatory diseases caused by microorganisms sensitive to ceftriaxone: abdominal organs (peritonitis, inflammatory diseases of the gastrointestinal tract (GIT), bile ducts, including cholangitis, empyema of the gallbladder, pelvic organs, lower respiratory tract (in t.ch.pneumonia, lung abscess, empyema), bones and joints, skin and soft tissues (including infected wounds and burns), the urinary tract infections (complicated and uncomplicated), acute otitis, uncomplicated gonorrhea, bacterial meningitis, bacterial septicemia, Lyme disease.

Prevention of postoperative infections.

Infectious diseases in persons with weakened immunity.

Contraindications:

Hypersensitivity (including to other cephalosporins, penicillins, carbapenems), hyperbilirubinemia in newborns, infants, which is shown in / in a solution containing calcium ions (Ca2 +).

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

Pregnancy and lactation:

The use of ceftriaxone in pregnancy is permissible if the expected benefit to the mother exceeds the potential risk to the fetus. If you need to use the drug during lactation at the time of treatment should stop breastfeeding.

Dosing and Administration:

Intravenous (intravenously), intramuscularly (in / m).

Do not use solutions containing Ca2 +!

In adults, the initial daily dose, depending on the type and severity of the infection, is 1-2 grams once a day, or divided into 2 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 IM 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 50-75 mg / kg divided into 2 divided doses (every 12 hours), the total daily dose should not exceed 2 g.

For bacterial meningitis in children, the initial dose is 100 mg / kg (but not more than 4 g) 1 time per

day, further 100 mg / kg / day (but not more than 4 g) 1 time per 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 IV IM is recommended in a dose of 50 mg / kg (but not more than 1 g).

When treating other infections in children, the recommended daily dose is 50-75 mg / kg divided into 2 divided doses (every 12 hours), the total daily dose should not exceed 2 g.

In children with a body weight of 50 kg and above, doses for adults are used.

In chronic renal failure (CRF) (CK 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).

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.

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, must be at least 10 days.

Preparation and introduction of solutions: Use only freshly prepared solutions.

For the / m introduction, 1 g of the drug is dissolved in 3.5 ml of a 1% solution of lidocaine. It is recommended to enter no more than 1 g in one buttock.

For intravenous injection, 1 g of the drug is dissolved in 10 ml of water for injection. Enter into / in slowly (2-4 minutes).

For intravenous infusions, 2 g of the drug is dissolved in 40 ml of a solution that does not contain Ca²⁺ (0,9 %

solution of sodium chloride, 5-10% dextrose solution, 5% solution of levulose).

Doses of 50 mg / kg or more should be administered intravenously in drip, for 30 minutes.

A solution of lidocaine can never be administered intravenously!

Side effects:

Allergic reactions: rash, itching, fever, or chills.

From the nervous system: headache, dizziness.

From the digestive system: diarrhea, nausea, vomiting, taste disorder, pseudomembranous colitis.

From the hematopoiesis: anemia (including hemolytic), leukopenia, lymphopenia, neutropenia, thrombocytopenia, thrombocytosis, eosinophilia.

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

Local reactions: with iv introduction - phlebitis, tenderness, compaction along the vein; with the / m introduction - soreness, sensation of warmth, tightness or condensation at the injection site.

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

Other: increased sweating, "hot flashes" of blood.

Undesirable reactions with a frequency of less than 0.1%: abdominal pain, agranulocytosis, allergic pneumonitis, anaphylaxis, basophilia, cholelithiasis, bronchospasm, colitis, dyspepsia, epistaxis, bloating, "sluggish phenomenon" of the gallbladder, gluekosuria, hematuria, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, palpitations, convulsions, serum sickness.

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

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:

Symptoms: nausea, vomiting, diarrhea, confusion, 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 solutions containing Ca²⁺ (including the solution of Hartman and Ringer), as well as with amsacrine, vancomycin, fluconazole, and aminoglycosides.

Does not contain Nmethylthiothetrazole group, therefore, when interacting with ethanol, does not lead to the development of disulfiram-like reactions inherent in some cephalosporins.

If you are taking other drugs, consult a doctor.

Special instructions:

Ceftriaxone is used only in a hospital. When concomitant severe renal and hepatic failure, as well as in patients on hemodialysis, should be regularly to determine the concentration of drug in 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 symptoms or signs indicating a possible gallbladder disease; or if there are ultrasound signs of a "sluggish phenomenon," it is recommended that the drug be discontinued.

When the drug is used, rare cases of pancreatitis that develop, possibly, as a result of biliary tract obstruction are described. 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. Ceftriaxone does not contain an N-methylthiotetrazol group, which causes disulfiram-like effects with simultaneous use of ethanol and bleeding that are inherent in some cephalosporins.

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 Ca2 + -containing solutions for intravenous administration and in other age groupspatients, therefore ceftriaxone should not be mixed with Ca2 + -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 T1 / 2 ceftriaxone, the interval between the administration of ceftriaxone and Ca2 + -containing solutions should be at least 48 hours. Data on the possible interaction of ceftriaxone with oral Ca2 + -containing preparations, as well as ceftriaxone for intramuscular administration with Ca2 + -containing drugs (in / in and oral) are absent.

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

Despite the detailed history, we can not exclude the possibility of developing an anaphylactic shock, which requires immediate therapy - first in / in injected epinephrine, then glucocorticosteroids.

Effect on the ability to drive transp. cf. and fur:Use caution to drivers of vehicles and people whose activities require increased concentration of attention and good coordination of movements.

Form release / dosage:

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

Packaging:

Powder for the preparation of solution for intravenous and intramuscular injection of 1.0 g of active substance in glass bottles with a capacity of 10 ml.

1 bottle with instructions for use in a pack of cardboard. 10 bottles with instructions for use in a cardboard box.

For hospitals:

- 50 bottles with an equal number of instructions for use in a cardboard box;

- from 1 to 50 bottles with an equal number of instructions for use in a cardboard box. Complete with a solvent.

Water for injection 5 ml or 10 ml in ampoules of glass.

1 bottle and 1 ampoule 10 ml or 2 ampoules of 5 ml in a contiguous cell package (NLC) made of a PVC film with instructions for use in a pack of cardboard.

5 vials and 5 ampoules of 10 ml or 10 ampoules of 5 ml in separate KNU from the PVC film with instructions for use in a pack of cardboard. In the pack put a knife to open the ampoules or a scarifier ampoule. When using ampoules with incisions, rings or break points, the ampoule opener or ampoule scapula is not allowed to be inserted.

Storage conditions:

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

Keep out of the reach of children.

After the expiry date of the drug, unused bottles should be carefully opened to dissolve the contents in a large amount of water and drained into the drain.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:PL-000937

Date of registration:18.10.2011

Date of cancellation:2016-10-18

The owner of the registration certificate:KRASFARMA, JSC KRASFARMA, JSC Russia

Manufacturer: & nbsp

KRASFARMA, JSC Russia

Information update date: & nbsp17.11.2015

Illustrated instructions

Instructions

Ceftriaxone (Ceftriaxone)