Composition, form of production and packaging
Powder for the preparation of solution for iv and in / m introduction from white to white with a yellowish tint of color.
1 f.
ceftriaxone (in the form of the sodium salt) 1 g
Vials of colorless glass (1) - packs cardboard.
Vials of colorless glass (10) - packs cardboard.
Vials of colorless glass (50) - packs cardboard.
Powder for solution for injection from white to yellowish white.
1 f.
ceftriaxone (in the form of ceftriaxone disodium trisecihydrate) 250 mg
250 mg - bottles (1) - packs of cardboard.
250 mg - bottles (10) - packs of cardboard.
250 mg - bottles (50) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Cephalosporin antibiotic III generation of a broad spectrum of action for parenteral administration. It acts bactericidal, inhibiting the synthesis of the bacterial cell wall. Acetylates membrane-bound transpeptidases, thus violating the cross-linking of peptidoglycans necessary to ensure the strength and rigidity of the cell wall. It is resistant to ОІ-lactamases produced by most gram-positive and gram-negative bacteria.
It is active against Gram-positive aerobic bacteria: Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus viridans, Streptococcus bovis; Gram-negative aerobic bacteria: Acinetobacter lwoffii, Acinetobacter anitratus, Aeromonas hydrophila, Alcaligenes faecalis, Alcaligenes odorans, Citrobacter spp., Enterobacter spp. (some strains are resistant), Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae (including strains producing penicillinase), Haemophilus parainfluenzae, Klebsiella spp. (including Klebsiella pneumoniae), Moraxella spp., Morganella morganii, Neisseria gonorrhoeae (including strains producing penicillinase), Neisseria meningitidis, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris, Providencia spp., Salmonella spp. (including Salmonella typhi), Serratia spp. (including Serratia marsescens), Shigella spp., Vibrio spp. (including Vibrio cholerae), Yersinia spp. (including Yersinia enterocolitica), Pseudomonas aeruginosa (some strains); Gram-negative anaerobic bacteria: Bacteroides spp. (including some strains of Bacteroides fragilis), Clostridium spp. (except Clostridium difficile), Fusobacterium spp. (except Fusobacterium mortiferum and Fusobacterium varium), Peptococcus spp., Peptostreptococcus spp.
The drug is resistant to methicillin-resistant strains of Staphylococcus spp., Strains of Enterococcus spp. (Enterococcus faecalis), Clostridium difficile, many strains of Bacteroides spp. (producing? -lactamases).
PHARMACOKINETICS
Suction and distribution
After an / m introduction, ceftriaxone is quickly and completely absorbed into the systemic circulation. It penetrates well into the tissues and body fluids: respiratory tract, bones, joints, urinary tract, skin, subcutaneous fat and abdominal cavity organs. When inflammation of the meningeal membranes well penetrates into the cerebrospinal fluid. Bioavailability of ceftriaxone with a / m introduction is 100%.
With the / m introduction of ceftriaxone in a dose of 500 mg and 1 g of C max in blood plasma is 38 Ојg / ml and 76 Ојg / ml, respectively, with iv injection at a dose of 500 mg, 1 g and 2 g - 82 Ојg / ml , 151 Ојg / ml and 257 Ојg / ml, respectively. In adults, 2-24 hours after the administration of the drug at a dose of 50 mg / kg, the concentration in the cerebrospinal fluid is many times greater than the MIC for the most common meningitis pathogens.
The equilibrium state is established within 4 days of the drug administration.
Reversible binding to plasma proteins (albumins) is 83-95%.
V d is 5.78-13.5 l (0.12-0.14 l / kg), in children it is 0.3 l / kg.
Penetrates through the placental barrier in small amounts.
Excretion
T 1/2 is 6-9 hours, which allows to apply the drug 1 time / day.
The plasma clearance is 0.58-1.45 l / h, the renal clearance is 0.32-0.73 l / h.
In adult patients, for 48 hours 50-60% of the drug is excreted by the kidneys unchanged, 40-50% is excreted with bile into the intestine, where it is biotransformed into an inactive metabolite.
Pharmacokinetics in special clinical cases
In newborn infants, 70% of the drug is excreted by the kidneys.
In newborns and in the elderly (over the age of 75), as well as in patients with impaired renal and liver function, T 1/2 significantly increases.
In patients on hemodialysis (QC 0-5 ml / min), T 1/2 is 14.7 hours; with SC 5-15 ml / min - 15.7 hours; with SC 16-30 ml / min - 11.4 hours; with SC 31-60 ml / min - 12.4 hours.
In children with meningitis, T 1/2 after IV introduction at a dose of 50-75 mg / kg is 4.3-4.6 hours.
Ceftriaxone is not excreted by hemodialysis.
INDICATIONS
Treatment of infectious-inflammatory diseases caused by sensitive microorganisms:
- infections of the upper and lower respiratory tract (including pneumonia, lung abscess, pleural empyema);
- skin and soft tissue infections;
- infections of bones and joints;
- urinary tract infections (including pyelonephritis);
- inflammatory diseases of the gastrointestinal tract and biliary tract (including cholangitis, empyema of the gallbladder);
- infections of the pelvic organs;
- peritonitis;
- bacterial meningitis;
- bacterial endocarditis;
- sepsis;
- acute uncomplicated gonorrhea;
- Lyme disease;
- shigellosis;
- Salmonellosis.
Prevention and treatment of infectious postoperative complications.
DOSING MODE
The drug is given in / m or in / in a stream or drip.
For adults and children over 12 years, the average daily dose is 1-2 g 1 time / day. The maximum daily intake for adults is 4 g.
For newborns under 14 days of age, the dose is 20-50 mg / kg / day. The maximum daily dose of 50 mg / kg.
For children aged 15 days and up to 12 years, the daily dose is 20-80 mg / kg.
Children with a body weight of more than 50 kg are prescribed doses for adults.
A daily dose of 50 mg / kg or more should be used as infusions within 30 minutes.
The duration of the course usually does not exceed 10 days. The drug should be continued for 2-3 days after the normalization of body temperature and the disappearance of symptoms.
For the prevention of infections in the postoperative period, the drug is administered once for 30-90 minutes before the operation in a dose of 1-2 g (depending on the degree of infectious risk). In surgical interventions on the colon and rectum, additional administration of the drug from the 5-nitroimidazoles group is recommended.
In bacterial meningitis in infants and young children, the dose is 100 mg / kg 1 time / day. The maximum daily dose is 4 g. The duration of therapy depends on the type of pathogen and can range from 4 days with meningitis caused by Neisseria meningitidis to 10-14 days with meningitis caused by sensitive Enterobacteriaceae strains.
In acute uncomplicated gonorrhea, the drug is given once a day in a dose of 250 mg.
With Lyme disease, adults and children are prescribed 50 mg / kg once a day, the maximum daily dose is 2 g. The duration of treatment is 14 days.
In patients with impaired renal function, dose adjustment is required only for severe renal insufficiency (CC less than 10 ml / min) , in which case the daily dose of ceftriaxone should not exceed 2 g.
In patients with impaired renal function, there is no need for dose adjustment if the liver function remains normal.
In patients with impaired liver function, there is no need for dose adjustment if the kidney function remains normal.
When combination of renal failure and liver failure should regularly monitor the concentration of ceftriaxone in the plasma and, if necessary, adjust its dose.
Patients on hemodialysis do not need additional injection after dialysis. ceftriaxone is not removed during hemodialysis. The rate of excretion of ceftriaxone in such patients may vary, therefore, the concentration of ceftriaxone in the blood plasma should be monitored for possible dose adjustment.
Rules for the preparation and injection of injection solutions
Preparation of solution for the / m introduction
1 g of the drug is dissolved in 3.6 ml of water for injection, 1 ml of the resulting solution contains about 250 mg of ceftriaxone. If necessary, a more dilute solution may be used.
1 g of the drug is dissolved in 3.5 ml of a 1% solution of lidocaine chloride. Enter deep into a relatively large muscle (in the gluteus muscle or in the muscle of the thigh). Do not administer more than 1 g per muscle. It should be remembered that lidocaine chloride solution can not be administered iv.
Preparation of solution for intravenous injection
1 g of the drug is dissolved in 9.6 ml of sterile water for injection, 1 ml of the resulting solution contains about 100 mg of ceftriaxone. The solution is injected iv slowly for 2-4 minutes.
Preparation of a solution for intravenous infusions
2 g of the drug is dissolved in 40 ml of one of the solutions that do not contain calcium (0.9% sodium chloride solution, 0.45% sodium chloride solution + 2.5% dextrose solution, 5% dextrose solution, 10% dextrose solution, 6% dextran solution in 5% dextrose solution, 6-10% solution of hydroxyethylated starch). The duration of IV infusion is at least 30 minutes.
Freshly prepared solutions of ceftriaxone are stable for 6 hours at room temperature and for 24 hours when stored in a refrigerator at a temperature of 2 В° to 8 В° C.
SIDE EFFECT
From the side of the central nervous system: headache, dizziness.
From the side of the urinary system: renal dysfunction (azotemia, increased urea in the blood, hypercreatininaemia, glycosuria, cylindruria, hematuria, oliguria, anuria).
On the part of the digestive system: nausea, vomiting, taste disorder, flatulence, stomatitis, glossitis, diarrhea or constipation, pseudomembranous enterocolitis, pseudo-cholelithiasis (sluggish syndrome), dysbiosis, abdominal pain, increased activity of hepatic transaminases and alkaline phosphatase, hyperbilirubinemia, cholestatic jaundice.
On the part of the hematopoiesis system: anemia, leukopenia, leukocytosis, lymphopenia, neutropenia, granulocytopenia, thrombocytopenia, thrombocytosis, basophilia, hemolytic anemia.
From the coagulation system: hypocoagulation, reduction of plasma clotting factors (II, VII, IX, X), epistaxis, increased prothrombin time.
Allergic reactions: urticaria, rash, itching, fever, chills; rarely - bronchospasm, edema, eosinophilia, exudative erythema multiforme (including Stevens-Johnson syndrome), anaphylactic shock, serum sickness.
Local reactions: with intravenous injection - phlebitis, tenderness along the vein; with the / m introduction - soreness in the injection site.
Other: superinfection (including candidiasis).
CONTRAINDICATIONS
- hypersensitivity to the components of the drug;
- Hypersensitivity to other cephalosporins, penicillins and carbapenems.
With caution appoint the drug for violations of the liver and / or kidney function, premature and newborn children with hyperbilirubinemia, with NNC, as well as with enteritis or colitis associated with the use of antibacterial drugs.
PREGNANCY AND LACTATION
The use of Azaran in pregnancy is possible only in cases where the intended use for the mother exceeds the potential risk to the fetus (ceftriaxone penetrates the placental barrier).
If Azaran is needed during lactation, the question of stopping breastfeeding should be solved, since ceftriaxone is excreted in breast milk.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with impaired renal function, dose adjustment is required only for severe renal insufficiency (CC less than 10 ml / min) , in which case the daily dose of ceftriaxone should not exceed 2 g.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with impaired hepatic function, T 1/2 significantly increased.
APPLICATION FOR CHILDREN
Caution is prescribed to premature and newborn children.
It is necessary to correct the dosage regimen depending on the age of the child.
SPECIAL INSTRUCTIONS
The drug is used only in a hospital.
With simultaneous severe renal and hepatic insufficiency in patients on hemodialysis, the concentration of ceftriaxone in the blood plasma should be monitored regularly.
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 are observed, which disappear after the drug is discontinued (even if this phenomenon is accompanied by pain in the right hypochondrium, it is recommended to continue the prescription of the antibiotic and conduct symptomatic treatment).
When using the drug, you can not use ethanol, because possibly the development of disulfiramoid-like effects (reddening face, spastic pain in the abdomen and in the stomach, nausea, vomiting, headache, lowering blood pressure, tachycardia, dyspnea).
Against the backdrop of Azaran's use, older people and weakened patients may need vitamin K.
Despite the detailed collection of the anamnesis, which is the rule for other cephalosporin antibiotics, one can not exclude the possibility of developing an anaphylactic shock, which requires immediate therapy: first enter IV epinephrine, then GCS.
In vitro studies have shown that like other cephalosporins, ceftriaxone is able to displace bilirubin bound to serum albumin. Therefore, in newborns with hyperbilirubinemia and, especially in preterm infants, the use of ceftriaxone requires even greater caution.
OVERDOSE
At present, cases of drug overdose Azaran were not reported.
Treatment: symptomatic therapy. There is no specific antidote. To remove ceftriaxone from the body, hemodialysis and peritoneal dialysis are not effective.
DRUG INTERACTION
Ceftriaxone and aminoglycosides have a synergistic effect on many gram-negative bacteria (including Pseudomonas aeruginosa), drugs should be administered separately at the recommended doses.
Ceftriaxone, suppressing the intestinal flora, interferes with the synthesis of vitamin K. Therefore, with the simultaneous use with drugs that reduce platelet aggregation (NSAIDs, salicylates, sulfinpyrazone), the risk of bleeding increases.
With simultaneous use with anticoagulants, an increase in anticoagulant effect is noted.
With simultaneous use with "loop" diuretics and other nephrotoxic drugs, the risk of nephrotoxic action increases.
The drug is incompatible with ethanol.
Pharmaceutical interaction
Pharmaceutically incompatible with solutions containing other antibiotics (including vancomycin and aminoglycosides) and with solutions containing fluconazole.
Ceftriaxone should not be mixed with solutions containing calcium (including Ringer's solution).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of reach of children, protected from light at a temperature of 15 В° to 25 В° C. Shelf life - 3 years.
