Ceftriaxone, 1 g

Ceftriaxone is a third-generation broad-spectrum cephalosporin antibiotic. It acts bactericidally by inhibiting the synthesis of the cell wall of microorganisms. It is resistant against β-lactamases of most gram-positive and gram-negative bacteria.
Active against Gram-positive aerobic bacteria: Staphylococcus aureus (including penicillinase-producing strains), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans; Gram-negative aerobic bacteria: Acinetobacter calcoaceticus, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (including penicillinase-producing strains), Haemophilus parainfluenzae, Klebsiella spp. (including Klebsiella pneumoniae), Moraxella catarrhalis (including penicillinase-producing strains), Morganella morganii, Neisseria gonorrhoeae (including penicillinase-producing strains), Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Serratia spp. (including Serratia marcescens), Pseudomonas aeruginosa (separate strains); anaerobic bacteria: Bacteroides fragilis, Clostridium spp. (except Clostridium difficile), Peptostreptococcus spp.

It 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 also resistant to cephalosporins, including ceftriaxone. Many strains of group D streptococci and enterococci (including Enterococcus faecalis) are also resistant to ceftriaxone.

Pharmacokinetics

Absorption and distribution
After intramuscular administration ceftriaxone is quickly and completely absorbed into the systemic bloodstream. It penetrates well into the tissues and fluid media of the body: respiratory tract, bones, joints, urinary tract, skin, subcutaneous tissue and abdominal organs. In case of meningeal inflammation, it penetrates well into the cerebrospinal fluid. Bioavailability of ceftriaxone during intramuscular administration is 100%. After intramuscular administration Cmax is reached after 2-3 hours, when administered intravenously – at the end of the infusion.

In intramuscular administration of ceftriaxone at a dose of 500 mg and 1 g, the Cmax in plasma is 38 µg/ml and 76 µg/ml, respectively, when administered intravenously at doses of 500 mg, 1 g and 2 g, 82 µg/ml, 151 µg/ml and 257 µg/ml, respectively. In adults, 2-24 hours after administration of the drug at a dose of 50 mg/kg, the concentration in the cerebrospinal fluid is many times higher than the MPC for the most common causative agents of meningitis.

The equilibrium state is established within 4 days of the drug administration.

The irreversible binding to plasma proteins (albumin) is 83-95%.

Vd is 5.78-13.5 l (0.12-0.14 l/kg), in children – 0.3 l/kg.

Extraction
T1/2 is 6-9 hours. Plasma clearance is 0.58-1.45 l/hour, renal clearance 0.32-0.73 l/hour.

Pharmacokinetics in special clinical cases

In newborn children the kidneys excrete about 70% of the drug.

In newborns and elderly persons (over 75 years of age) and in patients with renal and hepatic dysfunction, the T1/2 is significantly increased.

In patients on hemodialysis at a CK of 0-5 ml/minute, the T1/2 is 14.7 hours; at a CK of 5-15 ml/minute, 15.7 hours; at a CK of 16-30 ml/minute, 11.4 hours; at a CK of 31-60 ml/minute, 12.4 hours.

In children with meningitis, the T1/2 after intravenous administration at a dose of 50-75 mg/kg is 4.3-4.6 hours.

Indications

Bacterial infections caused by sensitive microorganisms:

Prevention of postoperative infection.
Infectious diseases in immunocompromised individuals.

Active ingredient

Composition

1 vial contains:

the active ingredient:

ceftriaxone (in the form of dinatrium salt) 1 g.

How to take, the dosage

Ceftriaxone is administered intramuscularly or intravenously (by trickle or drip).

In adults and children over 12 years of age, the average daily dose is 1-2 g ceftriaxone once daily.

In severe cases or in cases of infections caused by moderately sensitive pathogens, the daily dose may be increased to 4 g (2 g 2 times a day).

In newborns (up to two weeks of age) the dose is 20-50 mg/kg/day.

For infants and children under 12 years of age, the daily dose is 20-80 mg/kg.

In children with a body weight of 50 kg or more, the adult dosage is used.

Dose over 50 mg/kg of body weight should be administered as intravenous infusion (drip infusion). The duration of treatment depends on the nature of the disease.

In bacterial meningitis in infants and young children the initial dose is 100 mg/kg once daily. The maximum daily dose is 4 g.

For the treatment of acute gonorrhea, the dose is 250 mg, once intramuscularly.

To prevent infections in the preoperative and postoperative periods 1-2 g ceftriaxone is administered 30-90 minutes before surgery.
In renal failure (creatinine clearance less than 10 ml/minute) the daily dose of ceftriaxone should not exceed 2 g.
In marked hepatic and renal dysfunction, as well as in patients on hemodialysis the plasma concentration of ceftriaxone should be monitored, since the rate of its excretion may decrease in them.Rules for preparation and administration of injection solutions

Injection solutions should be prepared immediately before use.

To prepare a solution for intramuscular injection 500 mg of the drug is dissolved in 2 ml, and 1 g of the drug is dissolved in 3.5 ml of 1% lidocaine solution. It is recommended to inject no more than 1 g into one gluteal muscle.

For preparation of solution for intravenous injection 500 mg of the drug is dissolved in 5 ml and 1 g of the drug is dissolved in 10 ml of sterile water for injection. The injectable solution is administered intravenously slowly over 2-4 minutes.

In order to prepare solution for intravenous infusion 2 g of the drug are dissolved in 40 ml of one of the following calcium-free solutions: 0.9% sodium chloride solution, 5-10% dextrose (glucose) solution, 5% levulose solution. The drug in a dose of 50 mg/kg or more should be administered intravenously by drip, for 30 minutes.

Freshly prepared ceftriaxone solutions are physically and chemically stable for 6 hours at room temperature.

Interaction

Ceftriaxone and aminoglycosides have synergism against many Gram-negative bacteria.

Concomitant administration with metronidazole, fluoroquinolones, vancomycin, rifampicin is possible (but not in the same syringe).
When used simultaneously with loop diuretics (such as furosemide), renal dysfunction is not observed.

Pharmaceutical interactions

Pharmaceutically incompatible with solutions containing other antibiotics.

Special Instructions

When using the drug, the risk of anaphylactic shock and the need for appropriate emergency therapy should be taken into account.

In in vitro studies it has been shown that ceftriaxone (like other cephalosporins) is able to displace bilirubin bound to serum albumin. Therefore, in neonates with hyperbilirubinemia and especially in premature infants, the use of ceftriaxone requires even greater caution.

In combination of severe renal failure and severe hepatic failure in patients on hemodialysis, plasma concentrations of the drug should be determined regularly.

Peripheral blood count, hepatic and renal function parameters should be monitored regularly during long-term treatment.

In rare cases of ultrasound investigation of gallbladder there may be obscuration, which disappears after discontinuation of treatment. Even if this phenomenon is accompanied by right-subcostal pain, continuation of therapy with Ceftriaxone and symptomatic treatment is recommended.

Elderly and frail patients may require vitamin K administration.

The use of alcohol is contraindicated during treatment because of possible disulfiram-like effects (facial hyperemia, abdominal and stomach cramps, nausea, vomiting, headache, decreased blood pressure, tachycardia, shortness of breath).

Contraindications

Hypersensitivity to the components of the drug Ceftriaxone; hypersensitivity to other cephalosporins, penicillins, carbapenems.

The drug is used with caution in newborn children with hyperbilirubinemia, premature infants, with renal and/or hepatic insufficiency, NSC, enteritis or colitis associated with the use of antibacterial agents, in pregnancy, during lactation.

Side effects

CNS disorders: headache, dizziness.

Urinary system disorders: oliguria, impaired renal function, glucosuria, hematuria, hypercreatininemia, increased urea.

In the digestive system: nausea, vomiting, indigestion, flatulence, stomatitis, glossitis, diarrhea, pseudomembranous enterocolitis, pseudocholithiasis (sludge syndrome), dysbacteriosis, abdominal pain, increased activity of liver transaminases and ALP, hyperbilirubinemia.

Hematopoietic system disorders: anemia, leukopenia, leukocytosis, lymphopenia, neutropenia, granulocytopenia, thrombocytopenia, thrombocytosis, basophilia, hemolytic anemia.

With the clotting system: nasal bleeding, increased (decreased) prothrombin time.

Allergic reactions: urticaria, rash, pruritus, erythema exudative multiforme, fever, chills, edema, eosinophilia, anaphylactic shock, serum sickness, bronchospasm.

Others: superinfection (including candidiasis).

Local reactions: when administered intravenously – phlebitis, soreness along the vein; when administered intramuscularly – soreness at the site of injection.

Overdose

Hemodialysis is ineffective for elimination of the drug from the body.

In case of clinical manifestations of overdose symptomatic therapy is recommended.

Pregnancy use

Prenatal use of the drug is possible only when the estimated benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding should be stopped if the drug has to be used during lactation.