The bactericidal activity of ceftriaxone results from inhibition of bacterial cell wall synthesis. Ceftriaxone exerts in-vitro activity against a wide range of gram-negative and gram-positive microorganisms. Ceftriaxone is highly stable to most b-lactamases, both penicillinases and cephalosporinases, of gram-positive and gram-negative bacteria. Ceftriaxone is usually active against the following microorganisms in vitro and in clinical infections (see Indications and usage.):
Gram-positive aerobes :
- Staphylococcus aureus (methicillin - sensitive)
- Staphylococci coagulase-negative
- Streptococcus pneumoniae
- Streptococcus group A (Str. pyogenes)
- Streptococcus group B (Str. agalactiae)
- Streptococcus viridans
- Streptococcus bovis
Note: Methicillin-resistant Staphylococcus spp. is resistant to cephalosporins, including ceftriaxone. Most strains of Enterococci (e.g. Enterococcus faecalis) are resistant.
Gram-negative aerobes :
- Acinetobacter spp.
- Aeromonas spp.
- Alcaligenes spp.
- Branhamella catarrhalis (b-lactamase negative and positive)
- Citrobacter spp.
- Enterobacter spp. (some strains are resistant)
- Escherichia coli
- Haemophilus ducreyi
- Haemophilus influenzae (including penicillinase-producing strains)
- Haemophilus parainfluenzae
- Klebsiella spp. (including Kl. pneumoniae)
- Moraxella spp.
- Morganella morganii
- Neisseria gonorrhoeae (including penicillinase-producing strains)
- Neisseria meningitidis
- Plesiomonas shigelloides
- Proteus mirabilis
- Proteus vulgaris
- Providentia spp.
- Pseudomonas aeruginosa (some strains are resistant)
- Salmonella spp. (including S. typhi)
- Serratia spp. (including S. marcescens)
- Shigella spp.
- Vibrio spp. (including V. cholerae)
- Yersinia spp. (including Y. enterocolitica)
* Some isolates of some species are resistant to ceftriaxone, mainly due to the production of the chromosomally encoded b-lactamase.
** Some isolates of some species are resistant due to production of extended spectrum, plasmid-mediated b-lactamase.
Note: Many strains of the above microorganisms that are multiple resistant to other antibiotics, e.g. amino-penicillins and ureido-penicillins, older cephalosporins and aminoglycosides, are susceptible to ceftriaxone.
Treponema pallidum is sensitive in vitro and in animal experiments. Clinical investigations indicate that primary and secondary syphilis respond well to ceftriaxone therapy. With a few exceptions clinical P. aeruginosa isolates are resistant to ceftriaxone.
Bacteroides spp. (including some strains of B. fragilis)
Clostridium spp. (except Cl. difficile)
Fusobacterium spp. (except F. mortiferum and F. varium)
* Some isolates of some species are resistant to ceftriaxone, due to b-lactamase-production.
Note: Many strains of b-lactamase-producing Bacteroides spp. (notably B. fragilis) are resistant.
Susceptibility to ceftriaxone can be determined by the disk diffusion test or by the agar or broth dilution test using standardized techniques for susceptibility testing such as those recommended by the National Committee for Clinical Laboratory Standards (NCCLS). The NCCLS issued the following interpretative breakpoints for ceftriaxone:
|Dilution test inhibitory concentrations in mg/l||= 8||16-32||= 64;|
|Diffusion test (disk with 30 mg ceftriaxone),inhibition zone diameter in mm||= 21||20-14||= 13|
Active ingredient: Ceftriaxone in the form of the disodium salt. Vials containing dry substance equivalent to 0.25 g, 0.5 g, 1 g and 2 g ceftriaxone.
Solvent for parenteral use: The solvent ampoule for i.m. injection contains 1% lidocaine hydrochloride solution, and for i.v. injection sterile water for injections.
1 ml solvent for i.m. injection contains 10.66 mg lidocaine hydrochloride monohydrate equivalent to 10 mg anhydrous lidocaine hydrochloride.
Rofecin® contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone.
Standard dosage Adults and children over 12 years: The usual dosage is 1-2 g of Rofecin® once daily (every 24 hours). In severe cases or in infections caused by moderately sensitive organisms, the dosage may be raised to 4 g, once daily. Neonates, infants and children up to 12 years: The following dosage schedules are recommended for once daily administration: Neonates (up to 14 days): A daily dose of 20-50 mg/kg bodyweight, not to exceed 50 mg/kg, on account of the immaturity of the infant’s enzyme systems. It is not necessary to differentiate between premature and term infants. Infants and children (15 days to 12 years): A daily dose of 20-80 mg/kg. For children with bodyweights of 50 kg or more, the usual adult dosage should be used. Intravenous doses of ≥50 mg/kg body weight should be given by infusion over at least 30 minutes. Elderly patients: The dosages recommended for adults require no modification in the case of geriatric patients. Duration of therapy : The duration of therapy varies according to the course of the disease. As with antibiotic therapy in general, administration of Rofecin® should be continued for a minimum of 48-72 hours after the patient has become afebrile or evidence of bacterial eradication has been obtained. Combination therapy : Synergy between Rofecin® and aminoglycosides has been demonstrated with many gram-negative bacteria under experimental conditions. Although enhanced activity of such combinations is not always predictable, it should be considered in severe, life threatening infections due to microorganisms such as Pseudomonas aeruginosa. Because of physical incompatibility the two drugs must be administered separately at the recommended dosages. Special dosage instructions Meningitis: In bacterial meningitis in infants and children, treatment begins with doses of 100 mg/kg (not to exceed 4 g) once daily. As soon as the causative organism has been identified and its sensitivity determined, the dosage can be reduced accordingly. The best results have been found with the following duration of therapy:
|Neisseria meningitidis||4 days|
|Haemophilus influenzae||6 days|
|Streptococcus pneumoniae||7 days|
Gastrointestinal complaints (about 2% of cases) : loose stools or diarrhea, nausea, vomiting, stomatitis and glossitis.
Hematological changes (about 2%): eosinophilia, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia.
Skin reactions (about 1%): exanthema, allergic dermatitis, pruritus, urticaria, edema, erythema multiforme.
Other, rare side effects: headache and dizziness, increase in liver enzymes, gallbladder sludge, oliguria, increase in serum creatinine, mycosis of the genital tract, shivering and anaphylactic or anaphylactoid reactions.
Pseudomembranous enterocolitis and coagulation disorders have been reported as very rare side effects.
Local side effects In rare cases, phlebitic reactions occurred after i.v. administration. These may be minimized by slow (two to four minutes) injection.
Intramuscular injection without lidocaine solution is painful.
ceftriaxone is generally well tolerated. During the use of Rofecin®, the following side effects, which were reversible either spontaneously or after withdrawal of the drug, have been observed:
Ceftriaxone is contraindicated in patients with known hypersensitivity to the cephalosporin class of antibiotics. In patients hypersensitive to penicillin, the possibility of allergic cross-reactions should be borne in mind.
Hyperbilirubinaemic newborns and preterm newborns should not be treated with ceftriaxone. In vitro studies have shown that ceftriaxone can displace bilirubin from its binding to serum albumin and bilirubin encephalopathy can possibly develop in these patients.
Rofecin® should not be administered concurrently with calcium treatment in newborns because of the risk of precipitation of ceftriaxone-calcium salt (see
No impairment of renal function has so far been observed after concurrent administration of large doses of Rofecin® and potent diuretics (e.g. furosemide). There is no evidence that Rofecin® increases renal toxicity of aminoglycosides. No effect similar to that of disulfiram has been demonstrated after ingestion of alcohol subsequent to the administration of Rofecin® . Ceftriaxone dose not contain an N-methylthiotetrazole moiety associated with possible ethanol intolerance and bleeding problems of certain other cephalosporins. The elimination of Rofecin® is not altered by probenecid.
Store below 30° C. Keep out of reach of children
For i.m injection
250mg with 1 ampoule containing 2ml of 1% Lidocaine solution in Blister Pack
500mg with 1 ampoule containing 2ml of 1% Lidocaine solution in Blister Pack
1g with 1 ampoule containing 3.5ml of 1% Lidocaine solution in Blister Pack
For i.v injection
250mg with 1 ampoule containing 5ml of water for injection in Blister Pack
500mg with 1 ampoule containing 5ml of water for injection in Blister Pack
1g with 1 ampoule containing 10ml of water for injection in Blister Pack
2g for infusion with 2 ampoules containing 10ml of water for injection in a tray
Stability : This medicine should not be used after the expiry date (Exp.) shown on the pack.