CEFTRIAXONE-AFT

What it is

CEFTRIAXONE-AFT is a powder for injection containing ceftriaxone sodium, available in strengths of 1000 mg or 2000 mg of ceftriaxone per vial. The 1000 mg strength is suitable for intramuscular injection, intravenous injection and intravenous infusion, whilst the 2000 mg strength is for intravenous infusion only. Each gram of ceftriaxone sodium contains approximately 83 mg of sodium.

Approved indications —

Lower respiratory tract infections caused by susceptible aerobic organisms including Streptococcus pneumoniae, Streptococcus species, methicillin sensitive Staphylococcus aureus, Haemophilus influenzae and related species, Klebsiella species, Escherichia coli and related species, and Serratia marcescens. — Skin and skin structure infections caused by methicillin sensitive staphylococci, streptococci, Escherichia coli, Enterobacter species, Klebsiella species, Proteus mirabilis, Morganella morganii and Serratia marcescens. — Uncomplicated and complicated urinary tract infections caused by Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii and Klebsiella species. — Uncomplicated gonorrhoea (cervical/urethral and rectal) caused by Neisseria gonorrhoeae, including both penicillinase and non-penicillinase producing strains. — Bacterial septicaemia caused by Streptococcus pneumoniae, Escherichia coli and Haemophilus influenzae. — Bone infections caused by methicillin sensitive staphylococci, streptococci, Escherichia coli, Enterobacter species, Proteus mirabilis and Klebsiella pneumoniae. — Joint infections caused by methicillin sensitive Staphylococcus aureus, Streptococcus pneumoniae, streptococci, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae and Enterobacter species. — Meningitis: initial treatment as a single agent in children and immunocompetent adults when presumed or proven to be caused by Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae or Enterobacteriaceae pending culture and sensitivity results. — Surgical prophylaxis: preoperative administration to reduce the incidence of post-operative infections in patients undergoing vaginal or abdominal hysterectomy, cholecystectomy in high risk patients, contaminated or potentially contaminated surgical procedures, and coronary artery bypass surgery.

Dosing overview

The recommended adult daily dose is 1000 to 2000 mg given once a day or in equally divided doses twice a day depending on the type and severity of the infection, with the lower dose appropriate for less severe infections. For uncomplicated gonococcal infections, a single intramuscular dose of 250 mg is recommended. For preoperative use in cardiovascular surgery, biliary tract surgery in high risk patients and vaginal and abdominal hysterectomy, a single dose of 1000 mg administered one-half to two hours before surgery is recommended. For serious miscellaneous infections in children, the recommended total daily dose is 50–75 mg/kg (not to exceed 2000 mg), given once per day or in divided doses every 12 hours. In meningitis, the dose should be divided and administered every twelve hours.

Key safety warnings

Careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins or other drugs, and the product should be given cautiously to penicillin-sensitive patients. There have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute allergic coronary arteriospasm that can result in myocardial infarction), and anaphylactic reactions with fatal outcome have been reported even in patients not known to be allergic, with serious acute hypersensitivity reactions potentially requiring subcutaneous adrenaline (epinephrine) and other emergency measures. Severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalised exanthematous pustulosis have been reported in patients taking beta-lactam antibiotics, and when suspected, ceftriaxone should be discontinued immediately and alternative treatment considered. Ceftriaxone must not be mixed or administered simultaneously with any calcium-containing intravenous solutions, even via different infusion lines or at different infusion sites; however, in patients older than 28 days of age ceftriaxone and calcium-containing solutions may be administered sequentially if infusion lines at different sites are used, or if infusion lines are replaced or thoroughly flushed between infusions with physiological salt solution. Clostridium difficile associated diarrhoea has been reported with use of nearly all antibiotic agents including ceftriaxone and may range from mild diarrhoea to fatal colitis, and must be considered in all patients who present with diarrhoea following antibiotic use. Immune mediated haemolytic anaemia has been observed in patients receiving cephalosporin antibacterials including ceftriaxone, with severe cases including fatalities reported during treatment in both adults and children, and if a patient develops anaemia while on ceftriaxone, the diagnosis of cephalosporin associated anaemia should be considered and ceftriaxone discontinued until the aetiology is determined. Ceftriaxone may precipitate in the gallbladder and kidneys and be detectable as shadows on ultrasound, which can happen in patients of any age but is more likely in infants and small children usually given a larger dose on a body weight basis, and in children, doses greater than 80 mg/kg body weight should be avoided except for meningitis because of the increased risk of biliary precipitates.

Contraindications

Ceftriaxone is contraindicated in patients with known hypersensitivity to beta-lactam antibiotics, and in patients hypersensitive to penicillin, the possibility of allergic cross-reactions should be borne in mind. Hyperbilirubinaemic neonates, especially premature, should not be treated with ceftriaxone, as in vitro studies have shown that ceftriaxone can displace bilirubin from its binding to serum albumin and bilirubin encephalopathy can possibly develop. Ceftriaxone is contraindicated in premature newborns up to a corrected age of 41 weeks and full-term newborns up to 28 days of age with jaundice, or who are hypoalbuminaemic or acidotic, and if they require or are expected to require intravenous calcium treatment or calcium-containing infusions because of the risk of precipitation of ceftriaxone-calcium.

PBS listing

CEFTRIAXONE-AFT 500 mg powder for injection is listed on the PBS as 3 items with restricted access, with an ex-manufacturer price of A$2.50.

Regulatory history

CEFTRIAXONE-AFT was first registered on the ARTG on 20 February 2012, with three strengths registered: 500 mg, 1000 mg and 2000 mg powder for injection vials.