CEFAZOLIN-AFT

What it is

CEFAZOLIN-AFT is supplied in vials containing cefazolin sodium equivalent to 500 mg, 1 g and 2 g cefazolin. It is a white to almost white powder for injection which reconstitutes with Sterile Water for Injection to give a colourless solution. Cefazolin is a semisynthetic cephalosporin for parenteral administration. The sodium content is 50 mg/g of cefazolin sodium.

Approved indications

— Respiratory tract infections due to Streptococcus pneumoniae, Klebsiella species, Haemophilus influenzae, Staphylococcus aureus (penicillin sensitive and penicillin resistant) and group A beta-haemolytic streptococci. — Genitourinary tract infections due to Escherichia coli, Proteus mirabilis, Klebsiella species and some strains of Enterobacter and Enterococci. — Skin and skin structure infections due to Staphylococcus aureus (penicillin sensitive and penicillin resistant) and group A beta-haemolytic Streptococci and other strains of Streptococci. — Bone and joint infections due to Staphylococcus aureus. — Septicaemia due to Streptococcus pneumoniae, Staphylococcus aureus (penicillin sensitive and penicillin resistant), Proteus mirabilis, Escherichia coli and Klebsiella species. — Endocarditis due to Staphylococcus aureus (penicillin sensitive and penicillin resistant) and group A beta-haemolytic streptococci.

Dosing overview

The usual dosage for mild Gram positive infections is cefazolin 250 to 500 mg every eight hours. In mild to moderate infections of the respiratory tract caused by Streptococcus pneumoniae, or mild to moderate infections of the genitourinary tract caused by susceptible organisms, a dosage of 500 mg to 1 g every 12 hours may be used. In moderate or severe infections, the usual adult dosage is cefazolin 500 mg to 1 g every six to eight hours. Cefazolin has been administered in dosages of 6 g/day in serious infections such as endocarditis. For children, a total daily dosage of 25 to 50 mg/kg bodyweight, divided into three or four equal doses, is effective for most mild to moderately severe infections, with total daily dosage may being increased to 100 mg/kg bodyweight for severe infections. Safety for use in premature infants and in infants aged under one month has not been established, and the use of cefazolin in these patients is not recommended. In patients with renal impairment, cefazolin is not readily excreted. After a loading dose of 500 mg, maintenance dosage recommendations are adjusted according to degree of renal function.

Key safety warnings

CEFAZOLIN-AFT is contraindicated in patients with known allergy to the cephalosporin group of antibiotics or previous major allergy to penicillin. Cephalosporin derivatives should be given cautiously in penicillin sensitive patients, and careful inquiry should be made concerning previous hypersensitivity reactions to cephalosporins and penicillin before therapy is instituted. Serious acute hypersensitivity reactions may require adrenaline and other emergency measures. There is partial cross allergenicity between penicillins and cephalosporins, and patients have been reported to have had severe reactions including anaphylaxis to both drugs. Antibiotic-associated pseudomembranous colitis has been reported with many antibiotics including cefazolin. A toxin produced by Clostridium difficile appears to be the primary cause, and the severity may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use, which may occur up to several weeks after cessation of antibiotic therapy. 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. When such reactions are suspected, CEFAZOLIN-AFT should be discontinued immediately and an alternative treatment should be considered. Seizures may occur if inappropriately high doses are administered to patients with impaired renal function. Encephalopathy has been reported with the use of cefazolin in patients with renal failure, with symptoms including tonic-clonic seizures, lethargy, disorientation, memory loss and myoclonus. Toxicity has been attributed to increased cefazolin serum levels and increased permeability of the blood brain barrier caused by uraemia. Intrathecal administration of cefazolin is not an approved route of administration; there have been reports of severe CNS toxicity including seizures when cefazolin was administered in this manner.

Contraindications

Known allergy to the cephalosporin group of antibiotics or previous experience of a major allergy to penicillin. Lidocaine (lignocaine) should not be used as a diluent for intramuscular injection in patients who are hypersensitive to lidocaine (lignocaine).

PBS listing

CEFAZOLIN-AFT powder for injection 1 g is listed on the PBS as restricted with an ex-manufacturer price of A$4.04.

Regulatory history

CEFAZOLIN-AFT 500 mg and 1 g received initial approval on 6 March 2012, while CEFAZOLIN-AFT 2 g received approval on 7 February 2022.