IZACEF INJECTION 500 mg

INDICATIONS CONTRA-INDICATIONS DOSAGE SIDE-EFFECTS PREGNANCY OVERDOSE IDENTIFICATION PATIENT INFORMATION

IZACEF INJECTION 500 mg

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

IZACEF INJECTION 500 mg

COMPOSITION:
Each vial contains cefazolin sodium equivalent to 500 mg cefazolin.

PHARMACOLOGICAL CLASSIFICATION:
A20.1.1 Broad and medium spectrum antibiotics.

PHARMACOLOGICAL ACTION:
Izacef (Cefazolin sodium) is a first generation cephalosporin and is bactericidal, acting by inhibiting synthesis of the bacterial cell wall.
Izacef (Cefazolin sodium) is 84% bound to plasma proteins. It has a half-life of about 1,8 hours. This is increased in the presence of renal impairment. Izacef (Cefazolin sodium) diffuses into bone and ascitic, pleural and synovial fluid, crosses the placenta, but not into the cerebrospinal fluid. High biliary concentrations have been reported. Izacef (Cefazolin sodium) is excreted unchanged by the kidneys.

INDICATIONS:
Clinical studies have shown the cephalosporins to be effective as both therapeutic and prophylactic agents.
Peri-operative prophylaxis: The prophylactic administration of Izacef pre-operatively, intra-operatively, and post-operatively may reduce the incidence of post-operative wound infections in patients undergoing abdominal hysterectomy. The prophylactic administration of Izacef should usually be discontinued within a 24-hour period after the surgical procedure.
Izacef (Cefazolin sodium) is indicated in the treatment of the following conditions caused by susceptible organisms:

Respiratory tract infections due to: Strep. pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, Staph. aureus, Strep. pyogenes, anaerobic Streptococci. The agent of choice for streptococcal infection and prevention of rheumatic fever is penicillin.

Genito-urinary tract infections due to: Strep. bovis,E. coli, Proteus mirabilis, Klebsiella pneumoniae.

Skin and soft tissue infections due to: Staph. aureus, anaerobic Streptococci.

Bone and joint infections due to: Staph. aureus.
Septicaemia due to: Staph. aureus, E. coli, Klebsiella, Streptococcus agalactiae, Proteus mirabilis.
Endocarditis due to: Staph. aureus, Streptococcus of the viridans group, anaerobic Streptococcus. Strep. pneumoniae.
Culture and sensitivity studies to determine the susceptibility of the causative organisms of Izacef (Cefazolin sodium) are necessary.

Prophylaxis during and after surgery is another area where cephalosporins have found wide use; there are numerous instances where first-generation cephalosporins, like Izacef injection have been shown to be safe and effective for this purpose.

It includes biliary-tract infections, endo-carditis (staphylococcal), endometritis (surgical infection prophylaxis at caesarean section), peritonitis (associated with continuous ambulatory peritoneal dialysis), and surgical infection (prophylaxis).

Izacef Injection is recommended for the prevention of wound infection and sepsis in surgical patients, as well as for second-trimester abortion, clean cardiovascular surgery, total joint replacement, clean-contaminated head and neck surgery. For ocular surgery a subconjunctival injection of Izacef Injection may be given at the end of the operation.

Other Procedures include abdominal or vaginal hysterectomy, joint repair, reduction of fractures, cholecystectomy, gastric resection, and cardiothoracic and vascular surgery.

CONTRA-INDICATIONS:
Izacef (Cefazolin sodium) is contra-indicated in patients with a known sensitivity to the cephalosporins.

Cephalosporins cross the placenta and are also found in mother's s milk. The safely of this product has not been established during pregnancy, lactation and in infants under one month of age or in premature babies.

WARNINGS:
About 10% of penicillin sensitive patients will also be allergic to cephalosporins. Great care should be taken in administration of Izacef (Cefazolin sodium) to penicillin-sensitive patients and patients with a known history of allergy.

Use with caution in patients with renal impairment.

DOSAGE AND DIRECTIONS FOR USE:
Izacef (Cefazolin sodium) may be administered either intramuscularly or intravenously after reconstitution . Other routes of administration used include intraperitoneal administration in peritoneal dialysis solutions and intra-ocular injections.

Intramuscular Administration:
Reconstitute Izacef Injection 500 mg with 2 mL Water for Injections or 0,9% Sodium Chloride for Injection. Shake well until dissolution is complete. This will result in a concentration of 225 mg/mL.

For Intermittent intravenous infusion:
Izacef Injection 500 mg may be dissolved in 50 mL of either 0,9% Sodium Chloride for Injections or Dextrose 5% for Injections, giving a concentration of 10 mg/mL.

Intravenous Administration:
Dilute Izacef Injection 500 mg with 7 mL Water for Injections. It should be administered slowly over a period of 3–5 minutes. This may be administered directly into the vein or through the tubing for patients receiving the above parenteral fluids.

The dosage for intravenous and intramuscular injection is the same.

USUAL ADULT DOSAGE:

Type of infection	Dose	Frequency
Mild infection	250–500 mg	every 8 hours
Moderate infection	500 mg	every 6–8 hours
Severe infection	500 mg–1 g	every 6 hours

Maximum dose: 6 g per 24 hours in severe cases of infection.

Adult dose in Renal Impairment
An initial loading dose of 500 mg is given, followed by:

Clearance	Maintenance dose
Anuria	up to 200 mg	every 24 hours
20 mL/min	75 to 400 mg	every 24 hours
40 mL/min	125 to 600 mg	every 12 hours
70 mL/min	250 mg to 1,25 g	every 12 hours

Paediatric dosage:
Izacef (Cefazolin sodium) should not be given to children under 1 month of age or to premature babies.

The dosage should be calculated as:
25 mg –50 mg/kg body mass daily in 3 to 4 divided doses to a maximum of 100 mg/kg body mass daily in severe infections.
Children with renal impairment: an initial loading dose is followed by:

Clearance	Maintenance dose
<70 mL/min	15 to 60 mg/kg body mass daily in divided doses
<40 mL/min	6,25 to 25 mg/kg body mass daily in divided doses
<20 mL/min	2,5 to 10 mg/kg body mass daily in divided doses

For prophylaxis it is customary to give Izacef (Cefazolin sodium) systemically as a single pre-operative dose or for 24 hours perioperatively. Systemic administration, usually by the intravenous route, is generally preferred.

For the prophylaxis of infection during surgery, a 1 g dose is given half to one hour prior to the operation, followed by 0,5 to 1 g during surgery for lengthy procedures. A dose of 0,5 to 1 g is given every 6 to 8 hours postoperatively for 24 hours or up to 5 days in certain cases.

Prophylaxis prior to biliary surgery could be with single doses of Izacef (Cephazolin Sodium).

Antibiotic prophylaxis may be given at caesarean section after cord clamping to prevent postpartum endometritis as well as wound infection. An intravenous dose has been suggested in high-risk patients.

Peri-operative prophylactic use:
To prevent post-operative infection in contaminated or potentially contaminated abdominal hysterectomy the recommended doses are as follows:

(a)	1 g IV or IM administered one-half to 1 hour prior to the start of surgery.
(b)	For lengthy operative procedures (e.g. 2 hours or longer) 1 g IV or IM during surgery (administration modified according to the duration of the operative procedure).
(c)	1 g IV or IM every 6 to 8 hours for a maximum of 24 hours post-operatively has been used.

It is important that:

1.	The pre-operative dose be given just prior (one-half to 1 hour) to the start of surgery so that adequate antibiotic levels are present in the serum and tissues at the time of initial surgical incision.
2.	If exposure to infections organisms is likely, Izacef must be administered to appropriate intervals during surgery in order that sufficient levels of the antibiotic be present when needed.

RECOMMENDATIONS FOR PROPHYLACTIC USE OF IZACEF (CEPHAZOLIN SODIUM)

OPERATIONS	BACTERIA	INTRAVENOUS ADMINISTRATION	DOSE
Cardiac: all with sternotomy, cardiopulmonary bypass	Staphylococcus aureus, Staphylococcus epidermidis. diphtheroids, gram-negative enterics	Izacef >(Cefazolin)	1–2 g preinduction, 1–2 g every 8 h for 48 h
Noncardiac vascular: aortic resection & prosthetic bypass	S. aureus, S epidermidis, diphtheroids, gram-negative enterics	Izacef >(Cefazolin)	1 g preinduction, 2 postoperative doses
Orthopedic: insertion of prosthetic joints, open operations	S. aureus, S. epidermidis	Izacef >(Cefazolin)	1 g preinduction
Neurosurgery	S. aureus, S. epidermidis	Izacef >(Cefazolin)	1 g preinduction
Head and neck: operations involving the mucous membranes and deep tissue	Oral aerobes and anaerobes, S. aureus, streptococci	Izacef (Cefazolin)	2 g preinduction
General thoracic: pulmonary and esophageal	Oral anaerobes, S. aureus, streptococci gram-negative enterics	Izacef (Cefazolin)	1–2 g preinduction
Gastroduodenal, bariatric, ulcer patients treated with H₂ blockers, bleeding duodenal ulcer, genitourinary or gastric cancer	Oropharyngeal flora and gram-negative enterics, S. aureus	Izacef (Cefazolin)	1–2 g preinduction
Biliary: all open and laparoscopic procedures (chronically intubated biliary tact)	Gram-negative enterics, S. aureus, Enterococcus fecalis, clostridia (above plus Pseudomonas species)	Izacef (Cefazolin) (culture based selection)	1–2 g preinduction (preinduction dose and repeat interval based on drug kinetics)
Cesarean section	Enteric aerobes and anaerobes, E. fecalis, group B streptococci	Izacef (Cefazolin)	1 g after the umbilical cord is clamped
Hysterectomy	Enteric aerobes and anaerobes, E. fecalis, group B streptococci	Izacef (Cefazolin)	1 g preinduction (See dosage instructions under "Peri-operative prophylactic use" above

Current data suggest repeat dosing for operations lasting longer than the serum half-life. Preinduction indicates in operating room before initiating anaesthesia.

> Appropriate adjustments in prophylactic regimens should be made in hospitals with a high incidence of MRSA and/or MRSE if the overall rate of infection mandates it.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Allergic reactions including skin rashes, urticaria, eosinophilia, fever, reactions resembling serum sickness and anaphylaxis. Should an allergic reaction occur, the medication must be discontinued and the patient treated supportively with e.g. adrenaline, anti-histamines and corticosteroids. Neutropenia, leucopenia, thrombocytopenia and haemolytic anaemia have been reported. Also nephrotoxicity, particularly where renal impairment already exists, or in patients receiving concomitant nephrotoxic medication.

Liver enzyme values may be elevated.

Neurological disturbances including encephalopathy have occurred.

Pain at the site of intramuscular administration is reported as well as thrombophlebitis following intravenous infusion. Gastro-intestinal adverse effects have been reported, and prolonged use may result in overgrowth of non-susceptible organisms and pseudomembranous colitis.

Positive Coombs' reaction appears frequently in patients receiving large doses.

Urine from patients may give a false positive reaction for glucose using copper-reducing agents. Glucose oxidase urine sugar analysis tests will however not be affected.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See "Side-effects and special precautions".
Treatment is supportive and symptomatic.

IDENTIFICATION:
A white to slightly yellow powder in a clear vial, sealed with a rubber stopper and an aluminium cap .

PRESENTATION:
Izacef (Cefazolin) sodium is supplied in cartons of 10 vials

STORAGE INSTRUCTIONS:
Store vials below 25°C and protect from light.
Reconstituted vials can be stored below 25°C for 24 hours and for 96 hours at 0 to 5°C.
Keep out of reach of children.

REGISTRATION NUMBER:
Izacef Injection 500 mg: V/20.1.1/390

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
INTRAMED (PTY) LTD
6 Gibaud Road
PORT ELIZABETH 6001

DATE OF PUBLICATION OF THIS PACKAGE INSERT:

May 1992	12-187/5-94
	Tradepak PE