Zepilen

Cefazolin sodium.

Pharmacology: Pharmacodynamics: Cefazolin is a cephalosporin antibiotic with bactericidal properties. It acts by interference of the final stage of bacterial cell wall synthesis in both gram-positive and gram-negative bacteria.
Pharmacokinetics: The parenteral route of administration is used for cefazolin due to the poor absorption from the gastrointestinal tract. Following IM administration of a 500 mg dose, peak plasma levels ca 30 g/mL, occur in about 1 hr. Plasma protein-binding is about 90%. With normal renal function the half life is about 1.8 hrs. Cefazolin is excreted unchanged in the urine with about 80% the dose being recovered over 24 hrs post administration.
Toxicology: Preclinical Safety Data: Animal studies showed no sign of reduced fertility or teratogenicity. Animal studies have indicated that concurrent use with potent diuretics may lead to an increased risk of renal toxicity.
Microbiology: Cefazolin, in vitro, is active against: Gram Positive Organisms: Staphylococcus aureus (both penicillin sensitive and resistant), Staphylococcus epidermidis, group A β-haemolytic streptococci, and other strains of streptococci (many enterococci strains are resistant), Streptococci pneumoniae.
Gram Negative Organisms: Enterobacter aerogenes, Escherichia coli, Haemophilus influenzae, Klebsiella sp, Proteus mirabilis.

Treatment of the following infections caused by susceptible bacteria: Biliary tract infections; bone and joint infections; endocarditis; genitourinary tract infections; respiratory tract infections; skin and soft tissue infections; septicaemia.
It may also be used as a prophylactic, for perioperative administration to patients undergoing contaminated or potentially contaminated surgical procedures (hysterectomy, cholecystectomy, open heart surgery, bone and joint surgery), or in whom postoperative infection would be serious. In such cases it may reduce the incidence of postoperative infection.

Adults: Usual adult dosage is as follows: Mild Infections caused by Susceptible Gram Positive Cocci: 250-500 mg, administered every 8 hrs.
Moderate to Severe Infections: 500 mg to 1 g, administered every 6-8 hrs.
Severe Life Threatening Infection, eg, Endocarditis or Septicaemia: 1-1.5 g administered every 6 hrs. Note that in rare instances a daily dosage of up to 12 g cefazolin has been used.
Acute Uncomplicated Urinary Tract Infection: 1 g administered every 12 hrs.
Pneumonia Due to Pneumococcal Infection: 500 mg administered every 12 hrs.
Prophylactic Use in Surgery: 1 g, by the IM or IV route, 30-60 min prior to surgery. This should be followed by a dose of 500 mg to 1 g, every 6-8 hrs post operation for 24 hrs. In cases where surgery is of greater duration than 2 hrs, an additional dose of 500 mg to 1 g should be administered during the surgical procedure. Patients who have undergone open heart surgery, or prosthesis implantation, should have prophylactic administration prolonged for 3-5 days post surgery.
Hepatic Impairment: No dosage adjustment is required.
Renal Impairment: See Table 1.

Click on icon to see table/diagram/image

Special Populations: Renal Impairment: The following dosage adjustments are recommended in children with renal impairment.
Mild to Moderate Renal Impairment, [Creatinine Clearance (CrCl) 70-40 mL/min]: Following an initial loading dose, 60% of the normal daily dose, administered in divided doses every 12 hrs.
Moderate Renal Impairment, (CrCl) 40-20 mL/min: Following an initial loading dose, one quarter the normal daily dose, administered in divided doses every 12 hrs.
Severe Renal Impairment, (CrCl) 20-5 mL/min: Following an initial loading dose, one tenth the normal daily dose, administered every 24 hrs.
Neonates: Safety of use in neonates and infants under 1 month old has not been established.
Children: Mild to moderate infections a total daily dose of 25 mg/kg body weight to 50 mg/kg body weight, administered as 3 or 4 equally divided doses, is recommended. In severe infection a total daily dosage of up to 100 mg/kg body weight, administered as 3 or 4 equally divided doses, may be used.
Elderly: The usual adult dosage is recommended.
Administration: Zepilen is administered IM or IV. To reconstitute the vials, for intramuscular administration, use sterile water for injection in accordance with the table as follows. Following addition of the water for injection, the vial should be shaken well to ensure total dissolution of the cefazolin sodium. (See Table 2.)

Click on icon to see table/diagram/image

Solutions for IV injections or infusions are prepared by dissolving the dry substance in water for injection or 0.9% sodium chloride solution. Use at least 4 mL of the diluent for each gram of dry substance.
Up to a dose of cefazolin 1 g may be administered by slow IV injection. Higher doses are administered by infusion (over 20-30 min).
For preparing solutions for IV infusion fill up the infusion bottle with sodium chloride solution 0.9%, allow dry substance to dissolve and infuse slowly.
Intramuscular (IM) Administration: Following reconstitution as directed, the required dosage should be injected into a large muscle mass.
Intravenous (IV) Injection: Following reconstitution as directed, the vial should be further diluted with sterile water for injection to a minimum volume of 10 mL, and the solution should be injected slowly over a period of 3-5 min. The period of injection must not be <3 min. Injection may be made directly into a vein, or if the patient is receiving 1 of the infusion fluids listed under intermittent IV infusion, into the tubing.
Intermittent IV Infusion: For preparing solutions for IV infusion fill up the infusion bottle with 0.9% sodium chloride solution, allow dry substance to dissolve and infuse slowly.
Dosage recommendations are identical, irrespective of route of administration.

Symptoms: Symptoms may include pain, phlebitis and inflammation at site of injection. Dizziness, headache, paresthesia may occur, seizures are possible, especially in renally impaired patients. Laboratory test results may include elevation of bilirubin, BUN, creatinine, liver enzymes, positive Coombs' test and eosinophilia, leucopoenia, thrombocytopenia, thrombocytosis and lengthening of prothrombin time.
Treatment: Treatment should be symptomatic and supportive. It is recommended to monitor coagulation status, haematological, hepatic and renal functions until the patient stabilizes. In the event of seizures, immediately discontinue Zepilen and use anticonvulsant therapy as appropriate and clinically justified. Combined haemodialysis and haemoperfusion may be useful, although no data is available on such use. Peritoneal dialysis is ineffective.

Known allergy to cephalosporin antibiotics.

Administer with caution to patients who have had previous hypersensitivity reactions to cephalosporins, penicillins or other drugs. There is some evidence of partial cross, allergenicity between cephalosporins and penicillins.
Susceptible patients may have severe reactions, including anaphylaxis. Serious acute hypersensitivity reactions may need adrenaline and other emergency measures.
Absorption of cephalosporins to red cell membrane surface may occur, with reaction to antibodies against Zepilen. This may result in a false positive Coombs' test, very rarely in haemolytic anaemia. It is possible for cross-reactivity with penicillins to occur for this reaction. This reaction may also occur in neonates where cephalosporin was administered to the mother predelivery.
Patients who develop diarrhoea may have pseudomembranous colitis, which has been reported with all broad spectrum antibiotics. Severity can range from mild to life-threatening.
Drug withdrawal is usually satisfactory for mild cases, more severe cases need appropriate measures.
Cefazolin should be discontinued if an allergic reaction occurs, and treatment with adrenaline, antihistamines or corticosteroids initiated as required.
In patients with a history of gastrointestinal disease, especially colitis, caution should be exercised in the use of broad spectrum antibiotics.
Prolonged use of cefazolin may lead to overgrowth of non susceptible organisms, in the case of such superinfection, appropriate measures should be taken. Patients should be carefully observed during long-term therapy for signs of superinfection.
Dosage reduction is necessary in patients with impaired renal function (see Dosage & Administration).
Administration of cefazolin by the intrathecal route is not an approved route of administration, use of this route of administration has resulted in severe central nervous system toxicity, including seizures.
Use in pregnancy & lactation: There are inadequate studies in pregnant women. There is no evidence of impaired fertility or teratogenicity from animal studies. Caution should be exercised in use in pregnancy, and the benefits weighed against the potential hazard. In cases where cefazolin was administered prior to caesarean section, cord blood levels were 25-33% maternal levels. There appeared to be no adverse effect on the foetus.
Very low concentrations of cefazolin have been found in breast milk. Caution should be exercised, and it is preferable to discontinue breastfeeding.

There are inadequate studies in pregnant women. There is no evidence of impaired fertility or teratogenicity from animal studies. Caution should be exercised in use in pregnancy, and the benefits weighed against the potential hazard. In cases where cefazolin was administered prior to caesarean section, cord blood levels were 25-33% maternal levels. There appeared to be no adverse effect on the foetus.
Very low concentrations of cefazolin have been found in breast milk. Caution should be exercised, and it is preferable to discontinue breastfeeding.

Although generally well tolerated, the following undesirable effects have been reported: Dermatological: There are infrequent reports of pain, on occasion accompanied by indurations, following IM injection. Following IV injection there have been observations of phlebitis at the injection site.
Gastrointestinal System: Pseudomembranous colitis symptoms may occur during or after treatment. Anorexia, diarrhoea, nausea, oral candidiasis and vomiting have been reported.
Genital System: Reports of genital and anal pruritus, genital candidiasis and vaginitis.
Haematological: Positive direct and indirect Coombs' test, leucopoenia, neutropenia, thrombocythaemia, sporadic cases of hypoprothrombinemia reversible by vitamin K have been reported, thrombocytopenia.
Hepatic System: Rare observation of transient rise in ALP, ALT and AST levels. There are rare reports of transient cholestatic jaundice and hepatitis.
Hypersensitivity: Anaphylaxis, drug fever, eosinophilia, rash, Stevens-Johnson syndrome and vulvar pruritus.
Neurological System: Occasional reports of convulsions, often associated with high dose administration in marked renal impairment.
Renal System: Transient rise in blood urea nitrogen, unaccompanied by clinically evident renal impairment. Rare reports of interstitial nephritis and other renal disorders. Most of these reports were from seriously ill patients on multiple drug therapy, definite causality has not been determined.

Ethacrynic Acid: On the basis of animal studies, concurrent use may increase the risk of renal toxicity. This may occur with any potent diuretic.
Frusemide: On the basis of animal studies, concurrent use may increase the risk of renal toxicity. This may occur with any potent diuretic.
Probenecid: Concurrent use may result in increased and prolonged blood levels of cefazolin, probably due to decreased renal tubular secretion of cefazolin.
Laboratory Tests: Test for glucose in the urine, using Benedict's, Fehling's solutions or copper sulphate test tablets, may give false positive results. This does not occur with specific glucose oxidase test methods.
False positive Coombs' test results may occur, these can also occur in neonates where cephalosporins were administered to the mother predelivery.
Incompatibilities: Use of cefazolin sodium in a mixture with other antibiotics, including aminoglycosides, is not recommended.

Instruction for Use/Handling: Reconstitution and administration of the vial contents should be done under suitable conditions with aseptic precautions. Prior to administration the solution should be inspected visually for particulate matter and discolouration. Zepilen vials are for single use only, any unused solution should be discarded.

Store below 30°C.
Shelf-Life: Powder for Injection: Thirty (30) months.
Reconstituted Solution: Following reconstitution the solution should be used immediately. It maintains adequate potency for 24 hrs if stored under refrigeration (2-8°C).

Cephalosporins

J01DB04 - cefazolin ; Belongs to the class of first-generation cephalosporins. Used in the systemic treatment of infections.

POM