ZINACEF is a bactericidal cephalosporin antibiotic which is resistant to most beta-lactamases and is active against a wide range of Gram-positive and Gram-negative organisms.

 

It is indicated for the treatment of infections before the infecting organism has been identified or when caused by sensitive bacteria. Susceptibility to ZINACEF will vary with geography and time and local susceptibility data should be consulted where available (see Pharmacological properties, Pharmacodynamics).

 

Indications include:

 

–      respiratory tract infections for example, acute exacerbation of chronic bronchitis, infected bronchiectasis, bacterial pneumonia, lung abscess and post-operative chest infections

 

–      ear, nose and throat infections for example, sinusitis, tonsillitis, pharyngitis and otitis media

 

–      urinary tract infections for example, acute and chronic pyelonephritis, cystitis and asymptomatic bacteriuria

 

–      soft-tissue infections for example, cellulitis, erysipelas and wound infections

 

–      bone and joint infections for example, osteomyelitis and septic arthritis

 

–      obstetric and gynaecological infections, pelvic inflammatory diseases

 

–      gonorrhoea particularly when penicillin is unsuitable

 

–      other infections including septicaemia, meningitis and peritonitis

–      prophylaxis against infection in abdominal, pelvic, orthopaedic, cardiac, pulmonary, oesophageal and vascular surgery where there is increased risk from infection.

 

Usually ZINACEF will be effective alone, but when appropriate it may be used in combination with an aminoglycoside antibiotic, or in conjunction with metronidazole (orally or by suppository or injection), especially for prophylaxis in colonic or gynaecological surgery.

 

Where appropriate ZINACEF is effective when used prior to oral therapy with ZINNAT (cefuroxime axetil) in the treatment of pneumonia and acute exacerbations of chronic bronchitis.

Pharmaceutical forms:

ZINACEF Injection: Powder for suspension or solution for injection and Powder for solution for infusion

ZINACEF Injection is for intravenous (i.v.) and/or intramuscular (i.m.) administration only.

ZINACEF is also available as the axetil ester (ZINNATfor oral administration. This permits the use of sequential therapy with the same antibiotic, when a change from parenteral to oral therapy is clinically indicated.

No more than 750 mg should be injected at one intramuscular site.

 

GENERAL DOSING RECOMMENDATIONS 

 

Adults

Many infections respond to 750 mg three times daily by i.m. or i.v. injection. For more severe infections the dose should be increased to 1.5 g three times daily given i.v. The frequency of administration may be increased to 6-hourly if necessary, giving total daily doses of 3 to 6 g. Where clinically indicated, some infections respond to 750 mg or 1.5 g twice daily (i.v. or i.m.) followed by oral therapy with ZINNAT.

 

Infants and Children

30 to 100 mg/kg/day given as 3 or 4 divided doses. A dose of 60 mg/kg/day is appropriate for most infections.

 

Neonates

30 to 100 mg/kg/day given as 2 or 3 divided doses (see Pharmacokinetics).

 

GONORRHOEA

Adults

1.5 g as a single dose (as 2 x 750 mg injections given i.m.with different sites e.g. each buttock).

 

MENINGITIS

ZINACEF is suitable for sole therapy of bacterial meningitis due to sensitive strains.

 

Adults:         - 3 g given i.v. every 8 hours.

Infants and Children:  - 150 to 250 mg/kg/day given i.v. in 3 or 4 divided doses

Neonates:     - the dosage should be 100 mg/kg/day given i.v.

 

PROPHYLAXIS

The usual dose is 1.5 g given i.v. with induction of anaesthesia for abdominal, pelvic and orthopaedic operations. This may be supplemented with two 750 mg i.m. doses 8 and

16 hours later.

 

In cardiac, pulmonary, oesophageal and vascular operations, the usual dose is 1.5 g given

i.v. with induction of anaesthesia, continuing with 750 mg given i.m. three times daily for a further 24 to 48 hours.

 

In total joint replacement, 1.5 g ZINACEF powder may be mixed dry with each pack of methyl methacrylate cement polymer before adding the liquid monomer.

 

SEQUENTIAL THERAPY

Adults

Duration of both parenteral and oral therapy is determined by the severity of the infection and the clinical status of the patient.

 

Pneumonia

1.5 g ZINACEF three times daily or twice daily (given i.v. or i.m.) for 48 to 72 hours, followed by 500 mg twice daily ZINNAT (cefuroxime axetil) oral therapy for 7 to10 days.

Acute exacerbations of chronic bronchitis

 

750 mg ZINACEF three times daily or twice daily (given i.v. or i.m.) for 48 to 72 hours, followed by 500 mg twice daily ZINNAT (cefuroxime axetil) oral therapy for 5 to10 days.

 

RENAL IMPAIRMENT

 

Cefuroxime is excreted by the kidneys. Therefore, as with all such antibiotics, in patients with markedly impaired renal function it is recommended that the dosage of ZINACEF should be reduced to compensate for its slower excretion.

 

It is not necessary to reduce the standard dose (750 mg to 1.5 g three times daily) until the creatinine clearance falls to 20 ml/min or below.

 

In adults with marked impairment (creatinine clearance 10 to 20 ml/min) 750 mg twice daily is recommended and with severe impairment (creatinine clearance <10 ml/min)

750 mg once daily is adequate.

 

For patients on haemodialysis a further 750 mg dose should be given i.v. or i.m. at the end of each dialysis. In addition to parenteral use, ZINACEF can be incorporated into the peritoneal dialysis fluid (usually 250 mg for every 2 litres of dialysis fluid).

 

For patients in renal failure on continuous arteriovenous haemodialysis or high-flux haemofiltration in intensive therapy units a suitable dosage is 750 mg twice daily. For low-flux haemofiltration follow the dosage recommended under impaired renal function.

Hypersensitivity to cephalosporin antibiotics.

Special care is indicated in patients who have experienced an allergic reaction to penicillins or other beta-lactams.

 

Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with potent diuretics such as furosemide or aminoglycosides, as renal impairment has been reported with these combinations. Renal function should be monitored in these patients, the elderly, and those with pre-existing renal impairment (see Dosage and Administration).

 

As with other therapeutic regimens used in the treatment of meningitis, mild-to-moderate hearing loss has been reported in a few paediatric patients treated with ZINACEF. Persistence of positive cerebral spinal fluid (CSF) cultures of Haemophilus influenzae at 18-36 hours has also been noted with ZINACEF injection, as well as with other antibiotic therapies; however, the clinical relevance of this is unknown.

As with other antibiotics, use of ZINACEF may result in the overgrowth of Candida.

Prolonged use may also result in the overgrowth of other non-susceptible organisms (e.g. enterococci and Clostridioides difficile), which may require interruption of treatment.

 

Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further.

 

Intracameral use and ocular toxicity

Serious ocular toxicity, including corneal opacity, retinal toxicity and visual impairment has been reported following off-label intracameral use of ZINACEF. ZINACEF should not be administered intracamerally.

 

With a sequential therapy regime the timing of change to oral therapy is determined by severity of the infection, clinical status of the patient and susceptibility of the pathogens involved. If there is no clinical improvement within 72 hours, then the parenteral course of treatment must be continued.

 

Refer to the relevant prescribing information for ZINNAT before initiating sequential therapy.

 

In common with other antibiotics, ZINACEF may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

 

ZINACEF does not interfere in enzyme-based tests for glycosuria.

 

Slight interference with copper reduction methods (Benedict's, Fehling's, Clinitest) may be observed. However, this should not lead to false-positive results, as may be experienced with some other cephalosporins.

 

It is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving ZINACEF.

 

This antibiotic does not interfere in the alkaline picrate assay for creatinine.

There is no experimental evidence of embryopathic or teratogenic effects attributable to cefuroxime, but, as with all drugs, it should be administered with caution during the early months of pregnancy. Cefuroxime is excreted in human milk, and consequently caution should be exercised when ZINACEF is administered to a nursing mother.

None reported.

Adverse drug reactions are very rare (<1/10,000) and are generally mild and transient in nature.

 

The frequency categories assigned to the adverse reactions below are estimates, as for most reactions suitable data for calculating incidence are not available. In addition the incidence of adverse reactions associated with ZINACEF may vary according to the indication.

 

Data from clinical trials were used to determine the frequency of very common to rare undesirable effects. The frequencies assigned to all other undesirable effects (i.e., those occurring at <1/10,000) were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency.

The following convention has been used for the classification of frequency:

Very common ≥1/10,

Common ≥1/100 to <1/10,

Uncommon ≥1/1000 to <1/100,

Rare ≥1/10,000 to <1/1000, Very rare <1/10,000.

 

Infections and infestations

 

Rare                               Candida overgrowth

 

Blood and lymphatic system disorders

 

Common	Neutropenia, eosinophilia.
Uncommon	Leukopenia, decreased haemoglobin concentration, positive Coomb’s test.
Rare	Thrombocytopenia.
Very rare	Haemolytic anaemia.

 

 

Cephalosporins as a class tend to be absorbed onto the surface of red cell membranes and react with antibodies directed against the drug to produce a positive Coomb’s Test (which can interfere with cross matching of blood) and very rarely haemolytic anaemia.

 

 

Immune system disorders

 

Hypersensitivity reactions including

Uncommon                   Skin rash, urticaria and pruritus.

Rare                               Drug fever.

Very rare          Interstitial nephritis, anaphylaxis, cutaneous vasculitis.

See also Skin and subcutaneous tissue disorders and Renal and urinary disorders. Gastrointestinal disorders

Uncommon                   Gastrointestinal disturbance.

 

Very rare Pseudomembranous colitis (see Warnings and Precautions).

 

 

Hepatobiliary disorders

 

Common                       Transient rise in liver enzymes.

 

Uncommon                   Transient rise in bilirubin.

 

 

Transient rises in serum liver enzymes or bilirubin occur, particularly in patients with pre-existing liver disease, but there is no evidence of harm to the liver.

 

Skin and subcutaneous tissue disorders

 

Very rare            Erythema multiforme, toxic epidermal necrolysis and Stevens

Johnson Syndrome.

 

See also Immune system disorders.

 

Renal and urinary disorders

 

Very rare                     Elevations in serum creatinine, elevations in blood urea nitrogen and decreased creatinine clearance (see Warnings and Precautions).

 

See also Immune system disorders.

 

General disorders and administration site conditions

 

Common                     Injection site reactions which may include pain and thrombophlebitis.

 

Pain at the intramuscular injection site is more likely at higher doses. However, it is unlikely to be a cause for discontinuation of treatment.

 

To report any side effect(s):

 

Kingdom of Saudi Arabia

-National Pharmacovigilance centre (NPC)

•             Fax: +966-11-205-7662

•             Reporting Hotline: 19999E-mail: npc.drug@sfda.gov.sa

•             Website: https://ade.sfda.gov.sa

-GlaxoSmithKline - Head Office, Jeddah

•             Tel: 00966(012)6536666

•             Mobile: +966-56-904-9882

•             Email: saudi.safety@gsk.com 

•             Website: https://gskpro.com/en-sa/

•             P.O Box 55850, Jeddah 21544, Saudi Arabia.

For any information about this medicinal product, please contact:

GlaxoSmithKline - Head Office, Jeddah

• Tel:  +966-12-6536666
• Mobile: +966-56-904-9882
• Email: gcc.medinfo@gsk.com
• Website: https://gskpro.com/en-sa/
• P.O. Box 55850, Jeddah 21544, Saudi Arabia

Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. Serum levels of cefuroxime can be reduced by haemodialysis or peritoneal dialysis.

Cefuroxime is a well characterised and effective antibacterial agent which has bactericidal activity against a wide range of common pathogens, including _β-lactamase producing strains. Cefuroxime has good stability to bacterial _β-lactamase, and consequently is active against many ampicillin-resistant or amoxycillin-resistant strains.

 

The bactericidal action of cefuroxime results from inhibition of cell wall synthesis by binding to essential target proteins.

 

The prevalence of acquired resistance is geographically and time dependent and for select species may be very high. Local information on resistance is desirable, particularly when treating severe infections.

 

In vitro susceptibility of micro-organisms to Cefuroxime Where clinical efficacy of cefuroxime has been demonstrated in clinical trials this is indicated with an asterisk (*).

Commonly Susceptible Species

Gram-Positive Aerobes: Staphylococcus aureus (methicillin susceptible)*

 

Coagulase negative staphylococcus (methicillin susceptible) Streptococcus pyogenes* Betahemolytic streptococci

Gram-Negative Aerobes: Haemophilus influenzae including ampicillin resistant strains* Haemophilus parainfluenzae* Moraxella catarrhalis* Neisseria gonorrhoea* including penicillinase and non-penicillinase producing strains Neisseria meningitidis Shigella spp.

Gram-Positive Anaerobes: Peptostreptococcus spp. Propionibacterium spp.

Spirochetes: Borrelia burgdorferi*

Organisms for which acquired resistance may be a problem

Gram-Positive Aerobes: Streptococcus pneumoniae* Viridans group streptococcus Gram-Negative Aerobes: Bordetella pertussis Citrobacter spp. not including C. freundii Enterobacter spp. not including E. aerogenes and E. cloacae Escherichia coli* Klebsiella spp. including K. pneumoniae* Proteus mirabilis Proteus spp. not including P. penneri and P. vulgaris Providencia spp. Salmonella spp.

Gram-Positive Anaerobes:

Clostridium spp.

Gram-Negative Anaerobes: Bacteroides spp. not including B. fragilis Fusobacterium spp.

Inherently resistant organisms

Gram-Positive Aerobes: Enterococcus spp. including E. faecalis and E. faecium Listeria  monocytogenes

Gram-Negative Aerobes: Acinetobacter spp. Burkholderia cepacia Campylobacter spp. Citrobacter freundii Enterobacter aerogenes Enterobacter cloacae Morganella morganii Proteus penneri Proteus vulgaris Pseudomonas spp. including P. aeruginosa Serratia spp. Stenotrophomonas maltophilia

Gram-Positive Anaerobes: Clostridioides difficile

Gram-Negative Anaerobes: Bacteroides fragilis

Others: Chlamydia species Mycoplasma species Legionella species

 

 

 

Peak levels of cefuroxime are achieved within 30 to 45 minutes after i.m. administration.

 

Protein binding has been variously stated as 33 - 50% depending on the methodology used.

 

Concentrations of cefuroxime in excess of the minimum inhibitory levels for common pathogens can be achieved in bone, synovial fluid and aqueous humour. Cefuroxime passes the blood-brain barrier when the meninges are inflamed.

 

Cefuroxime is not metabolised and is excreted by glomerular filtration and tubular secretion.

 

The serum half-life after either i.m. or i.v. injection is approximately 70 minutes.

 

In the first weeks of life the serum half-life of cefuroxime can be 3 to 5 times that in the adult.

 

Concurrent administration of probenecid prolongs the excretion of the antibiotic and produces an elevated peak serum level.

 

There is an almost complete recovery (85 to 90%) of unchanged cefuroxime in urine within 24 hours of administration. The major part is excreted in the first 6 hours.

 

Serum levels of cefuroxime are reduced by dialysis.

No additional data of relevance.

None.

Each 750 mg vial contains 42 mg sodium (1.8 mEq).

ZINACEF should not be mixed in the syringe with aminoglycoside antibiotics.

 

The pH of 2.74% w/v Sodium Bicarbonate Injection BP considerably affects the colour of the solution and therefore this solution is not recommended for the dilution of ZINACEF. However, if required, for patients receiving Sodium Bicarbonate Injection by infusion ZINACEF may be introduced into the tube of the giving set.

The expiry date of the powder is indicated on the packaging. The unopened pack storage temperature requirements are indicated on the packaging. If unopened product previously stored below 25oC Shelf life after reconstitution and dilution under controlled and validated aseptic conditions: suspension and solution for Injection -5 hours below 25oC or 72 hours at 2 to 8oC Shelf life if reconstitution and dilution has not taken place in controlled and validated aseptic conditions: The product should be used immediately or within 24 hours if stored at 2 to 8oC. If unopened product previously stored below 30oC Shelf life after reconstitution and dilution under controlled and validated aseptic conditions: Suspension and solution for Injection - 5 hours below 25oC or 72 hours at 2 to 8oC Solution for Infusion - Use immediately or within 24 hours at 2° to 8°C Shelf life if reconstitution and dilution has not taken place in controlled and validated aseptic conditions: The product should be used immediately or within 24 hours if stored at 2° to 8°C.

The storage conditions are detailed on the packaging.

Store in original package to protect from light.

 

Some increase in the colour of prepared solutions and suspensions of ZINACEF may occur on storage.

As registered locally.

Use and Handling

 

Intramuscular

 

Add 3 ml Water for Injections to

750 mg ZINACEF. Shake gently to produce an opaque suspension.

 

Intravenous

 

Dissolve ZINACEF in Water for Injections using, at least 6 ml for 750 mg, or 15 ml for 1.5 g.

 

Intravenous infusion

 

Dissolve 1.5 g of ZINACEF in 15 ml of Water for Injections.  Add the reconstituted solution of ZINACEF to 50 or 100 ml of a compatible infusion fluid (see information on Compatibility below) These solutions may be given directly into the vein or introduced into the tubing of the giving set if the patient is receiving parenteral fluids.

 

Compatibility

1.5 g ZINACEF constituted with 15 ml Water for Injections may be added to metronidazole injection (500 mg/100 ml)

 

1.5 g ZINACEF is compatible with azlocillin 1 g (in 15 ml) or 5 g (in 50 ml) .

 

ZINACEF (5 mg/ml) is compatible with 5% w/v or 10% w/v xylitol injection .

 

ZINACEF may be constituted for i.m use with aqueous solutions containing up to 1% lidoocaine hydrochloride.

 

ZINACEF is compatible with the following more commonly used i.v. infusion fluids:

 

Sodium Chloride Injection BP 0.9% w/v 5% Dextrose Injection BP.

0.18% w/v Sodium Chloride plus 4% Dextrose Injection BP

5% Dextrose and 0.9% Sodium Chloride Injection

5% Dextrose and 0.45% Sodium Chloride Injection

5% Dextrose and 0.225% Sodium Chloride Injection

10% Dextrose Injection

10% Invert Sugar in Water for Injection Ringer's Injection USP

Lactated Ringer's Injection USP

M/6 Sodium Lactate Injection

Compound Sodium Lactate Injection BP (Hartmann's Solution).

 

The stability of ZINACEF in Sodium Chloride Injection BP 0.9% w/v and in 5%

Dextrose Injection is not affected by the presence of hydrocortisone sodium phosphate.

 

ZINACEF has also been found compatible admixed in i.v. infusion with: Heparin (10 and 50 units/ml) in 0.9% Sodium Chloride Injection; Potassium Chloride (10 and 40 mEqL) in 0.9% Sodium Chloride Injection.

 

 

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