Ziftum 750mg/1G Inj

Ziftum

Qualitative & Quantitative composition

Each vial contains:

Sterile Cefuroxime sodium USP

equivalent to Cefuroxime…. 750 mg/1.5 g

Clinical Particulars

Therapeutic indications.

Cefuroxime for Injection 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. In addition, it is an effective prophylactic against postoperative infection in a variety of operations. Usually Cefuroxime for Injection 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.

In situations where mixed aerobic and anaerobic infections are encountered or suspected (e.g. peritonitis, aspiration pneumonia, abscesses in the lung, pelvis and brain), or are likely to occur (e.g. in association with colorectal or gynaecological surgery) it is appropriate to administer Cefuroxime for Injection in combination with metronidazole.

Most of these infections will respond to an i.v. regimen of Cefuroxime for Injection (750mg) plus metronidazole injection (500mg/100ml) administered eight-hourly. In more severe or well established mixed infections, an i.v. regimen of Cefuroxime for Injection (1.5g) plus metronidazole injection (500mg/100ml) eight-hourly may be indicated. For the prophylaxis of infection in surgery (e.g. colorectal and gynaecological a single dose of 1.5g Cefuroxime for Injection plus metronidazole injection (500mg/100ml) is appropriate.

Alternatively, this may be followed by two 750mg doses of Cefuroxime for Injection plus metronidazole.

Indications include:

Respiratory tract infections for example, acute and chronic bronchitis, infected bronchiectasis, bacterial pneumonia, lung abscess and post operative chest infections.

Ear, nose and throat infections for example, sinusitis, tonsillitis and pharyngitis.

Urinary tract infections for example acute and chronic pyelonephritis, cystitis and asymptomatic bacteriuria.

Soft-tissue infections for example cellulitis, erysipelas, peritonitis 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 and meningitis.

Prophylaxis against infection in abdominal, pelvic, orthopaedic, cardiac, pulmonary, osophageal and vascular surgery where there is increased risk from infection.

Cefuroxime is also available as the axetil ester (Cefuroxime axetil) for oral administration.

This permits the use of sequential therapy with the same antibiotic, when a change from parenteral to oral therapy is clinically indicated. Where appropriate Cefuroxime for Injection is effective when used prior to oral therapy with Cefuroxime axetil (cefuroxime axetil) in the treatment of pneumonia and acute exacerbations of chronic bronchitis.

Posology and method of administration

Route of Administration:

By Intramuscular Injection:

Add 3ml of SWFI to 750mg Cefuroxime for Injection. Shake gently to produce an opaque suspension.

By Intravenous Injection

Dissolve Cefuroxime for Injection in sterile water for injection using at least 6ml for 750mg or 15ml for 1.5g. These solutions may be given directly into the vein or introduced into the tubing of the giving set if the patients receiving parenteral fluids.

General Recommendations

Adults: Many infections will respond to 750mg t.i.d. by IM or IV injection. For more severe infections, this dose should be increased to 15g t.i.d. IV. The frequency of IM or IV injection can be increased to six-hourly if necessary, giving total doses of 3g to 6g daily.

Where clinically indicated adults with pneumonia and acute exacerbations of chronic bronchitis have been shown to respond to 750mg or 1.5g b.d., followed by oral therapy with Cefuroxime axetil.

Infants and Children: Doses of 30 to 100mg/kg/day given as three or four divided doses. A dose of 60mg/kg/day will be appropriate for most infections.

Neonates: Doses of 30 to 100mg/kg/day given as two or three divided doses. In the first weeks of life the serum half-life of cefuroxime can be three to five times that in adults.

Elderly: See dosage in adults.

Other Recommendations

Gonorrhoea: 1.5g should be given as a single dose. This may be given as 2 x 750mg injections into different sites eg each buttock.

Meningitis: Cefuroxime for Injection is suitable for sole therapy of bacterial meningitis due to sensitive strains. The following dosages are recommended.

Infants and Children: 200 to 240mg/kg/day IV in three or four divided doses. This dosage may be reduced to 100mg/kg/day IV after three days or when clinical improvement occurs.

Neonates: The initial dosage should be 100mg/kg/day IV. A reduction to 50mg/kg/day iv may be made when clinically indicated.

Adults: 3g IV every eight hours. Data are not yet sufficient to recommend a dose for intrathecal administration.

Prophylaxis: The usual dose is 1.5g IV with induction of anaethesia for abdominal, pelvic and orthopaedic operations, but may be supplemented with two 750mg IM doses eight and sixteen hours later. In cardiac pulmonary oesophageal and vascular operations, the usual dose is 1.5g IV with induction of anaesthesia continuing with 750mg IM t.d.s. for a further 24 to 48 hours.

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

Sequential therapy:

Pneumonia:

1.5g b.d. (IV or IM) for 48-72 hours, followed by 500mg b.d. Cefuroxime axetil oral therapy for 7 days.

Acute exacerbations of chronic bronchitis:

750mg bd (iv or im) for 48-72 hours, followed by 500mg b.d. Cefuroxime axetil oral therapy for 5-7 days.

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

Dosage in impaired renal function

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 Cefuroxime for Injection should be reduced to compensate for its slower excretion. However, itis not necessary to reduce the dose until the creatinine clearance falls below 20ml/min. In adults with marked impairment (creatinine clearance 10-20ml/min) 750mg b.d. is recommended and with severe impairment (creatinine clearance < 10ml/min) 750mg once daily is adequate. For patients on haemodialysis a further 750mg dose should be given at the end of each dialysis. When continuous peritoneal dialysis is being used, a suitable dosage is usually 750mg twice daily.

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

Cefuroxime is also available as the axetil ester (Cefuroxime axetil) for oral administration. This permits parenteral therapy with cefuroxime to be followed by oral therapy in situations where a change from parenteral to oral is clinically indicated.

Contraindications

Hypersensitivity to cephalosporin antibiotics

Special warnings and precautions for use

Special care is indicated in patients who have experienced an allergic reaction to penicillins or 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. Clinical experience with Cefuroxime for Injection has shown that this is not likely to be a problem at the recommended dose levels.

There may be some variation on the results of biochemical tests of renal function, but these do not appear to be of clinical importance. As a precaution, renal function should be monitored if this is already impaired.

Delayed sterilisation of the CS in patients with Haemophilus influenzae meningitis may result in an adverse outcome such as deafness and /or neurological sequelae. Persistence of positive CS cultures of H. influenzae at 18-36 hours has been noted in some patients treated with Cefuroxime for Injection injection and, as with other therapeutic regimens used in the treatment of meningitis, hearing loss has been reported in some children.

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. The change to oral therapy should only be made once there is a clear clinical improvement. If there has been no clinical improvement after 72 hours of parenteral treatment, then the patient’s treatment should be reviewed. Please refer to the relevant prescribing information for cefuroxime axetil before initiating sequential therapy.

As with other antibiotics, prolonged use of cefuroxime may result in the overgrowth of non-susceptible organisms (e.g. Candida, enterococci, Clostridium difficile), which may require interruption of treatment.

Interaction with other medicinal products and other forms of interaction.

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

As with other cephalosporin antibiotics in combination with potent diuretics such as furosemide or aminoglycosides, Cefuroxime for Injection may adversely affect renal function.

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

Pregnancy and lactation

There is no experimental evidence of embryopathic or teratogenic effects attributable to Cefuroxime for Injection 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 Cefuroxime for Injection is administered to a nursing mother.

Effects on ability to drive and use machines

None reported.

Undesirable effects

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 Cefuroxime for Injection 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 <1/1000) 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 and <1/10, uncommon ≥ 1/1000 and <1/100, rare ≥ 1/10,000 and <1/1000, very rare <1/10,000.

Infections and infestations
Rare	Candida overgrowth from prolonged use.
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.

Uncommon	Gastrointestinal disturbance.
Very Rare	Pseudomembranous colitis.
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 also Immune system disorders.

General disorders and administration site conditions
Common	Injection site reactions which may include pain and thrombophlebtiis

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

Overdose

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

Pharmacological Properties

Pharmacodynamic properties

Cefuroxime 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 highly active against Staphylococcus aureus, including strains which are resistant to penicillin (but not the rare methicillin resistant strains), Staph. epidermidis, Haemophilus influenzae, Klebsiella spp., Enterobacter spp., Streptococcus pyogenes, Escherichia coli, Str. mitis (viridans group), Clostridium spp., Proteus mirab ilis, Pr. rettgeri, Salmonella typhi, S. typhimurium and other Salmonella spp., Shigella spp., Neisseria spp. (including beta-lactamase producing strains of N. gonorrhoea) and Bordetella pertussis. It is also moderately active against strains of Pr. vulgaris, Morganella morganii (formerly Protes morgani and Bacteroides fragilis.

The following organisms are not susceptible to cefuroxime: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetob acter calcoaceticus, Legionella spp. and methicillin-resistant strains of Staph. aureus and Staph. epidermidis.

Some strains of the following genera have also been found notto be susceptible to Cefuroxime for Injection:

Strep. faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp., Citrobacter spp., Serratia spp. and Bacteroides fragilis.

In vitro the activities of Cefuroxime for Injection and aminoglycoside antibiotics in combination have been shown to be at least additive with occasional evidence of synergy.

Pharmacokinetic properties

Peak levels of cefuroxime are achieved within 30 to 45 minutes after intramuscular administration. The serum half-life after either intramuscular or intravenous injection is approximately 70 minutes. Concurrent administration of probenecid prolongs the excretion of the antibiotic and produces an elevated peak serum level. There is almost complete recovery of unchanged cefuroxime in the urine within 24 hours of administration, the major part being eliminated in the first six hours. Approximately 50% is excreted through the renal tubules and approximately 50% by glomerular filtration. Concentrations of cefuroxime in excess of the minimum inhibitory levels for common pathogens can be achieved in bone, synovial fluid and aqueous humor. Cefuroxime passes the blood-brain barrier when the meninges are inflamed.

Preclinical safety data

Not stated

Pharmaceutical Particulars

List of excipients

None

Incompatibilities

None

Shelf life

ZIFTUM 1.5 g: 36 months

ZIFTUM 750 mg: 24 months

Storage:

Store in a dry place at temperature below 30°C.

Protected from light.

Nature and contents of container

Ziftum 750 mg Injection: 10 mL vials of clear glass closed with rubber stopper and PP disk.

Ziftum 1.5 g njection: 15 mL vials of clear glass closed with rubber stopper and PP disk.

Presentation

1 x 750 mg/1 x 1.5 g vial in a carton with SWFI & pack insert.

 

Updated on 9/Feb/2024