Each vial contains: 

Cephradine ……………...............................................................…………………………. 500 mg or 1 g

(As cephradine with L-arginine).

CEPHRADINE is indicated for the treatment of infections of the urinary and respiratory tracts and of skin and soft tissues, these include:

Upper respiratory infections: Pharyngitis, sinusitis, otitis media, tonsillitis, laryngo-tracheo bronchitis. 

Lower respiratory infections: Acute and chronic bronchitis, lobar and bronchopneumonia. 

Urinary tract infections: Cystitis, urethritis, pyelonephritis. 

Skin and Soft tissuse infections: Abscess, cellulitis, furunculosis, impetigo.

Cephradine has been shown to be effective in reducing the incidence of post-operative infections in patients undergoing surgical procedures associated with a high risk of infection, it is also of value where post-operative infections would be disastrous and where patients have a reduced host resistance to bacterial infection. Protection is best ensured by achieving adequate local tissue concentrations at the time contamination is likely to occur. Thus, CEPHRADINE should be administered immediately prior to surgery and treatment should be continued during the post-operative period.

Bacteriological studies to determine the causative organisms and their sensitivity to cephradine should be performed. Therapy may be instituted prior to receiving the results of the sensitivity test.

CEPHRADINE Parentral formulations: 

For the treatment of: 

Bone and joint infections. 

Septicaemia and endocarditis.

Sterile CEPHRADINE for injection is indicated primarily for those patients unable to tolerate oral medication. 

CEPHRADINE is also indicated for intravenous use either by direct injection or by intravenous infusion for the treatment of serious and life-threatening infections.

As with antibiotic treatment in general, therapy should be continued for a minimum of 48-72 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained.

In infections caused by group A beta-hemolytic streptococci, a minimum of 10 days of treatment is recommended to guard against the risk of rheumatic fever or glomerulo-nephritis.

In the treatment of Chronic urinary tract infections, frequent bacteriologic and clinical appraisal is necessary during therapy and may be necessary for several months afterwards. Persistent infections may require treatment for several weeks. Doses smaller than those indicated above should not be used.

Parenteral therapy may be followed by oral cephradine.

Routes of Administration: 

For Intramuscular use.

For Intravenous use.

CEPHRADINE may be given intravenously or by deep intramuscular injection.

To minimize pain and induration, intramuscular injections should be made into a large muscle mass, such as the gluteus or lateral aspect of the thigh. Reference is made to the use of local anaesthetics in the section on Use and Handling.

Since sterile abscesses have been reported following accidental subcutaneous injection, the preparation should be administered by deep intramuscular injection (see Undesirabe Effects).

Intravenously, CEPHRADINE may be administered by either direct intravenous injection or by intravenous infusion.

For direct intravenous injection, the solution may be slowly injected directly into a vein over a 3-5 minute period or may be given as a supplementary injection through the injection site on an administration set when the infusion solution is compatible with CEPHRADINE.

For Usage Instructions, see Use and Handling.

Adults: 

The Usual Daily Dose is 2-4 g daily in four equally divided doses intramuscularly or intravenously (e.g. 500 mg to 1 g four times a day).

A dosage of 500 mg four times a day is adequate in uncomplicated pneumonia, skin and skin structure infections, and most urinary tract infections.

In bone infections: the usual dosage is 1 g four times a day administered intravenously.

In severe infections such as endocarditis, 2 g four times a day given intravenously is recommended. Alternatively, in severe infections, the dose may be increased by giving injections every four hours. The maximum dose should not exceed 8 g per day.

Prophylaxis: 

To prevent post-operative infection in contaminated or potentially contaminated surgery, recommended doses are as follows:

1-2 g intravenously or intramuscularly.

1 g every 4-6 hours after the first dose for one to two doses, or for up to 24 hours post-operatively.

Prophylaxis in Caesarean section: 

The first dose of 1 g is administered intravenously as soon as the umbilical cord is clamped. The second and third doses should be given as l g intravenously or intramuscularly at 6 and 12 hours after the first dose.

Children: 

The usual dose range is 50-100 mg/kg/day (approximately 23-45 mg/lb/day) in equally divided doses four times a day and should be regulated by age, weight of the patient, and severity of the infection being treated. The maximum pediatric daily dose should not exceed the dose recommended for adults (see Warnings and Precautions).

Elderly: 

There are no specific dosage recommendations or precautions for use in the elderly except, as with other drugs, to monitor those patients with impaired renal or hepatic function.

Renal impairment: 

Patients not on dialysis: 

The following dosage schedule based on a dosage of 500 mg every 6 hours and on creatinine clearance is suggested as a guideline. Further modification in the dosage schedule may be required because of the dosage selected and individual variation.

Patients on Chronic, Intermittent Haemodialysis: 

250 mg start, 250 mg at 12 hours, 250 mg 36-48 hours (after start).

Children may require dosage modification proportional to their weight and severity of infection.

See also section Warnings and Precautions.

Hepatic Impairment: 

There are no relevant data available.

CEPHRADINE is contraindicated in: 

Patients with known hypersensitivity to the cephalosporin antibiolics or to any component of the product.

Previous immediate and/or severe hypersensitivity reaction to a penicillin or to any other beta-lactam medicinal products.

Renal impairment: 

Use of CEPHRADINE in patients with renal dysfunction should be monitored intensively. A modified dosage schedule in patients with decreased renal function is necessary (see Dosage and Administration).

False positive reaction for glucose: 

Following administration of cephradine, a false positive reaction for glucose in the urine may occur with Benedict's or Fehling's solution or with reagent tablets such as Clinitest, but not with enzyme-based tests such as Clinistix or Diastix.

Prolonged use: 

As with all antibiotics, prolonged use may result in overgrowth of non-susceptible organisms.

Hypersensitivity phenomena: 

Hypersensitivity phenomena are more likely to occur in individuals who have previously demonstrated hypersensitivity and those with a history of allergy, asthma, hay fever or urticaria (see Undesirabe Effects). Special caution is required to determine any other type of previously hypersensitivity reactions to penicillin or to other beta-lactam medicinal products because patients hypersensitive to these medicines may be hypersensitive to CEPHRADINE as well as (cross-allergy).

History of Colitis/Gastrointestinal disorders: 

CEPHRADINE should be used with caution in those patients with a known history of colitis/gastrointestinal disorders.

Pediatric use: As these products contain arginine they should be used with caution in pediatric population.

Use and Handling: 

For Intramuscular use: 

Aseptically add sterile Water for Injection or Bacteriostatic water for Injection according to the following table (Not for use in neonates if benzyl alcohol is the bacteriostat present.

Shake to effect solution and withdraw the required amount.

CEPHRADINE contains no bacteriostat and is not intended for multiple-dose use.

Solutions should be used within 2 hours if held at room temperature; if stored in the refrigerator (5°C), solutions retain full potency for 24 hours.

Reconstituted solutions may vary in colour from light to straw yellow; however, this does not affect the potency.

For Direct Intravenous Injection: 

Suitable intravenous injection diluents are: 

Sterile Water for injection.

5% Dextrose injection.

Sodium Chloride injection.

Aseptically add 5 ml of diluent to the 500 mg vials, 10 ml to the l g vial.

Shake to effect solution and withdraw the entire contents.

These solutions should be used within 2 hours when held at room temperature; if stored at 5°C, solutions retain full potency for 24 hours.

For Continuous or Intermittent Intravenous Infusion: 

Suitable intravenous infusion solutions for CEPHRADINE are: 

5 % or 10 % Dextrose injection.

Sodium Chloride injection.

Sodium Lactate injection (M/6 sodium lactate).

Dextrose and Sodium Chloride injection (5% : 0.9%)or (5% : 0.45%).

10% Invert Sugar in water for injection.

Normosol-R,

Ionosol B with Dextrose 5%.

Sterile Water for Injection may be used as an intravenous infusion solution for a cephradine concentration of 30 to 50 mg/ml (30 mg/ml is approximately isotonic).

To prepare CEPHRADINE for transfer into an intravenous infusion container, aseptically add 10 ml of Sterile Water for Injection, or a suitable infusion solution, to the 1 g vial, and shake to effect solution. Aseptically transfer the entire content to the intravenous infusion container.

For prolonged infusions, replace the infusion every 10 hours with a freshly prepared solulion.

Extemporaneous mixtures of CEPHRADINE with other antibiotics are not recommended.

Incompatibilities: 

There are no relevant data available.

Penicillins: 

There is evidence of partial cross-allergenicity between penicillins and cephalosporins. Therefore CEPHRADINE should be used with caution in those patients with known hypersensitivity to penicillins.

There have been instances of patients who have had reactions to both drug classes (including anaphylaxis) (see Undesirabe Effects).

Loop diuretics: 

Loop diuretics may increase nephrotoxicity of cephalosporins.

Probenecid: 

Probenecid has been seen to raise serum concentrations of cephradine, by reducing renal clearance of the cephalosporins.

Active drug substances of high molecular weight: These are incompatible with cephalosporins in parenteral mixtures.

Oral contraceptives: 

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

Warfarin: 

The concomitant use of cephradine with warfarin may result in increased INR and thereby increase the risk for bleeding. The mechanism of the interaction appears to involve alterations in intestinal flora that synthesis vilamin K. In a nested case-control study, there was an association between cephalosporin use in patients on warfarin therapy and an increased risk of bleeding. When possible, substitute an antibiotic with a low-risk profile for bleeding. If concomitant use is deemed necessary, more frequent monitoring of INR is recommended especially during initiation and discontinuation of the antibiotic.

Live Typhoid Vaccine: 

CEPHRADINE, like other antibiotics with antibacterial activity against Salmonella typhi organisms, may interfere with the immunological response of the live typhoid vaccine. The appropriate period of time (24 hours or more) should elapse between the administration of the last dose of the antibiotic and the live typhoid vaccine.

Pregnancy: 

CEPHRADINE should not be used during pregnancy unless considered essential by the physician.

Although animal studies have not demonstrated any teratogenicity, safety in pregnancy has not been established.

Lactation: 

CEPHRADINE should not be used during Lactation unless considered essential by the physician.

Cephradine is excreted in breast milk (see Warnings and Precautions).

Fertility: 

There are no relevant data available.

Since this medicine may cause dizziness, patients should be cautioned about operating hazardous machinery, including automobiles.

Clinical Trial Data: Not relevant for this product.

Post Marketing Data: 

Adverse reactions are ranked under headings of frequency using the following convention: Very common: (≥1/10); Common: (≥1/100 to<1/10); Uncommon: (≥1/1000 to <1/100); Rare: (≥1/10000 to <1/1000); (Very rare <1/10000); Not known (cannot be estimated from the available data).

Infections and Infestations: 

Not known: Vaginal infection, candidiasis, pseudomembranous colitis.

Blood and Lymphatic system disorders: 

Not known: Eosinophilia, leukopenia, neutropenia, Coombs direct test positive.

Immune system disorders: 

Not known: Hypersensitivity (see Skin and subcutaneous tissue disorders), anaphylactic reaction.

Nervous system disorders: 

Not known: Dizziness, headache.

Gastrointestinal disorders: 

Not known: Glossitis, dyspepsia, nausea, vomiting, diarrhoea, abdominal pain, gastrointestinal disorder.

Hepatobiliary disorders: 

Not known: Hepatitis, cholestatic jaundice, increased alanine aminotransferase, increased aspartate aminotransferase, increased blood bilirubin, increased blood alkaline phosphatase.

Renal and Urinary disorders: 

Not known: Tubulointerstitial nephritis, increased blood urea, increased blood creatinine.

Skin and Subcutaneous tissue disorders: 

Not known: Erythema multiforme, Stevens Johnson syndrome, toxic epidermal necrolysis, urticaria, rash, pruritus.

Musculoskeletal and Connective tissue disorders: 

Not known: Arthralgia.

Respiratory disorders: 

Not known: Chest discomfort, oedema, pyrexia.

Vascular disorders: 

Not known: Thrombophlebitis.

General disorders and Administration site conditions: 

Not known: Injection site pain.

There are no relevant data available.

Pharmacodynamics: 

Pharmacotherapeutic group:  Anti-infectives for systemic use; First generation cephalosporins.

Mechanism of Action and Pharmacodynamic effects: 

Cephradine is a broad-spectrum, bactericidal antibiotic active against both Gram-positive and Gram-negative bacteria. It is also highly active against most strains of penicillinase-producing Staphylococci.

Microbiology: 

The following organisms have shown in vitro sensitivity to cephradine. 

Gram-positive: 

Staphylococci (both penicillin sensitive and resistant strains), Streptococci, Streptococcus pyogenes (beta haemolytic) and Streptococcus pneumonia.

Gram-negative: 

Escherichia coli, Klebsiella spp., Proteus mirabilis, Haemophilus influenzae, Shigella spp., Salmonella spp. (including Salmonella typhi) and Neisseria spp..

Because cephradine is unaffected by penicillinase, many strains of Escherichia coli and Staphylococcus aureus which produce this enzyme are susceptible to cephradine but resistant to ampicillin.

Pharmacokinetics: 

Absorption: Following intramuscular administration of a single 1 g dose of cephradine to normal volunteers, the average peak serum concentration was 15.1 ml at approximately 1 hour, and declined to 6.2 μg/ml at 3 hours and 1.5 μg/ml at 6 hours. A single 1 g intravenous dose resulted in serum concentrations of 86 μg/ml at 5 minutes and declined to 12 μg/ml at 1 hour and 1 μg/ml at 4 hours.

Continuous infusion of 500 mg per hour in a 70 kg man maintained a concentration of about 21.4 μg/ml cephradine activity. A serum concentration of approximately 3 μg/ml can be obtained for each milligram of cephradine administered per kg of body weight per hour of infusion.

Distribution: Measurable serum levels are present 6 hours after administration. 48 hours after the administration of 100 mg/kg/day of cephradine for treatment of otitis media, the average concentration of cephradine in middle ear exudates was 3.6 μg/ml.

Cephradine does not cross the blood-brain barrier to any appreciable extent.

Cephradine is minimally bound to serum proteins (8-17%). Assays of bone and cardiac tissue (atrial appendage) obtained at surgery have shown that cephradine penetrates these tissues.

Elimination: Cephradine is excreted unchanged in the urine. The kidneys excrete 57%-80% of an intramuscular dose in the first six hours; this results in a high urine concentration.

Clinical Studies: Not relevant for this product.

Non-clinical information:  There are no relevant data available.

Store at room temperature.

CEPHRADINE 500 mg Vials: Box containing 1 vial and 1 ampoule (5 ml) of Sterile Water for Injection solvent.

CEPHRADINE 1 g Vials: Box containing 1 vial and 2 ampoules (5 ml) of Sterile Water for Injection solvent.