VELOSEF CAPSULES 250MG & 500MG

VELOSEF SYRUP 250MG/5ML

Capsules 250mg: Opaque, orange body with opaque blue cap printed Squibb and 113 in white on each half. Each capsule contains 250mg cefradine.

Capsules 500mg: Opaque blue printed in white with Squibb and 114 on each half. Each capsule contains 500mg cefradine.

Syrup 250mg/5ml: When reconstituted contains 250mg cefradine per 5 ml.

Oral Capsules.

Oral powder for reconstitution.

In the treatment of infections of the urinary and respiratory tracts and of the 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 tissue infections - abscess, cellulitis, furunculosis, impetigo.

Cefradine has been shown to be effective in reducing the incidence of postoperative infections in patients undergoing surgical procedures associated with a high risk of infection. It is also of value where postoperative 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, cefradine should be administered immediately prior to surgery and continued during the postoperative period.

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

Cefradine may be given without regard to meals.

Adults:

For urinary tract infections the usual dose is 500mg four times daily or 1g twice daily; severe or chronic infections may require larger doses. Prolonged intensive therapy is needed for complications such as prostatitis and epididymitis. For respiratory tract infections and skin and soft tissue infections the usual dose is 250mg or 500mg four times daily or 500mg or 1g twice daily depending on the severity and site of infections.

Children:

The usual dose is from 25 to 50mg/kg/day total, given in two or four equally divided doses.

For otitis media daily doses from 75 to 100mg/kg in divided doses every 6 to 12 hours are recommended. Maximum dose 4g per day.

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.

All patients, irrespective of age and weight

Larger doses (up to 1g four times daily) may be given for severe or chronic infections. 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 haemolytic strains of streptococci, a minimum of 10 days' treatment is recommended to guard against the risk of rheumatic fever or glomerulonephritis. In the treatment of chronic urinary tract infections, frequent bacteriological and clinical appraisal is necessary during therapy and may be necessary for several months afterwards. Persistent infections may require treatment for several weeks. Smaller doses than those indicated above should not be used. Doses for children should not exceed doses recommended for adults. As cefradine is available in both injectable and oral form, patients may be changed from the cefradine injectable to cefradine oral at the same dosage level.

Renal Impairment Dosage:

Patients not on dialysis:

The following dosage schedule is suggested as a guideline based on a dosage of 500mg Q6H and on creatinine clearance. Further modification in the dosage schedule may be required because of the dosage selected and individual variation.

Patients on chronic, intermittent haemodialysis:

Further modification of the dosage schedule may be necessary in children.

Patients with known hypersensitivity to the cephalosporin antibiotics or to any component of the formulation.

There is evidence of partial cross-allergenicity between the penicillins and the cephalosporins. Therefore cefradine 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).

Dosage should be reduced in renal failure (see Section 4.2.).

After treatment with cefradine, 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*.

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

Loop diuretics may increase nephrotoxicity of cephalosporins.

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

Although animal studies have not demonstrated any teratogenicity, safety in pregnancy has not been established. Cefradine is excreted in breast milk and should be used with caution in lactating mothers.

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

Limited essentially to gastro-intestinal disturbances and on occasion to hypersensitivity phenomena. The latter are more likely to occur in individuals who have previously demonstrated hypersensitivity and those with a history of allergy, asthma, hay fever or urticaria. The majority of reported side-effects have been mild and are rare, and include glossitis, heartburn, dizziness, tightness in the chest, headache, nausea, vomiting, diarrhoea, abdominal pain, vaginitis, candidal overgrowth. Skin and hypersensitivity reactions include urticaria, pruritus, skin rashes, fever, athralgia and oedema.

As with other cephalosporins, there have been rare reports of erythema multiforme, Stevens Johnson Syndrome, anaphylaxis and toxic epidermal necrolysis. Also, mild transient eosinophilia, leucopenia and neutropenia, rarely positive direct Coombs tests and pseudomembraneous colitis have been reported.

Elevations of BUN and serum creatinine and reversible interstitial nephritis have been reported. Transient hepatitis and cholestatic jaundice have been reported very rarely. Elevations of ALT, AST, total bilirubin and alkaline phosphatase have been observed.

None known.

Actions:

Cefradine 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 cefradine.

Gram-positive - Staphylococci (both penicillin sensitive and resistant strains), Streptococci, Streptococcus pyogenes (beta-haemolytic) and Streptococcus pneumoniae.

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

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

Cefradine has a high degree of stability to many beta-lactamases. It has a low degree of protein-binding and a large volume of distribution. Therefore, tissue levels are generally found to be high. Oral cefradine can be given twice or four times daily, and is well absorbed.

Human Pharmacology: Cefradine is acid stable and is rapidly absorbed following oral administration in the fasting state. Following doses of 250mg, 500mg and 1000mg average peak serum levels of approximately 9, 16.5, and 24.2 micrograms/ml, respectively, were obtained at one hour. The presence of food in the gastrointestinal tract delays the absorption but does not affect the total amount of cefradine absorbed. Measurable serum levels are present six hours after administration. Over 90% of the drug is excreted unchanged in the urine within 6 hours. Peak urine concentrations are approximately 1600 micrograms/ml following a 250mg dose, 3200 micrograms/ml following a 500mg dose, and 4000 micrograms/ml following a 1000mg dose. After 48 hours' administration of 100mg/kg/day of cefradine for the treatment of otitis media, cefradine has been measured in the middle ear exudate at an average level of 3.6 microgram/ml.

No relevant further data available.

Capsules 250mg: Erythrosine, gelatin capsules, indigo carmine, iron oxide, lactose, magnesium stearate, titanium dioxide.

Capsules 500mg: Gelatin capsules, indigo carmine, lactose, magnesium stearate, titanium dioxide.

Syrup: Citric acid, blood orange flavour, cinnamon flavour and tutti frutti flavour, guar gum, methylcellulose, sodium citrate, sucrose.

None known

Not applicable

E. R. Squibb & Sons Limited

Uxbridge Business Park

Sanderson Road

Uxbridge

Middlesex

UB8 1DH

June 2005