SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Cefradine 250mg Capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 250mg cefradine anhydrous

For excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Capsule, hard.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Cefradine 250mg Capsules are used in the treatment of bacterial infections of the respiratory and urinary tracts and of the skin and soft tissues. These include the following:

Upper respiratory tract infections - sinusitis, pharyngitis, tonsillitis, laryngo-tracheo bronchitis and otitis media.

Lower respiratory tract infections - acute and chronic bronchitis, lobar and bronchopneumonia.

Urinary tract infections - cystitis, urethritis and pyelonephritis.

Skin and soft tissue infections - impetigo, abscess, cellulitis, furunculosis.

Cefradine 250mg Capsules are also used in the prophylaxis of postoperative infections following surgical procedures associated with a high risk of infection and for patients with a reduced host resistance to bacterial infection. Cefradine should be administered immediately prior to surgery in order to ensure sufficient local tissue concentrations at the time that contamination is likely to occur. Treatment should be continued during the post operative period.

Laboratory testing should be carried out to determine the causative agents and their sensitivity to cefradine. However, therapy may commence prior to receipt of the sensitivity test results.

Posology

Adults

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 infection.

Urinary tract infections - the usual dose is 500mg four times daily or 1g twice daily. This may need to be increased for severe or chronic infections. Prolonged intensive therapy is needed for complications such as prostatitis and epididymitis.

Elderly

As for adults. Patients with impaired renal or hepatic function should be monitored as modifications of the dosage schedule may be required.

Paediatric population

The usual dose is 25 to 50 mg/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.

Cefradine may be taken without regard to meals.

All patients irrespective of age and weight: In the case of severe or chronic infection larger doses of up to 1g four times daily may be given. Administration should be continued for a minimum of 48-72 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. For infections caused by haemolytic strains of streptococci, a minimum of 10 days treatment is recommended to guard against the risk of rheumatic fever or glomerulo-nephritis. For 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 those recommended for adults. As cefradine is available in both injectable and oral forms, patients may be changed from injection to capsules at the same dosage level.

Dosage in renal impairment:

For patients not on dialysis: The following dosage schedule guideline is based on a dosage of 500mg 6 hourly and on creatinine clearance:

Adjustments to the dosage schedule provided may be necessary because of the dosage selected and individual variation.

For patients on chronic, intermittent haemodialysis:

250mg    At start of haemodialysis

250mg    6-12 hours after start

250mg    36-48 hours after start

250mg    At start of next haemodialysis if >30 hours after previous dose.

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

4.3 Contraindications

Hypersensitivity to the active substance or to any or the excipients listed in section 6.1

4.4 Special warnings and precautions for use

Following administration of 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. This does not occur with enzyme based tests such as Clinistix or Diastix.

Prolonged use of antibiotics may result in overgrowth of non-susceptible organisms.

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

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Loop diuretics may increase nephrotoxicity of cephalosporins.

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

There is evidence of partial 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).

Fertility

Although animal studies have shown no teratogenic effects, safety in pregnancy has not been established.

Pregnancy

As with all medicines, use should be avoided in pregnancy especially in the first trimester, unless considered essential by the physician.

Breast-feeding

Cefradine is excreted in breast milk and therefore should be used with caution in lactating mothers.

4.7 Effects on ability to drive and use machines

Cefradine has no or negligible influence on the ability to drive or use machines.

4.8 Undesirable effects

Undesirable effects are uncommon and mainly mild in nature. They are limited essentially to gastrointestinal disturbances and on occasion to hypersensitivity phenomena.

Infections and infestations

Rarely:    Antibiotic-associated colitis

Frequency unknown: Vaginitis, candidal overgrowth, candidiasis

Blood and lymphatic system disorders

Frequency unknown: Eosinophilia, blood disorders (including thrombocytopenia,

leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia)

Immune system disorders

Frequency unknown: Fever, athralgia, serum sickness-like reactions, anaphylaxis Psychiatric disorders

Frequency unknown: Confusion, sleep disturbances Nervous system disorders

Frequency unknown: Hypersensitivity, hyperactivity, hypertonia, dizziness,

nervousness

Rarely:    Headache

Gastrointestinal disorders

Frequency unknown: Diarrhoea, nausea, glossitis, heartburn

Hepatobiliary disorders

Frequency unknown: Liver, enzyme disturbances, transient hepatitis, cholestatic jaundice

Skin and subcutaneous tissue disorders

Frequency unknown: Rashes, toxic epidermal necrolysis, pruritis, urticaria, erythema

multiforme, Stevens-Johnson syndrome, oedema

Renal and urinary disorders

Frequency unknown: Reversible interstitial nephritis

General disorders and administration site conditions Frequency unknown: Tightness in the chest

Investigations

Frequency unknown:    Elevation of blood urea nitrogen, serum creatinine, alanine

aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphates, positive direct Coombs’ test

Musculoskeletal and connective tissue disorder Frequency unknown: joint pain

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

None known.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: first generation cephalosporin, ATC code: J01DB09 Mechanism of action

Cefradine is a broad-spectrum, bactericidal first generation

cephalosporin antibiotic active against both Gram-positive and Gram-negative

bacteria. It is also highly active against most strains of

penicillinase producing Staphylococci. The anti-bacterial action of cefradine is through inhibition of bacterial cell wall synthesis, probably by acylation of membrane - bound transpeptidase enzymes. This prevents cross-linkage of peptidoglycan chains which is necessary for bacterial cell wall strength and rigidity.

Susceptibility : The following organisms have shown in vitro sensitivity to Cefradine.

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

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

Insusceptible microorganisms:

The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections.

In general, bacterial resistance to cephalosporins usually results both from the production of a P-lactamase and the presence of permeability barriers to the drug.

5.2 Pharmacokinetic properties

Absorption

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. Cefradine is acid stable and is rapidly absorbed following oral administration in the fasting state.

Distribution

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.

Elimination

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.

5.3 Preclinical safety data

There are no preclinical safety data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Magnesium stearate Lactose monohydrate

The capsule shell contains:

Gelatin

Titanium dioxide (E171)

Yellow iron oxide (E172)

Erythrosin (E127)

Indigo carmine (E132)

6.2 Incompatibilities

None.

6.3 Shelf life

24 months.

6.4 Special precautions for storage

Do not store above 25^oC.

6.5 Nature and contents of container

PVC/PVDC blister foil, 0.25 +/- 5% mm thick with an aluminium lidding foil 0.025 mm thick containing 10, 20 or 100 capsules.

6.6 Special precautions for disposal

No special instructions.

7 MARKETING AUTHORISATION HOLDER

Athlone Pharmaceuticals Limited

Ballymurray

Co. Roscommon

Ireland

8    MARKETING AUTHORISATION NUMBER(S)

PL 30464/0086

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

24/02/2010

10 DATE OF REVISION OF THE TEXT

13/05/2016