Summary of Product Characteristics (SmPC) - Cefradine 500 mg capsules
1 NAME OF THE MEDICINAL PRODUCT
Cefradine 500mg Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains cefradine monohydrate equivalent to 500mg cefradine.
Excipient(s) with known effect: lactose monohydrate.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Capsule, hard.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Cefradine 500mg 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 500mg 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.
4.2 Posology and method of administration
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:
Creatinine Clearance Dose Time interval
More than 20ml/min 500mg 6 hours
5-20ml/min 250mg 6 hours
less than 5 ml/min 250mg 50-70 hours
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, total 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).
4.6 Fertility, Pregnancy and lactation
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
Since the medicine may cause dizziness, patients should be cautioned about operating hazardous machinery, including automobiles.
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
Rarely: Vomiting, abdominal discomfort,
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 or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
The symptoms of cefradine overdose are non-specific and are generally nausea, vomiting, diarrhoea and gastric upsets. Treatment is mainly supportive although gastric lavage will be necessary if a large amount has been ingested.
5 PHARMACOLOGICAL PROPERTIES
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 β-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)
Indigo carmine (E132)
6.2 Incompatibilities
None.
6.3 Shelf life
24 months.
6.4 Special precautions for storage
Do not store above 25oC.
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
Kent Pharma UK Limited,
2nd Floor, Connect 38,
1, Dover Place,
Ashford,
Kent,
TN23 1FB
England,
8 MARKETING AUTHORISATION NUMBER(S)
PL 51463/0114
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
8 January 2003
10 DATE OF REVISION OF THE TEXT
15/01/2024