Summary of Product Characteristics (SmPC) - Ceporex tablets 500 mg
1 NAME OF THE MEDICINAL PRODUCT
Ceporex Tablets 500mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Cefalexin Ph. Eur. 500mg per tablet
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet
4.1 Therapeutic indications
Ceporex is a semisynthetic cephalosporin antibiotic for oral administration. It is indicated in the treatment of the following, infection due to susceptible micro organisms:
Respiratory tract infections:
Otitis media.
Skin and soft tissue infections.
Bone and joint infections
Genito urinary tract infections, including acute
prostatitis
Dental infections.
4.2 Posology and method of administration
Posology
Adults
The adult dosage ranges from 1-4g daily in divided doses; most infections will respond to a dosage of 500 mg every 8 hours. For skin and soft tissue infections, streptococcal pharyngitis and mild, uncomplicated urinary tract infections, the usual dosage is 250 mg every 6 hours, or 500 mg every 12 hours.
For more severe infections or those caused by less susceptible organisms, larger doses may be needed. If daily doses of cefalexin greater than 4g are required, parenteral cephalosporins, in appropriate doses, should be considered.
The elderly and patients with impaired renal function As for adults. Reduce dosage if renal function is markedly impaired (see section 4.4).
Paediatric population
The usual recommended daily dosage for children is 25-50 mg/kg (10-20 mg/lb) in divided doses. For skin and soft tissue infections, streptococcal pharyngitis and mild, uncomplicated urinary tract infections, the total daily dose may be divided and administered every 12 hours. For most infections the following schedule is suggested:
Children under 5 years: 125 mg every 8 hours.
Children 5 years and over: 250 mg every 8 hours.
In severe infections, the dosage may be doubled. In the therapy of otitis media, clinical studies have shown that a dosage of 75 to 100 mg/kg/day in 4 divided doses is required.
In the treatment of beta-haemolytic streptococcal infections, a therapeutic dose should be administered for at least 10 days.
Method of administration
For oral use
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Cefalexin is contra-
indicated in patients with known allergy to the
cephalosporin group of antibiotics.
4.4 Special warnings and precautions for use
Before instituting therapy with cefalexin, every effort should be made to determine whether the patient has had previous hypersensitivity reactions to the cephalosporins, penicillins or other drugs. Cefalexin should be given cautiously to penicillin-sensitive patients, There is some clinical and laboratory evidence of partial cross- allergenicity of the penicillins and cephalosporins. Patients have had severe reactions (including anaphylaxis) to both drugs.
Pseudomembranous colitis has been reported with virtually all broad-spectrum antibiotics, including macrolides, semisynthetic penicillins and cephalosporins. It is important, therefore, to consider its diagnosis in patients who develop diarrhoea in association with the use of antibiotics. Such colitis may range in severity from mild to life-threatening. Mild cases of pseudomembranous colitis usually respond to drug discontinuance alone. In moderate to severe cases, appropriate measures should be taken.
If an allergic reaction to cefalexin occurs, the drug should be discontinued and the patient treated with the appropriate agents.
Prolonged use of cefalexin may result in the overgrowth of non-susceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Reports of neurotoxicity have been identified in association with cephalosporin treatment. Symptoms may include encephalopathy, myoclonus and seizures. Elderly patients, patients with severe renal impairment or central nervous system disorders are particularly at risk. Cefalexin should be administered with caution in the presence of markedly impaired renal function. Careful clinical and laboratory studies should be made because safe dosage may be lower than that usually recommended. If dialysis is required for renal failure, the daily dose of cefalexin should not exceed 500mg. If cefalexin associated neurotoxicity is suspected, discontinuation of cefalexin should be considered
Concurrent administration with certain other drug substances, such as aminoglycosides, other cephalosporins, or furosemide, (frusemide) and similar potent diuretics, may increase the risk of nephrotoxicity.
Positive direct Coombs' tests have been reported during treatment with the cephalosporin antibiotics. In haematological studies, or in transfusion cross- matching procedures when antiglobulin tests are performed on the minor side, or in Coombs' testing of newborns whose mothers have received cephalosporin antibiotics before parturition, it should be recognised that a positive Coombs' test may be due to the drug.
A false positive reaction for glucose in the urine may occur with Benedict’s or Fehling’s solutions or with copper sulphate test tablets.
Acute generalised exanthematous pustulosis (AGEP) has been reported in association with cefalexin treatment. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, cefalexin should be withdrawn immediately and an alternative treatment considered. Most of these reactions occurred most likely in the first week during treatment.
4.5 Interaction with other medicinal products and other forms of
interaction
As with other beta-lactam drugs, renal excretion of cefalexin is inhibited by probenecid.
In a single study of 12 healthy subjects given single 500 mg doses of cefalexin and metformin, plasma metformin Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin renal clearance decreased by an average of 14%. No side-effects were reported in the 12 healthy subjects in this study. No information is available about the interaction of cefalexin and metformin following multiple dose administration. The clinical significance of this study is unclear, particularly as no cases of “lactic acidosis” have been reported in association with concomitant metformin and cefalexin treatment.
Hypokalaemia has been described in patient taking cytotoxic drugs for leukaemia when they were given gentamicin and cefalexin.
4.6 Fertility, pregnancy
and lactation
Pregnancy
Although laboratory and clinical studies have shown no evidence of teratogenicity, caution should be exercised when prescribing for the pregnant patient.
Breast-feeding
The excretion of cefalexin in human breast milk increased up to 4 hours following a 500mg dose. The drug reached a maximum level of 4 micrograms/ml, then decreased gradually and had disappeared 8 hours after administration. Caution should be exercised when cefalexin is administered to a nursing woman, since the neonate is presented with the risk of candidiasis and CNS toxicity due to immaturity of the blood-brain barrier. There is a theoretical possibility of later sensitisation.
4.7 Effects on ability to drive and use machines
Not relevant.
4.8 Undesirable effects
Gastro-intestinal:
Symptoms of pseudomembranous colitis may appear either during or after antibiotic treatment. Nausea and vomiting have been reported rarely. The most frequent side-effect has been diarrhoea. It was very rarely severe enough to warrant cessation of therapy. Dyspepsia and abdominal pain have also occurred. As with some penicillins and some other cephalosporins transient hepatitis and cholestatic jaundice. have been reported rarely.
Hype
rsensi
tivity
Allergic reactions observed in the form of rash, urticaria, angioedema, and rarelyerythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis, These reactions usually subsided upon discontinuation of the drug, although in some cases supportive therapy may be necessary. Anaphylaxis has also been reported.
Haemic and Lymphatic System: Eosinophilia, neutropenia, thrombocytopenia and haemolytic anaemia have been reported.
Skin and subcutaneous tissue disorders
Acute generalised exanthematous pustulosis (AGEP) (has been reported with unknown frequency)
Other
These have included genital and anal pruritus, genital candidiasis, vaginitis and vaginal discharge, dizziness, fatigue, headache, agitation, confusion, hallucinations, arthralgia, arthritis and, joint disorder and acute generalized exanthematous pustulosis (AGEP). Reversible interstitial nephritis has been reported rarely. Slight elevations in AST and ALT have been reported. There have been reports of neurological sequelae including tremor, myoclonia, convulsions, encephalopathy with drugs belonging to the class of cephalosporins. Most cases occurred in patients with renal impairment who received doses that exceeded the recommended dose and resolved following discontinuation of treatment.
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: Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
Symptoms of oral overdose may include nausea, vomiting, epigastric distress, diarrhoea and haematuria.
In the event of severe overdosage, general supportive care is recommended, including close clinical and laboratory monitoring of haematological, renal and hepatic functions, and coagulation status until the patient is stable. Forced diuresis, peritoneal dialysis, haemodialysis, or charcoal haemoperfusion have not been established as beneficial for an overdose of cefalexin. It would be extremely unlikely that one of these procedures would be indicated.
Unless 5 to 10 times the normal total daily dose has been ingested, gastro- intestinal decontamination should not be necessary.
There have been reports of haematuria without impairment of renal function in children accidentally ingesting more than 3.5g of cefalexin in a day.
Treatment has been supportive (fluids) and no sequelae have been reported.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antibacterials for systemic use, first-generation cephalosporins, ATC code: J01DB01.
In vitro tests demonstrate that cephalosporins are bactericidal because of their inhibition of cell-wall synthesis.
Cefalexin is active against the following organisms in vitro: Beta-haemolytic streptococci
Staphylococci, including coagulase-positive, coagulase-negative and penicillinase- producing strains.
Streptococcus pneumoniae
Escherichia coli
Proteus mirabilis
Klebsiella species
Haemophilus influenzae
Branhamella catarrhalis
Most strains of enterococci (Streptococcus faecalis) and a few strains of staphylococci are resistant to cefalexin. It is not active against most strains of Enterobacter species, Morganella morganii and Pr. vulgaris. It has no activity against Pseudomonas or Herellea species or Acinetobacter calcoaeticus. Penicillin-resistant Streptococcus pneumoniae is usually cross-resistant to beta-lactam antibiotics. When tested by in-vitro methods, staphylococci exhibit cross-resistance between cefalexin and methicillin-type antibiotics.
5.2 Pharmacokinetic properties
Absorption
Human pharmacology - cefalexin is acid stable and may be given without regard to meals. It is rapidly absorbed after oral administration. Following doses of 250 mg, 500 mg and 1g, average peak serum levels of approximately 9, 18 and 32 mg/L respectively were obtained at 1 hour. Measurable levels were present 6 hours after administration.
Cefalexin is almost completely absorbed from the gastro-intestinal tract, and 75-100% is rapidly excreted in active form in the urine. Absorption is slightly reduced if the drug is administered with food. The half-life is approximately 60 minutes in patients with normal renal function,
Haemodialysis and peritoneal dialysis will remove cefalexin from the blood
Distribution
Peak blood levels are achieved one hour after administration, and therapeutic levels are maintained for 6-8 hours. Approximately 80% of the active drug is excreted in the urine within 6 hours. No accumulation is seen with dosages above the therapeutic maximum of 4 g/day.
The half-life may be increased in neonates due to their renal immaturity, but there is no accumulation when given at up to 50 mg/kg/day.
Elimination
Cefalexin is not excreated in the urine by glomerular filtration and tubular secretion. Studies showed that over 90% of the drug was excreted unchanged in the urine. within 8 hours. During this period peak urine
following the 250 mg, 500 mg and 1 g doses were approximately 1000, 2200 and 5000 mg/L respectively.
5.3 Preclinical safety data
The daily oral administration of cefalexin to rats in doses of 250 or 500mg/kg prior to and during pregnancy, or to rats and mice during the period of organogenesis only, had no adverse effect on fertility, foetal viability, foetal weight, or litter size.
Cefalexin showed no enhanced toxicity in weanling and newborn rats as compared with adult animals.
The oral LD50 of cefalexin in rats is 5,000mg/kg.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Microcrystalline Cellulose EP
Magnesium Stearate EP
Film-Coating:
Hydroxypropyl
methylcellulose
EP
Macrogol 400 EP
Opadry OY-S-6927 In-House
Purified Water BP
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
36 months
6.4 Special precautions for storage
The product is stored at a temperature not exceeding 30°C, protected from light.
6.5 Nature and contents of container
- 1) Tubular glass vial with polyethene snap-plug closure.
- 2) Tamper evident polypropylene container with low density polyethylene lid. One or more cartridges of activated charcoal according to pack size are included.
- 3) Tablets are sealed into individual pockets in an aluminium polyethylene/ foil laminate (30 and 38 micrometres respectively).
- 4) Tablets are sealed into individual pockets in an aluminium foil blister with an aluminium lid (43 and 20 micrometres respectively).
All container presentations contain 20, 21, 28, 100 or 500 tablets.
6.6 Special precautions for disposal
None stated
7. MARKETING AUTHORISATION HOLDER
Crescent Pharma Limited
Key House, Sarum Hill,
Basingstoke, RG21 8SR,
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 20416/0648
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
March 1970
10 DATE OF REVISION OF THE TEXT
07/02/2025