Cefalexin Capsules 250mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Cefalexin Capsules BP 250 mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Cefalexin BP 250 mg Excipients
Each capsule contains 26.6 mg of lactose.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Capsules
Grey and orange Size 2 capsule containing white powder, printed CHX 250 with a twin triangle logo.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Cefalexin is indicated in the treatment of the following infections due to susceptible micro-organisms: respiratory tract infections; otitis media; skin and soft tissue infections; bone and joint infections; genito-urmary infections, including acute prostatitis; dental infections.
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. When tested by in vitro methods, staphylococci exhibit cross-resistance between cefalexin and metbicillin-type antibiotics.
4.2 Posology and method of administration
Route of administration: oral.
Many infections in adults will respond to oral dosage of 1 gram to 2 grams per day in divided doses; however, for most infections, the following simple dosage scheme will be found satisfactory:
Adults and children over 12 years: 1g b.d.
The following additional information should also be considered:
Adults:
The adult dosage ranges from 1-4 g 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 severe or deep-seated infections, especially when less sensitive organisms are involved, the dosage should be increased to 1g t.d.s. or 3g b.d.
For prophylaxis of recurrent urinary tract infections in adults, a dose of 125mg each night is recommended and may be continued for several months (other dosage formulations are available for this purpose).
If daily doses of cefalexin greater than 4 g are required parenteral cephalosporins, in appropriate doses, should be considered.
Elderly:
As for adults. Reduce dosage if renal function is markedly impaired.
Children:
The usual recommended daily dosage for children is 25-60 mg/kg/day (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 1 year (25 to 60mg/kg/day)
62.5 to 125mg b.d.
Children 1-6 years 250mg - 500mg b.d.
Children 7-12 years 500mg - 1g b.d.
In chronic, severe or deep-seated infections, the dosage may be doubled. In the therapy of otitis media, clinical studies have shown that a dosage of 75-100 mg/kg/day in 4 divided doses is required (maximum 4g/day). In the treatment of beta-haemolytic streptococcal infections, a therapeutic dose should be administered for at least 10 days.
Renal Impairment:
Cefalexin has not been shown to have a toxic effect on the kidney, but as with other antibiotics which are excreted mainly by the kidneys, unnecessary accumulation may occur in the body when renal function is below about half of normal. Therefore, the maximum recommended dosages (i.e. Adults 6g/day, children 4 g/day) should be reduced proportionately in these patients. Adult patients receiving intermittent dialysis should be given an additional 500mg cefalexin after each dialysis, i.e., a total dosage of up to 1g on that day. Children should receive an additional 8mg per kg.
Notes: For most acute infections, treatment should continue for at least two days after signs have returned to normal and symptoms have subsided, but in chronic, recurrent or complicated urinary tract infections, treatment for two weeks (giving 1g b.d.) is recommended. For gonorrhoea, a single dose of 3g with 1g probenecid for males or 2g with 0.5g probenecid for females is usually effective. Concurrent administration of probenecid delays excretion of cefalexin and raises the serum levels by 50 to 100%.
4.3 Contraindications
Cefalexin is contraindicated in patients with known allergy to the cephalosporins group of antibiotics.
Cefalexin should be given cautiously to patients who have shown hypersensitivity to other drugs. Cephalosporins should be given with caution to penicillin-sensitive patients, as there is some evidence of partial crossallergenicity between the penicillins and the cephalosporins. Patients have had severe reactions (including anaphylaxis) to both drugs.
Cefalexin is contraindicated in patients with porphyria.
4.4 Special warnings and precautions for use
If an allergic reaction to cefalexin occurs the drug should be discontinued and the patient treated with the appropriate agents.
Special care is indicated in patients who have experienced an allergic reaction to penicillin or any other beta-lactams.
As with other broad-spectrum antibiotics, prolonged use may result in the overgrowth of non-susceptible organisms (e.g. Candida, Enterococci, Clostridium difficile), which may require interruption of treatment. Pseudomembranous colitis has been reported with the use of broad-spectrum antibiotics, therefore, it is important to consider its diagnosis in patients who develop severe diarrhoea during or after antibiotic use.
As with other antibiotics that are excreted mainly by the kidneys, cefalexin should be administered with caution in the presence of markedly impaired renal function. Dosage of cefalexin should be suitably reduced (see section 4.2)
With reference to the presence of lactose in the formulation, 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
Probenecid causes reduced excretion of cefalexin, leading to increased plasma concentration.
Concurrent treatment with high doses of cephalosporins and nephrotoxic drugs such as aminoglycosides or potent diuretics (e.g. Furosemide, etacrynic acid and piretanide) may adversely affect renal function. Clinical experience has shown that it is not likely to be a problem with cefalexin at the recommended dosage levels.
In common with other antibiotics, Cefalexin may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
A false positive reaction for glucose in the urine may occur with Benedict’s or Fehling’s solutions or with copper sulphate test tablets, but not with enzyme-based tests.
Positive direct Coombs’ tests have been reported during treatment with the cephalosporin antibiotics.
Cefalexin can interfere with the alkaline picrate assay for creatinine, giving a falsely high reading, but the degree of elevation is unlikely to be of clinical importance.
4.6 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.
Lactation
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.
4.7 Effects on ability to drive and use machines
Cefalexin may be associated with dizziness, confusion, agitation and hallucinations that may interfere with their ability to drive or operate machinery. Patients should not drive or use machines as long as these symptoms persist.
4.8 Undesirable effects
Gastro-intestinal-nausea, vomiting, dyspepsia, and abdominal pain have occurred. Diarrhoea has been reported infrequently. It is rarely severe enough to warrant cessation of therapy. As with other broad-spectrum antibiotics, colitis, including rare instances of pseudomembranous colitis, has been reported.
Hypersensitivity - Allergies (in the form of rashes (both urticarial and maculopapular) and angioedema), and rarely erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis have been observed. These reactions usually subside upon discontinuation of the drug. Anaphylaxis has also been reported.
Haematological - eosinophilia, reversible neutropenia, thrombocytopenia and positive Coombe’s test have been reported.
Hepatic - slight elevations of AST and ALT have been observed. As with some penicillins and some other cephalosporins, transient hepatitis and cholestatic jaundice have been reported rarely.
Miscellaneous - other reactions have included genital and anal pruritus, genital moniliasis, dizziness, fatigue, headache, agitation, confusion, hallucinations, arthralgia, arthritis and joint disorder. As with other antibiotics, prolonged use may result in the overgrowth of non-susceptible organisms, e.g., Candida. This may present as vulvo-vaginitis or vaginal discharge.
Reversible interstitial nephritis has been reported rarely.
Overdose
4.9
Symptoms of overdosage may include nausea, vomiting, epigastric distress, diarrhoea and haematuria.
Treatment of overdosage - serum levels can be considerably reduced by haemodialysis or peritoneal dialysis.
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.
Unless 5 - 10 times the normal total daily dose has been ingested, gastrointestinal decontamination should not be necessary.
Serum levels of cefalexin can be reduced greatly by peritoneal dialysis or haemodialysis.
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 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Bacteriology:
Cefalexin is bactericidal and has antimicrobial activity similar to that of cephaloridine or cephalothin against both gram-positive and gram-negative organisms. The bactericidal activity is due to inhibition of bacterial wall synthesis of actively dividing cells by binding to essential target proteins, penicillin binding proteins (PBPs). Cefalexin also decreases the availability of murein hydrolase, an enzyme essential for cell division, and therefore preventing bacterial cell division.
Breakpoints:
The following MIC breakpoints for cefalexin 500mg oral dose, separating susceptible (S) from resistant (R) micro-organisms have been provided by a report from the British Society of Antimicrobial Chemotherapy Working Party (J Antimicrob Chemo 1991; Suppl D to Vol 27):
Staphylococcus aureus: S □ 8mcg/ml, R > 8mcg/ml
Streptococci: S □ 2mcg/ml, R > 2mcg/ml
Enterobacteriacae: S □ 8mcg/ml, R > 8mcg/ml
Susceptibility:
The prevalence of resistance may vary geographically and with time for selected species. Local information on resistance is desirable, particularly when treating severe infections. This information gives only an approximate guidance on the probabilities whether micro-organisms will be susceptible to cefalexin or not.
Other information:
Certain micro-organisms which are resistant to first and second generation cephalosporins and to other beta-lactam antibiotics may exhibit resistance to cefalexin.
5.2 Pharmacokinetic properties
Absorption
Cefalexin is almost completely absorbed in the upper portions of the gastrointestinal tract. Following oral administration, absorption is rapid and peak plasma concentrations levels (4.5pg/ml for a 125mg dose, 9pg/ml for 250mg dose, 18pg/ml for a 500mg dose and 32pg/ml for a 1000mg dose) are usually reached after 1 hour. These are about the same as the concentration produced by an equal dose of cephaloridine given intramuscularly and greater than that produced by cephalothin. In patients with normal renal function, serum levels persist for 4 to 6 hours and disappear within 8 hours. If cefalexin is taken with or shortly after food there is delayed, but the total amount absorbed is not altered. There may be delayed elimination from the plasma. About 10 to 15% of a dose is bound to plasma proteins.
Absorption of cefalexin is not adversely affected by coeliac disease, partial gastrectomy, achlorhydria, jaundice or diverticulosis (duodenal or jejunal).
The biological half-life has been reported to range from 0.6 to at least 1.2 hours and this increases with reduced renal function. The serum half-life is usually about 1 hour, but is longer in the newborn (see section 4.2). About 80% or more of a dose is excreted unchanged in the urine in the first 6 hours by glomerular filtration and tubular secretion; urinary concentrations greater than 1 mg per ml have been achieved after a dose of 500 mg. Probenecid delays urinary excretion and has been reported to increase biliary excretion.
In patients with impaired renal function, an increase in serum half-life of cefalexin occurs. Clinical practice indicates that in view of the wide therapeutic window of cefalexin, the standard recommended doses should be halved only in those patients with creatinine clearance < 50ml/min. The maximum recommended dose (i.e. adults 6g/day, children 4g/day) should be reduced to 50% in mild (40 - < 50ml/min), 25% in moderate (>10 - < 40 ml/min) and 12.5% in severe renal impairment (< 10ml/min).
Distribution
Cefalexin is widely distributed in body tissues, and high concentration are found in all organs, particularly in the liver and kidneys, but does not enter the cerebrospinal fluid in significant quantities unless the meninges are inflamed. It diffuses across the placenta and small quantities are found in the milk of nursing mothers.
Cefalexin reaches therapeutic levels in the blood, urine, bile, synovial fluid, tonsillar tissue, amniotic fluid, cord blood and foetal blood.
Metabolism and Elimination
Cefalexin is not metabolised in the body and is rapidly excreted unchanged in the urine. High concentrations (80-100%) of an orally administered dose are recoverable in the urine within 6 to 8 hours. Cefalexin is excreted in human milk in low concentrations.
Concurrent administration of probenecid delays excretion of cefalexin and raises serum levels by 50 to 100% (see section 4.2).
5.3 Preclinical safety data
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose BP
Magnesium stearate BP
Capsule shell:
Black iron oxide E172 Titanium dioxide E171 Erytbrosin E127 Quinoline yellow E104 Gelatin NFXVI
6.2 Incompatibilities
None known.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Store in a cool dry place not exceeding 25°C.
6.5 Nature and contents of container
Each container consists of a polypropylene tubular container with an open end
equipped to accept a polyethylene closure, with a tamper-evident tear strip or
2
PVC/aluminium blisters or PVdC coated PVC/Aluminium blisters (60g/m PVdC on 250pm PVC/20pm Al) of an appropriate size to accommodate 7, 14, 20, 21, 28, 30, 50, 56, 60, 100 or 500 capsules.
6.6 Special precautions for disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Norton Healthcare Limited T/A IVAX Pharmaceuticals UK Albert Basin Royal Docks London E16 2QJ
8 MARKETING AUTHORISATION NUMBER(S)
PL 00530/0320
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
18/06/1991 / 09/10/2002
10
DATE OF REVISION OF THE TEXT
24/01/2011