SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Cefalexin 500mg Capsules

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Each capsule contains Cefalexin monohydrate Ph.    Eur.    equivalent to

anhydrous Cefalexin 500mg.

Excipients with known effect:

Lactose monohydrate and sunset yellow (E110)

For the full list of excipients, see section 6.1

3    PHARMACEUTICAL FORM

Capsules

Dark green/Light green, self locked hard gelatine capsules of size ‘0’ Imprinted with ‘RX657’ in black edible ink containing white to off white granular powder/pellets.

4    CLINICAL PARTICULARS

4.1 Therapeutic indications

Cefalexin is a semisynthetic cephalosporin antibiotic for oral administration.

Cefalexin is indicated in the treatment of the following infections due to susceptible micro-organisms:

Respiratory tract infection 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

Cefalexin is administered orally.

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 250mg every 6 hours, or 500mg 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.

Older 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: 125mg every 8 hours.

Children 5 years and over: 250mg 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 100mg/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.

4.3 Contraindications

Cefalexin is contraindicated in patients with known hypersensitivity to penicillins, cephalosporins group of antibiotics, penicillin derivatives or penicillamine and patients with porphyria.

Cefalexin is contraindicated in patients with known hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Severe systemic infections, which require parenteral cephalosporin treatment, should not be treated orally during the acute stage.

4.4 Special warnings and precautions for use

Any patient who has a relative with porphyria should be screened and advised about the potential for cephalosporins to induce acute porphyric crises.

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.

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.

Positive direct Coombs’ tests have been reported during treatment with the cephalosporin antibiotics. In haematological studies, or in transfusion crossmatching 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 recognized that 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.

This medicine contains lactose. 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

As with other beta-lactam drugs, renal excretion of cefalexin is inhibited by probenicid.

In a single study of 12 healthy subjects given single 500mg 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.

Breastfeeding

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

Not known

4.8 Undesirable effects

Infections and infestations

As with other broad-spectrum antibiotics prolonged use may result in the overgrowth of non-susceptible organisms, e.g. candida (Genital candidiasis). This may present a vulvo-vaginitis.

Blood and lymphatic system disorders

Eosinophilia, neutropenia, thrombocytopenia and haemolytic anaemia have been reported.

Immune system disorders

Allergic reactions have been observed in the form of rash, urticaria, angioedema and rarely erythema 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.

Nervous and psychiatric system disorders

Dizziness, fatigue, headache, agitation, confusion, hallucinations.

Gastrointestinal disorders

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.

Hepatobiliary disorders

As with some penicillin and some other cephalosporins, transient hepatitis and cholastatic jaundice have been reported rarely.

Musculoskeletal, connective tissue and bone disorders

Arthralgia, arthritis and joint disorder.

Renal and urinary disorders

Reversible interstitial nephritis has been reported rarely.

Reproductive system and breast disorders

Genital and anal pruritis, vaginal discharge.

Investigations

Slight elevations in AST and ALT have been reported.

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

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, gastrointestinal 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 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: ATC code: JO1DB01 First generation cephalosporins

Cefalexin is an oral broad-spectrum antibiotic belonging to the group known as cephalosporins.

In-vitro tests demonstrate that the 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 penicillinaseproducing strains.

Streptococcus pneumonia

Escherichia coli

Proteus mirabilis

Kiebsiella species

Haemophilus influenza

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 calcoaceticus. Penicillin-resistant Steptococcus pneumonia is usually cross-resistant to beta-lactam antibiotics. When tested by in-vitro methods, staphylococci exhibit cross-resistance between cefalexin and methicillin-type antibiotics.

Pharmacokinetic properties

Human pharmacology - cefalexin is acid stable and may be given without regard to meals.

It is rapidly absorbed after oral administration. Following doses of 250mg, 500mg and 1g, average peak serum levels of approximately 9, 18 and 32mg/L respectively were obtained at 1 hour. Measurable levels were present 6 hours after administration. Cefalexin is excreted 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 concentrations following the 250mg, 500mg and 1g doses were approximately 1000, 2200 and 5000mg/l respectively.

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.

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 4g/day.

The half-Life may be increased in neonates due to their renal immaturity, but there is no accumulation when given at up to 50mg/kg/day.

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

Lactose monohydrate Magnesium Stearate

Capsule Shell

Gelatin

Iron oxide yellow (E172) Titanium dioxide (E171) FD & C Blue 1 (E133) FD & C yellow 6 (E110) Water

Printing ink

Shellac

Dehydrated alcohol Isopropyl alcohol Butyl alcohol Propylene glycol Stong ammonia solution Black iron oxide (E172) Potassium hydroxide Purified water

6.2 Incompatibilities

Not applicable 6.3. Shelf Life

Shelf life: Two years

6.4 Special precautions for storage

Do not store above 25° C.

Store in the original package in order to protect from moisture.

6.5 Nature and contents of container

HDPE Bottle pack comprise of white opaque high-density polyethylene with neck and screw cap with induction seal liner containing 100 capsules.

Strip pack containing 20, 21 or 28 capsules.

6.6 Special precautions for disposal

No special requirements

7 MARKETING AUTHORISATION HOLDER

Ranbaxy (UK) Limited Building 4, Chiswick Park,

566 Chiswick high road,

London, United Kingdom.

W4 5YE

8. MARKETING AUTHORISATION NUMBER(S)

PL 14894 /0011

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

02/02/2009

10 DATE OF REVISION OF THE TEXT

09/02/2015