Document: spc-doc_PL 35646-0015 change

• spc-doc_PL 30684-0208
• spc-doc_PL 35646-0015

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SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Cefalexin 500 mg Capsules

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Each hard gelatin capsule contains Cefalexin (Monohydrate) equivalent to 500 mg of Cefalexin.

Excipient with known effect: Lactose anhydrous 40.13 mg /Capsule For a full list of excipients, see section 6.1

3. PHARMACEUTICAL FORM

Capsule Hard.

White to off white powder filled in light green cap and light green body of size ‘0’ hard gelatin capsule printed “CEP” on cap and “500” on body with black ink.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Cefalexin is indicated in the treatment of the following infections due to susceptible micro-organisms (see also section 4.4 and 5.1):

Skin and soft tissue infections

Consideration should be given to official guidance on the appropriate use of antibacterial agents

4.2 Posology and method of administration

Cefalexin is administered orally.

Adults: For skin and soft tissue infections, the usual dosage is 250mg every 6 hours or 500 mg every 12 hours.

The elderly and patients with impaired renal function: As for adults. Reduce dosage if renal function is markedly impaired (see section 4.4).

Children > 5 years to 12 years and adolescents.

250mg every 8 hours

In severe infections, the dosage may be doubled.

This medicine is not recommended for the use in the children under 5 years of age.

4.3 Contraindications

Cefalexin is contra-indicated in patients with known allergy to the cephalosporin group of antibiotics.

Cefalexin is contraindicated in patients with previous immediate and severe hypersensitivity reactions to penicillin or any other type of beta-lactam drug

4.4 Special warnings and precautions for use

Special caution is required to determine any other type of previous hypersensitivity reactions to _penicillin or to other beta-lactam-medicinal _products because of potential cross-allergy.

In case of severe acute hypersensitivity reactions (e.g. anaphylaxis) treatment with cefalexin capsules 500 mg must be discontinued immediately and adequate and appropriate emergency measures have to be initiated.

Pseudomembranous colitis has been reported with virtually all broad-spectrum antibiotics, including macrolides, semi-synthetic 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. Antiperistaltics are contraindicated.

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 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.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsoption 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 probenecid.

In a single study of 12 healthy subjects given single 500mg doses of cefalexin and metformin, plasma metformin C_max 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 leukemia when they were given gentamicin and Cefalexin.

Concurrent administration with certain other drug substances, such as aminoglycosides, other cephalosporin’s, or furosemide, and similar potent diuretics, may increase the risk of nephrotoxicity

Interaction studies have only been performed in adult.

4.6 Fertility, pregnancy and lactation

Pregnancy: Although laboratory and clinical studies have shown no evidence of teratogenicity (see section 5.3), caution should be exercised when prescribing for the pregnant patient.

Lactation: The excretion of cefalexin in human milk increased up to 4 hours following a 500mg dose. The drug reached a maximum level of 4 micrograms/ml, decreased gradually and was not detectable at 8 hours post dose. Caution should be exercised when cefalexin is administered to a nursing woman.

Fertility: In the rat, cefalexin had no effects on fertility (see Section 5.3); however, the effect on fertility in humans is unknown.

4.7 Effects on ability to drive and use machines

None known.

4.8 Undesirable effects

_Med DRA frequency convention

<Very common (>/10),_

<common (>/100, <1/10),_

<uncommon (>1/1000, <1/100),_

<rare (>1/10,000, <1/1000)

<very rare (<1/10,000)._

Med DRA system organ class
Infections and infestations
Rare	Genital and anal pruritis, Vaginitis
Frequency not known	Genital candidiasis
Blood and lymphatic system disorders
Uncommon	Eosinophilia
Rare	Neutropenia, Thrombocytopenia, Haemolytic anaemia
Immune System Disorder
Rare	Anaphylactic reaction
Nervous system disorder
Rare	Dizziness, Headache
Gastrointestinal Disorder
Common	Diarrhoea, nausea
Rare	Abdominal pain, vomiting, dyspepsia, Pseudomembranous colitis
Hepatobiliary disorders
Rare	Hepatitis, cholestatic icterus
Skin and subcutaneous tissue disorders
Uncommon	Rash, Urticaria, Pruritus
Rare	Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis (Lyell's syndrome), angioedema
Musculoskeletal and connective tissue disorders
Frequency not known	Arthralgia, arthritis
Renal and urinary Disorders
Rare	Reversible interstitial nephritis
General disorders and administration site conditions
Rare	Tiredness
Frequency not known	Fever
Investigations
Uncommon	Increase in ASAT and ALAT (reversible)
Frequency not known	Positive direct coombs test. False positive reaction to glucose in the urine

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    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotheraupeutic group:

First generation cephalosporin ATC code: J01DB01

Mechanism of action:

cefalexin is an antibacterial agent of the cephalosporin class. Like other cephalosporin’s cefalexin exerts anti bacterial activity by binding to and inhibiting the action of penicillin-binding proteins involved in the synthesis of bacterial cell walls. This leads to bacterial cells lysis and cell death.

Mechanism of Resistance:

Bacterial resistance to cerfalexin may be due to one or more of following mechanism:

Hydrolysis by extended-spectrum beta-lactamase and/or by plasmid- or chromosomally-encoded (AmpC) enzymes that may be induced or de-repressed in certain aerobic gram-negative bacterial species.

-    Reduced affinity of penicillin-binding proteins.

-    Reduced permeability of the outer membrane of certain gram-negative organisms restricting access to penicillin-binding proteins.

-    Drug efflux pumps

More than one of these mechanism of resistance may co-exists in a single bacterial cell. Depending on the mechanism(s) present, bacteria may express

cross resistance to several or all other beta-lactams and/or antibacterial medicinal products of other classes.

Breakpoints

Breakpoints (MIC, mg/L)
Microorganism	Susceptibility (<)	Resistant (>)
Enterobacter spp	16.0	16.0
Escherichia coli	16.0	16.0
Klebsiella spp	16.0	16.0
Morganella morganii	16.0	16.0
Proteus mirabilis	16.0	16.0
Proteus vulgaris	16.0	16.0

Susceptibility

The prevalence of resistance may vary geographically and over time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

5.2 Pharmacokinetic properties Absorption:

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 1,000, 2,200, and 5,000mg/l, respectively.

Cefalexin is almost completely absorbed from the gastro-intestinal tract, and 75100% 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 4g/day.

Elimination:

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.

PHARMACEUTICAL PARTICULARS

6.1. List of excipients

Capsule Content	Capsule Shell
Lactose Anhydrous (SuperTab 21AN)	Gelatin
Colloidal Silicon Dioxide	Sodium lauryl sulphate
Magnesium Stearate	Water
Imprinting Ink	Brilliant Blue (E 133)
Shellac	Quinoline Yellow (E 104)
Dehydrated alcohol	Titanium Dioxide (E 171)
Isopropyl alcohol
Butyl alcohol
Propylene Glycol
Strong ammonia solution
Black Iron oxide (E 172)
Potassium Hydroxide
Purified water

6.2 Incompatibilities

Not Applicable

6.3 Shelf life

24 months.

6.4 Special precautions for storage

Store below 30⁰C.

6.5 Nature and contents of container

The capsules are packed in blister strips of 7 or 10 consisting of PVDC coated PVC with aluminum backing. Each carton contains 21, 28, 30, 50, 56, 60 and 100 capsules.