KEFORAL 500 mg Cpr pell Plq/10

VIDAL
Medicines
Update of 23/01/2020

KEFORAL^®
cefalexin

Forms and presentations

Film-coated tablet at 1 g (orange-yellow):  Box of 6, under blister pack.
Film-coated tablet at 500 mg (orange-yellow):  Box of 10, under blister pack.
Powder for oral suspension (white) at 250 mg/5 mL: Bottle corresponding to 60 mL of reconstituted suspension (i.e. 12 measuring spoons of 5 mL), single-unit box.

Composition

Lozenge:	p cp
Cefalexin monohydrate	1 g
or	500 mg

Excipients (common): sodium carboxymethyl starch, magnesium stearate, povidone, hypromellose, glycerol, talc, titanium dioxide (E171), methylcellulose, yellow iron oxide (E172), red iron oxide (E172).

Powder for oral suspension:	p c mes
Cefalexin monohydrate	250 mg

Excipients: guarana-type flavouring - 51880 TP (gum arabic, propylene glycol, orange essential oil, benzyl alcohol, vanillin, ethyl butyrate, amyl acetate, allyl caproate), sodium lauryl sulfate, Allura red (E129), methylcellulose 15, dimeticone 350, xanthan gum, pregelatinised starch, sucrose.

Excipient with known effect: 2972,45 mg of sucrose per 5 mL after reconstitution.

Indications

They derive from the antibacterial activity and pharmacokinetic characteristics of cefalexin. They take into account both the clinical studies the medicinal product has undergone and its place among the antibacterial products currently available.
They are limited to infections due to susceptible organisms when these infections permit oral antibiotic therapy and excluding meningeal localisations, in particular:

• ENT infections: documented group A beta-haemolytic streptococcal tonsillitis, sinusitis, otitis;
  
• lower respiratory tract infections:
  
  • superinfections of acute bronchitis,
    
  • exacerbations of chronic bronchitis,
    
  • community-acquired pneumonia in subjects: without risk factors, without signs of clinical severity, in the absence of arguments suggesting resistance to penicillin, in the absence of arguments suggestive of atypical pneumonia; Streptococcus pneumoniae to penicillin, in the absence of arguments suggestive of atypical pneumonia;
    
• uncomplicated urinary tract infections, except prostatitis and pyelonephritis.
  

Official recommendations concerning the appropriate use of antibacterial agents should be taken into account.

Dosage and administration

Dosage

Method of administration:

To be taken preferably away from meals, particularly in children, due to a bioavailability reduced by 40% with milk intake.

Contraindications

This medicine must never be used:

• in case of allergy to antibiotics of the cephalosporin group;
  
• tablet: in children under 6 years, due to the pharmaceutical form.
  

Warnings and precautions

• The occurrence of any allergic reaction requires discontinuation of the treatment.
  
• Cases of acute generalised exanthematous pustulosis (AGEP) have been reported with cephalexin treatment. At the time of prescription, patients must be informed of the signs and symptoms, and closely monitored for skin reactions. If signs or symptoms suggestive of these reactions appear, cephalexin must be stopped immediately and alternative treatment should be considered. Most of these reactions have probably occurred during the first week of treatment.
  
• Prescribing cephalosporins requires prior questioning of the patient.
  
• Allergy to penicillins is cross-reactive with allergy to cephalosporins in 5 to 10% of cases:
  • the use of cephalosporins must be extremely cautious in patients sensitive to penicillins; strict medical monitoring is required from the first administration,
    
  • The use of cephalosporins is strictly contraindicated in subjects with a history of immediate-type allergy to cephalosporins. In case of doubt, the physician must be present with the patient at the first administration in order to treat a possible anaphylactic reaction.
    
• Hypersensitivity reactions (anaphylaxis) observed with these two types of substances may be severe and sometimes fatal.
  
• In case of renal insufficiency, adjust the dosage according to creatinine clearance or serum creatinine (see Posology/Method of administration).
  
• It is prudent to monitor renal function during treatment when cephalexin is combined with potentially nephrotoxic antibiotics (aminoglycosides in particular) or potent diuretics.
  
• As with other broad-spectrum antibiotics, prolonged use of cephalexin may lead to selection of non-susceptible organisms, which may necessitate discontinuation of treatment.
  
• The exceptional occurrence of severe and persistent diarrhoea during or after use of the antibiotic may be symptomatic of pseudomembranous colitis and requires discontinuation of treatment. Diagnosis established after colonoscopy requires initiation of specific antibiotic therapy.
  
• Beta-lactams expose patients to the risk of encephalopathy (confusion, impaired consciousness, epilepsy, or abnormal movements), particularly in cases of overdose or renal insufficiency.
  

Interactions

Particular problems with INR imbalance:

Many cases of increased activity of oral anticoagulants have been reported in patients receiving antibiotics. A marked infectious or inflammatory context, age and general condition of the patient appear to be risk factors. In these circumstances, it is difficult to distinguish between the infectious disease and its treatment in the occurrence of the INR imbalance. However, certain classes of antibiotics are more involved: these include fluoroquinolones, macrolides, cyclines, cotrimoxazole and certain cephalosporins.

Fertility, pregnancy and breastfeeding

Pregnancy:

Animal studies have not shown any teratogenic effect. In the absence of a teratogenic effect in animals, a malformative effect in humans is not expected. Indeed, to date, substances responsible for malformations in humans have been shown to be teratogenic in animals in well-conducted studies in two species.

In clinical practice, analysis of a large number of exposed pregnancies apparently revealed no particular malformative or foetotoxic effect of cephalexin. However, only epidemiological studies would allow verification of the absence of risk.

Consequently, cephalexin may be prescribed during pregnancy if needed.

Breastfeeding:

The passage of cephalexin into breast milk is low and the quantities ingested are far below therapeutic doses. Consequently, breastfeeding is possible when this antibiotic is taken.

However, interrupt breastfeeding (or the medicinal product) if diarrhoea, candidiasis or skin rash occurs in the infant.

Driving and using machines

Kéforal may have a significant influence on the ability to drive vehicles and use machines, notably due to the possible occurrence of encephalopathy (see Warnings and Precautions for UseAdverse effectsOverdose).

Adverse effects

• Allergic manifestations: skin eruptions, fever, anaphylactic shock, Quincke's oedema, ano-genital pruritus (with or without candidiasis), very exceptionally erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome.
  
• Skin and subcutaneous tissue disorders: acute generalised exanthematous pustulosis (AGEP).
  
• Haematological manifestations: eosinophilia, thrombocytopenia, leukopenia reversible on discontinuation of treatment, haemolytic anaemia.
  
• Gastrointestinal manifestations: diarrhoea, nausea, vomiting. As with other broad-spectrum antibiotics, rare cases of pseudomembranous colitis have been reported.
  
• Hepatic manifestations: transient elevation of transaminases ASAT and ALAT, hepatic impairment, jaundice.
  
• Nephrotoxicity: as with other cephalosporins, a few rare cases of reversible interstitial nephritis have been reported.
  

As with any antibiotic, prolonged use of the medicinal product may lead to the emergence of resistance in the organisms involved.

Beta-lactams expose patients to the risk of encephalopathy (confusion, impaired consciousness, epilepsy, or abnormal movements), particularly in cases of overdose or renal insufficiency.

Reporting of suspected adverse reactions:

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres. Website: www.signalement-sante.gouv.fr.

Overdose

Beta-lactams expose patients to the risk of encephalopathy (confusion, impaired consciousness, epilepsy, or abnormal movements), particularly in cases of overdose or renal insufficiency.

Pharmacodynamics

Pharmacotherapeutic class: Antibacterials for systemic use (ATC code: J01DA01; J: anti-infectives).

Antibacterial antibiotic of the beta-lactam family, cephalosporin group, of 1^re generation.

This bactericidal antibiotic acts by inhibiting bacterial cell wall synthesis.

Spectrum of antibacterial activity:

The critical concentrations separate susceptible strains from strains of intermediate susceptibility, and the latter from resistant strains: S ≤ 8 mg/l and R > 32 mg/l.

The prevalence of acquired resistance can vary according to geography and time for certain species. It is therefore useful to have information on local resistance prevalence, especially for the treatment of severe infections. These data can only provide guidance on the probabilities of the susceptibility of a bacterial strain to this antibiotic.

When the variability of resistance prevalence in France is known for a bacterial species, the frequency of acquired resistance in France (> 10 %; extreme values) is indicated in parentheses.

Susceptible species:

• Aerobic Gram-positive: Corynebacterium diphtheriae, Propionibacterium acnes, Staphylococcus methicillin-S, Streptococcus, Streptococcus pneumoniae (30 - 70 %).
  
• Aerobic Gram-negative: Branhamella catarrhalis, Citrobacter koseri, Escherichia coli (20 - 30 %), Klebsiella (0 - 30 %), Neisseria gonorrhoeae, Pasteurella.
  
• Anaerobes: Fusobacterium (10 - 20 %), Prevotella (60 - 70 %).
  

Moderately susceptible species (in vitro of intermediate susceptibility):

• Aerobic Gram-negative: Haemophilus influenzae, Proteus mirabilis.
  
• Anaerobes: Clostridium perfringens, Peptostreptococcus.
  

Resistant species:

• Gram-positive aerobes: enterococci, Listeria monocytogenes, Staphylococcus spp. methicillin-R^*.
  
• Aerobic Gram-negative: Acinetobacter, Citrobacter freundii, Enterobacter, Morganella morganii, Proteus vulgaris, Providencia, Pseudomonas, Serratia.
  
• Anaerobes: Bacteroides, Clostridium difficile.
  

^*  The frequency of methicillin resistance is approximately 30 to 50 % of all staphylococci and is found mostly in hospital settings.

Pharmacokinetics

Storage conditions

HANDLING/DISPOSAL INSTRUCTIONS

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Prescription, supply and reimbursement

LIST I

Marketing authorisation (AMM)	3400931986522 (1983, SmPC rev 09.01.2019) cp 1 g.
	3400931357520 (1983, SmPC rev 09.01.2019) cp 500 mg.
	3400932121458 (1983, SmPC rev 09.01.2019) powder.

Price:	4,57 euros (6 tablets 1 g).
	3,75 euros (10 tablets 500 mg).
	3,13 euros (1 vial 250 mg/5 mL).
Reimbursed by Social Security at 65 %. Collective.

Laboratoire SCIENCEX
9, rue Nicolas-Charlet. 75015 Paris
Tel: 01 40 65 95 99