CLOXACILLINE VIATRIS 500 mg Gél Plq/16

Capsule.

White opaque capsule.

Cloxacillin sodium monohydrate

Quantity corresponding to cloxacillin base............................................................................................500 mg

For one capsule.

Excipient with known effect: sodium (26,4 mg).

Excipients:

CLOXACILLIN VIATRIS is indicated in adults and children for the treatment of mild skin infections due to susceptible staphylococci and/or streptococci (see section Pharmacodynamics), requiring oral treatment from the outset.

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

Dosage

The dosage depends on the patient's body weight, renal function and/or hepatic function.

Adult

• In patients with normal renal function

50 mg/kg/day in 3 daily doses, not exceeding 3 to 4 g/day.

• Renal impairment

• Creatinine clearance > 30 mL/min: no dose adjustment;
• Creatinine clearance < 30 mL/min: halve the daily dose.

• Hepatic impairment

If hepatic impairment is combined with renal impairment, regardless of the degree of renal impairment: halve the daily dose.

Paediatric population

• In patients with normal renal function

50 mg/kg/day in 3 daily doses, not exceeding 3 to 4 g/day.

The dosage in children with renal and/or hepatic impairment has not been studied.

Method of administration

Oral use.

This medicine should preferably be taken half an hour before meals.

Capsules must be swallowed whole without opening them, with a glass of water.

Hypersensitivity to cloxacillin, to other antibiotics of the beta-lactam family (penicillins and cephalosporins) or to any of the excipients mentioned in section Composition.

Taking the capsule is contraindicated in children under 6 years of age, as it may cause aspiration.

The occurrence of any allergic reaction requires discontinuation of treatment and the initiation of appropriate treatment.

Severe and sometimes fatal hypersensitivity reactions (anaphylaxis) have exceptionally been observed in patients treated with beta-lactams. Their administration therefore requires a prior medical history review. In the presence of a history of typical allergy to these products, the contraindication is absolute.

Allergy to penicillins is cross-reactive with allergy to cephalosporins in 5 to 10% of cases. This leads to penicillins being avoided when the subject is a known allergic person to cephalosporins.

Pseudomembranous colitis has been reported with virtually all antibiotics, including cloxacillin. This diagnosis should be considered in patients with persistent and/or severe diarrhoea during or after antibiotic treatment. In this situation, appropriate therapeutic measures should be initiated immediately. Discontinuation of antibiotic treatment should be considered. Medicinal products that inhibit peristalsis are contraindicated in this situation (see section Adverse effects).

Hypokalaemia (which may be life-threatening) has been reported with the use of cloxacillin (in particular with the IV formulation). Monitoring of potassium levels should be considered depending on the clinical condition of the patient and other potential risk factors.

In cases of renal impairment, dose adjustment is required if creatinine clearance is less than 30 mL/min (see section Dosage and administration).

Acute kidney injuries have been reported during the post-marketing period in patients treated with cloxacillin (see section Adverse effects). These cases have generally been reported in patients who received a high dose of cloxacillin (in particular with the IV formulation) and/or who presented one or more risk factors for acute kidney injury (elderly subjects, type II diabetes, (arterial) hypertension, pre-existing renal impairment or concomitant use of nephrotoxic medicinal products). Cloxacillin should be used with caution in these patients.

In cases of hepatic impairment associated with renal impairment, regardless of the degree of renal impairment, dose adjustment is required (see section Dosage and administration).

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

This medicinal product should generally not be used in combination with methotrexate (see section Interactions).

This medicinal product contains 2,3 mmol (52,8 mg) of sodium per gram of cloxacillin (i.e. 26,4 mg of sodium per capsule dosed at 500 mg). To be taken into account in patients on a strict low-sodium diet.

Combinations not recommended

• Methotrexate

Increased effects and haematological toxicity of methotrexate: inhibition of renal tubular secretion of methotrexate by penicillins.

Specific problems with INR imbalance

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

Pregnancy

The use of cloxacillin may be considered if needed during pregnancy, regardless of the stage. Indeed, clinical data on a limited number of patients and animal data have not shown any malformative or foetotoxic effect.

Breast-feeding

The passage of penicillins into breast milk is low, and the quantities ingested are much lower than neonatal 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.

This medicine may have a significant influence on the ability to drive vehicles and use machines, in particular due to the possible occurrence of encephalopathy (see sections Warnings and precautions, Adverse effects, Overdose).

The frequency of possible undesirable effects listed below is defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), frequency not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

Frequency not known: reversible haematological disorders: anaemia, thrombocytopenia, leukopenia, neutropenia and agranulocytosis.

Immune system disorders

Frequency not known: urticaria, angioedema, anaphylactic shock, eosinophilia (see section Warnings and precautions).

Metabolism and nutrition disorders

Frequency not known: hypokalaemia (see section Warnings and precautions).

Nervous system disorders

Frequency not known: beta-lactams expose patients to the risk of encephalopathy (confusion, disturbances of consciousness, epilepsy or abnormal movements), particularly in cases of overdose or renal insufficiency.

Gastrointestinal disorders

Rare: pseudomembranous colitis (see section Warnings and precautions).

Frequency not known: nausea, vomiting, diarrhoea.

Hepato-biliary disorders

Rare: rare and moderate increase in transaminases (AST and ALT).

Frequency not known: cholestatic hepatitis.

Skin and subcutaneous tissue disorders

Frequency not known: maculopapular rash of allergic or non-allergic origin, DRESS syndrome (drug hypersensitivity syndrome with eosinophilia and systemic symptoms).

Isolated cases of erythroderma and severe bullous skin reactions (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis).

Renal and urinary disorders

Frequency not known: immunoallergic acute interstitial nephropathies, acute renal failure.

General disorders and administration site conditions

Frequency not known: fever.

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 reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr.

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

Manifestations of overdose, neuropsychiatric, renal and digestive effects have been reported with M penicillins.

Pharmacotherapeutic class: PENICILLINS RESISTANT TO BETA-LACTAMASES, ATC code: J01CF02.

Cloxacillin is an antibiotic of the beta-lactam family, from the group of M penicillins.

ANTIBACTERIAL ACTIVITY SPECTRUM

Susceptibility testing breakpoints

The criteria for interpreting minimum inhibitory concentrations (MICs) for susceptibility testing have been established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for cloxacillin and are listed below: https://www.ema.europa.eu/documents/other/minimum-inhibitory-concentration-mic-breakpoints_en.xlsx  

The prevalence of acquired resistance may vary by geography and over time for certain species. It is therefore useful to have information on local resistance prevalence, especially for the treatment of severe infections. If necessary, specialist advice should be sought, mainly when the usefulness of the drug in certain infections may be called into question because of the level of local resistance prevalence.

Classes
USUALLY SUSCEPTIBLE SPECIES
Gram-positive aerobes
Streptococcus pyogenes
Anaerobes
Clostridium perfringens
INCONSISTENTLY SENSITIVE SPECIES (ACQUIRED RESISTANCE ≥ 10 %)
Gram-positive aerobes
Staphylococcus aureus (1)
Coagulase-negative staphylococci (+)

(+) The prevalence of bacterial resistance is ≥ 50 % in France.

(1) The frequency of methicillin resistance is approximately 20 to 30 % in Staphylococcus aureus and is encountered mainly in hospital settings.

Absorption

Cloxacillin is stable in gastric fluid. It is well absorbed by the digestive mucosa (70 %).

Distribution

• After oral administration, maximum blood concentrations are obtained after 1 hour and are proportional to the dose administered. They are in the order of 9 mg/L for a dose of 500 mg.

• After intravenous injection of 2 g as an infusion over 20 minutes, the serum peak obtained at the end of the infusion has a value of 280 mg/L.

• The half-life is in the order of 45 minutes in patients with normal renal function.

• Binding to plasma proteins is in the order of 90 %.

• Cloxacillin diffuses into amniotic fluid, fetal blood, synovial fluid and bone tissue.

Biotransformation

Cloxacillin is minimally metabolized.

Elimination

After oral administration, the unabsorbed fraction is eliminated via the intestine in inactive form. Elimination of the absorbed fraction occurs in active form essentially via the urinary route, and at 10 % via the biliary route.

After administration by injection, elimination is:

• urinary, in active form, within 6 hours, approximately 70 to 80 % of the injected dose;

• biliary, in active form, 20 to 30 % of the injected dose.

32 months.

To be stored at a temperature not exceeding 30°C.

No special requirements.

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

List I
Possible repackaging

Marketing authorisation (AMM)

CIP 3400927369988 (Plq/16).

Price:

3,21 euros (Plq/16).

Social security reimbursement at 65% under the indications:

• Indication(s) appearing in the marketing authorisation at the date of publication of this decree

Collection.