Flucloxacilline Sandoz

Flucloxacilline Sandoz Sodium is indicated for the treatment of infections due to sensitive Gram-positive organisms, including β-lactamase-producing staphylococci and streptococci. Typical indications include:

Skin and soft tissue infections:

Boils, Cellulitis, Infected burns, Abscesses, Infected skin conditions, e.g. ulcer, eczema, and acne, Protection for skin grafts, Carbuncles, Furunculosis, Infected wounds and Impetigo

Respiratory tract infections:

Pneumonia, Lung abscess, Empyema, Sinusitis, Pharyngitis, Otitis media and externa, Tonsillitis and Quinsy

Other infections caused by Flucloxacilline Sandoz-sensitive organisms:

Osteomyelitis, Urinary tract infection, Enteritis, Meningitis, Endocarditis and Septicaemia

Flucloxacilline Sandoz Sodium is also indicated for use as a prophylactic agent during major surgical procedures when appropriate; for example cardiothoracic and orthopaedic surgery.

Parenteral usage is indicated where oral dosage is inappropriate.

Flucloxacilline Sandoz is indicated for the treatment of infections due to sensitive Gram-positive organisms, including β-lactamase-producing staphylococci and streptococci. Typical indications include:

Skin and soft tissue infections:

Respiratory tract infections:

Other infections caused by Flucloxacilline Sandoz-sensitive organisms:

Flucloxacilline Sandoz is also indicated for use as a prophylactic agent during major surgical procedures when appropriate; for example cardiothoracic and orthopaedic surgery.

Parenteral usage is indicated where oral dosage is inappropriate.

Depends on the age, weight and renal function of the patient, as well as the severity of the infection.

Usual adult dosage (including elderly patients)

Oral- 10ml four times daily

Usual children's dosage

2-10 years: 5ml four times daily

Under 2 years: 2.5ml four times daily

Osteomyelitis, endocarditis:

Up to 8 g daily, in divided doses six to eight hourly. Surgical prophylaxis - 1 to 2 g IV at induction of anaesthesia followed by 500 mg six hourly IV, IM or orally for up to 72 hours.

Abnormal renal function:

In common with other penicillins, Flucloxacilline Sandoz usage in patients with renal impairment does not usually require dosage reduction. However, in the presence of severe renal failure (creatinine clearance < 10 ml/min) a reduction in dose or an extension of dose interval should be considered. Flucloxacilline Sandoz is not significantly removed by dialysis and hence no supplementary dosages need to be administered either during, or at the end of the dialysis period

Hepatic impairment:

Dose reduction in patients with reduced hepatic function is not necessary.

Administration

Oral: Oral doses should be administered half to one hour before meals

Premature infants, neonates, sucklings and infants

Other pharmaceutical forms/strengths may be more appropriate for administration to this population.

Depends on the age, weight and renal function of the patient, as well as the severity of the infection.

Usual adult dosage (including elderly patients)

Oral - 250 mg four times a day.

Osteomyelitis, endocarditis - Up to 8 g daily, in divided doses six to eight hourly.

Surgical prophylaxis - 1 to 2 g IV at induction of anaesthesia followed by 500 mg six hourly IV, IM or orally for up to 72 hours.

Usual children's dosage

2-10 years: half adult dose.

Under 2 years: quarter adult dose.

Abnormal renal function: In common with other penicillins, Flucloxacilline Sandoz usage in patients with renal impairment does not usually require dosage reduction. However, in the presence of severe renal failure (creatinine clearance < 10 ml/min) a reduction in dose or an extension of dose interval should be considered. Flucloxacilline Sandoz is not significantly removed by dialysis and hence no supplementary dosages need to be administered either during, or at the end of the dialysis period. The maximum recommended dose in adults is 1 g every 8 to 12 hours.

Hepatic impairment¹

Dose reduction in patients with reduced hepatic function is not necessary.

Administration

Oral: Oral doses should be administered half to one hour before meals.

Flucloxacilline Sandoz should not be given to patients with a history of hypersensitivity to β-lactam antibiotics (e.g. penicillins, cephalosporins) or excipients.

Flucloxacilline Sandoz is contra-indicated in patients with a previous history of Flucloxacilline Sandoz-associated jaundice/hepatic dysfunction.

Flucloxacillin should not be given to patients with a history of hypersensitivity to β-lactam antibiotics (e.g. penicillins, cephalosporins) or excipients.

Flucloxacillin is contra-indicated in patients with a previous history of flucloxacillin-associated jaundice/hepatic dysfunction.

Before initiating therapy with Flucloxacilline Sandoz, careful enquiry should be made concerning previous hypersensitivity reactions to β-lactams.

As for other penicillins contact with the skin should be avoided as sensitisation may occur. Patients with a known history of allergy are more likely to develop a hypersensitivity reaction.

Cross-sensitivity between penicillins and cephalosporins is well documented.

Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving β-lactam antibiotics. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral therapy. These reactions are more likely to occur in individuals with a history of β-lactam hypersensitivity.

If anaphylaxis occurs Flucloxacilline Sandoz should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions may require immediate emergency treatment with adrenaline (epinephrine). Ensure adequate airway and ventilation and give 100% oxygen. IV crystalloids, hydrocortisone, antihistamine and nebulised bronchodilators may also be required.

Hepatitis and cholestatic jaundice have been reported. These reactions are related neither to the dose nor to the route of administration. Flucloxacilline Sandoz should be used with caution in patients with evidence of hepatic dysfunction, patients >50 years or patients with underlying disease all of whom are at increased risk of hepatic reactions. The onset of these hepatic effects may be delayed for up to two months post-treatment. In several cases, the course of the reactions has been protracted and lasted for some months. In very rare cases, a fatal outcome has been reported.

The use of Flucloxacilline Sandoz (like other penicillins) in patients with renal impairment does not usually require dosage reduction. In the presence of severe renal failure (creatinine clearance less than 10ml/min), however, a reduction in dose or an extension of dose interval should be considered because of the risk of neurotoxicity.

Special caution is essential in the newborn because of the risk of hyperbilirubinaemia. Studies have shown that, at high dose following parenteral administration, Flucloxacilline Sandoz can displace bilirubin from plasma protein binding sites, and may therefore predispose to kernicterus in a jaundiced baby. In addition, special caution is essential in the newborn because of the potential for high serum levels of Flucloxacilline Sandoz due to a reduced rate of renal excretion.

During prolonged treatments (e.g. osteomyelitis, endocarditis), regular monitoring of hepatic and renal functions is recommended.

Prolonged use may occasionally result in overgrowth of non-susceptible organisms.

Flucloxacilline Sandoz oral solution contains approximately 10.72mg of sodium per 5ml.

The occurrence at the treatment initiation of a feverish generalised erythema associated with pustule may be a symptom of acute generalised exanthematous pustulosis (AGEP). In case of AGEP diagnosis, Flucloxacilline Sandoz should be discontinued and any subsequent administration of Flucloxacilline Sandoz contra-indicated.

Before initiating therapy with flucloxacillin, careful enquiry should be made concerning previous hypersensitivity reactions to β-lactams. Cross-sensitivity between penicillins and cephalosporins is well documented.

Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving β-lactam antibiotics. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral therapy. These reactions are more likely to occur in individuals with a history of β-lactam hypersensitivity.

If anaphylaxis occurs flucloxacillin should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions may require immediate emergency treatment with adrenaline (epinephrine). Ensure adequate airway and ventilation and give 100% oxygen. IV crystalloids, hydrocortisone, antihistamine and nebulised bronchodilators may also be required.

Flucloxacillin should be used with caution in patients with evidence of hepatic dysfunction, patients > 50 years and those with serious underlying disease. In these patients, hepatic events may be severe, and in very rare circumstances, deaths have been reported.

The use of flucloxacillin (like other penicillins) in patients with renal impairment does not usually require dosage reduction. In the presence of severe renal failure (creatinine clearance less than 10ml/min), however, a reduction in dose or an extension of dose interval should be considered because of the risk of neurotoxicity.

During prolonged treatments (e.g. osteomyelitis, endocarditis), regular monitoring of hepatic and renal functions is recommended.

Prolonged use may occasionally result in overgrowth of non-susceptible organisms.

Flucloxacilline Sandoz capsules contain approximately 51 mg sodium per g. This should be included in the daily allowance of patients on sodium restricted diets.

The following convention has been utilised for the classification of undesirable effects: Very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/1000), very rare (<1/10,000).

Unless otherwise stated, the frequency of the adverse events has been derived from more than 30 years of post-marketing reports.

Blood and lymphatic system disorders

Very rare: Neutropenia (including agranulocytosis) and thrombocytopenia. These are reversible when treatment is discontinued. Haemolytic anaemia.

Immune system disorders

Very rare: Anaphylactic shock (exceptional with oral administration) (see Item 4.4 Warnings), angioneurotic oedema.

If any hypersensitivity reaction occurs, the treatment should be discontinued. (See also Skin and subcutaneous tissue disorders).

Gastrointestinal disorders

*Common: Minor gastrointestinal disturbances.

Very rare: Pseudomembranous colitis.

If pseudomembranous colitis develops, Flucloxacilline Sandoz treatment should be discontinued and appropriate therapy, e.g. oral vancomycin should be initiated.

Hepato-biliary disorders

Hepatitis and cholestatic jaundice may be delayed for up to two months post-treatment; in several cases the course of the reactions has been protracted and lasted for some months. Hepatic events may be severe and in very rare circumstances a fatal outcome has been reported. Most reports of deaths have been in patients >50 years and in patients with serious underlying disease.

There is evidence that the risk of Flucloxacilline Sandoz induced liver injury is increased in subjects carrying the HLA-B*5701 allele. Despite this strong association, only 1 in 500-1000 carriers will develop liver injury. Consequently, the positive predictive value of testing the HLA-B*5701 allele for liver injury is very low (0.12%) and routine screening for this allele is not recommended

Skin and subcutaneous tissue disorders

*Uncommon: Rash, urticaria and purpura.

Very rare: Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.

(See also Immune system disorders).

Frequency not known: AGEP - acute generalized exanthematous pustulosis

Musculoskeletal and connective tissue disorders

Very rare: Arthralgia and myalgia sometimes develop more than 48 hours after the start of the treatment.

Renal and urinary disorders

Very rare: Interstitial nephritis.

This is reversible when treatment is discontinued.

General disorders and administration site conditions

Very rare: Fever sometimes develops more than 48 hours after the start of the treatment.

*The incidence of these AEs was derived from clinical studies involving a total of approximately 929 adult and paediatric patients taking Flucloxacilline Sandoz.

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; website: www.mhra.gov.uk/yellowcard

The following convention has been utilised for the classification of undesirable effects:- Very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/1000), very rare ( <1/10,000).

Unless otherwise stated, the frequency of the adverse events has been derived from more than 30 years of post-marketing reports.

*The incidence of these AEs was derived from clinical studies involving a total of approximately 929 adult and paediatric patients taking flucloxacillin.

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; website: www.mhra.gov.uk/yellowcard

Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and should be treated symptomatically.

Flucloxacilline Sandoz is not removed from the circulation by haemodialysis.

Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and should be treated symptomatically.

Flucloxacillin is not removed from the circulation by haemodialysis.

Pharmacotherapeutic Group: Beta-Lactamase Resistant Penicillins

ATC CODE: J01CF05

Properties: Flucloxacilline Sandoz is a narrow-spectrum antibiotic of the group of isoxazolyl penicillins; it is not inactivated by staphylococcal β-lactamases.

Activity: Flucloxacilline Sandoz, by its action on the synthesis of the bacterial wall, exerts a bactericidal effect on streptococci except those of group D (Enterococcus faecalis) staphylococci. It is not active against methicillin-resistant staphylococci.

There is evidence that the risk of Flucloxacilline Sandoz induced liver injury is increased in subjects carrying the HLA-B*5701 allele. Despite this strong association, only 1 in 500-1000 carriers will develop liver injury. Consequently, the positive predictive value of testing the HLA-B*5701 allele for liver injury is very low (0.12%) and routine screening for this allele is not recommended

Properties: Flucloxacillin is a narrow-spectrum antibiotic of the group of isoxazolyl penicillins; it is not inactivated by staphylococcal β-lactamases.

Activity: Flucloxacillin, by its action on the synthesis of the bacterial wall, exerts a bactericidal effect on streptococci except those of group D (Enterococcus faecalis) staphylococci. It is not active against methicillin-resistant staphylococci.

There is evidence that the risk of flucloxacillin induced liver injury is increased in subjects carrying the HLA-B*5701 allele. Despite this strong association, only 1 in 500-1000 carriers will develop liver injury. Consequently, the positive predictive value of testing the HLA-B*5701 allele for liver injury is very low (0.12%) and routine screening for this allele is not recommended

Absorption: Flucloxacilline Sandoz is stable in acid media and can therefore be administered either by the oral or parenteral route. The peak serum levels of Flucloxacilline Sandoz reached after one hour are as follows.

- After 250mg by the oral route (in fasting subjects): Approximately 8.8mg/l.

- After 500mg by the oral route (in fasting subjects): Approximately 14.5mg/l.

- After 500mg by the IM route: Approximately 16.5mg/l.

The total quantity absorbed by the oral route represents approximately 79% of the quantity administered.

Distribution: Flucloxacilline Sandoz diffuses well into most tissue. Specifically, active concentrations of Flucloxacilline Sandoz have been recovered in bones: 11.6mg/l (compact bone) and 15.6mg/l (spongy bone), with a mean serum level of 8.9mg/l.

Crossing the meningeal barrier: Flucloxacilline Sandoz diffuses in only small proportion into the cerebrospinal fluid of subjects whose meninges are not inflamed.

Crossing into mothers' milk: Flucloxacilline Sandoz is excreted in small quantities in mothers' milk.

Metabolism: In normal subjects approximately 10% of the Flucloxacilline Sandoz administered is metabolised to penicilloic acid. The elimination half-life of Flucloxacilline Sandoz is in the order of 53 minutes.

Excretion: Excretion occurs mainly through the kidney. Between 65.5% (oral route) and 76.1% (parenteral route) of the dose administered is recovered in unaltered active form in the urine within 8 hours. A small portion of the dose administered is excreted in the bile. The excretion of Flucloxacilline Sandoz is slowed in cases of renal failure.

Protein binding: The serum protein-binding rate is 95%.

Absorption: Flucloxacillin is stable in acid media and can therefore be administered either by the oral or parenteral route. The peak serum levels of flucloxacillin reached after one hour are as follows.

- After 250 mg by the oral route (in fasting subjects): Approximately 8.8 mg/l.

- After 500 mg by the oral route (in fasting subjects): Approximately 14.5mg/l.

- After 500 mg by the IM route: Approximately 16.5 mg/l.

The total quantity absorbed by the oral route represents approximately 79% of the quantity administered.

Distribution: Flucloxacillin diffuses well into most tissue. Specifically, active concentrations of flucloxacillin have been recovered in bones: 11.6 mg/l (compact bone) and 15.6 mg/l (spongy bone), with a mean serum level of 8.9 mg/l.

Crossing the meningeal barrier: Flucloxacillin diffuses in only small proportion into the cerebrospinal fluid of subjects whose meninges are not inflamed.

Crossing into mother's milk: Flucloxacillin is excreted in small quantities in mother's milk.

Metabolism: In normal subjects approximately 10% of the flucloxacillin administered is metabolised to penicilloic acid. The elimination half-life of flucloxacillin is in the order of 53 minutes.

Excretion: Excretion occurs mainly through the kidney. Between 65.5% (oral route) and 76.1% (parenteral route) of the dose administered is recovered in unaltered active form in the urine within 8 hours. A small portion of the dose administered is excreted in the bile. The excretion of flucloxacillin is slowed in cases of renal failure.

Protein binding: The serum protein-binding rate is 95%.

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

No further information of relevance to add.

As for Penicillin. Incompatible with Colistin Polymixin B Sulphate. Loss of potency after mixing with Streptomycin has also been reported.

None known.

To reconstitute, add 58ml of water, replace the lid and shake the bottle well.

None stated.