Flucloxacillin

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications: 

• Infections caused by susceptible Gram-positive organisms, including beta-lactamase producing staphylococci and streptococci:
  - Skin and soft tissue infections
  - Infected wounds and burns
  - Otitis media
  - Urinary tract infections
  - Respiratory tract infections caused by penicillinase producing organisms
  - Orthopaedic infections
  - Septicaemia
  - Meningitis
  - Endocarditis
  - Enterocolitis

Registered contraindications in South Africa & other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to β-lactam antibiotics (e.g. penicillins, cephalosporins)
• Previous history of flucloxacillin-associated jaundice or hepatic dysfunction

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment (CrCl <10ml/min)
• Hepatic impairment
• Elderly
• Patients with underlying disease at risk of hepatic reactions (See additional prescribing points)
• Prolonged use
• Contact with the skin
• Newborns
• Patients on sodium restricted diets
• Sepsis
• Malnutrition
• Coadministration with paracetamol

Forms avail. in SA and covered in this monograph: cap

Dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages

Infections caused by: Gram-positive organisms, particularly penicillinase-producing strains of Staphylococcus aureus, Streptococci (except those of group D (Enterococcus faecalis)); Staphylococci (except methicillin-resistant staphylococci)

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Septic arthritis
- If good clinical response after 2 weeks of IV therapy
Acute osteomyelitis
- If good clinical response after 2 weeks of IV therapy

• Oral (cap): 1g, 6hrly; Treatment duration: 2 weeks 
  (STG, Adult 2019)

Furuncle
Abscess

• Oral (cap): 500mg, 6hrly; Treatment duration: 5-10 days (depending on clinical response)
  (STG, Adult 2019)

Boil
Cellulitis
Erysipelas
Impetigo
Secondary infection of herpes zoster lesions
Secondary infection of eczematous lesions
Acute paronychia
Mastitis
Otitis externa - furuncular

• Oral (cap): 500mg, 6hrly; Treatment duration: 5 days
  (STG, Adult 2019; PHC 2020; PHC 2023)

Surgical wound infections
- Once patient can swallow and temperature <37.8°C for 24hrs

• Oral (cap): 500mg, 6hrly; Treatment duration: ≤7 days 
  (STG, Adult 2019)

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South African registered indications and dosages

Infections caused by susceptible Gram-positive organisms, including beta-lactamase producing staphylococci and streptococci:
- Skin and soft tissue infections
- Infected wounds and burns
- Otitis media
- Urinary tract infections
- Respiratory tract infections caused by penicillinase producing organisms
- Orthopaedic infections, including osteomyelitis
- Septicaemia
- Meningitis
- Endocarditis
- Enterocolitis

• Oral (cap): 250mg, 6hrly taken 1hr before meals; In severe infections: Doses may be doubled; For endocarditis and osteomyelitis: Up to 8g/day, in 3-4 divided doses may be given 

Paed. forms avail. in SA and covered in this monograph: cap

Dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages

Infections caused by: Gram-positive organisms, particularly penicillinase-producing strains of Staphylococcus aureus, Streptococci (except those of group D (Enterococcus faecalis)); Staphylococci (except methicillin-resistant staphylococci)

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Staphylococcal scalded skin syndrome
Erysipelas
- Non-severe disease

• Oral (cap): 25mg/kg/dose, 6hrly; Treatment duration: 7 days
  (STG, Paed. 2023)

Septic arthritis (Pyogenic)
- Following sustained clinical improvement with IV treatment, resolution of fever and CRP <30mg/L in children able to swallow a capsule

• Oral (cap): 12.5-25mg/kg/dose, 6hrly; Treatment duration: 2-4 weeks
  (STG, Paed. 2023)

Acute osteitis/osteomyelitis
- Following sustained clinical improvement with IV treatment, resolution of fever and CRP <30mg/L

• Oral (cap): 25mg/kg/dose, 6hrly; Treatment duration: 4-6 weeks
  (STG, Paed. 2023)

Erythema multiforme with secondary infection
Stevens-Johnson Syndrome/ Toxic epidermal necrosis with secondary infection

• Oral (cap): 25mg/kg/dose, 6hrly
  (STG, Paed. 2023)

Boil
Abscess
Impetigo
Acute eczema, moist or weeping with secondary infection 
Otitis externa
- Furuncular

7 years and younger

• Oral (cap): 12-25mg/kg/dose, 6hrly; Treatment duration: 5 days

Older than 7 years

• Oral (cap): 500mg, 6hrly; Treatment duration: 5 days
  (STG, PHC 2020)

Cellulitis

• Oral (cap): 25mg/kg, 6hrly; Treatment duration: 7 days
  (STG, Paed. 2023)

OR

7 years and younger

• Oral (cap): 12-25mg/kg/dose, 6hrly; Treatment duration: 5 days

Older than 7 years

• Oral (cap): 500mg, 6hrly; Treatment duration: 5 days 
  (STG, PHC 2020)

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South African registered indications and dosages

• Not established for use

Pregnancy

• Caution; no evidence of risk in studies
• Animal studies with flucloxacillin have shown no teratogenic effects. Flucloxacillin has been in clinical use since 1970 and the limited number of reported cases of use in human pregnancy have shown no evidence of untoward effects
• Flucloxacillin should only be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment

Breastfeeding

• Caution
• Flucloxacillin is secreted into breastmilk and may occasionally cause sensitisation of the infant. The possibility of hypersensitivity reactions must be considered in breastfeeding infants. Therefore, flucloxacillin should be administered to a breastfeeding mother when the potential benefits outweigh the potential risks associated with the treatment

Fertility

• No information available

• Mild to moderate (CrCl ≥10ml/min): No dose adjustment recommended
• Severe (CrCl <10ml/min): Caution; dose adjustment recommended
  In CrCl <10ml/min, a reduction in dosage may be necessary
  Flucloxacillin is not significantly removed by dialysis and no supplementary dosages need to be administered either during or at the end of the dialysis period

• Caution; no dose adjustment recommended
  Use with caution in patients with evidence of hepatic dysfunction or in patients with underlying disease as all of whom are at increased risk of hepatic reactions

• Caution; no dose adjustment recommended
  Patients >50 years are at increased risk of hepatic reactions

Gastrointestinal Disorders

• Minor gastrointestinal disturbances
• Pseudomembranous colitis

Hepatobiliary Disorders

• Hepatitis
• Cholestatic jaundice
• Changes in hepatic function tests
• Severe hepatic events (with fatal outcome), including flucloxacillin-induced hepatic injury

Genitourinary Disorders

• Interstitial nephritis

Endocrine and Metabolic Disorders

• High anion gap metabolic acidosis (Coadministration with paracetamol - See additional prescribing points)

Musculoskeletal Disorders

• Athralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Rash
• Urticaria
• Purpura
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Acute generalised exanthematous pustulosis

Immune, Blood and Lymphatic System Disorders

• Neutropenia (including agranulocytosis)
• Thrombocytopenia
• Eosinophilia
• Haemolytic anaemia
• Anaphylactic shock
• Hypersensitivity reaction
• Angioneurotic oedema
• Fever

• Probenecid
• Sulfinpyrazone
• Agents excreted via renal tubular secretion
• Piperacillin
• Oral typhoid vaccine
• Methotrexate
• Sugammadex
• Warfarin
• Bacteriostatic agents
• Paracetamol (See additional prescribing points)

None routine. Specific cases may require

• Hepatic function
• Renal function
• Acid-base disorders, namely HAGMA and urinary 5-oxoproline (coadministration with paracetamol)
• International Normalised Ratio (INR) and Prothrombin Time (coadministration with warfarin)

Coadministration with paracetamol

• Caution is advised when flucloxacillin is administered concomitantly with paracetamol due to the increased risk of high anion gap metabolic acidosis (HAGMA)
• Patients at high risk for HAGMA are in particular those with severe renal impairment, sepsis or malnutrition especially if the maximum daily doses of paracetamol are used
• After coadministration of flucloxacillin and paracetamol, a close monitoring is recommended in order to detect the appearance of acid–base disorders, namely HAGMA, including the search of urinary 5-oxoproline
• If flucloxacillin is continued after cessation of paracetamol, it is advisable to ensure that there are no signals of HAGMA, as there is a possibility of flucloxacillin maintaining the clinical picture of HAGMA

Hepatic reactions

• Hepatitis and cholestatic jaundice have been reported. These reactions are related neither to the dose nor to the route of administration. Flucloxacillin 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
• 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

Flucloxacillin is a narrow-spectrum antibiotic of the group isoxazolyl penicillins that is not inactivated by staphylococcal β-lactamases. Flucloxacillin exerts a bactericidal effect by its action on the synthesis of the bacterial wall

Spectrum of activity: Gram-positive organisms, particularly penicillinase-producing strains of Staphylococcus aureus, Streptococci (except those of group D (Enterococcus faecalis)); Staphylococci (except methicillin-resistant staphylococci)

Capsule 250mg

• Flupen (Dezzo Trading)
• Indo flucloxacillin (Unimed Healthcare)
• Medreich Flucloxacillin (Oethmaan Biosims)
• Sandoz flucloxacillin (Sandoz SA)
• Septapen (Innovata Pharmaceuticals)

COMBINATION PREPARATIONS

Ampicillin/ Flucloxacillin

Capsule 250mg/250mg

• Macropen 500 (Xixia)
• Megapen 500 (Pharmacare)

Suspension (per 5ml) 125mg/125mg

• Megapen S (Pharmacare)
• Macropen S  (Xixia)