Source: Health Products Regulatory Authority (IE) Revision Year: 2021 Publisher: Actavis Group PTC ehf, Reykjavikurvegi 76-78, 220 Hafnarfjördur, Iceland
Flucloxacillin should not be given to patients with a history of hypersensitivity to beta‑lactam antibiotics (e.g. penicillins, cephalosporins) or excipients.
Flucloxacillin is contraindicated in patients with a previous history of flucloxacillin-associated jaundice/hepatic dysfunction.
Ocular or subconjunctival administration.
Before initiating therapy with flucloxacillin, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactams. Cross-sensitivity between penicillins and cephalosporins is well documented.
Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving beta-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 beta-lactam hypersensitivity. If an allergic reaction occurs, flucloxacillin should be discontinued and the appropriate therapy instituted. Serious anaphylactoid reactions may require immediate emergency treatment with adrenaline. Oxygen, i.v. steroids, and airway management, including intubation, may also be required.
The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthematous pustulosis (AGEP) (see section undesirable effects). In case of AGEP diagnosis, flucloxacillin should be discontinued and any subsequent administration of flucloxacillin contra-indicated
Flucloxacillin should be used with caution in patients with evidence of hepatic dysfunction, patients > 50 years of age, and those with serious underlying disease. In these patients, hepatic events may be severe, and in extremely rare circumstances, deaths have been reported (see section 4.8).
Dosage should be adjusted in renal impairment (see section 4.2).
Special caution is essential in the newborn because of the risk of hyperbilirubinemia. Studies have shown that, at high dose following parenteral administration, flucloxacillin 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 flucloxacillin 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.
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 co-administration 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 (see section 4.5).
Hypokalaemia (potentially life threatening) can occur with the use of flucloxacillin, especially in high doses. Hypokalaemia caused by flucloxacillin can be resistant to potassium supplementation. Regular measurements of potassium levels are recommended during the therapy with higher doses of flucloxacillin. Attention for this risk is warranted also when combining flucloxacillin with hypokalaemia-inducing diuretics or when other risk factors for the development of hypokalaemia are present (e.g. malnutrition, renal tubule dysfunction).
Sodium content:Floxapen injection contains approximately 51 mg sodium per g. This should be included in the daily allowance of patients on sodium restricted diets.
Probenecid decreases the tubular secretion of flucloxacillin. Concurrent administration of probenecid delays the renal excretion of flucloxacillin.
Bacteriostatic drugs (chloramphenicol, erthromycins, sulphonamides, and tetracyclines) may interfere with the bactericidal action of flucloxacillin.
Methotrexate, reduced excretion may occur with flucloxacillin (increased risk of toxicity).
Caution should be taken when flucloxacillin is used concomitantly with paracetamol as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risk factors. (see section 4.4.)
Penicillins may produce false-positive results with the direct antiglobulin (Coombs') test, falsely high urinary glucose results with the copper sulphate test and falsely high urinary protein results, but glucose enzymatic tests (e.g. Clinistix) and bromophenol blue tests (e.g. Multistix or Albustix) are not affected.
Animal studies with flucloxacillin have shown no teratogenic effects. Limited information is available on the use of flucloxacillin in human pregnancy. Flucloxacillin should only be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.
During lactation, trace quantities of penicillins can be detected in breast milk. Flucloxacillin may be administered during the period of lactation. With the exception of risk of sensitisation there are no other detrimental effects for the breast fed infant.
None known.
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.
Very rare: Neutropenia (including agranulocytosis) and thrombocytopenia. These are reversible when treatment is discontinued. Eosinophilia, haemolytic anaemia.
Very rare: Anaphylactic shock (exceptional with oral administration) (see section 4.4), angioneurotic oedema. If any hypersensitivity reaction occurs, the treatment should be discontinued. (See also Skin and subcutaneous tissue disorders).
Very rare: In patients suffering from renal failure, neurological disorders with convulsions are possible with the I.V. injection of high doses.
Common*: Minor gastrointestinal disturbances.
Very rare: Pseudomembranous colitis.
If pseudomembranous colitis develops, flucloxacillin treatment should be discontinued and appropriate therapy, e.g. oral vancomycin should be initiated.
Very rare: Hepatitis and cholestatic jaundice (see section 4.4). Changes in liver function laboratory test results (reversible when treatment is discontinued).
Hepatitis and cholestatic jaundice may be delayed for up to two months post-treatment. In some cases the course has been protracted and lasted for several months. Hepatic events may be severe, and in very rare circumstances, deaths have been reported. Most reports of deaths have been in patients >50 years of age and in patients with serious underlying disease.
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 500-1,000 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.
Uncommon*: Rash, urticaria and purpura.
Very rare: Erythema multiforme Stevens-Johnson syndrome, and toxic epidermal necrolysis(See also Immune system disorders).
Not known: AGEP – acute generalized exanthematous pustulosis (see section special warnings and precautions for use)
Very rare: Arthralgia and myalgia sometimes develop more than 48 hours after the start of the treatment.
Very rare: Interstitial nephritis.
This is reversible when treatment is discontinued.
Very rare: Fever sometimes develops more than 48 hours after the start of the treatment.
Not known: Hypokalaemia
Post marketing experience: very rare cases of high anion gap metabolic acidosis, when flucloxacillin is used concomitantly with paracetamol, generaly in the presence of risk factors (see section 4.4).
* The incidence of these AEs was derived from clinical studies involving a total of approximately 929 adult and paediatric patients taking flucloxacillin.
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 HPRA Pharmacovigilance, Website: www.hpra.ie.
Floxapen should not be mixed with blood products or other proteinaceous fluids (e.g. protein hydrolysates) or with intravenous lipid emulsions.
If Floxapen is prescribed concurrently with an aminoglycoside, the two antibiotics should not be mixed in the same syringe, intravenous fluid container or giving set; precipitation may occur.
This medicinal product must not be mixed with other medicinal products except those mentioned in 6.6.
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