Chemical formula: C₁₉H₁₇ClFN₃O₅S Molecular mass: 453.872 g/mol PubChem compound: 21319
Floxacillin interacts in the following cases:
Since bacteriostatic drugs such as chloramphenicol and tetracycline may interfere with the bactericidal effect of penicillins in the treatment of meningitis or in other situations in which a rapid bactericidal effect is necessary, it is best to avoid concurrent therapy.
Flucloxacillin should be used with caution in patients with evidence of hepatic dysfunction.
In severe renal failure (creatinine clearance less than 10ml/min) a reduction in dose or extension of dose interval should be considered.
Flucloxacillin may decrease the efficacy of oestrogen-containing oral contraceptives.
Oral typhoid vaccine may be inactivated by flucloxacillin.
Flucloxacillin reduces the excretion of methotrexate which can cause methotrexate toxicity.
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.
Plasma concentrations of flucloxacillin are enhanced if probenecid is given concurrently.
Flucloxacillin may reduce the response to sugammadex.
There are cases of altered international normalised ratio (INR) in patients taking warfarin and prescribed a course of flucloxacillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored during addition or withdrawal of flucloxacillin.
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.
Animal studies with flucloxacillin have shown no teratogenic effects. The product 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. The decision to administer any drug during pregnancy should be taken with the utmost care. Therefore flucloxacillin should only be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.
Trace quantities of flucloxacillin can be detected in breast milk. The possibility of hypersensitivity reactions must be considered in breast-feeding infants. Therefore flucloxacillin should only be administered to a breast-feeding mother when the potential benefits outweigh the potential risks associated with the treatment.
Flucloxacillin has no or negligible influence on the ability to drive or operate and use machines.
The following convention has been utilised for the classification of undesirable effects: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1,000), 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), angioneurotic oedema.
If any hypersensitivity reaction occurs, the treatment should be discontinued. (See also Skin and subcutaneous tissue disorders).
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.
Not Known: Oesophageal pain and related events*
* oesophagitis, burn oesophageal, throat irritation, oropharyngeal pain or oral pain
Very rare: Hepatitis and cholestatic jaundice. Changes in liver function laboratory test results (reversible when treatment is discontinued). These reactions are related to neither the dose nor to the route of administration.
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 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.
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.
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.
* The incidence of these AEs was derived from clinical studies involving a total of approximately 929 adult and paediatric patients taking flucloxacillin.
Blood and lymphatic system disorders: Transient leucopenia, thrombocytopenia, haemolytic anaemia, agranulocytosis and neutropenia (which might have some immunological basis); prolongation of bleeding time and defective platelet function are generally associated with large intravenous doses of flucloxacillin or impaired renal function.
Immune system disorders: The most common adverse effects are sensitivity reactions including urticaria, maculo-papular rashes, pruritus, fever, joint pains and angioedema.
Anaphylaxis occasionally occurs and has sometimes been fatal. Late sensitivity reactions may include serum sickness-like reactions (featuring symptoms such as arthralgia, rash, urticaria, fever, angioedema, lymphadenopathy), haemolytic anaemia, nephropathy and acute interstitial nephritis, which is reversible when treatment is discontinued.
Some patients with spirochaete infections such as syphilis or leptospirosis may experience a Jarisch-Herxheimer reaction shortly after treatment with a penicillin is started. Symptoms include fever, chills, headache and reaction at the site of lesions. The reaction can be dangerous in cardiovascular syphilis or where there is a serious risk of increased local damage such as with optic atrophy.
Metabolism and nutrition disorders: Electrolyte disturbances, such as hypokalaemia, due to administration of large amounts of sodium, are generally associated with large intravenous doses of flucloxacillin or impaired renal function.
Post marketing experience: very rare cases of high anion gap metabolic acidosis, when flucloxacillin is used concomitantly with paracetamol, generally in the presence of risk factors.
Psychiatric disorders: Hallucinations.
Nervous system disorders: Convulsions and other signs of central nervous system toxicity are generally associated with large intravenous doses of flucloxacillin or impaired renal function. Encephalopathy has been reported following intrathecal administration and can be fatal. Coma may develop with high doses of flucloxacillin.
Respiratory, thoracic and mediastinal disorders: Acute, severe dyspnoea; bronchospasm.
Gastrointestinal disorders: Diarrhoea, nausea and vomiting, reported with flucloxacillin, commonly occur after oral or parenteral administration. Pseudomembranous colitis has been reported with most antibiotics. Prolonged use of penicillins may lead to the development of oral candidiasis.
Hepatobiliary disorders: Changes in liver function test results may occur, but are reversible when treatment is discontinued. Hepatitis and cholestatic jaundice have been reported. These reactions are related neither to the dose nor to the route of administration; administration for more than two weeks and increasing age are risk factors. The onset of these 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, almost always 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 500-1000 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: Erythema multiforme; Stevens-Johnson syndrome; toxic epidermal necrolysis (Lyell’s syndrome); erythema nodosum; pemphigoid reactions; non-thrombocytopenic purpura; vasculitis.
Frequency not known: AGEP – acute generalized exanthematous pustulosis.
Congenital, familial and genetic disorders: Acute attacks of porphyria.
General disorders and administration site conditions: Phlebitis has followed intravenous infusion.
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