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| Trade names | Floxapen, others[1] |
| Other names | BRL-2039 |
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| Routes of administration | By mouth,intramuscular,intravenous,intrapleural,intraarticular |
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| Pharmacokinetic data | |
| Bioavailability | 50–70% |
| Metabolism | Liver |
| Eliminationhalf-life | 0.75–1 hour[5] |
| Excretion | Kidney[5] |
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| ECHA InfoCard | 100.023.683 |
| Chemical and physical data | |
| Formula | C19H17ClFN3O5S |
| Molar mass | 453.87 g·mol−1 |
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Flucloxacillin, also known asfloxacillin, is anantibiotic used to treatskin infections,external ear infections, infections of leg ulcers, diabetic foot infections, andinfection of bone.[6] It may be used together with other medications to treatpneumonia, andendocarditis.[6] It may also be used prior to surgery to preventStaphylococcus infections.[6] It is not effective againstmethicillin-resistantStaphylococcus aureus (MRSA).[7] It is taken by mouth or given by injection into a vein or muscle.[6]
Common side effects include an upset stomach.[6] Other side effects may include muscle or joint pains, shortness of breath, and liver problems.[6][8] It appears to be safe during pregnancy and breastfeeding.[6] It should not be used in those who are allergic topenicillin.[6] It is anarrow-spectrumbeta-lactam antibiotic of thepenicillin class.[8] It is similar in effect tocloxacillin anddicloxacillin, being active againstpenicillinase forming bacteria.[9]
Flucloxacillin was patented in 1961.[10]
Flucloxacillin is not available in the United States.
Flucloxacillin is anantibiotic used to treatlactational mastitis (drug of choice),skin infections,external ear infections, infections of leg ulcers,diabetic foot infections, andinfection of bone.[6]
Flucloxacillin is used for bothstaphylococcal andstreptococcal skin infections.[11] These includefolliculitis,carbuncles,[12]impetigo,ecthyma,cellulitis,erysipelas,necrotising fasciitis, and infections of skin conditions such aseczema,scabies, ulcers andacne.[6][11][13] Due to the widespread belief that dual-therapy is needed to cover bothStaphylococcus andStreptococcus in cellulitis, flucloxacillin is sometimes given with the addition ofbenzylpenicillin for more severe cellulitis.[5] However, support for this practice has lessened since findings in a study published in theEmergency Medicine Journal in 2005 did not show this combination to give additional clinical benefit.[14][15][16] In the UK, using flucloxacillin alone is the first choice for treating cellulitis. Some other countries vary.[17]
Infections of leg ulcers can be treated with flucloxacillin.[6] With diabetic foot infections the dose is adjusted according to whether the infection appears mild, moderate or severe.[6]
Despite having a lower than optimum drug penetration into bone ratio of 10–20%, flucloxacillin appears effective in treatingosteomyelitis.[18][19]
Depending on local guidance it may be used in the treatment ofinfection of joints while waiting for culture results.[5][20]
It may be used in combination with other antibiotics to treatpneumonia and can be used to prevent infection before surgery, particularly heart, lung, or bone surgery.[6][13] When used to treatendocarditis, in combination with other antibiotics or alone, the dose of flucloxacillin may need to exceed the usual dose.[6]
Despite flucloxacillin being insensitive to beta-lactamases, some organisms have developed resistance to it and other narrow-spectrum β-lactam antibiotics includingmethicillin. Such organisms includemethicillin-resistantStaphylococcus aureus, which has developed resistance to flucloxacillin and other penicillins by having an altered penicillin-binding protein.[21]
Common side effects associated with the use of flucloxacillin include:diarrhoea,nausea,rash,urticaria,pain andinflammation at injection site,superinfection (includingcandidiasis),allergy, and transient increases in liver enzymes and bilirubin.[22]
Rarely, in fewer than 1 in 1,000 people,cholestatic jaundice (also referred to as cholestatic hepatitis) has been associated with flucloxacillin therapy. It may appear as pale stool with dark urine, and yellowish eyes and skin.[23] The reaction may occur up to several weeks after treatment has stopped, and takes weeks to resolve. The estimated incidence is one in 15,000 exposures, and is more frequent in people over the age of 55, females, and those with a treatment duration of longer than two weeks.[6][23][22]
Flucloxacillin is contraindicated in those with a previous history of allergy to penicillins,cephalosporins, orcarbapenems. It should also not be used in the eye, or administered to those with a history ofcholestatic hepatitis associated with the use of dicloxacillin or flucloxacillin.[22]
It should be used with caution in the elderly, patients with renal impairment where a reduced dose is required, and those with hepatic impairment, due to the risk of cholestatic hepatitis.[22]
It should be taken on an empty stomach, as absorption is reduced when taken with food,[23][24] though some studies suggest that this does not compromise flucloxacillin plasma concentrations in most circumstances.[25]
Flucloxacillin can reduce the excretion ofmethotrexate, potentially resulting in a risk of methotrexate toxicity. The level of flucloxacillin in the blood may rise in kidney failure and with the use ofprobenecid.[9]
Flucloxacillin is anarrow-spectrumantibiotic belonging to thepenicillin group ofantibiotics.[8][26] It works by breaking down the bacterial cell wall.[26]
Like other β-lactam antibiotics, flucloxacillinacts by inhibiting the synthesis of bacterialcell walls. It inhibits cross-linkage between the linearpeptidoglycan polymer chains that make up a major component of the cell wall ofGram-positive bacteria.[citation needed]
Flucloxacillin is more acid-stable than many other penicillins and can be given orally, in addition toparenteral routes. However, likemethicillin, it is less potent thanbenzylpenicillin against non-β-lactamase-producing Gram-positive bacteria.[citation needed]
Flucloxacillin has similarpharmacokinetics, antibacterial activity, and indications to dicloxacillin, and the two agents are considered interchangeable. It is reported to have higher, though rare, incidence of severe hepaticadverse effects than dicloxacillin,[27] but a lower incidence of renal adverse effects.[22]
Flucloxacillin is insensitive tobeta-lactamase (also known as penicillinase) enzymes secreted by many penicillin-resistant bacteria. The presence of theisoxazolyl group on theside chain of the penicillin nucleus facilitates the β-lactamase resistance, since they are relatively intolerant of side chainsteric hindrance. Thus, it is able to bind topenicillin-binding proteins and inhibit peptidoglycan crosslinking, but is not bound by or inactivated by β-lactamases.[citation needed]
Flucloxacillin was developed in the 1960s following an increase in penicillin-resistant (beta-lactamase producing) staphylococcal infections due to the widespread use ofbenzylpenicillin by 1960.[28][29] All the natural penicillins and first semi-synthetic penicillins were destroyed by staphylococcal beta-lactamase, leadingBeecham (laterGlaxoSmithKline) to search for more stable antibiotics. By 1962, a series of similarly structured acid-stable penicillins (oxacillin,cloxacillin,dicloxacillin and flucloxacillin), with the potential for being taken by mouth, were developed. Flucloxacillin and dicloxacillin showed particular stability against the beta-lactamase enzyme ofStaph. aureus and could withstand acid.[28][29] Beecham further developed cloxacillin and popularised flucloxacillin in the UK, whileBristol Laboratories concentrated on marketing oxacillin and dicloxacillin in the United States, leading to the difference in use in both countries.[30][31] Flucloxacillin was first marketed in Europe in the 1970s.[8]
Both the oral and intravenous preparations of flucloxacillin are inexpensive and are available as the sodium salt flucloxacillin sodium, incapsules (250 or 500 mg), oralsuspensions (125 mg/5 ml or 250 mg/5 ml), and injections (powder for reconstitution, 250, 500, 1000 and 2000 mg per vial).[5][32]
Flucloxacillin is not commonly used in the United States or Canada as of 2011,[8] but is the most commonly prescribed narrow-spectrum penicillinase-resistant penicillin in the UK.[33] It is supplied under a variety of trade names including Floxapen, Flopen, Flubex, Flupen, Phylopen, and Staphylex.[1]
Flucloxacillin is combined withampicillin inco-fluampicil.[6]
