Flucloxacillin 3219247 225752444 2008-07-15T06:29:40Z SashatoBot 743015 robot Adding: [[sr:Флуклоксацилин]] {{drugbox | | image = Flucloxacillin structure.svg | width = 250 | image2 = Flucloxacillin3d.png | IUPAC_name = 6-((''S'')-3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-<br />4-carboxamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo<br />[3.2.0]heptane-2-carboxylic acid | CAS_number = 5250-39-5 | ATC_prefix = J01 | ATC_suffix = CF05 | PubChem = 21319 | DrugBank = APRD00609 | C = 19 | H = 17 | Cl = 1 | F = 1 | N = 3 | O = 5 | S = 1 | molecular_weight = 453.87 g/mol | bioavailability = 50–70% | metabolism = [[Liver|Hepatic]] | elimination_half-life = 0.75–1 hour | excretion = [[Kidney|Renal]] | pregnancy_AU = B1 | pregnancy_US = | legal_AU = S4 | legal_UK = POM | legal_US = | routes_of_administration = Oral, [[intramuscular injection|IM]], [[intravenous therapy|IV]], [[intrapleural]], [[intraarticular]] }} '''Flucloxacillin''' ([[International Nonproprietary Name|INN]]) or '''floxacillin''' ([[United States Approved Name|USAN]]) is a [[narrow-spectrum antibiotic|narrow spectrum]] [[beta-lactam antibiotic]] of the [[penicillin]] class. It is used to treat infections caused by susceptible [[Gram-positive]] [[bacteria]]. Nowadays, it is no longer recommended against [[beta-lactamase]]-producing organisms such as ''[[Staphylococcus aureus]]'', since like in other [[penicillin]]s, it has become not active against such infections. It is very similar to [[dicloxacillin]] and these two agents are considered interchangeable. Flucloxacillin is available under a variety of trade names including '''Flopen''' ([[CSL Limited|CSL]]) and '''Floxapen''' ([[GlaxoSmithKline|GSK]]). ==Mode of action== {{main|Beta-lactam antibiotic}} Like other β-lactam antibiotics, flucloxacillin acts by inhibiting the synthesis of bacterial [[cell wall]]s. It inhibits cross-linkage between the linear [[peptidoglycan]] polymer chains that make up a major component of the cell wall of [[Gram-positive]] bacteria. ==Medicinal chemistry== Flucloxacillin is insensitive to [[beta-lactamase]] (also known as penicillinase) enzymes secreted by many penicillin-resistant bacteria. The presence of the [[isoxazole|isoxazolyl]] group on the [[side chain]] of the penicillin nucleus facilitates the β-lactamase resistance, since they are relatively intolerant of side-chain [[steric hindrance]]. Thus it is able to bind to [[penicillin binding protein]]s (PBPs) and inhibit [[peptidoglycan]] crosslinking, but is not bound by or inactivated by β-lactamases. ==Clinical use== Flucloxacillin is more acid-stable than many other penicillins and can be given orally, in addition to [[parenteral]] routes. However, like [[methicillin]], it is less potent than [[benzylpenicillin]] against non-β-lactamase-producing [[Gram-positive]] bacteria. Flucloxacillin has similar [[pharmacokinetics]], antibacterial activity and indications to dicloxacillin and the two agents are considered interchangeable. It is believed to have higher incidence of severe hepatic [[adverse effect (medicine)|adverse effects]] than dicloxacillin, but a lower incidence of renal adverse effects.<ref name="AMH2006">Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006.</ref> ===Available forms=== Flucloxacillin is commercially available as the sodium salt '''flucloxacillin sodium''', in [[tablet|capsule]]s (250 or 500 [[milligrams|mg]]), oral [[Suspension (chemistry)|suspension]]s (125 mg/5 [[millilitre|mL]] or 250 mg/5 mL), and injections (powder for reconstitution, 250, 500 and 1000 mg per vial). ===Indications=== Flucloxacillin is indicated for the treatment of infections caused by susceptible bacteria. Specific approved indications include:<ref name="AMH2006" /><ref name="BNF50">Joint Formulary Committee. [[British National Formulary]], 50th edition. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2005.</ref> *[[Staphylococcus|Staphylococcal skin infections]] and [[cellulitis]] – including [[impetigo]], [[otitis externa]], [[folliculitis]], [[boil]]s, [[carbuncles]], and [[mastitis]] *[[Pneumonia]] (adjunct) *[[Osteomyelitis]], [[septic arthritis]] *[[Septicaemia]] *[[Empirical treatment]] for [[endocarditis]] *Surgical [[prophylaxis]] Flucloxacillin has relatively poor activity, as noted above, against non-β-lactamase-producing bacteria including ''[[Streptococcus pyogenes]]''. Therefore empirical therapy for significant cellulitis often involves dual-therapy to cover both [[Staphylococcus|staphylococci]] and [[Streptococcus|streptococci]], using either [[penicillin]] or [[ampicillin]] in addition to flucloxacillin. The latter is available as a standardised combination preparation [[co-fluampicil]] (flucloxacillin+ampicillin). ===Precautions/contraindications=== Flucloxacillin is contraindicated in those with a previous history of allergy to [[penicillin]]s, [[cephalosporin]]s or [[carbapenem]]s. It should also not be used in the eye, or those with a history of [[cholestasis|cholestatic hepatitis]] associated with the use of dicloxacillin or flucloxacillin.<ref name="AMH2006" /> 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.<ref name="AMH2006" /> ==Adverse effects== Common [[adverse drug reaction]]s (ADRs) associated with the use of flucloxacillin include: [[diarrhoea]], [[nausea]], [[rash]], [[urticaria]], [[pain]] and [[inflammation]] at injection site, [[superinfection]] (including [[candidiasis]]), [[allergy]], and transient increases in liver enzymes and bilirubin.<ref name="AMH2006" /> Rarely, [[cholestasis|cholestatic jaundice]] (also referred to as cholestatic hepatitis) has been associated with flucloxacillin therapy. The reaction may occur up to several weeks after treatment has stopped, and takes weeks to resolve. The estimated incidence is 1 in 15,000 exposures, and is more frequent in people >55 years, females, and those with treatment longer than 2 weeks.<ref name="AMH2006" /><ref name="BNF50" /> ==Resistance== Despite flucloxacillin being insensitive to beta-lactamases, some organisms have developed resistance to it and other narrow-spectrum β-lactam antibiotics including methicillin. Such organisms include [[Methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']] (MRSA). ==See also== *[[Beta-lactam antibiotic]] *[[Dicloxacillin]] ==References== <references /> {{PenicillinAntiBiotics}} [[Category:Beta-lactam antibiotics]] [[Category:Isoxazoles]] [[nl:Flucloxacilline]] [[pt:Flucloxacilina]] [[sr:Флуклоксацилин]] [[sv:Flukloxacillin]] [[th:ฟลูคลอกซาซิลลิน]]