Flucloxacillin unpredictably alters the anticoagulant effect of warfarin (may ↑ or ↓ INR), with bleeding or thrombosis risk; the BNF classifies it as a severe interaction.
Combined mechanisms: reduced vitamin K–synthesising gut flora (↑ INR) and enzyme induction of warfarin metabolism (↓ INR); BNF/NICE: "Flucloxacillin potentially alters the anticoagulant effect of warfarin. Manufacturer advises monitor INR and adjust dose. Severity: Severe".
Frequent INR during and 1–2 weeks after the course; bleeding and thrombosis signs.
Bruising, gum bleeding, dark urine (↑ INR) or DVT/embolism (↓ INR).
Measure INR 3–5 days after starting and after finishing the antibiotic; adjust the warfarin dose; counsel the patient on bleeding and thrombosis signs.
BNF/NICE — Warfarin interactions: flucloxacillin (Severity: Severe): https://bnf.nice.org.uk/interactions/warfarin/; EMC-UK — Flucloxacillin Capsules 500 mg SmPC [Flamingo Pharma], sec. 4.5: https://www.medicines.org.uk/emc/product/14151/smpc; DailyMed — Warfarin Sodium Tablet label [RLD Coumadin]: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=654ca5d2-d4c1-48f8-90c4-130a21162bb0
Probenecid reduces the renal excretion of flucloxacillin, raising its plasma levels (sometimes used intentionally, but with increased adverse effect risk).
Probenecid inhibits the renal tubular secretion of penicillins; EMC-UK Flucloxacillin SmPC 4.5: "Probenecid and sulfinpyrazone slow down the excretion of flucloxacillin".
Plasma levels if critically ill; renal function; GI and hepatic effects.
Nausea, vomiting, jaundice (cholestatic hepatotoxicity at high doses).
If co-administration is intentional (potentiation), monitor doses; otherwise avoid; adjust dose in renal impairment.
EMC-UK — Flucloxacillin Capsules 500 mg SmPC [Flamingo Pharma], sec. 4.5: https://www.medicines.org.uk/emc/product/14151/smpc; Flucloxacillin 500 mg capsules, hard SmPC [Brown & Burk]: https://www.medicines.org.uk/emc/product/12636/smpc
Food significantly reduces flucloxacillin absorption — doses should be taken 30–60 minutes BEFORE meals.
Take 30–60 minutes before meals, with a glass of water.
EMC-UK — Flucloxacillin SmPC 4.2 (take on empty stomach) / Prontuário 6.1.1.
Flucloxacillin causes severe idiosyncratic cholestatic hepatitis (increased risk with pre-existing hepatic dysfunction) — avoid with prior biliary disease.
Exclude biliary disease before starting; if jaundice develops during treatment, stop immediately (cholestasis can be late and prolonged).
Prontuário Terapêutico INFARMED, 6.1.1 (flucloxacillin — cholestasis reported); EMC-UK Flucloxacillin SmPC 4.4 (hepatotoxicity warning).
Annex 1 refers to Penicillins: "no fetal risk" (factor B). Flucloxacillin is the antistaphylococcal penicillin of choice in pregnancy infections when indicated; usual dose 250–500 mg 4×/day. Note: take on an empty stomach (30–60 min before meals) to maximise absorption — see the drug-food interaction in 280.
Compatible in all trimesters; use when indicated by susceptibility.
Compatible: penicillins pass into milk "in amounts too small to be harmful" (Annex 2, l. 43017-19); monitor the infant for thrush and gut flora changes.
Prontuário Terapêutico INFARMED — Annex 1: "Flucloxacillin — See Penicillins" (l. 40277) and "Penicillins — No fetal risk" (l. 41286-87); Annex 2 (l. 43017-19).
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Bactericidal against sensitive S. aureus (including β-lactamase+); tissue peaks > 0.5 mg/L maintain deep-infection activity.
Inhibition of penicillin-binding proteins (PBPs) → block of peptidoglycan wall transpeptidation; resistance to staphylococcal β-lactamase via steric shielding by the isoxazol substituent.
Oral: rapid absorption but reduced by food (fasting recommended); IM: 100%; high protein binding (> 90%).
Hepatic: hydroxylation and deacetylation to inactive metabolites; biliary and renal (tubular) excretion.
~ 0.75–1 h (prolonged in severe renal impairment).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
