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Penicillinase-Resistant Penicillin — Staphylococcal Infections Pregnancy: Safe in pregnancy — penicillins generally considered safe; neonatal cholestatic jaundice reported (rare)

Flucloxacillin

Brand names: Floxapen

Adult dose

Dose: Mild-moderate: 250–500 mg every 6 hours orally; Severe (cellulitis, septic arthritis, osteomyelitis): 1–2 g IV every 6 hours
Route: Oral or IV
Frequency: 4 times daily (every 6 hours)
Max: 8 g/day IV (severe infections)
Take oral formulation on an empty stomach (30 minutes before food — food reduces absorption). IV formulation: give over 30–60 minutes (undiluted rapid injection causes phlebitis). First-line for MSSA (methicillin-sensitive Staphylococcus aureus) — cellulitis, skin and soft tissue, osteomyelitis, septic arthritis, endocarditis.

Paediatric dose

Dose: 12.5–25 mg/kg mg/kg
Route: Oral or IV
Frequency: 4 times daily
Max: Adult dose (2 g/dose IV for severe infections)
BNFc: neonates — 25 mg/kg every 6–12 hours depending on age and weight; used for neonatal MSSA infections

Dose adjustments

Renal

No dose adjustment required for mild-moderate renal impairment; reduce dose in severe renal failure

Hepatic

Use with caution — can cause cholestatic hepatitis; MHRA warning

Paediatric weight-based calculator

BNFc: neonates — 25 mg/kg every 6–12 hours depending on age and weight; used for neonatal MSSA infections

Clinical pearls

  • MHRA Safety Alert 2016: flucloxacillin associated with cholestatic hepatitis — onset can be delayed up to 2 months after stopping; jaundice and elevated ALP are characteristic; usually resolves on stopping but can be severe
  • Flucloxacillin is resistant to staphylococcal penicillinase — first-line for MSSA; ineffective against MRSA (use vancomycin/daptomycin)
  • Must be taken on empty stomach — food reduces oral absorption by up to 50%
  • IV route preferred in severe infections — oral bioavailability only 50–70%
  • Osteomyelitis and septic arthritis: typically 6 weeks of treatment (initially IV then step-down to oral guided by clinical response and CRP)

Contraindications

  • Penicillin allergy
  • Previous flucloxacillin-associated jaundice/hepatic dysfunction

Side effects

  • GI upset (nausea, diarrhoea)
  • Cholestatic hepatitis (rare but serious — MHRA alert)
  • Hypersensitivity/anaphylaxis
  • Rash
  • Phlebitis (IV)
  • Neutropenia (prolonged courses)

Interactions

  • Warfarin — enhanced anticoagulant effect
  • Methotrexate — reduced renal clearance of methotrexate
  • Probenecid — increases flucloxacillin levels

Monitoring

  • LFTs (if prolonged course — monitor for cholestatic hepatitis)
  • Renal function
  • FBC (neutropenia in prolonged courses)
  • CRP and inflammatory markers (treatment response)

Reference: BNFc; BNF 90; MHRA Drug Safety Update 2016 (Flucloxacillin Hepatotoxicity); NICE CG121 (Cellulitis); Public Health England Antibiotic Guidelines. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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