Nafcillin !
An intravenous antistaphylococcal penicillin cleared in bile; beware of extravasation and its effect on warfarin.
Updated 2026-11-01
The figure shows Staphylococcus aureus PBP4 with nafcillin bonded to the active-site serine.
Mechanism of action
Nafcillin carries a bulky naphthyl side chain. It belongs to the penicillins resistant to staphylococcal β-lactamase: its bulky side chain keeps penicillinase from opening the β-lactam ring, so it acylates the PBPs of penicillinase-producing staphylococci. It does not work against MRSA, whose PBP2a has low affinity for β-lactams. Its oral absorption is erratic, so it is given parenterally.
- Staphylococcal penicillinase cannot open its ring
- Acylates the staphylococcal PBPs
- Peptidoglycan cross-linking stops
- The staphylococcus lyses
Pharmacokinetics
- Absorption
- Intravenous or intramuscular; oral absorption is erratic.
- Elimination
- Mainly by the liver and bile; kidney failure barely changes its half-life, but liver and biliary disease reduce its clearance.
- Half-life
- 33 to 61 minutes intravenously.
Indications
- Skin and soft-tissue infections due to penicillinase-producing staphylococci. Cellulitis of the leg →
- Staphylococcal osteomyelitis and septic arthritis. Osteomyelitis →
- Bacteraemia and endocarditis due to methicillin-susceptible S. aureus. Infective endocarditis →
Adverse effects
Common
- Phlebitis and pain at the infusion site
- Rash, fever
- Diarrhoea, nausea
Contraindications
- History of a hypersensitivity reaction to any penicillin
Key interactions
- Warfarin
- Nafcillin decreases warfarin's effect; prothrombin time is monitored.
- Ciclosporin
- Subtherapeutic ciclosporin levels in transplant patients; levels are monitored.
- Tetracyclines
- Bacteriostatic: they can antagonise the bactericidal effect; the combination is avoided.
What is monitored
- INR and ciclosporin levels if applicable
- Infusion site
- Liver and kidney function and blood count in long courses
Administration and safety
- Intravenous through a well-flowing line; check the site often: extravasation can necrose the skin.
- If extravasation is suspected, stop the infusion and follow the institutional protocol.
- Do not confuse nafcillin with other antistaphylococcal penicillins.
Nursing care
- Before the first dose: ask about allergy to penicillins, cephalosporins and other β-lactams, and what the reaction was.
- Inspect the infusion site for pain, swelling or blanching.
- Check whether the patient takes warfarin or ciclosporin.
- Teach the patient to report watery or bloody diarrhoea, even weeks after the course ends.
Pregnancy and breastfeeding
Animal studies showed no fetal harm and there are no controlled studies in pregnant women; used if clearly needed.
Test yourself
Think of the answer, then tap the question to see it.
How is nafcillin cleared, and what does that mean in kidney failure?
Mainly by the liver and bile; kidney failure barely changes its half-life.
What local risk does a nafcillin infusion carry?
Extravasation can cause severe tissue necrosis with skin sloughing.
What happens to the INR of a warfarin patient who starts nafcillin?
It tends to fall, because nafcillin decreases warfarin's effect; it is monitored and adjusted.
Related drugs
Related conditions
← Back to the class: Beta-lactams
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Nafcillin Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - NAFCILLIN injection, powder, for solution (DailyMed (U.S. National Library of Medicine), 2026); RCSB PDB - 5TY7: Crystal structure of wild-type S. aureus penicillin binding protein 4 (PBP4) in complex with nafcillin (RCSB Protein Data Bank, 2026); Farmacología básica y clínica (Katzung), cap. 43 (McGraw Hill, 2025).
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Representative model, for educational purposes only.