[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Beta-lactams](https://durgical.com/en/pharmacology/classes/beta-lactams/) › Nafcillin [Pharmacology](https://durgical.com/en/pharmacology/) · [Beta-lactams](https://durgical.com/en/pharmacology/classes/beta-lactams/) # Nafcillin An intravenous antistaphylococcal penicillin cleared in bile; beware of extravasation and its effect on warfarin. Updated 2026-11-01 - Class: [Beta-lactams](https://durgical.com/en/pharmacology/classes/beta-lactams/) - Enzyme: Penicillin-binding proteins (bacterial transpeptidases) - ATC code: J01CF06 ✂**Penicillin-binding proteins (bacterial transpeptidases)**Nafcillin ⓘ The figure shows Staphylococcus aureus PBP4 with nafcillin bonded to the active-site serine. **Target in 3D:** Penicillin-binding proteins (bacterial transpeptidases). PDB structure 5TY7 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/5TY7) · Drag to rotate · pinch to zoom ## 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 →](https://durgical.com/en/conditions/cellulitis-of-the-leg/) - Staphylococcal osteomyelitis and septic arthritis. [Osteomyelitis →](https://durgical.com/en/conditions/osteomyelitis/) - Bacteraemia and endocarditis due to methicillin-susceptible S. aureus. [Infective endocarditis →](https://durgical.com/en/conditions/infective-endocarditis/) ## Adverse effects ### Common - Phlebitis and pain at the infusion site - Rash, fever - Diarrhoea, nausea ### Serious (rare, important) - Anaphylaxis - Severe tissue necrosis with sloughing if it extravasates - Interstitial nephritis and neutropenia (rare) - Clostridioides difficile diarrhoea, from mild to severe colitis ## 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. ## Memory aid 'Nafcillin = bile, not kidney': no renal adjustment, lowers warfarin and burns the skin if it leaves the vein. ## 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. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/nafcillin/) ## Related drugs - [Oxacillin](https://durgical.com/en/pharmacology/oxacillin/) - [Cefazolin](https://durgical.com/en/pharmacology/cefazolin/) - [Ceftaroline](https://durgical.com/en/pharmacology/ceftaroline/) ## Related conditions - [Cellulitis of the leg](https://durgical.com/en/conditions/cellulitis-of-the-leg/) - [Osteomyelitis](https://durgical.com/en/conditions/osteomyelitis/) - [Infective endocarditis](https://durgical.com/en/conditions/infective-endocarditis/) [← Back to the class: Beta-lactams](https://durgical.com/en/pharmacology/classes/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](https://medlineplus.gov/druginfo/meds/a685019.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [DailyMed - NAFCILLIN injection, powder, for solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d271b9a-a667-0fd2-e063-6294a90a3b4a) (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](https://www.rcsb.org/structure/5TY7) (RCSB Protein Data Bank, 2026); Farmacología básica y clínica (Katzung), cap. 43 (McGraw Hill, 2025). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/nafcillin/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/nafcillin/