Nafcillin

Mechanism-of-action classes: Enzyme Activators; Transpeptidase Inhibitors.

• Nafcillin is indicated in the treatment of infections caused by penicillinase-producing staphylococci which have demonstrated susceptibility to the drug. Culture and susceptibility tests should be performed initially to determine the causative organism and its susceptibility to the drug (see CLINICAL PHARMACOLOGY - Susceptibility Testing ).

• A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication.contraindicated

Nafcillin for Injection, in the Pharmacy Bulk Package Bottle is for intravenous injection only. The usual intravenous dosage for adults is 500 mg every 4 hours. For severe infections, 1 gram every 4 hours is recommended. Administer slowly over at least 30 to 60 minutes to minimize the risk of vein irritation and extravasation. Bacteriologic studies to determine the causative organisms and their susceptibility to nafcillin should always be performed. Duration of therapy varies with the type and severity of infection as well as the overall condition of the patient; therefore, it should be determined by the clinical and bacteriological response of the patient. In severe staphylococcal infections, therapy with nafcillin should be continued for at least 14 days. Therapy should be continued for at least 48 hours after the patient has become afebrile, asymptomatic, and cultures are negative. The treatment of endocarditis and osteomyelitis may require a longer duration of therapy. Nafcillin-probenecid therapy is generally limited to those infections where very high serum levels of nafcillin are necessary. No dosage alterations are necessary for patients with renal dysfunction, including those on hemodialysis. Hemodialysis does not accelerate nafcillin clearance from the blood. For patients with hepatic insufficiency and renal failure, measurement of nafcillin serum levels should be performed and dosage adjusted accordingly. With intravenous administration, particularly in elderly patients, care should be taken because of the possibility of thrombophlebitis.

SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH NAFCILLIN, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, NAFCILLIN SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Nafcillin for Injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use.

Body as a Whole The reported incidence of allergic reactions to penicillin ranges from 0.7 to 10 percent (see WARNINGS ). Sensitization is usually the result of treatment, but some individuals have had immediate reactions to penicillin when first treated. In such cases, it is thought that the patients may have had prior exposure to the drug via trace amounts present in milk or vaccines. Two types of allergic reactions to penicillins are noted clinically, immediate and delayed. Immediate reactions usually occur within 20 minutes of administration and range in severity from urticaria and pruritus to angioneurotic edema, laryngospasm, bronchospasm, hypotension, vascular collapse, and death. Such immediate anaphylactic reactions are very rare (see WARNINGS ) and usually occur after parenteral therapy but have occurred in patients receiving oral therapy. Another type of immediate reaction, an accelerated reaction, may occur between 20 minutes and 48 hours after administration and may include urticaria, pruritus, and fever. Although laryngeal edema, laryngospasm, and hypotension occasionally occur, fatality is uncommon. Delayed allergic reactions to penicillin therapy usually occur after 48 hours and sometimes as late as 2 to 4 weeks after initiation of therapy. Manifestations of this type of reaction include serum sickness-like symptoms (i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain) and various skin rashes.

Pregnancy: Teratogenic Effects Pregnancy Category B Reproduction studies have been performed in the mouse with oral doses up to 20 times the human dose and orally in the rat at doses up to 40 times the human dose and have revealed no evidence of impaired fertility or harm to the rodent fetus due to nafcillin. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, nafcillin should be used during pregnancy only if clearly needed.

Neurotoxic reactions similar to those observed with penicillin G may arise with intravenous doses of nafcillin especially in patients with concomitant hepatic insufficiency and renal dysfunction (see PRECAUTIONS ). In the case of overdosage, discontinue nafcillin, treat symptomatically and institute supportive measures as required. Hemodialysis does not increase the rate of clearance of nafcillin from the blood.

• Oct 31, 1989NDANDA050655Baxter Hlthcare
• Apr 20, 2011ANDAANDA090005Istituto Bio Ita Spa
• Jun 30, 2011ANDAANDA090002Istituto Bio Ita Spa
• Oct 3, 2011ANDAANDA090560Antibiotice
• Dec 26, 2012ANDAANDA091613Eugia Pharma Speclts
• Dec 26, 2012ANDAANDA091614Eugia Pharma Speclts
• Apr 7, 2014ANDAANDA200002Onesource Specialty

1. 1Renal Failure Acute647.1%
2. 2Rash566.2%
3. 3Drug Ineffective556.1%
4. 4Acute Kidney Injury495.4%
5. 5Pyrexia444.9%
6. 6Tubulointerstitial Nephritis434.7%
7. 7Hypokalaemia404.4%
8. 8Renal Failure394.3%
9. 9Blood Creatinine Increased364.0%
10. 10Drug Interaction353.9%
11. 11Diarrhoea303.3%
12. 12Nausea283.1%
13. 13Vomiting283.1%
14. 14Anxiety273.0%
15. 15Drug Hypersensitivity273.0%

Recent PubMed references pinned to Nafcillin as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Incidence of Acute Kidney Injury With the Use of Nafcillin Versus Oxacillin.
  Pharmacotherapy · 2026 · Perez AD, Brenner AL, Pieta E, et al.
  PMID 41998805DOI 10.1002/phar.70145
• Impact of nafcillin and diosmin on the attachment, invasion, and stress survival of Salmonella Typhimurium.
  Scientific reports · 2025 · Narimisa N, Bostanghadiri N, Khoshbayan A, et al.
  PMID 39984662DOI 10.1038/s41598-025-90808-4
• Inhibitory effects of nafcillin and diosmin on biofilm formation by Salmonella Typhimurium.
  BMC microbiology · 2024 · Narimisa N, Khoshbayan A, Gharaghani S, et al.
  PMID 39695365DOI 10.1186/s12866-024-03646-1
• Physical Compatibility of Intravenous Ondansetron Hydrochloride and Nafcillin Sodium.
  International journal of pharmaceutical compounding · 2024 · Beran C, Howard MS, Baki G, et al.
  PMID 39094045
• Effects of sub-inhibitory concentrations of nafcillin, vancomycin, ciprofloxacin, and rifampin on biofilm formation of clinical methicillin-resistant Staphylococcus aureus.
  Microbiology spectrum · 2024 · Park K-H, Kim D, Jung M, et al.
  PMID 38651875DOI 10.1128/spectrum.03412-23
• Frequency of drug-induced liver injury in children receiving anti-staphylococcal penicillins.
  The Journal of antimicrobial chemotherapy · 2022 · Tang K, Coombs S, Gwee A, et al.
  PMID 36203386DOI 10.1093/jac/dkac325
• Methicillin-Susceptible Staphylococcus Aureus Bacteremia: Cefazolin in Prime But Nafcillin Not Ready for an Exit.
  The American journal of the medical sciences · 2020 · Sarria JC
  PMID 32439151DOI 10.1016/j.amjms.2020.04.007
• Comparison of Nafcillin and Cefazolin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia.
  The American journal of the medical sciences · 2020 · Twilla JD, Algrim A, Adams EH, et al.
  PMID 32376001DOI 10.1016/j.amjms.2020.04.006

The 10 most recently updated of 19 ClinicalTrials.gov registrations naming Nafcillin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Prophylactic Antibiotics Useful With Antibiotic Impregnated External Ventricular Drains (EVDs)?
  Recruiting · Phase 1 · Interventional · 84 enrolled · Montefiore Medical Center
  NCT05001750updated 2026-02-02
• Combination Antibiotic Therapy for Staphylococcus Aureus Bacteremia
  Not yet recruiting · Phase 4 · Interventional · 2,096 enrolled · Intermountain Health Care, Inc.
  NCT07376889updated 2026-01-29
• Cefazolin Versus Antistaphylococcal Penicillins for Methicillin Susceptible Staphylococcus Aureus Bacteremia
  Active not recruiting · Observational · 5,000 enrolled · Central Hospital, Nancy, France
  NCT07186894updated 2025-09-22
• Does Staphylococcus Aureus Bacteremia Early Dual Therapy Improve Outcomes?
  Enrolling by invitation · Phase 4 · Interventional · 300 enrolled · West Virginia University
  NCT07148960updated 2025-09-17
• DOTS: Dalbavancin as an Option for Treatment of Staphylococcus Aureus Bacteremia
  Completed · Phase 2 · Interventional · 200 enrolled · National Institute of Allergy and Infectious Diseases (NIAID)
  NCT04775953updated 2024-12-10
• Dalbavancin For The Treatment of Gram Positive Osteoarticular Infections
  Completed · Phase 4 · Interventional · 41 enrolled · Infectious Diseases Physicians, Inc.
  NCT03426761updated 2023-10-03
• Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care
  Completed · Observational · 3,520 enrolled · Daniel Benjamin
  NCT01431326updated 2023-09-06
• Patients Response to Early Switch To Oral:Osteomyelitis Study
  Terminated · Early phase 1 · Interventional · 11 enrolled · Julio Ramirez
  NCT02099240updated 2021-04-06
• A Phase 3 Telavancin Staphylococcus Aureus (S. Aureus) Bacteremia Trial
  Terminated · Phase 3 · Interventional · 121 enrolled · Cumberland Pharmaceuticals
  NCT02208063updated 2020-02-17
• Safety and Efficacy of CEM-102 With Rifampin Compared to Standard Therapy in Patients With Prosthetic Joint Infections or Spacer Infection
  Terminated · Phase 2 · Interventional · 14 enrolled · Arrevus Inc.
  NCT01756924updated 2019-04-19

Frequently asked questions

How does Nafcillin work?

Mechanism-of-action classes: Enzyme Activators; Transpeptidase Inhibitors.

What is Nafcillin used for?

According to FDA labeling, Nafcillin carries indications including: Nafcillin is indicated in the treatment of infections caused by penicillinase-producing staphylococci which have demonstrated susceptibility to the drug. Culture and susceptibility tests should be performed initially to determine the causative organism and its susceptibility to the drug (see CLINICAL PHARMACOLOGY - Susceptibility Testing ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Nafcillin?

Nafcillin is classified as Beta-lactamase resistant penicillins, Penicillin-class Antibacterial, Enzyme Activators, Transpeptidase Inhibitors, Decreased Cell Wall Integrity, Decreased Cell Wall Synthesis & Repair.

What are the contraindications for Nafcillin?

Nafcillin labeling lists contraindications including: A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication.. Always consult the full prescribing information and a clinician.