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Nafcillin Side Effects

For the Consumer

Applies to nafcillin: parenteral injection, parenteral powder for injection

Side effects include:

Hypersensitivity reactions; local reactions (phlebitis, thrombophlebitis); renal, hepatic, or nervous system effects with high dosage.

For Healthcare Professionals

Applies to nafcillin: injectable powder for injection, intravenous solution, oral capsule


Gastrointestinal side effects have included nausea, vomiting, diarrhea, stomatitis, black or hairy tongue, gastrointestinal irritation, and pseudomembranous colitis.[Ref]


Local side effects have included pain, swelling, phlebitis, thrombophlebitis, and skin sloughing after intravenous administration. Intramuscular injections may cause pain at the injection site. Extravasation may result in severe chemical irritation. Subcutaneous extravasation has been associated with severe tissue necrosis.[Ref]


Hypersensitivity reactions have included urticaria, pruritus, angioneurotic edema, laryngeal edema, laryngospasm, bronchospasm, hypotension, vascular collapse, anaphylaxis, serum sickness-like reactions, fever, and death.[Ref]


Hematologic side effects have included agranulocytosis, neutropenia, bone marrow depression, and platelet dysfunction. These reactions are usually reversible upon discontinuation of nafcillin.[Ref]

At least three cases of platelet dysfunction with prolonged bleeding times have been reported with nafcillin therapy. All cases resolved following discontinuation of nafcillin.[Ref]


Renal side effects have included renal tubular damage and interstitial nephritis. Symptoms may include rash, fever, eosinophilia, hematuria, proteinuria, and renal insufficiency.[Ref]


Hepatic adverse effects are rare, but cases of hepatotoxicity associated with nafcillin therapy have been reported.[Ref]

Nervous system

Nervous system side effects have included neurotoxicity with high intravenous or intraventricular doses, especially in patients with both hepatic and renal impairment.[Ref]


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2. "Product Information. Unipen (nafcillin)." Wyeth-Ayerst Laboratories, Philadelphia, PA.

3. Zenk KE, Dungy CI, Greene GR "Nafcillin extravasation injury. Use of hyaluronidase as an antidote." Am J Dis Child 135 (1981): 1113-4

4. Kitzing W, Nelson JD, Mohs E "Comparative toxicities of methicillin and nafcillin." Am J Dis Child 135 (1981): 52-5

5. Tilden SJ, Craft JC, Cano R, Daum RS "Cutaneous necrosis associated with intravenous nafcillin therapy." Am J Dis Child 134 (1980): 1046-8

6. Klein JO, Finland M "The new penicillins (concluded)." N Engl J Med 269 (1963): 1129-34

7. Alexander DP, Russo ME, Fohrman DE, Rothstein G "Nafcillin-induced platelet dysfunction and bleeding." Antimicrob Agents Chemother 23 (1983): 59-62

8. Jeter EK, Scott A, Kizer J, Lazarchick J "Impaired platelet function associated with parenteral nafcillin." Ann Clin Lab Sci 20 (1990): 79-84

9. Carpenter J "Neutropenia induced by semisynthetic penicillin." South Med J 73 (1980): 745-8

10. Alexander DP, Russo ME, Fohrman DE, Rothstein G "Nafcillin-induced platelet dysfunction and bleeding." Antimicrob Agents Chemother 23 (1983): 59-62

11. Greene GR, Cohen E "Nafcillin-induced neutropenia in children." Pediatrics 61 (1978): 94-7

12. Walbroehl GS, John PG "Antibiotic-associated neutropenia." Am Fam Physician 45 (1992): 2237-41

13. Couchonnal GJ, Hinthorn DR, Hodges GR, Liu C "Nafcillin-associated granulocytopenia." South Med J 71 (1978): 1356-8

14. Andreoli SP, Kleiman MB, Glick MR, Bergstein JM "Nafcillin, pseudoproteinuria, and hypokalemic alkalosis." J Pediatr 97 (1980): 841-2

15. Bodendorfer TW "Nafcillin-induced interstitial nephritis." JAMA 244 (1980): 2609

16. Barriere SL, Conte JE Jr "Absence of nafcillin-associated nephritis." West J Med 133 (1980): 472-7

17. Guharoy SR, Kar S, McGalliard J "Suspected nafcillin-induced interstitial nephritis." Ann Pharmacother 27 (1993): 170-3

18. Whitman CB, Wike MJ "Possible case of nafcillin-induced acute interstitial nephritis." Am J Health Syst Pharm 69 (2012): 1049-53

19. Mohr JA, Clark RM, Waack TC, Whang R "Nafcillin-associated hypokalemia." JAMA 242 (1979): 544

20. Presti ME, Janney CG, Neuschwandertetri BA "Nafcillin-associated hepatotoxicity: report of a case and review of the literature." Dig Dis Sci 41 (1996): 180-4

21. Lestico MR, Vick KE, Hetsko CM "Hepatic and renal dysfunction following nafcillin administration." Ann Pharmacother 26 (1992): 985-90

Some side effects of nafcillin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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