Classifications: antibiotic, penicillin; antistaphylococcal penicillin;
Therapeutic: penicillin antibiotic

Prototype: Penicillin G
Pregnancy Category: B


250 mg, 500 mg capsules; 250 mg/5 mL suspension; 250 mg, 500 mg, 1 g, 2 g, 4 g injection


Semisynthetic, acid-stable, penicillinase-resistant isoxazolyl penicillin. Oxacillin inhibits final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) located within the bacterial cell wall. This leads to destruction of the cell wall of the organism.

Therapeutic Effect

It is highly active against most penicillinase-producing staphylococci, and is generally ineffective against gram-negative bacteria and methicillin-resistant staphylococci (MRSA).


Primarily, infections caused by penicillinase-producing staphylococci and penicillin-resistant staphylococci. As with other penicillins, serum concentrations are enhanced by concurrent use of probenecid.


Hypersensitivity to penicillins or cephalosporins.

Cautious Use

History of or suspected atopy or allergy (hives, eczema, hay fever, asthma); history of GI disease; hepatic disease; renal disease; premature infants, neonates, lactation (may cause infant diarrhea), pregnancy (category B).

Route & Dosage

Staphylococcal Infections
Adult: PO 500 mg–1 g q4–6h IM/IV 250 mg–1 g q4–6h (max: 12 g/d)
Child: PO 50–100 mg/kg/d divided q4–6h IM/IV 100–200 mg/kg/d divided q4–6h (max: 12 g/d)
Neonate: IV 50–100 mg/kg/d divided q6–12h


Note: The total sodium content (including that contributed by buffer) in each gram of oxacillin is approximately 3.1 mEq or 71 mg.

  • Give with a full glass of water on an empty stomach (either 1 h before meals or 2 h after meals). Food reduces absorption.
  • Reconstitute each 250 mg with 1.4 mL sterile water for injection to yield 250 mg/1.5 mL. Shake vial vigorously until drug is completely dissolved. Discard unused portions after 3 d at room temperature or 7 d under refrigeration.
  • Administer deep IM to adults by deep intragluteal injection. Follow agency policy for IM site in young children and infants. Rotate injection sites.

Note: Verify correct IV concentration and rate of infusion/injection with physician before IV administration to neonates, infants, children.

PREPARE: Direct: Reconstitute each 500 mg or fraction thereof with 5 mL with sterile water for injection or NS to yield 250 mg/1.5 mL.  Intermittent: Further dilute in 50–100 mL of D5W, NS, D5/NS, or RL.  Continuous: Further dilute in up to 1000 mL of compatible IV solutions.  

ADMINISTER: Direct: Give at a rate of 1 g or fraction thereof over 10 min.  Intermittent: Give over 15–30 min.  Continuous: Give over 6 h.  

INCOMPATIBILITIES Solution: additive: Caffeine citrate, cephalothin, cytarabine, erythromycin, hyaluronidase, hydrocortisone, nitrofurantoin, pentobarbital, phenobarbital, tetracyclines, warfarin. Y-site: Sodium bicarbonate, verapamil.

Adverse Effects (≥1%)

Body as a Whole: Thrombophlebitis (IV therapy), superinfections, wheezing, sneezing, fever, anaphylaxis. GI: Nausea, vomiting, flatulence, diarrhea, hepatocellular dysfunction (elevated AST, ALT, hepatitis). Hematologic: Eosinophilia, leukopenia, thrombocytopenia, granulocytopenia, agranulocytosis; neutropenia (reported in children). Skin: Pruritus, rash, urticaria. Urogenital: Interstitial nephritis, transient hematuria, albuminuria, azotemia (newborns and infants on high doses).

Diagnostic Test Interference

Oxacillin in large doses can cause false-positive urine protein tests using sulfosalicylic acid methods.


Absorption: Incompletely and erratically absorbed orally. Peak: 30–120 min IM; 15 min IV. Duration: 4 h PO; 4–6 h IM. Distribution: Distributes into CNS with inflamed meninges; crosses placenta; distributed into breast milk, 90% protein bound. Metabolism: Enters enterohepatic circulation. Elimination: Primarily in urine, some in bile. Half-Life: 0.5–1 h.

Nursing Implications

Assessment & Drug Effects

  • Ask patient prior to first dose about hypersensitivity reactions to penicillins, cephalosporins, and other allergens.
  • Lab tests: periodic liver functions, CBC with differential, platelet count, and urinalysis.
  • Hepatic dysfunction (possibly a hypersensitivity reaction) has been associated with IV oxacillin; it is reversible with discontinuation of drug. Symptoms may resemble viral hepatitis or general signs of hypersensitivity and should be reported promptly: hives, rash, fever, nausea, vomiting, abdominal discomfort, anorexia, malaise, jaundice (with dark yellow to brown urine, light-colored or clay-colored stools, pruritus).
  • Withhold next drug dose and report the onset of hypersensitivity reactions and superinfections (see Appendix F).

Patient & Family Education

  • Take oral medication around the clock; do not miss a dose. Take all of the medication prescribed even if you feel better, unless otherwise directed by physician.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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