OXACILLIN SODIUM

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration
Reconstitution
-Vials: Reconstitute each 250 mg and 500 mg vial with 5 ml of Sterile Water for Injection or 0.9% NaCl (NS). The resultant concentration will be approximately 50 mg/ml for the 250 mg vial and approximately 100 mg/ml for the 500 mg vial. Reconstitute each 1 g vial with 10 ml and each 2 g vial with 20 ml of Sterile Water for Injection or 0.9% NaCl (NS); the resultant concentration will be approximately 100 mg/ml. Vigorously shake vials until solution is clear.
-Storage: Reconstituted solutions are stable for 3 days at room temperature (70 degrees F) or 7 days under refrigeration (40 degrees F).
-Pharmacy bulk package: Reconstitute each 10 g vial with 93 ml of Sterile Water for injection or 0.9% NaCl (NS) for a resultant concentration of 100 mg/ml.
-Storage: Use reconstituted pharmacy bulk package within 4 hours from initial entry.
-ADD-Vantage vials: For IV infusion only. Reconstitute only with 50 or 100 ml of NS or D5W in the appropriate flexible diluent container.
-Storage:-ADD-vantage vials reconstituted in NS to concentrations of 10-40 mg/ml are stable for 4 days at room temperature (25 degrees C).
-ADD-vantage vials reconstituted in D5W to concentrations of 10-40 mg/ml are stable for 6 hours at room temperature.


Dilution
-For Intermittent IV Injection: No further dilution is required; maximum concentration for direct IV injection is 100 mg/ml.
-For Intermittent IV Infusion: Further dilute reconstituted solution with NS or D5W to a usual concentration of 10-40 mg/ml.-For peripheral vein infusion, a concentration of <= 20 mg/ml is preferred to help lessen the risk of phlebitis, unless fluid restriction is necessary for the patient.

-Storage:-Solutions diluted in Sterile Water for Injection or NS to a concentration of 10-100 mg/ml are stable for 4 days at room temperature (25 degrees C) or 7 days under refrigeration (4 degrees C).
-Solutions diluted in D5W to a concentration of 0.5-2 mg/ml are stable for 6 hours at room temperature (25 degrees C). Solutions diluted in D5W to a concentration of 10-30 mg/ml are stable for 4 days under refrigeration (4 degrees C).

-GALAXY bags: No further dilution is required.

Thawing Frozen Pre-mixed Bags
-Frozen GALAXY bags: Thaw frozen container at room temperature or under refrigeration. Do not force thaw by immersion in water baths or by microwave irradiation.
-Storage: The thawed solution remains stable for 21 days under refrigeration or for 48 hours at room temperature. Do not refreeze.

IV Push
-Inject slowly over at least 10 minutes. To minimize vein irritation, inject as slowly as possible.

Intermittent IV Infusion
-Infuse IV slowly over 30-60 minutes to reduce the risk for phlebitis and extravasation. For peripheral vein infusion, consider infusion over 60 minutes.

Intramuscular Administration
Reconstitution
-Reconstitute each vial with the following volumes of Sterile Water for Injection to give a concentration of 167 mg/mL (250 mg/1.5 mL):-250 mg vial - reconstitute with 1.4 mL
-500 mg vial - reconstitute with 2.7 mL
-1 g vial - reconstitute with 5.7 mL
-2 g vial - reconstitute with 11.5 mL

-Vigorously shake vial until solution is clear.
-Storage: Reconstituted solutions are stable for 3 days at room temperature (70 degrees F) or 7 days under refrigeration (40 degrees F).

Intramuscular Injection
-Inject deeply into a large muscle (e.g., anterolateral thigh or deltoid [children and adolescents only]). If multiple doses are given IM, consider alternating injection sites.
-In general, IM administration of antibiotics in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

Hepatotoxicity, resembling hepatitis and manifested by elevated hepatic enzymes and hepatomegaly, has occurred more frequently with oxacillin than other antistaphylococcal penicillins. Several cases of reversible oxacillin-induced hepatotoxicity have been reported in pediatric patients. Hepatitis was reported in approximately 22% of pediatric patients receiving oxacillin (n = 41) in a retrospective review of outpatient parenteral antimicrobial therapy; in this same study, no patients receiving nafcillin experienced hepatotoxicity. In all patients, symptoms resolved after discontinuation of the drug (mean, 14.2 days after therapy discontinuation). In a another small trial, 1 out of 8 children developed elevated hepatic enzymes; enzyme concentrations slowly returned to baseline after oxacillin discontinuation. Most drug-induced hepatic injuries are thought to be idiosyncratic reactions and are often immune-mediated. The presence of extrahepatic signs such as rash and increased eosinophils suggest an immune-mediated reaction. It has been suggested that HIV-infected patients are more susceptible to oxacillin-induced hepatotoxicity than HIV-negative patients. Monitor liver function tests during oxacillin therapy, particularly in children receiving prolonged high-dose therapy and HIV-positive patients.

A local injection site reaction, including pain and induration, can occur after IM injection of oxacillin. In addition, intravenous oxacillin can be irritating to veins; phlebitis can occur. When a peripheral venous line is be used for administration, the following recommendations have been suggested in an attempt to minimize the risk of phlebitis: rotation of the peripheral IV site every 72 hours, limit the oxacillin concentration to 20 mg/ml unless the patient is fluid-restricted, and infuse each dose over 60 minutes. Monitor the administration site for signs of phlebitis or extravasation.

Interstitial nephritis, a hypersensitivity reaction with renal tubular necrosis (damage), has been reported infrequently with oxacillin use. Characterized by rash, eosinophilia, hematuria, proteinuria, and renal insufficiency, the reaction usually regresses with discontinuation of the drug. Eosinophilia has also been associated with idiosyncratic hepatotoxicity that may occur with oxacillin use. Evaluate patients presenting with eosinophilia for possible drug-induced kidney or liver injury.

Although penicillin allergy has been reported in up to 20% of patients in the general population, up to 90% of those patients lack penicillin-specific IgE antibodies and can safely tolerate the antibiotic. Careful assessment of patients who report a penicillin allergy is critical; while many of these reports are not real hypersensitivity reactions, those patients with a true allergy to penicillins are at risk for severe reactions upon re-exposure to a drug in the penicillin class, such as oxacillin. The actual prevalence of penicillin allergy in the general population is likely no greater than 5%. Severe immediate anaphylactoid reactions are very rare and usually occur within 20 minutes of administration; these reaction may include anaphylactic shock, angioedema, laryngospasm, laryngeal edema, bronchospasm, hypotension, vascular collapse, and even death. Other immediate reactions that occur between 20 minutes and 48 hours after administration include urticaria, pruritus, fever, and occasionally laryngeal edema, laryngospasm, and hypotension. Serum sickness-like symptoms (fever, malaise, myalgia, arthralgia) are delayed and typically occur > 48 hours and sometimes 2-4 weeks after administration. While rash may be a presenting sign of a hypersensitivity reaction, non-allergic macular rashes are also associated with penicillin antibiotics. In patients who have not received a penicillin antibiotic previously, this type of rash typically begins at least 4-5 days after treatment is started ; the rash may be extensive, covering the entire body, and usually disappears in 3-7 days. Rash (unspecified) was reported in approximately 32% of pediatric patients receiving oxacillin (n = 41) in a retrospective review of outpatient parenteral antimicrobial therapy; the incidence of rash was lower with nafcillin (10%). Severe reactions, such as anaphylactoid reactions and anaphylactic shock, are rare and can also include angioedema, laryngospasm, laryngeal edema, bronchospasm, hypotension, vascular collapse, and even death. Other reactions include urticaria, pruritus, fever, and serum sickness-like symptoms (fever, malaise, myalgia, arthralgia). Other skin reactions that occur infrequently, but can be serious, include Stevens-Johnson syndrome, exfoliative dermatitis, and toxic epidermal necrolysis.

Neutropenia has been associated with oxacillin therapy and cases have been reported in children. In clinical studies of pediatric patients receiving oxacillin, neutropenia has been reported in approximately 12% of patients. Neutropenia has resolved after discontinuation of oxacillin therapy. Agranulocytosis and bone marrow depression have also been associated with oxacillin therapy. Monitor complete blood counts in children receiving oxacillin therapy, particularly those receiving prolonged treatment with high doses.

In the general population, gastrointestinal adverse events may occur in 2-5% of patients receiving penicillins. Adverse effects reported with oxacillin include nausea, vomiting, diarrhea, abdominal pain, stomatitis, black or hair tongue (tongue discoloration), or other symptoms of gastrointestinal irritation. Persistent or severe diarrhea may also be a sign of Clostridium difficile associated diarrhea (CDAD); carefully evaluate all patients who develop significant diarrhea. In addition, nausea and vomiting may be presenting symptoms of hepatotoxicity; patients presenting with significant or persistent nausea and vomiting should be evaluated for possible liver injury.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with oxacillin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate.

Neurotoxic reactions, such as seizures, have been reported when large doses of penicillins were administered to patients with renal impairment. Seizures are rarely reported with oxacillin.

A false-positive reaction for glucose in the urine has been observed in patients receiving penicillin antibiotics, such as oxacillin, and using copper-reduction tests (e.g., Benedict's solution, Fehling's solution, and Clinitest tablets). This reaction, however, has not been observed with glucose oxidase tests (e.g., Tes-tape, Clinistix, Diastix).

Oxacillin is a penicillin, and should not be used in patients with penicillin hypersensitivity. Oxacillin should be used cautiously in patients with carbapenem hypersensitivity or cephalosporin hypersensitivity because its structural similarity to the cephalosporins and carbapenems causes these patients to be more susceptible to hypersensitivity reactions. Patients with allergies or allergic conditions including asthma, eczema, hives, or hay fever may have a greater risk for hypersensitivity reactions to penicillins.

Use oxacillin with caution in patients with hepatic disease. Hepatotoxicity, resembling hepatitis and manifested by elevated hepatic enzymes and hepatomegaly, has been associated with oxacillin therapy. Monitor liver function tests during oxacillin therapy, particularly in children receiving prolonged high-dose therapy.

Oxacillin should be used cautiously in patients with renal impairment because it is known to be substantially excreted by the kidney. The risk of toxic reactions to this drug may be greater in patients with renal dysfunction. Seizures are possible if excessively large doses are administered to patients with renal failure.

Use oxacillin cautiously in patients with fluid and electrolyte imbalance and those who are particularly sensitive to sodium intake (e.g., newborns, patients with heart failure or hypertension). Oxacillin contains approximately 2.5-4.02 mEq of sodium per gram depending on the particular product; consult specific product labeling for precise sodium content.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including oxacillin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

Description: Oxacillin is a semisynthetic antistaphylococcal penicillin. Unlike penicillin, ampicillin, or the extended-spectrum penicillins, oxacillin resists hydrolysis by penicillinase. As a result, oxacillin, along with other agents in the same group (e.g., nafcillin, dicloxacillin), is active against penicillinase-producing S. aureus. Oxacillin is used for bacteremia, meningitis, endocarditis, skin and soft-tissue infections, respiratory tract infections, and bone and joint infections due to methicillin-susceptible Staphylococcus aureus. A higher incidence of adverse effects (hepatotoxicity and rash) has been reported in children receiving long-term therapy with oxacillin compared to those receiving therapy with nafcillin. Oxacillin is FDA-approved for use in pediatric patients as young as neonates.

General dosing information:
-Oxacillin is FDA-approved for the treatment of moderate to severe infections due to penicillinase-producing Staphylococcus sp. only.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Staphylococcus aureus (MSSA), Staphylococcus sp.
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

For the treatment of bacteremia due to methicillin-sensitive S. aureus:
Intravenous or Intramuscular dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV or IM every 12 hours for 14 days. The FDA-approved dose is 25 mg/kg/day IV or IM. Guidelines recommend oxacillin as a first-line therapy for methicillin-sensitive S. aureus bacteremia.
Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV or IM every 8 hours for 14 days. The FDA-approved dose is 25 mg/kg/day IV or IM. Guidelines recommend oxacillin as a first-line therapy for methicillin-sensitive S. aureus bacteremia.
Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV or IM every 8 hours for 14 days. The FDA-approved dose is 25 mg/kg/day IV or IM. Guidelines recommend oxacillin as a first-line therapy for methicillin-sensitive S. aureus bacteremia.
Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV or IM every 6 hours for 14 days. The FDA-approved dose is 25 mg/kg/day IV or IM. Guidelines recommend oxacillin as a first-line therapy for methicillin-sensitive S. aureus bacteremia.
Infants, Children, and Adolescents weighing less than 40 kg: 100 to 200 mg/kg/day IV or IM divided every 4 to 6 hours for 7 to 14 days. The FDA-approved dose is 100 mg/kg/day IV or IM divided every 4 to 6 hours for severe infections. Guidelines recommend oxacillin as a first-line therapy for methicillin-sensitive S. aureus bacteremia.
Children and Adolescents weighing 40 kg or more: 100 to 200 mg/kg/day IV or IM divided every 4 to 6 hours (Max: 2 g/dose) for 7 to 14 days. The FDA-approved dose is 1 g IV or IM every 4 to 6 hours for severe infections. Guidelines recommend oxacillin as a first-line therapy for methicillin-sensitive S. aureus bacteremia.

For the treatment of infective endocarditis:
Intravenous dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV every 12 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV every 6 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Infants: 100 to 200 mg/kg/day IV or IM divided every 4 to 6 hours. The FDA-approved dosage for severe infections is 100 mg/kg/day IV or IM divided every 4 to 6 hours.
Children and Adolescents weighing less than 40 kg: 200 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours. The FDA-approved dosage for severe infections is 100 mg/kg/day IV divided every 4 to 6 hours. Oxacillin is an alternative therapy for penicillin-susceptible staphylococcal native valve endocarditis (NVE). Oxacillin is a preferred therapy for penicillin-resistant, methicillin-sensitive S. aureus (MSSA) NVE; may consider adding gentamicin for the first 3 to 5 days. Treat NVE for at least 4 to 6 weeks. For MSSA prosthetic valve endocarditis (PVE), treat with nafcillin plus rifampin for 6 weeks; add gentamicin for the first 2 weeks.
Children and Adolescents weighing 40 kg or more: 200 mg/kg/day IV divided every 4 to 6 hours (Max: 12 g/day). The FDA-approved dosage for severe infections is 1 g IV every 4 to 6 hours. Oxacillin is an alternative therapy for penicillin-susceptible staphylococcal native valve endocarditis (NVE). Oxacillin is a preferred therapy for penicillin-resistant, methicillin-sensitive S. aureus (MSSA) NVE; may consider adding gentamicin for the first 3 to 5 days. Treat NVE for at least 4 to 6 weeks. For MSSA prosthetic valve endocarditis (PVE), treat with nafcillin plus rifampin for 6 weeks; add gentamicin for the first 2 weeks.

For the treatment of bacterial meningitis:
Intravenous dosage:
Neonates 0 to 7 days weighing 2 kg or less: 50 mg/kg/dose IV every 12 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates 0 to 7 days weighing more than 2 kg: 50 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates older than 7 days weighing 2 kg or less: 50 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates older than 7 days weighing more than 2 kg: 50 mg/kg/dose IV every 6 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Infants, Children, and Adolescents weighing less than 40 kg: 200 mg/kg/day (Max: 12 g/day) IV divided every 6 hours is recommended for methicillin-sensitive S. aureus meningitis. The FDA-approved dosage for severe infections is 100 mg/kg/day IV divided every 4 to 6 hours.
Children and Adolescents weighing 40 kg or more: 200 mg/kg/day (Max: 12 g/day) IV divided every 6 hours is recommended for methicillin-sensitive S. aureus meningitis. The FDA-approved dosage for severe infections is 1 g IV every 4 to 6 hours.

For the treatment of lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP):
-for the treatment of nonspecific lower respiratory tract infections (LRTIs):
Intravenous or Intramuscular dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV or IM every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose for all neonates is 25 mg/kg/day IV or IM.
Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV or IM every 8 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose for all neonates is 25 mg/kg/day IV or IM.
Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV or IM every 8 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV or IM every 6 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose is 25 mg/kg/day IV or IM.
Infants, Children, and Adolescents weighing less than 40 kg: 150 to 200 mg/kg/day IV or IM divided every 4 to 6 hours (Max: 2 g/dose). The FDA-approved dose is 50 mg/kg/day IV or IM divided every 6 hours for mild to moderate infection and 100 mg/kg/day IV or IM divided every 4 to 6 hours for severe infections.
Children and Adolescents weighing 40 kg or more: 150 to 200 mg/kg/day IV or IM divided every 4 to 6 hours (Max: 2 g/dose). The FDA-approved dose is 250 to 500 mg IV or IM every 4 to 6 hours for mild to moderate infections and 1 g IV or IM every 4 to 6 hours for severe infections.
-for the treatment of community-acquired pneumonia (CAP):
Intravenous or Intramuscular dosage:
Infants 4 to 11 months, Children, and Adolescents: 150 to 200 mg/kg/day IV or IM divided every 4 to 8 hours (Max: 2 g/dose) for 10 days. Guidelines recommend a semisynthetic penicillin for hospitalized patients with infections due to methicillin-susceptible S. aureus.

For the treatment of neonatal mastitis:
Intravenous dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV every 12 hours.
Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV every 8 hours.
Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV every 8 hours.
Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV every 6 hours.
Infants 1 to 2 months: 100 to 200 mg/kg/day IV divided every 4 to 6 hours.

For the treatment of bone and joint infections, including osteomyelitis, infectious arthritis, and infectious bursitis:
-for the treatment of osteomyelitis due to methicillin-sensitive S. aureus:
Intravenous dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV every 6 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.
Infants 1 to 2 months: 100 to 200 mg/kg/day IV divided every 4 to 6 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 3 to 11 months: 100 to 200 mg/kg/day IV divided every 4 to 6 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Children and Adolescents weighing less than 40 kg: 100 to 200 mg/kg/day IV divided every 4 to 6 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Children and Adolescents weighing 40 kg or more: 100 to 200 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections. The FDA-approved dosage is 1 g IV every 4 to 6 hours for severe infections.
-for the treatment of infectious arthritis due to methicillin-sensitive S. aureus:
Intravenous dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV every 6 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.
Infants 1 to 2 months: 100 to 200 mg/kg/day IV divided every 4 to 6 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 3 to 11 months: 100 to 200 mg/kg/day IV divided every 4 to 6 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Children and Adolescents weighing less than 40 kg: 100 to 200 mg/kg/day IV divided every 4 to 6 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Children and Adolescents weighing 40 kg or more: 100 to 200 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections. The FDA-approved dosage is 1 g IV every 4 to 6 hours for severe infections.
-for the treatment of infectious bursitis due to methicillin-sensitive S. aureus:
Intravenous dosage:
Children and Adolescents weighing less than 40 kg: 100 to 200 mg/kg/day IV divided every 4 to 6 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
Children and Adolescents weighing 40 kg or more: 100 to 200 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration. The FDA-approved dosage is 1 g IV every 4 to 6 hours for severe infections.

For the treatment of skin and skin structure infections, including cellulitis, erysipelas, skin abscesses, furunculosis, carbuncle, necrotizing infections, and pyomyositis:
-for the treatment of nonpurulent skin infections, including cellulitis and erysipelas, due to methicillin-sensitive S. aureus:
Intravenous or Intramuscular dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV or IM every 12 hours for 5 to 14 days. The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV or IM every 8 hours for 5 to 14 days. The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV or IM every 8 hours for 5 to 14 days. The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV or IM every 6 hours for 5 to 14 days. The FDA-approved dose is 25 mg/kg/day IV or IM.
Infants, Children, and Adolescents weighing less than 40 kg: 100 to 150 mg/kg/day IV or IM divided every 6 hours for 5 to 14 days. The FDA-approved dose is 50 mg/kg/day IV or IM divided every 6 hours for mild to moderate infections and 100 mg/kg/day IV or IM divided every 4 to 6 hours for severe infections.
Children and Adolescents weighing 40 kg or more: 100 to 150 mg/kg/day IV or IM divided every 6 hours (Max: 2 g/dose) for 5 to 14 days. The FDA-approved dose is 250 to 500 mg IV or IM every 4 to 6 hours for mild to moderate infections and 1 g IV or IM every 4 to 6 hours for severe infections.
-for the treatment of purulent skin infections, including carbuncle, furunculosis, and skin abscesses, due to methicillin-sensitive S. aureus:
Intravenous or Intramuscular dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV or IM every 12 hours for 5 to 10 days plus incision and drainage. The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV or IM every 8 hours for 5 to 10 days plus incision and drainage. The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV or IM every 8 hours for 5 to 10 days plus incision and drainage. The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV or IM every 6 hours for 5 to 10 days plus incision and drainage. The FDA-approved dose is 25 mg/kg/day IV or IM.
Infants, Children, and Adolescents weighing less than 40 kg: 100 to 150 mg/kg/day IV or IM divided every 6 hours for 5 to 10 days plus incision and drainage. The FDA-approved dose is 50 mg/kg/day IV or IM divided every 6 hours for mild to moderate infections and 100 mg/kg/day IV or IM divided every 4 to 6 hours for severe infections.
Children and Adolescents weighing 40 kg or more: 100 to 150 mg/kg/day IV or IM divided every 6 hours (Max: 2 g/dose) for 5 to 10 days plus incision and drainage. The FDA-approved dose is 250 to 500 mg IV or IM every 4 to 6 hours for mild to moderate infections and 1 g IV or IM every 4 to 6 hours for severe infections.
-for the treatment of necrotizing infections of the skin, fascia, and muscle due to methicillin-sensitive S. aureus:
Intravenous or Intramuscular dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV or IM every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV or IM every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV or IM every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV or IM every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. The FDA-approved dose is 25 mg/kg/day IV or IM.
Infants, Children, and Adolescents weighing less than 40 kg: 50 mg/kg/dose IV or IM every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. The FDA-approved dose is 100 mg/kg/day IV or IM divided every 4 to 6 hours for severe infections.
Children and Adolescents weighing 40 kg or more: 50 mg/kg/dose (Max: 2 g/dose) IV or IM every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. The FDA-approved dose is 1 g IV or IM every 4 to 6 hours for severe infections.
-for the treatment of pyomyositis due to methicillin-sensitive S. aureus:
Intravenous or Intramuscular dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV or IM every 12 hours for 14 to 21 days. The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV or IM every 8 hours for 14 to 21 days. The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV or IM every 8 hours for 14 to 21 days. The FDA-approved dose is 25 mg/kg/day IV or IM.
Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV or IM every 6 hours for 14 to 21 days. The FDA-approved dose is 25 mg/kg/day IV or IM.
Infants, Children, and Adolescents weighing less than 40 kg: 100 to 150 mg/kg/day IV or IM divided every 6 hours for 14 to 21 days. The FDA-approved dose is 100 mg/kg/day IV or IM divided every 4 to 6 hours for severe infections.
Children and Adolescents weighing 40 kg or more: 100 to 150 mg/kg/day IV or IM divided every 6 hours (Max: 2 g/dose) for 14 to 21 days. The FDA-approved dose is 1 g IV or IM every 4 to 6 hours for severe infections.

Maximum Dosage Limits:
-Neonates
25 mg/kg/day IV or IM is the FDA-approved dosage for all neonates; however, this dose is not typically used in clinical practice. The following doses have been used off-label:
0 to 7 days weighing 2 kg or less : up to 100 mg/kg/day IV/IM.
0 to 7 days weighing more than 2 kg : up to 150 mg/kg/day IV/IM.
older than 7 days weighing 2 kg or less : up to 150 mg/kg/day IV/IM.
older than 7 days weighing more than 2 kg : up to 200 mg/kg/day IV/IM.
-Infants
100 mg/kg/day IV/IM is the FDA-approved dosage; however, up to 200 mg/kg/day IV/IM has been used off-label.
-Children
weight less than 40 kg: 100 mg/kg/day IV/IM is the FDA-approved dosage; however, up to 200 mg/kg/day IV/IM has been used off-label.
weight 40 kg or more: 6 g/day IV/IM is the FDA-approved dosage; however, up to 200 mg/kg/day IV/IM (Max: 12 g/day) has been used off-label.
-Adolescents
weight less than 40 kg: 100 mg/kg/day IV/IM is the FDA-approved dosage; however, up to 200 mg/kg/day IV/IM has been used off-label.
weight 40 kg or more: 6 g/day IV/IM is the FDA-approved dosage; however, up to 200 mg/kg/day IV/IM (Max: 12 g/day) has been used off-label.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available. However, oxacillin is significantly eliminated by the kidneys and dosage adjustments may be necessary in patients with renal impairment.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Oxacillin, a beta-lactam antibiotic, is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. PBPs are responsible for several steps in cell wall synthesis and are found in quantities of several hundred to several thousand molecules per bacterial cell. PBPs vary among different bacterial species. Thus, the intrinsic activity of oxacillin and other beta-lactams against a particular organism depends on their ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, oxacillin's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.

Oxacillin, because of its side chain, resists destruction by beta-lactamases. This makes it useful for treating bacteria that resist penicillin due to the presence of penicillinase. Oxacillin is ineffective, however, against methicillin-resistant S. aureus (MRSA). These organisms appear to resist oxacillin and related antistaphylococcal penicillins due to the presence of a relatively insensitive PBP, although this mechanism is not fully understood.

Beta-lactams, including oxacillin, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T above MIC). This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Penicillins require free drug concentrations to exceed the MIC for 30% of the dosing interval to achieve bacteriostatic activity and 50% of the dosing interval to achieve bactericidal activity.

The susceptibility interpretive criteria for oxacillin are delineated by pathogen. The MICs are defined for S. aureus and S. lugdunensis as susceptible at 2 mcg/mL or less and resistant at 4 mcg/mL or more. The MICs are defined for other Staphylococcus sp. as susceptible at 0.5 mcg/mL or less and resistant at 1 mcg/mL or more.

Pharmacokinetics: Oxacillin is administered intravenously and intramuscularly. Protein binding is approximately 89-94%; binding is primarily to serum albumin. Oxacillin is distributed into lungs; bone; bile; sputum; and pleural, pericardial, peritoneal, and synovial fluids. Low concentrations are achieved in ascitic fluid and cerebrospinal fluid (CSF); however, higher concentrations are present in the CSF when meninges are inflamed. Oxacillin is primarily eliminated as unchanged drug in the urine via tubular secretion and glomerular filtration. Hepatic inactivation and excretion in the bile also contribute to elimination of the drug. The elimination half-life of oxacillin in adults is approximately 20-30 minutes.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Intravenous Route
Peak concentrations are reached approximately 5 minutes after infusion completion. In adults, a peak concentration of approximately 43 mcg/ml is achieved after an IV dose of 500 mg.

Intramuscular Route
Peak serum concentrations are achieved approximately 30 minutes after IM administration in most patients; however, in premature neonates, peak concentrations are achieved after approximately 60 minutes. A peak concentration of approximately 47-51 mcg/ml was achieved after an oxacillin dose of 20 mg/kg IM in neonates in one pharmacokinetic study (n = 10; 8 premature infants). In a very small study of infants and children, peak concentrations of 45-86 mcg/ml were achieved approximately 30 minutes after an IM oxacillin dose of 25 mg/kg. In adults, oxacillin 250 mg IM produces a peak concentration of approximately 5.3 mcg/ml and 500 mg IM produces a peak of approximately 10.9 mcg/ml.


-Special Populations
Pediatrics
Neonates
After a single IM oxacillin dose of 20 mg/kg, an elimination half-life of 1.6 hours was calculated using data from 8 premature neonates (postnatal age, 8-15 days; gestational age not reported); a half-life of 1.2 hours was reported for 2 neonates (20 and 21 days postnatal age).

Infants and Children
A mean elimination half-life of 1.3 hours (range, 53-109 minutes) was reported from a small trial in 5 children (ages 1 week to 2 years) receiving 25 mg/kg/dose IM every 6 hours.

Renal Impairment
Pharmacokinetic data are unavailable in pediatric patients with renal impairment. Oxacillin is significantly eliminated by the kidneys and dosage adjustments may be necessary in patients with renal impairment.