General dosing (nonmeningitis):
Age-directed dosing (Ref): IV, IM:
Gestational Age |
Postnatal Age |
Dose |
---|---|---|
≤34 weeks |
≤7 days |
25 mg/kg/dose every 12 hours |
8 to 28 days |
25 mg/kg/dose every 8 hours | |
>34 weeks |
≤7 days |
25 mg/kg/dose every 8 hours |
8 to 28 days |
25 mg/kg/dose every 6 hours |
Weight-directed dosing (Ref): IV, IM:
Body Weight |
Postnatal Age |
Dose |
---|---|---|
<1 kg |
≤14 days |
25 mg/kg/dose every 12 hours |
15 to 28 days |
25 mg/kg/dose every 8 hours | |
29 to 60 days |
37.5 mg/kg/dose every 6 hours | |
1 to 2 kg |
≤7 days |
25 mg/kg/dose every 12 hours |
8 to 28 days |
25 mg/kg/dose every 8 hours | |
29 to 60 days |
37.5 mg/kg/dose every 6 hours | |
>2 kg |
≤7 days |
25 mg/kg/dose every 8 hours |
8 to 28 days |
25 mg/kg/dose every 6 hours | |
29 to 60 days |
37.5 mg/kg/dose every 6 hours |
Meningitis (Ref): IV, IM:
Body Weight |
Postnatal Age |
Dose |
---|---|---|
<1 kg |
≤14 days |
50 mg/kg/dose every 12 hours |
15 to 28 days |
50 mg/kg/dose every 8 hours | |
29 to 60 days |
75 mg/kg/dose every 6 hours | |
1 to 2 kg |
≤7 days |
50 mg/kg/dose every 12 hours |
8 to 28 days |
50 mg/kg/dose every 8 hours | |
29 to 60 days |
75 mg/kg/dose every 6 hours | |
>2 kg |
≤7 days |
50 mg/kg/dose every 8 hours |
8 to 28 days |
50 mg/kg/dose every 6 hours | |
29 to 60 days |
75 mg/kg/dose every 6 hours |
General dosing: Infants, Children, and Adolescents: IV, IM: 100 to 200 mg/kg/day in divided doses every 4 to 6 hours; maximum daily dose: 12 g/day (Ref).
Endocarditis, treatment: Children and Adolescents: IV: 200 mg/kg/day in divided doses every 4 to 6 hours; maximum daily dose: 12 g/day. Treat for at least 4 to 6 weeks; duration should be individualized based on presentation, valve type, and response to therapy (Ref).
Meningitis/Ventriculitis: Infants, Children, and Adolescents: IV: 200 mg/kg/day in divided doses every 6 hours; maximum daily dose: 12 g/day (Ref).
Osteoarticular infection, acute (eg, septic arthritis, osteomyelitis): Infants, Children, and Adolescents: IV: 150 to 200 mg/kg/day divided every 4 to 6 hours; maximum daily dose: 12 g/day (Ref). May transition to oral therapy as appropriate (eg, response to initial parenteral therapy, oral option available). Minimum total duration is 2 to 3 weeks for septic arthritis and 3 to 4 weeks for osteomyelitis; however, duration should be individualized based on several factors, including causative pathogen, response to therapy, and normalization of inflammatory markers (Ref).
Pneumonia, community-acquired (CAP) moderate to severe infection, methicillin-susceptible Staphylococcus aureus (MSSA):
Infants >3 months, Children, and Adolescents: IV: 150 to 200 mg/kg/day divided every 6 to 8 hours (Ref).
Skin and soft tissue infection (Ref):
Infants, Children, and Adolescents:
MSSA (non-necrotizing infection): IV: 100 to 150 mg/kg/day in divided doses every 6 hours; maximum daily dose: 12 g/day.
Necrotizing infection due to MSSA: IV: 200 mg/kg/day in divided doses every 6 hours; maximum daily dose: 12 g/day; continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function:
Infants, Children, and Adolescents: IV, IM: There are no dosage adjustments provided in the manufacturer's labeling; however, oxacillin is eliminated via the kidney; monitoring is recommended. High oxacillin concentrations and neurotoxicity have been reported in adult patients with severe kidney impairment; monitor closely (Ref).
Hemodialysis: Not significantly dialyzed (Ref):
Infants, Children, and Adolescents: IV, IM: No specific dosage adjustment recommended; however, high oxacillin concentrations and neurotoxicity have been reported in adult patients with severe kidney impairment; monitor closely (Ref).
Peritoneal dialysis: Minimally dialyzed (5%) (Ref):
Infants, Children, and Adolescents: IV, IM: No specific dosage adjustment recommended; however, high oxacillin concentrations and neurotoxicity have been reported in adult patients with severe kidney impairment; monitor closely (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Oxacillin: Drug information")
Usual dosage range: IV: 1 to 2 g every 4 to 6 hours; may also administer total daily dose as a continuous infusion over 24 hours (eg, for a dose of 2 g every 4 hours, administer 12 g over 24 hours) (Ref).
Bloodstream infection: Pathogen-directed therapy for methicillin-susceptible staphylococci (off label): IV: 2 g every 4 hours; treat uncomplicated bacteremia for ≥14 days starting from day of first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (Ref)
Endocarditis, treatment: Pathogen-directed therapy for methicillin-susceptible staphylococci (off label):
Native valve: IV: 12 g/day in 4 or 6 divided doses (ie, 2 g every 4 hours or 3 g every 6 hours) for 6 weeks. For uncomplicated right-sided ineffective endocarditis, 2 weeks of therapy may be adequate (Ref)
Prosthetic valve: IV: 12 g/day in 6 divided doses (ie, 2 g every 4 hours) for ≥6 weeks; use with rifampin for entire duration of therapy and gentamicin for first 2 weeks (Ref).
Meningitis, bacterial: Pathogen-directed therapy for methicillin-susceptible staphylococci (off label): IV: 2 g every 4 hours; consider addition of rifampin if organism is susceptible and prosthetic material is present. Treatment duration is 10 to 14 days, depending on causative pathogen(s) and clinical response (Ref).
Osteomyelitis and/or discitis: Pathogen-directed therapy for methicillin-susceptible staphylococci (off label): IV: 1.5 to 2 g every 4 to 6 hours or via continuous infusion for ≥6 weeks depending on extent of infection, debridement, and clinical response (Ref).
Pneumonia: Pathogen-directed therapy for methicillin-susceptible S. aureus (off label): IV: 2 g every 4 hours (Ref). Minimum duration is generally 5 days for community-acquired pneumonia and 7 days for hospital-acquired or ventilator-associated pneumonia; patients should be clinically stable with normal vital signs before therapy is discontinued (Ref).
Prosthetic joint infection: Pathogen-directed therapy for methicillin-susceptible staphylococci (off label): IV: 1.5 to 2 g every 4 to 6 hours; duration ranges from 2 to 6 weeks depending on prosthesis management, use of rifampin, and other patient-specific factors (Ref).
Skin and soft tissue infection:
Cellulitis (nonpurulent) in patients without risk for methicillin-resistant S. aureus: IV: 1 to 2 g every 4 hours. Total duration of therapy is ≥5 days (including oral step-down therapy); may extend up to 14 days depending on severity and clinical response (Ref).
Necrotizing infection due to methicillin-susceptible S. aureus (MSSA) (off label): IV: 1 to 2 g every 4 hours; continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (Ref).
Surgical site incisional infection (trunk or extremity, not involving axilla or perineum) (off label): IV: 2 g every 6 hours; duration is dependent upon severity, need for debridement, and clinical response (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
CrCl ≥10 mL/minute: No dosage adjustment necessary (Ref).
CrCl <10 mL/minute: No specific dosage adjustment recommended; however, monitor closely as high oxacillin concentrations and neurotoxicity have been reported in this population (Ref). When treating less severe infections, a maximum daily dose of 8 g/day may be considered (Ref).
Intermittent hemodialysis (thrice weekly): Not significantly dialyzed (Ref): No specific dosage adjustment recommended; however, monitor closely as high oxacillin concentrations and neurotoxicity have been reported in this population (Ref). When treating less severe infections, a maximum daily dose of 8 g/day may be considered (Ref).
Peritoneal dialysis: Minimally dialyzed (5%) (Ref): No specific dosage adjustment recommended; however, monitor closely as high oxacillin concentrations and neurotoxicity have been reported in this population (Ref). When treating less severe infections, a maximum daily dose of 8 g/day may be considered (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Postmarketing:
Gastrointestinal: Clostridioides difficile-associated diarrhea, clostridioides difficile colitis (Thomas 1984)
Hematologic: Agranulocytosis, bone marrow depression, granulocytopenia (Brook 1977), leukopenia (Brook 1977), neutropenia (Passoff 1978)
Hepatic: Hepatitis (Al-Homaidhi 2002), hepatotoxicity, increased serum aspartate aminotransferase
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Sharpe 2019)
Renal: Acute renal tubular disease, interstitial nephritis
Hypersensitivity (eg, anaphylaxis) to oxacillin, any penicillin, or any component of the formulation.
Concerns related to adverse effects:
• Anaphylactic/hypersensitivity reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in patients with histories of significant allergies and/or asthma; discontinue treatment and institute appropriate therapy if an allergic reaction occurs
• Hepatitis: Acute hepatitis and reversible elevations of serum transaminases have been reported sometimes accompanied by rash and leukopenia; onset after 2 to 3 weeks of therapy (Dahlgren 1997; Faden 2009; Maraqa 2002).
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in severe impairment.
Special populations:
• Older adult: May contain a significant amount of sodium; consult product specific labeling for amount. Older adults may respond with a blunted natriuresis to salt loading. This may be clinically important in diseases such as congestive heart failure.
Hepatotoxicity and rash are more common with oxacillin compared to other parenteral antibiotics; in a study of pediatric patients (5 to 19 years) receiving outpatient parenteral antimicrobial therapy (oxacillin n=41; nafcillin n=58; "other" antibiotics n=146), significantly more hepatotoxicity (22%) and rash (31.7%) were reported in the oxacillin group compared to the nafcillin group (0% and 10.3%) or other antibiotics (1.4% and 1.4%) (Maraqa 2002).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 1 g/50 mL (50 mL); 2 g/50 mL (50 mL)
Solution Reconstituted, Injection:
Generic: 1 g (1 ea); 2 g (1 ea)
Solution Reconstituted, Injection [preservative free]:
Generic: 1 g (1 ea); 2 g (1 ea)
Solution Reconstituted, Intravenous:
Generic: 10 g (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 10 g (1 ea)
Yes
Solution (Oxacillin Sodium in Dextrose Intravenous)
1 gm/50 mL (per mL): $0.41
2 gm/50 mL (per mL): $0.59
Solution (reconstituted) (Oxacillin Sodium Injection)
1 g (per each): $13.50 - $14.50
2 g (per each): $10.80 - $29.00
Solution (reconstituted) (Oxacillin Sodium Intravenous)
10 g (per each): $66.30 - $145.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
May contain a significant amount of sodium; consult product specific labeling for amount.
Parenteral:
IM: Administer by deep IM injection into a large muscle mass (eg, gluteus maximus); avoid sciatic nerve injury.
IV:
Direct IV injection: Administer over 10 minutes at a concentration of 100 mg/mL.
Intermittent IV infusion: Administer over 15 to 30 minutes (Ref); extending the infusion over 60 minutes has been used for peripheral administration by some ambulatory centers to decrease the risk of phlebitis in home care patients (Ref).
IV: Administer IVP over 10 minutes or IVPB over 30 minutes. Total daily dose may also be administered over 24 hours as a continuous infusion (Ref).
Premixed infusions: Store in a freezer at -20°C (-4°F). Thaw at room temperature or under refrigeration only. Thawed bags are stable for 21 days under refrigeration or 48 hours at room temperature. Do not refreeze.
Vials: Store intact vials at 20°C to 25°C (68°F to 77°F); refer to manufacturer's labeling for specific storage instructions after dilution (varies by concentration and diluent).
Treatment of infections due to susceptible penicillinase-producing staphylococci (FDA approved in all ages).
Substrate of OAT1/3
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Acemetacin: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Antibiotics may decrease serum concentrations of the active metabolite(s) of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Sodium Benzoate: Penicillins may diminish the therapeutic effect of Sodium Benzoate. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Tetracyclines: May diminish the therapeutic effect of Penicillins. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Some products may contain sodium.
Oxacillin crosses the placenta.
Although it is highly protein bound, therapeutic concentrations can be found in the amniotic fluid following IV administration (Nau 1987).
As a class, penicillin antibiotics are widely used in pregnant women. Based on available data, penicillin antibiotics are generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Czeizel 1999; Damkier 2019; Lamont 2014; Muanda 2017a; Muanda 2017b).
CBC with differential, urinalysis, BUN, serum creatinine, AST and ALT; number and type of stools/day for diarrhea; observe IV site for extravasation.
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Distribution: Into bile, pleural fluids; insignificant concentrations in CSF and aqueous humor.
Protein binding: ~94% (mainly albumin).
Metabolism: Hepatic.
Half-life elimination:
Preterm neonates (PNA: 8 to 15 days): 96 minutes (Axline 1967).
Term neonates >1 week of age, Infants, and Children ≤2 years: 78 minutes; range: 53 to 109 minutes (Burckhart 1978).
Adults: 20 to 30 minutes; prolonged with renal impairment.
Time to peak, serum: IM: 30 minutes; IV: 5 minutes.
Excretion: Urine and bile (unchanged drug).
Anti-infective considerations:
Parameters associated with efficacy: Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC); goal: ≥50% fT > MIC (bactericidal) (Drusano 2003; Turnidge 1998).
Critically ill patients in the ICU: Minimum goal: ≥50% fT > MIC; preferred goal: ≥100% fT > MIC (Abdul-Aziz 2020; Al-Shaer 2020; Roberts 2014); some experts favor ≥100% fT > 4 times the MIC (Guilhaumou 2019).
Expected drug exposure:
Cmax (peak): Single dose: IV: Adults: 500 mg: 43 mg/L.
Postantibiotic effect: Minimal bacterial killing continues after concentration of penicillins fall below the MIC of targeted pathogen and varies based on the organism:
Gram-positive cocci: 1.5 to 3.5 hours (Craig 1991).
Gram-negative bacilli: 0 to 1.5 hours (Craig 1991).
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