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Oxacillin

Pronunciation

(oks a SIL in)

Index Terms

  • Methylphenyl Isoxazolyl Penicillin
  • Oxacillin Sodium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Bactocill in Dextrose: 1 g/50 mL (50 mL); 2 g/50 mL (50 mL)

Solution Reconstituted, Injection:

Generic: 1 g (1 ea); 2 g (1 ea); 10 g (1 ea)

Solution Reconstituted, Injection [preservative free]:

Generic: 1 g (1 ea); 2 g (1 ea); 10 g (1 ea)

Brand Names: U.S.

  • Bactocill in Dextrose

Pharmacologic Category

  • Antibiotic, Penicillin

Pharmacology

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, amniotic, and pleural fluids; insignificant concentrations in CSF and aqueous humor

Metabolism

Hepatic

Excretion

Urine and bile (unchanged drug)

Time to Peak

Serum: IM: 30 minutes; IV: 5 minutes

Half-Life Elimination

Neonates (PNA: 8 to 15 days): 1.6 hours

Infants and Children ≤2 years: 0.9 to 1.8 hours

Adults: 20 to 30 minutes; prolonged with renal impairment

Protein Binding

~94% (mainly albumin)

Use: Labeled Indications

Staphylococcal infections: Treatment of infections caused by penicillinase-producing staphylococci that have demonstrated susceptibility to the drug; empiric therapy in suspected cases of resistant staphylococcal infections.

Limitations of use: Oxacillin should not be used in infections caused by organisms susceptible to penicillin G.

Contraindications

Hypersensitivity (eg, anaphylaxis) to oxacillin, any penicillin, or any component of the formulation.

Dosing: Adult

Note: May contain a significant amount of sodium; consult product specific labeling for amount.

Catheter-related bloodstream infections (off-label use): IV: 2 g every 4 hours (Mermel 2009)

Endocarditis, treatment: Methicillin-susceptible Staphylococcus aureus (MSSA) (off-label dose; AHA [Baddour 2015]): IV:

Native valve: 12 g/day in 4 or 6 divided doses (ie, 2 g every 4 hours or 3 g every 6 hours) for 6 weeks. Note: Dosing intended for complicated right-sided infective endocarditis (IE) or left-sided IE. For uncomplicated right-sided IE, 2 weeks of therapy may be adequate

Prosthetic valve: 12 g/day in 6 divided doses (ie, 2 g every 4 hours) for at least 6 weeks (use with rifampin for entire course and gentamicin for first 2 weeks)

Mild-to-moderate infections: IM, IV: 250 to 500 mg every 4 to 6 hours

Prosthetic joint infection: IV: 2 g every 4 hours with rifampin

Severe infections: IM, IV: 1 g every 4 to 6 hours

Staphylococcus aureus, methicillin-susceptible infections, including brain abscess, bursitis, erysipelas, mastitis, mastoiditis, osteomyelitis, perinephric abscess, pneumonia, pyomyositis, scalded skin syndrome, toxic shock syndrome: IV: 2 g every 4 hours

Skin and soft tissue infections (IDSA [Stevens 2014]): IV:

Due to methicillin-susceptible Staphylococcus aureus (MSSA): 1 to 2 g every 4 hours for 7 to 14 days

Necrotizing infection due to MSSA (off-label use): 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

Surgical site infections (trunk or extremity [away from axilla or perineum]) (off-label use): IV: 2 g every 6 hours (IDSA [Stevens 2014])

Dosing: Geriatric

Refer to adult dosing. Note: May contain a significant amount of sodium; consult product specific labeling for amount. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important in diseases such as congestive heart failure.

Dosing: Pediatric

Note: May contain a significant amount of sodium; consult product specific labeling for amount.

Catheter-related bloodstream infections: Infants and Children: IV: 150 to 200 mg/kg/day divided every 4 to 6 hours (Mermel 2009)

Community-acquired pneumonia (CAP) (IDSA/PIDS 2011), moderate-to-severe infection, S. aureus (methicillin-susceptible) (preferred): Infants >3 months and Children: IV: 150 to 200 mg/kg/day divided every 6-8 hours

Mild-to-moderate infections: IM, IV: 50 mg/kg/day in divided doses every 6 hours (maximum: 4 g daily)

Severe infections: Infants and Children: IM, IV: 100 mg/kg/day in divided doses every 4-6 hours (maximum: 12 g daily)

Skin and soft tissue infections (IDSA [Stevens 2014]): IV:

Due to methicillin-susceptible Staphylococcus aureus (MSSA): IV: 100 to 150 mg/kg/day in divided doses every 6 hours for 7 to 14 days

Necrotizing infection due to MSSA (off-label use): 200 mg/kg/day in divided doses every 6 hours; continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling; however, manufacturer suggests considering a reduction in total dosage if renal impairment is known or suspected.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Reconstitution

IM: After reconstitution, vials will contain oxacillin 250 mg/1.5 mL. Refer to manufacturer's product labeling for more information.

IV:

1 gram vial: Add sterile water for injection or NS 10 mL; shake well.

2 gram vial: Add sterile water for injection or NS 20 mL; shake well.

10 gram vial: Add sterile water for injection or NS 93 mL; shake well. The resulting solution will contain oxacillin 100 mg/mL and requires further dilution prior to administration.

Administration

Administer IV or IM around-the-clock to promote less variation in peak and trough serum levels. Administer IVP over 10 minutes. Administer IVPB over 30 minutes.

Dietary Considerations

Some products may contain sodium.

Compatibility

Stable in D5W, D5LR, D51/4NS, D51/2NS, D5NS, LR, NS.

Y-site administration: Incompatible with caffeine citrate, sodium bicarbonate, verapamil.

Storage

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).

Drug Interactions

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Monitor therapy

Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Monitor therapy

Probenecid: May increase the serum concentration of Penicillins. Management: Avoid the routine use of penicillins and probenecid, but this combination may be used advantageously in select cases with careful monitoring. Monitor for toxic effects of penicillins if probenecid is initiated or the dose is increased. Consider therapy modification

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. Consider therapy modification

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

May interfere with urinary glucose tests using cupric sulfate (Benedict's solution, Clinitest®); may inactivate aminoglycosides in vitro; false-positive urinary and serum proteins

Adverse Reactions

Frequency not defined.

Central nervous system: Fever

Dermatologic: Rash

Gastrointestinal: Nausea, diarrhea, vomiting

Hematologic: Eosinophilia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis

Hepatic: Hepatotoxicity, AST increased

Renal: Acute interstitial nephritis, hematuria

Miscellaneous: Serum sickness-like reactions

Warnings/Precautions

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; monitor periodically throughout 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; dosage adjustment recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: May contain a significant amount of sodium; consult product specific labeling for amount. The elderly population may respond with a blunted natriuresis to salt loading. This may be clinically important in diseases such as congestive heart failure.

• Neonates: Use with caution in neonates; elimination of drug is decreased; dosage adjustment is needed.

Monitoring Parameters

Observe for signs and symptoms of anaphylaxis during first dose; monitor periodic CBC, urinalysis, BUN, serum creatinine, AST and ALT

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Oxacillin is distributed into the amniotic fluid and is detected in cord blood. Maternal use of penicillins has generally not resulted in an increased risk of adverse fetal effects.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, tongue discoloration, or diarrhea. Have patient report immediately to prescriber muscle pain, joint pain, mouth irritation, hematuria, dark urine, change in amount of urine passed, urinary retention, bruising, bleeding, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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