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Pronunciation

(oks a SIL in)

Generic Available (U.S.)

Yes

Index Terms

• Methylphenyl Isoxazolyl Penicillin
• Oxacillin Sodium

Pharmacologic Category

• Antibiotic, Penicillin

Pharmacologic Category Synonyms

• Penicillin Derivative Antibiotic

Use: Labeled Indications

Treatment of infections such as osteomyelitis, septicemia, endocarditis, and CNS infections caused by susceptible strains of Staphylococcus

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal studies; therefore, oxacillin is classified as pregnancy category B. Oxacillin is distributed into the amniotic fluid and is detected in cord blood. There was not an increased risk of teratogenic effects with oxacillin observed in an epidemiologic study.

Lactation

Enters breast milk/use caution

Breast-Feeding Considerations

Low levels of oxacillin are found in breast milk. The manufacturer recommends that caution be exercised when administering oxacillin to nursing women. Other penicillins distribute into human milk and are considered safe for use during breast-feeding. Nondose-related effects could include modification of bowel flora.

Contraindications

Hypersensitivity to oxacillin or other penicillins or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) 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 asthmatic patients.

• 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 patients with renal impairment; dosage adjustment recommended.

Special populations:

• Elderly: Use with caution in the elderly; dosage adjustment recommended.

• Neonates: Use with caution in neonates; elimination of drug is slow.

Adverse Reactions

Frequency not defined.

Central nervous system: Fever

Dermatologic: Rash

Gastrointestinal: Diarrhea, nausea, vomiting

Hematologic: Agranulocytosis, eosinophilia, leukopenia, neutropenia, thrombocytopenia

Hepatic: AST increased, hepatotoxicity

Renal: Acute interstitial nephritis, hematuria

Miscellaneous: Serum sickness-like reactions

Metabolism/Transport Effects

None known.

Drug Interactions

BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination

Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: 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. Risk C: Monitor therapy

Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: 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 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification

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

Storage

Reconstituted parenteral solution is stable for 3 days at room temperature and 7 days when refrigerated. For I.V. infusion in NS or D₅W, solution is stable for 6 hours at room temperature.

Compatibility

Stable in dextran 40 10% in dextrose, D₅LR, D₁₀W, hetastarch 6%, LR; variable stability (consult detailed reference) in D₅NS, D₅W, NS.

Y-site administration: Compatible: Acyclovir, cyclophosphamide, cyclosporine, diltiazem, famotidine, fluconazole, foscarnet, heparin, hydrocortisone sodium succinate, hydromorphone, labetalol, levofloxacin, magnesium sulfate, meperidine, methotrexate, milrinone, morphine, oxytocin, potassium chloride, tacrolimus, zidovudine. Incompatible: Caffeine citrate, sodium bicarbonate, verapamil. Variable (consult detailed reference): Doxapram, vitamin B complex with C.

Compatibility in syringe: Incompatible: Caffeine citrate.

Mechanism of Action

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.

Pharmacodynamics/Kinetics

Distribution: Into bile, synovial and pleural fluids, bronchial secretions; also distributes to peritoneal and pericardial fluids; penetrates the blood-brain barrier only when meninges are inflamed

Protein binding: ~94%

Metabolism: Hepatic to active metabolites

Half-life elimination: Children 1 week to 2 years: 0.9-1.8 hours; Adults: 23-60 minutes; prolonged in neonates and with renal impairment

Time to peak, serum: I.M.: 30-60 minutes

Excretion: Urine and feces (small amounts as unchanged drug and metabolites)

Dosage

Usual dosage range:

Infants and Children: I.M., I.V.: 100-200 mg/kg/day in divided doses every 6 hours (maximum: 12 g/day)

Adults: I.M., I.V.: 250-2000 mg every 4-6 hours

Indication-specific dosing:

Infants >3 months and Children:

Community-acquired pneumonia (CAP) (IDSA/PIDS, 2011), moderate-to-severe infection, S. aureus (methicillin-susceptible) (preferred): I.V.: 150-200 mg/kg/day divided every 6-8 hours

Children:

Arthritis (septic): I.V.: 37 mg/kg every 6 hours

Epiglottitis: I.V.: 150-200 mg/kg/day divided every 6 hours

Mild-to-moderate infections: I.M., I.V.: 100-150 mg/kg/day in divided doses every 6 hours (maximum: 4 g/day)

Severe infections: I.M., I.V.: 150-200 mg/kg/day in divided doses every 6 hours (maximum: 12 g/day)

Staphylococcal scalded-skin syndrome: I.V.: 150 mg/kg/day divided every 6 hours for 5-7 days

Adults:

Endocarditis: I.V.: 2 g every 4 hours with gentamicin

Mild-to-moderate infections: I.M., I.V.: 250-500 mg every 4-6 hours

Prosthetic joint infection: I.V.: 2 g every 4 hours with rifampin

Severe infections: I.M., I.V.: 1-2 g every 4-6 hours

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

Dosing adjustment in renal impairment: Cl_cr <10 mL/minute: Clinical practice varies; some clinicians recommend adjustment to the lower range of the usual dosage as based on severity of infection.

Hemodialysis: Not dialyzable (0% to 5%)

Administration: I.V.

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

Administration: I.V. Detail

Rapid administration may result in seizures.

Monitoring Parameters

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

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

Dietary Considerations

Some products may contain sodium.

Patient Education

This medication can only be administered by infusion or injection. Report immediately any redness, swelling, burning, or pain at injection/infusion site; respiratory difficulty or swallowing; chest pain; or rash. May cause nausea. Report signs of opportunistic infection (eg, fever, chills, sore throat, burning urination); changes in urinary elimination; yellowing of skin or sclera, dark urine, or pale stool; persistent diarrhea; rash or other persistent side effects; or if condition does not respond to treatment.

Geriatric Considerations

Oxacillin has not been studied in the elderly. Dosing adjustments are not necessary except in renal failure (eg, Cl_cr <10 mL/minute). Consider sodium content in patients who may be sensitive to volume expansion (ie, CHF).

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Prolonged use of penicillins may lead to development of oral candidiasis.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Penicillins reported to cause apprehension, illusions, hallucinations, depersonalization, agitation, insomnia, and encephalopathy

Mental Health: Effects on Psychiatric Treatment

May cause neutropenia; use caution with clozapine and carbamazepine

Nursing: Physical Assessment/Monitoring

Assess results of culture and sensitivity tests and patient's allergy history prior to beginning therapy. Rapid I.V. administration may result in seizures. With first infusion/injection, patient should be monitored closely for anaphylactic reaction. Monitor for hypersensitivity, opportunistic infection, hepatotoxicity, renal toxicity, and gastrointestinal upset.

Dosage Forms

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

Infusion, premixed iso-osmotic solution: 1 g (50 mL); 2 g (50 mL)

Injection, powder for reconstitution: 1 g, 2 g, 10 g

References

Bradley JS, Byington CL, Shah SS, et al. “The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America”, Clin Infect Dis, 2011, 53(7):e25-76.

Donowitz GR and Mandell GL, “Beta-Lactam Antibiotics,” N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.

Olans RN and Weiner LB, “Reversible Oxacillin Hepatotoxicity,” J Pediatr, 1976, 89(5):835-8.

Prober CG, Stevenson DK, and Benitz WE, “The Use of Antibiotics in Neonates Weighing Less Than 1200 Grams,” Pediatr Infect Dis J, 1990, 9(2):111-21.

Wright AJ, “The Penicillins,” Mayo Clin Proc, 1999, 74(3):290-307.

Yoshikawa TT, “Antimicrobial Therapy for the Elderly Patient,” J Am Geriatr Soc, 1990, 38(12):1353-72.

International Brand Names

• Bristopen (FR)
• Dicloxalox (PE)
• Oxacil (BR)
• Oxacilina (CO)
• Oxacillin (PL)
• Oxapen (PH)
• Oxatalis (PH)
• Penstapho (BE, IT)
• Prostafilina (VE)
• Prostaphlin (CZ, EE, HN, TW)
• Stafcil (PH)
• Staficilin-N (BR)
• Stapenor (AT)
• Syntarpen (PL)
• Wydox (PH)

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Last full review/revision January 2012

Content last modified January 2012