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Pronunciation:

(oks a SIL in)

Synonyms:

Methylphenyl Isoxazolyl Penicillin; Oxacillin Sodium

Generic Available:

Yes

Use:

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

Pregnancy Risk Factor:

Pregnancy Implications:

Teratogenicity not observed in animal studies.

Lactation:

Enters breast milk/compatible

Contraindications:

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

Warnings/Precautions:

Elimination rate will be slow in neonates; modify dosage in patients with renal impairment and in the elderly; use with caution in patients with cephalosporin hypersensitivity

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

Overdosage/Toxicology:

Symptoms of penicillin overdose include neuromuscular hypersensitivity (eg, agitation, hallucinations, asterixis, encephalopathy, confusion, and seizures). Electrolyte imbalance may occur if the preparation contains potassium or sodium salts, especially in renal failure. Hemodialysis may be helpful to aid in removal of the drug from blood; otherwise, treatment is supportive or symptom-directed.

Drug Interactions:

Methotrexate: Penicillins may increase the exposure to methotrexate during concurrent therapy; monitor.

Oral contraceptives: Anecdotal reports suggesting decreased contraceptive efficacy with penicillins have been refuted by more rigorous scientific and clinical data.

Probenecid, disulfiram: May increase levels of penicillins (oxacillin)

Warfarin: Effects of warfarin may be increased

Stability:

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 24 hours at room temperature

Compatibility:

Stable in dextran 70 6% in dextrose, 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, diltiazem, famotidine, fluconazole, foscarnet, heparin, hydrocortisone sodium succinate, hydromorphone, labetalol, levofloxacin, magnesium sulfate, meperidine, methotrexate, morphine, perphenazine, potassium chloride, tacrolimus, vitamin B complex with C, zidovudine. Incompatible: Sodium bicarbonate, verapamil

Compatibility when admixed: Compatible: Chloramphenicol, dopamine, potassium chloride, sodium bicarbonate. Incompatible: Cytarabine. Variable (consult detailed reference): Amikacin, verapamil

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, peritoneal, and pericardial fluids; crosses placenta; enters breast milk; 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:

I.M., I.V.:

Infants and Children:

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

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

Adults:

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

Severe infections: 1-2 g every 4-6 hours

Dosing adjustment in renal impairment: Clcr<10 mL/minute: Use lower range of the usual dosage

Hemodialysis: Not dialyzable (0% to 5%)

Administration:

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

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:

Sodium content of 1 g: 92.4 mg (4.02 mEq)

Patient Education:

Complete course of treatment as prescribed. You may experience nausea or vomiting; small, frequent meals and good mouth care may help. If you have diabetes, drug may cause false test results with Clinitest® urine glucose monitoring; use of glucose oxidase methods (Clinistix®) or serum glucose monitoring is preferable. Report persistent fever, sore throat, sores in mouth, diarrhea, unusual bleeding or bruising, respiratory difficulty, or skin rash. Notify prescriber if condition does not respond to treatment.

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

Dosage Forms:

Infusion [premixed iso-osmotic dextrose solution]: 1 g (50 mL); 2 g (50 mL)

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

International Brand Names:

Biolab Oxacilina® (BR); Bristopen® (FR); InfectoStaph® [inj.] (DE); Oxacil® (BR); Oxacilina® (BR, RO); Oxacilina Sodica® (BR); Oxacilin Leciva® (CZ); Oxacillin® (BG); Penstapho® (BE, IT, LU); Prostaphlin® (CZ, HU, SI); Staficilin-N® (BR)

References

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.

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