Label: OXACILLIN- oxacillin sodium injection, powder, for solution

Mode of Action

Penicillinase-resistant penicillins exert a bactericidal action against penicillin susceptible microorganisms during the state of active multiplication. All penicillins inhibit the biosynthesis of the bacterial cell wall.

Mechanism of Resistance

Resistance to penicillins may be mediated by destruction of the beta-lactam ring by a beta-lactamase, altered affinity of penicillin for target, or decreased penetration of the antibiotic to reach the target site.

Cross Resistance

Resistance to oxacillin (or cefoxitin) implies resistance to all other beta-lactam agents, except newer agents with activity against methicillin-resistant Staphylococcus aureus.

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

General

Oxacillin should generally not be administered to patients with a history of sensitivity to any penicillin. Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma. Whenever allergic reactions occur, penicillin should be withdrawn unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to penicillin therapy. The use of antibiotics may result in overgrowth of nonsusceptible organisms. If new infections due to bacteria or fungi occur, the drug should be discontinued and appropriate measures taken.

Prescribing Oxacillin for Injection, USP in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Laboratory Tests

Bacteriologic studies to determine the causative organisms and their susceptibility to oxacillin should be performed (see CLINICAL PHARMACOLOGY - Microbiology). In the treatment of suspected staphylococcal infections, therapy should be changed to another active agent if culture tests fail to demonstrate the presence of staphylococci.

Periodic assessment of organ system function including renal, hepatic, and hematopoietic should be made during prolonged therapy with oxacillin.

Blood cultures, white blood cell, and differential cell counts should be obtained prior to initiation of therapy and at least weekly during therapy with oxacillin.

Periodic urinalysis, blood urea nitrogen, and creatinine determinations should be performed during therapy with oxacillin and dosage alterations should be considered if these values become elevated. If any impairment of renal function is suspected or known to exist, a reduction in the total dosage should be considered and blood levels monitored to avoid possible neurotoxic reactions.

AST (SGOT) and ALT (SGPT) values should be obtained periodically during therapy to monitor for possible liver function abnormalities.

Drug Interactions

Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin and concurrent use of these drugs should be avoided.

Oxacillin blood levels may be increased and prolonged by concurrent administration of probenecid which blocks the renal tubular secretion of penicillins. Probenecid decreases the apparent volume of distribution and slows the rate of excretion by competitively inhibiting renal tubular secretion of penicillins.

Oxacillin-probenecid therapy should be limited to those infections where very high serum levels of oxacillin are necessary.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term animal studies have been conducted with these drugs. Studies on reproduction (nafcillin) in rats and rabbits reveal no fetal or maternal abnormalities before conception and continuously through weaning (one generation).

Pregnancy

Nursing Mothers

Penicillins are excreted in human milk. Caution should be exercised when penicillins are administered to a nursing woman.

Pediatric Use

Because of incompletely developed renal function in pediatric patients, oxacillin may not be completely excreted, with abnormally high blood levels resulting. Frequent blood levels are advisable in this group with dosage adjustments when necessary. All pediatric patients treated with penicillins should be monitored closely for clinical and laboratory evidence of toxic or adverse effects. Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Oxacillin for Injection did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Oxacillin for Injection contains 63.77 mg (2.77 mEq) of sodium per gram oxacillin. At the usual recommended doses, patients would receive between 63.77 and 382.62 mg/day (2.77 and 16.62 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.

Information for Patients

Patients should be counseled that antibacterial drugs including Oxacillin for Injection, USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Oxacillin for Injection, USP is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Oxacillin for Injection, USP or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Body as a Whole

The reported incidence of allergic reactions to penicillin ranges from 0.7 to 10 percent (see WARNINGS). Sensitization is usually the result of treatment but some individuals have had immediate reactions when first treated. In such cases, it is thought that the patients may have had prior exposure to the drug via trace amounts present in milk and vaccines.

Two types of allergic reactions to penicillins are noted clinically, immediate and delayed.

Immediate reactions usually occur within 20 minutes of administration and range in severity from urticaria and pruritus to angioneurotic edema, laryngospasm, bronchospasm, hypotension, vascular collapse and death. Such immediate anaphylactic reactions are very rare (see WARNINGS) and usually occur after parenteral therapy but have occurred in patients receiving oral therapy. Another type of immediate reaction, an accelerated reaction, may occur between 20 minutes and 48 hours after administration and may include urticaria, pruritus, and fever. Although laryngeal edema, laryngospasm, and hypotension occasionally occur, fatality is uncommon.

Delayed allergic reactions to penicillin therapy usually occur after 48 hours and sometimes as late as 2 to 4 weeks after initiation of therapy.

Manifestations of this type of reaction include serum sickness-like symptoms (i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain) and various skin rashes. Nausea, vomiting, diarrhea, stomatitis, black or hairy tongue, and other symptoms of gastrointestinal irritation may occur, especially during oral penicillin therapy.

Nervous System Reactions

Neurotoxic reactions similar to those observed with penicillin G may occur with large intravenous doses of oxacillin, especially with patients with renal insufficiency.

Urogenital Reactions

Renal tubular damage and interstitial nephritis have been associated with the administration of oxacillin. Manifestations of this reaction may include rash, fever, eosinophilia, hematuria, proteinuria, and renal insufficiency. Nephropathy induced by penicillins does not appear to be dose-related and is generally reversible upon prompt discontinuation of therapy.

Gastrointestinal Reactions

Pseudomembranous colitis has been reported with the use of oxacillin. The onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see WARNINGS).

Metabolic Reactions

Agranulocytosis, neutropenia, and bone marrow depression have been associated with the use of oxacillin. Hepatotoxicity, characterized by fever, nausea, and vomiting associated with abnormal liver function tests, mainly elevated SGOT levels, has been associated with the use of oxacillin.

To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals, Inc. at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

For Administration by Intravenous Drip

Reconstitute as directed below (Pharmacy Bulk Package) prior to further dilution.

Stability studies on Oxacillin Sodium at concentrations of 0.5 mg/mL and 2 mg/mL in various intravenous solutions listed below indicate the drug will lose less than 10% activity at room temperature (70°F) during a 6-hour period.

IV Solution

5% Dextrose in Normal Saline

10% D-Fructose in Water

10% D-Fructose in Normal Saline

10% Invert Sugar in Normal Saline

10% Invert Sugar Plus 0.3% Potassium Chloride in Water

Only those solutions listed above should be used for the intravenous infusion of Oxacillin Sodium. The concentration of the antibiotic should fall within the range specified. The drug concentration and the rate and volume of the infusion should be adjusted so that the total dose of oxacillin is administered before the drug loses its stability in the solution in use.

If another agent is used in conjunction with oxacillin therapy, it should not be physically mixed with oxacillin but should be administered separately.

Pharmacy Bulk Package

This glass Pharmacy Bulk Package bottle contains 10 grams Oxacillin Sodium and is designed for use in the pharmacy in preparing IV admixtures. Add 93 mL Sterile Water for Injection, USP or Sodium Chloride Injection, USP 0.9%. The resulting solution will contain 100 mg oxacillin per mL and will require further dilution.

CAUTION: NOT TO BE DISPENSED AS A UNIT.

Directions for Proper Use of Pharmacy Bulk Package

1. The container closure may be penetrated only one time after reconstitution, utilizing a suitable sterile dispensing set which allows measured distribution of the contents.
2. Use of this product is restricted to a suitable work area, such as a laminar flow hood.
3. Once this container closure has been punctured, withdrawal of the contents should be completed without delay. If prompt fluid transfer cannot be accomplished, discard the contents no later than 4 HOURS after initial closure puncture. This time limit should begin with the introduction of solvent for diluent into the Pharmacy Bulk Package.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not add supplementary medication to Oxacillin for Injection, USP.

Storage Conditions

Store dry powder at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Sterile, Nonpyrogenic, Preservative-free.
The container closure is not made with natural rubber latex.

Mfd. for SAGENT Pharmaceuticals
Schaumburg, IL 60195 (USA)
Made in India

novaplusTM+
Novaplus is a registered trademark of Vizient, Inc.

June 2018