Oxacillin Sodium

INDICATIONS AND USAGE Oxacillin is indicated in the treatment of infections caused by penicillinase producing staphylococci which have demonstrated susceptibility to the drug. Cultures and susceptibility tests should be performed initially to determine the causative organism and its susceptibility to the drug (See CLINICAL PHARMACOLOGY - Susceptibility Test Methods ). Oxacillin may be used to initiate therapy in suspected cases of resistant staphylococcal infections prior to the availability of susceptibility test results. Oxacillin should not be used in infections caused by organisms susceptible to penicillin G. If the susceptibility tests indicate that the infection is due to an organism other than a resistant Staphylococcus , therapy should not be continued with oxacillin. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Oxacillin for Injection, USP and other antibacterial drugs, Oxacillin for Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

DOSAGE AND ADMINISTRATION The intent of the pharmacy bulk package for this product is for preparation of solutions for IV infusion only. Bacteriologic studies to determine the causative organisms and their susceptibility to oxacillin should always be performed. Duration of therapy varies with the type of severity of infection as well as the overall condition of the patient; therefore, it should be determined by the clinical and bacteriological response of the patient. In severe staphylococcal infections, therapy with oxacillin should be continued for at least 14 days. Therapy should be continued for at least 48 hours after the patient has become afebrile, asymptomatic, and cultures are negative. Treatment of endocarditis and osteomyelitis may require a longer duration of therapy. With intravenous administration, particularly in elderly patients, care should be taken because of the possibility of thrombophlebitis. RECOMMENDED DOSAGES FOR OXACILLIN FOR INJECTION, USP Drug Adults Infants and Children <40 kg (88 lbs) Other Recommendations Oxacillin 250 to 500 mg IV every 4 to 6 hours (mild to moderate infections) 50 mg/kg/day IV in equally divided doses every 6 hours (mild to moderate infections) 1 gram IV every 4 to 6 hours (severe infections) 100 mg/kg/day IV in equally divided doses every 4 to 6 hours (severe infections) Premature and Neonates 25 mg/kg/day IV Directions for Use For Administration by Intravenous Drip Reconstitute as directed below ( Pharmacy Bulk Package ) prior to further dilution. STABILITY PERIODS FOR OXACILLIN FOR INJECTION, USP Concentration mg/mL Sterile Water for Injection 0.9% Sodium chloride Injection, USP M/6 Molar Sodium Lactate Solution 5% Dextrose in water 5% Dextrose in 0.45% sodium chloride 10% Invert Sugar Injection, USP Lactated Ringer’s Solution ROOM TEMPERATURE (25°C) 10-100 4 Days 4 Days 10-30 24 Hrs 24 Hrs 0.5-2 6 Hrs 6 Hrs 6 Hrs REFRIGERATION (4°C) 10-100 7 Days 7 Days 10-30 4 Days 4 Days 4 Days 4 Days 4 Days FROZEN (-15°C) 50-100 30 Days 250/1.5 mL 30 Days 100 30 Days 10-100 30 Days 30 Days 30 Days 30 Days 30 Days 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 Lactated Potassic Saline Injection 10% Invert Sugar in Normal Saline 10% Invert Sugar Plus 0.3% Potassium Chloride in Water Travert 10% Electrolyte #1 Travert 10% Electrolyte #2 Travert 10% Electrolyte #3 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 a. The container closure may be penetrated only one time after reconstitution, utilizing a suitable sterile dispensing set which allows measured distribution of the contents. b. Use of this product is restricted to a suitable work area, such as a laminar flow hood. c. 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 bottle. 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.

ADVERSE REACTIONS 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 FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.