oxacillin 2000 MG Injection

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) Oxacillin 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, USP 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 Ringers Solution ROOM TEMPERATURE (25°C) 10 to 100 4 Days 4 Days 10 to 30 24 Hrs 24 Hrs 0.5 to 2 6 Hrs 6 Hrs 6 Hrs REFRIGERATION (4°C) 10 to 100 7 Days 7 Days 10 to 30 4 Days 4 Days 4 Days 4 Days 4 Days FROZEN (-15°C) 50 to 100 30 Days 250/1.5 mL 30 Days 100 30 Days 10 to 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% 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 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. 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. 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, USP 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 Ringers Solution ROOM TEMPERATURE (25°C) 10 to 100 4 Days 4 Days 10 to 30 24 Hrs 24 Hrs 0.5 to 2 6 Hrs 6 Hrs 6 Hrs REFRIGERATION (4°C) 10 to 100 7 Days 7 Days 10 to 30 4 Days 4 Days 4 Days 4 Days 4 Days FROZEN (-15°C) 50 to 100 30 Days 250/1.5 mL 30 Days 100 30 Days 10 to 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% 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 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. 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.

WARNINGS Serious and occasionally fatal hypersensitivity (anaphylactic shock with collapse) reactions have occurred in patients receiving penicillin. The incidence of anaphylactic shock in all penicillin-treated patients is between 0.015 and 0.04 percent. Anaphylactic shock resulting in death has occurred in approximately 0.002 percent of the patients treated. When oxacillin therapy is indicated, it should be initiated only after a comprehensive patient drug and allergy history has been obtained. If an allergic reaction occurs, oxacillin should be discontinued and appropriate therapy instituted. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Oxacillin for Injection, USP, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.

CONTRAINDICATIONS: A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication.

CLINICAL PHARMACOLOGY: Intravenous administration provides peak serum levels approximately 5 minutes after the injection is completed. Slow I.V. administration of 500 mg gives a peak serum level of 43 mcg/mL after 5 minutes with a half-life of 20 to 30 minutes. Oxacillin sodium, with normal doses, has insignificant concentrations in the cerebrospinal and ascitic fluids. It is found in therapeutic concentrations in the pleural, bile, and amniotic fluids. Oxacillin Sodium is rapidly excreted as unchanged drug in the urine by glomerular filtration and active tubular secretion. The elimination half-life for oxacillin is about 0.5 hours. Nonrenal elimination includes hepatic inactivation and excretion in bile. Oxacillin sodium binds to serum protein, mainly albumin. The degree of protein binding reported varies with the method of study and the investigator, but generally has been found to be 94.2% ± 2.1%. Probenecid blocks the renal tubular secretion of penicillins. Therefore, the concurrent administration of probenecid prolongs the elimination of oxacillin and, consequently, increases the serum concentration. Intramuscular injections give peak serum levels 30 minutes after injection. A 250 mg dose gives a level of 5.3 mcg/mL while a 500 mg dose peaks at 10.9 mcg/mL. Intravenous injection gives a peak about 5 minutes after the injection is completed. Slow IV dosing with 500 mg gives a 5 minute peak of 43 mcg/mL with a half-life of 20 to 30 minutes. Microbiology 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. Microbiology 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. 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 Teratogenic Effects Pregnancy Category B Reproduction studies performed in the mouse, rat, and rabbit have revealed no evidence of impaired fertility or harm to the fetus due to the penicillinase-resistant penicillins. Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. There are, however, no adequate or well-controlled studies in pregnant women showing conclusively that harmful effects of these drugs on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing Mothers Penicillins are excreted in breast 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 64 mg (2.8 mEq) of sodium per gram Oxacillin. At the usual recommended doses, patients would receive between 64 and 383 mg (2.8 and 17 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.