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CLINICAL PHARMACOLOGY Aqueous penicillin G is rapidly absorbed following both intramuscular and subcutaneous injection. Initial blood levels following parenteral administration are high but transient. Penicillins bind to serum proteins, mainly albumin. Therapeutic levels of the penicillins are easily achieved under normal circumstances in extracellular fluid and most other body tissues. Penicillins are distributed in varying degrees into pleural, pericardial, peritoneal, ascitic, synovial, and interstitial fluids. Penicillins are excreted in breast milk. Penetration into the cerebrospinal fluid, eyes, and prostate is poor. Penicillins are rapidly excreted in the urine by glomerular filtration and active tubular secretion, primarily as unchanged drug. Approximately 60 percent of the total dose of 300,000 units is excreted in the urine within this 5-hour period. For this reason, high and frequent doses are required to maintain the elevated serum levels desirable in treating certain severe infections in individuals with normal kidney function. In neonates and young infants, and in individuals with impaired kidney function, excretion is considerably delayed. Microbiology Penicillin G exerts a bactericidal action against penicillin-susceptible microorganisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell wall mucopeptide rendering the cell wall osmotically unstable. It is not active against the penicillinase-producing bacteria, which include many strains of staphylococci. While in vitro studies have demonstrated the susceptibility of most strains of the following organisms, clinical efficacy for infections other than those included in the INDICATIONS AND USAGE section has not been documented. Penicillin G exerts high in vitro activity against staphylococci (except penicillinase-producing strains), streptococci (groups A, C, G, H, L, and M), and pneumococci. Other organisms susceptible to penicillin G are N. gonorrhoeae, Corynebacterium diphtheriae, Bacillus anthracis, Clostridia, Actinomyces bovis, Streptobacillus moniliformis, Listeria monocytogenes and Leptospira. Treponema pallidum is extremely sensitive to the bactericidal action of penicillin G. Some species of gram-negative bacilli are sensitive to moderate to high concentrations of the drug obtained with intravenous administration. These include most strains of Escherichia coli; all strains of Proteus mirabilis, Salmonella and Shigella; and some strains of Aerobacter aerogenes and Alcaligenes faecalis. Penicillin acts synergistically with gentamicin or tobramycin against many strains of enterococci. Susceptibility Testing: Penicillin G Susceptibility Powder or 10 units Penicillin G Susceptibility Discs may be used to determine microbial susceptibility to penicillin G using one of the following standard methods recommended by the National Committee for Laboratory Standards: M2-A3, “Performance Standards for Antimicrobial Disk Susceptibility Tests” M7-A, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically” M11-A, “Reference Agar Dilution Procedure for Antimicrobial Susceptibility Testing of Anaerobic Bacteria” M17-P, “Alternative Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria” Tests should be interpreted by the following criteria: Zone Diameter, nearest whole mm Susceptible Moderately Susceptible Resistant Staphylococci ≥ 29 - ≤ 28 N. gonorrhoeae ≥ 20 - ≤ 19 Enterococci - ≥ 15 ≤ 14 Non-enterococcal streptococci and L. monocytogenes ≥ 28 20-27 ≤ 19 Approximate MIC Correlates Susceptible Resistant Staphylococci ≤ 0.1 μg/mL β-lactamase N. gonorrhoeae ≤ 0.1 μg/mL β-lactamase Enterococci - ≥ 16 μg/mL Non-enterococcal streptococci and L. monocytogenes ≤ 0.12 μg/mL ≥ 4 μg/mL Interpretations of susceptible, intermediate, and resistant correlate zone size diameters with MIC values. A laboratory report of “susceptible” indicates that the suspected causative microorganism most likely will respond to therapy with penicillin G. A laboratory report of “resistant” indicates that the infecting microorganism most likely will not respond to therapy. A laboratory report of “moderately susceptible” indicates that the microorganism is most likely susceptible if a high dosage of penicillin G is used, or if the infection is such that high levels of penicillin G may be attained, as in urine. A report of “intermediate” using the disk diffusion method may be considered an equivocal result, and dilution tests may be indicated. Control organisms are recommended for susceptibility testing. Each time the test is performed the following organisms should be included. The range for zones of inhibition is shown below: Control Organism Zone of Inhibition Range Staphylococcus aureus (ATCC 25923) 27-35

CLINICAL PHARMACOLOGY After an intravenous infusion of penicillin G, peak serum concentrations are attained immediately after completion of the infusion. In a study of ten patients administered a single 5 million unit dose of penicillin G intravenously over 3-5 minutes, the mean serum concentrations were 400 mcg/mL, 273 mcg/mL and 3.0 mcg/mL at 5-6 minutes, 10 minutes and 4 hours after completion of the injection, respectively. In a separate study, five healthy adults were administered one million units of penicillin G intravenously, either as a bolus over 4 minutes or as an infusion over 60 minutes. The mean serum concentration eight minutes after completion of the bolus was 45 mcg/mL and eight minutes after completion of the infusion was 14.4 mcg/mL. The mean β-phase serum half-life of penicillin G administered by the intravenous route in ten patients with normal renal function was 42 minutes, with a range of 31-50 minutes. The clearance of penicillin G in normal individuals is predominantly via the kidney. The renal clearance, which is extremely rapid, is the result of glomerular filtration and active tubular transport, with the latter route predominating. Urinary recovery is reported to be 58-85% of the administered dose. Renal clearance of penicillin is delayed in premature infants, neonates and in the elderly due to decreased renal function. The serum half-life of penicillin G correlates inversely with age and clearance of creatinine and ranges from 3.2 hours in infants 0 to 6 days of age to 1.4 hours in infants 14 days of age or older. Nonrenal clearance includes hepatic metabolism and, to a lesser extent, biliary excretion. The latter routes become more important with renal impairment. Probenecid blocks the renal tubular secretion of penicillin. Therefore, the concurrent administration of probenecid prolongs the elimination of penicillin G and, consequently, increases the serum concentrations. Penicillin G is distributed to most areas of the body including lung, liver, kidney, muscle, bone and placenta. In the presence of inflammation, levels of penicillin in abscesses, middle ear, pleural, peritoneal and synovial fluids are sufficient to inhibit most susceptible bacteria. Penetration into the eye, brain, cerebrospinal fluid (CSF) or prostate is poor in the absence of inflammation. With inflamed meninges, the penetration of penicillin G into the CSF improves, such that the CSF/serum ratio is 2-6%.  Inflammation also enhances its penetration into the pericardial fluid. Penicillin G is actively secreted into the bile resulting in levels at least 10 times those achieved simultaneously in serum. Penicillin G penetrates poorly into human polymorphonuclear leukocytes. In the presence of impaired renal function, the β-phase serum half-life of penicillin G is prolonged. β- phase serum half-lives of one to two hours were observed in azotemic patients with serum creatinine concentrations < 3 mg/100 mL and ranged as high as 20 hours in anuric patients. A linear relationship, including the lowest range of renal function, is found between the serum elimination rate constant and renal function as measured by creatinine clearance. In patients with altered renal function, the presence of hepatic insufficiency further alters the elimination of penicillin G. In one study, the serum half-lives in two anuric patients (excreting < 400 mL urine/day) were 7.2 and 10.1 hours. A totally anuric patient with terminal hepatic cirrhosis had a penicillin half-life of 30.5 hours, while another patient with anuria and liver disease had a serum half-life of 16.4 hours.  The dosage of penicillin G should be reduced in patients with severe renal impairment, with additional modifications when hepatic disease accompanies the renal impairment. Hemodialysis has been shown to reduce penicillin G serum levels. Microbiology Penicillin G is bactericidal against penicillin-susceptible microorganisms during the stage of active multiplication. It acts by inhibiting biosynthesis of cell-wall mucopeptide. It is not active against the penicillinase-producing bacteria, which include many strains of staphylococci. Penicillin G is highly active in vitro against staphylococci (except penicillinase-producing strains), streptococci (groups A, B, C, G, H, L and M), pneumococci and Neisseria meningitidis. Other organisms susceptible in vitro to penicillin G are Neisseria gonorrhoeae, Corynebacterium diphtheriae, Bacillus anthracis, clostridia, Actinomyces species, Spirillum minus, Streptobacillus moniliformis, Listeria monocytogenes, and leptospira; Treponema pallidum is extremely susceptible. Some species of gram-negative bacilli were previously considered susceptible to very high intravenous doses of penicillin G (up to 80 million units/day) including some strains of Escherichia coli, Proteus mirabilis, salmonella, shigella, Enterobacter aerogenes (formerly Aerobacter aerogenes) and Alcaligenes faecalis. Penicillin G is no longer considered a drug of choice for infections caused by these organisms. Susceptibility Test Methods When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and communityacquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial. Dilution Techniques Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on dilution method1,2 (broth, agar or microdilution) or equivalent using standardized inoculum and concentrations of penicillin. The MIC values should be interpreted according to the criteria in Table 1. Diffusion Techniques Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2,3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 10 units of penicillin to test the susceptibility of microorganisms to penicillin. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for penicillin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 10 unit penicillin disk should be interpreted according to the following criteria in Table 1. Table 1:Susceptibility Test Interpretive Criteria for Penicillin2,4 Pathogen MIC (mcg/mL) Disk Diffusion (zone diameter in mm) * Susceptible (S) Intermediate (I) Resistant (R) Susceptible (S) Intermediate (I) Resistant (R) Staphylococci ≤ 0.12† - ≥ 0.25 ≥ 29† - ≤ 28 Neisseria gonorrhoeae‡ ≤ 0.06 0.12 - 1 ≥ 2 ≥ 47 27 - 46 ≤ 26 Streptococcus pneumoniae( meningitis) ≤ 0.06 - ≥ 0.12 - - - Streptococcus pneumoniae (pneumonia) ≤ 2 4 ≥ 8 - - - β-hemolytic streptococci§ ≤ 0.12¶ - - ≥ 24¶ - - Streptococcus spp. Viridans group. ≤ 0.12 0.25 - 2 ≥ 4 - - - Listeria monocytogens ≤ 2¶ - - - - - Bacillus anthracis# ≤ 0.12 - ≥ 0.25 - - - *Organisms for which no values for disk susceptibility appear cannot be reliably tested with this method †Penicillin-resistant strains of staphylococci produce β-lactamase. An induced β-lactamase test should be performed on all S. aureus isolates for which the penicillin MIC is ≤ 0.12 mcg/mL or zone diameter is ≥ 29 mm before reporting as penicillin susceptible. Rare isolates of staphylococci that contain genes for β-lactamase production may not produce a positive induced β-lactamase test. For serious infections requiring penicillin therapy, laboratories should perform MIC tests and induced beta-lactamase testing on all subsequent isolates from the same patient.2 ‡A positive N. gonorrhoeae β-lactamase test predicts one form of resistance to penicillin. Strains with chromosomally mediated resistance can be detected only by agar dilution or disk diffusion susceptibility test methods. Isolates with zone diameters ≤ 19 mm generally produce 2 β-lactamase.2,3 §Susceptibility testing of penicillins for treatment of β-hemolytic streptococcal infections need not be performed routinely, because non-susceptible isolates are extremely rare in any β-hemolytic streptococcus and have not been reported from Streptococcus pyogenes. Any β -hemolytic streptococcal isolate found to be non-susceptible to penicillin should be re-identified, retested, and, if confirmed, submitted to a public health authority.2,3 ¶The current absence of resistant isolates precludes defining results other than “Susceptible”. Isolates yielding results suggestive of “Nonsusceptible” should be submitted to a reference laboratory for further testing. #B. anthracis strains may contain inducible β-lactamases. In vitro penicillinase induction studies suggest that penicillin MICs may increase during therapy. However, β-lactamase testing of clinical isolates of B. anthracis is unreliable and should not be performed.4 Quality Control Standardized susceptibility test procedures require the use of laboratory control microorganisms to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test. Standard penicillin powder should provide MIC values provided below. For the diffusion technique, the 10 unit penicillin disk should provide the following zone diameters with the quality control strains: Table 2: In Vitro Susceptibility Test Quality Control Ranges for Penicillin Organism (ATTC #) MIC range mcg/mL Disk diffusion range (mm) Staphylococcus aureus (29213) 0.25 - 2 Not applicable Staphylococcus aureus (25923) Not applicable 26 - 37 Streptococcus pneumoniae (49619) 0.25 - 1 24 - 30 Neisseria gonorrhoeae (49226) 0.25 - 1* 26 - 34 * Using agar dilution method only. No criteria for broth microdilution are available.2 REFERENCES 1. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard – Ninth Edition, CLSI document M07-A9. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2012. 2. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement, CLSI document M100-S22. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2012. 3. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard – Eleventh Edition, CLSI document M02-A11. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2012. 4. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Approved Guideline-Second Edition, CLSI document M45-A2. Clinical and Laboratory Standards Institute. Wayne, PA. August, 2010.

Find Lowest Prices on Buffered PFIZERPEN (penicillin G potassium) for Injection To reduce the development of drug-resistant bacteria and maintain the effectiveness of Pfizerpen (penicillin g potassium) ® and other antibacterial drugs, Pfizerpen (penicillin g potassium) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. DESCRIPTION Buffered Pfizerpen (penicillin G potassium) for Injection is a sterile, pyrogen-free powder for reconstitution. Buffered Pfizerpen (penicillin g potassium) for Injection is an antibacterial agent for intramuscular, continuous intravenous drip, intrapleural or other local infusion, and intrathecal administration. Each million units contains approximately 6.8 milligrams of sodium (0.3 mEq) and 65.6 milligrams of potassium (1.68 mEq). Chemically, Pfizerpen (penicillin g potassium) is monopotassium 3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo (3.2.0) heptane-2-carboxylate. It has a molecular weight of 372.48 and the following chemical structure: Formula C16H17KN2O4S Penicillin G potassium is a colorless or white crystal, or a white crystalline powder which is odorless, or practically so, and moderately hygroscopic. Penicillin G potassium is very soluble in water. The pH of the reconstituted product is between 6.0-8.5.

Penicillin G Potassium (penicillin g) Injection, Solution In PL 2040 Plastic Container To reduce the development of drug-resistant bacteria and maintain the effectiveness of Penicillin G Potassium Injection, USP and other antibacterial drugs, Penicillin G Potassium Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. DESCRIPTION Penicillin G Potassium, USP is a natural penicillin. It is chemically designated 4-Thia-1- azabicyclo[3.2.0]heptane-2-carboxylic acid,3,3-dimethyl-7-oxo-6-[(phenylacetyl)amino]-, monopotassium salt, [2S-(2α, 5α, 6β)]. It is crystalline. It is freely soluble in water, in isotonic sodium chloride solution and in dextrose solutions. The structural formula is as shown below. Penicillin G Potassium Injection, USP (equivalent to 1, 2, or 3 million units of penicillin G) is a 50 mL premixed, iso-osmotic, sterile, nonpyrogenic, frozen solution for intravenous administration. Dextrose, USP has been added to the above dosages to adjust osmolality (approximately 2 g, 1.2 g, and 350 mg as dextrose hydrous, respectively). Sodium Citrate, USP has been added as a buffer. The pH has been adjusted with hydrochloric acid and may have been adjusted with sodium hydroxide. The pH is 6.5 (5.5 to 8.0). The solution is contained in a single dose GALAXY container (PL 2040 Plastic) and is intended for intravenous use after thawing to room temperature. This GALAXY container is fabricated from a specially designed multilayer plastic (PL 2040). Solutions are in contact with the polyethylene layer of this container and can leach out certain chemical components of the plastic in very small amounts within the expiration period. The suitability of the plastic has been confirmed in tests in animals according to the USP biological tests for plastic containers as well as by tissue culture toxicity studies.

INDICATIONS Aqueous penicillin G (parenteral) is indicated in the therapy of severe infections caused by penicillin G-susceptible microorganisms when rapid and high penicillin levels are required in the conditions listed below. Therapy should be guided by bacteriological studies (including susceptibility tests) and by clinical response. The following infections will usually respond to adequate dosage of aqueous penicillin G (parenteral): Streptococcal infections. NOTE: Streptococci in groups A, C, H, G, L, and M are very sensitive to penicillin G. Some group D organisms are sensitive to the high serum levels obtained with aqueous penicillin G. Aqueous penicillin G (parenteral) is the penicillin dosage form of choice for bacteremia, empyema, severe pneumonia, pericarditis, endocarditis, meningitis, and other severe infections caused by sensitive strains of the gram-positive species listed above. Pneumococcal infections. Staphylococcal infections-penicillin G sensitive. Other infections Anthrax. Actinomycosis. Clostridial infections (including tetanus). Diphtheria (to prevent carrier state). Erysipeloid (Erysipelothrix insidiosa) endocarditis. Fusospirochetal infections-severe infections of the oropharynx (Vincent's), lower respiratory tract and genital area due to Fusobacterium fusiformisans spirochetes. Gram-negative bacillary infections (bacteremias)-(E. coli, A. aerogenes, A. faecalis, Salmonella, Shigella and P. mirabilis). Listeria infections (Listeria monocytogenes). Meningitis and endocarditis. Pasteurella infections (Pasteurella multocida). Bacteremia and meningitis. Rat-bite fever (Spirillum minus or Streptobacillus moniliformis). Gonorrheal endocarditis and arthritis (N. gonorrhoeae). Syphilis (T. pallidum) including congenital syphilis. Meningococcic meningitis. Although no controlled clinical efficacy studies have been conducted, aqueous crystalline penicillin G for injection and penicillin G procaine suspension have been suggested by the American Heart Association and the American Dental Association for use as part of a combined parenteral-oral regimen for prophylaxis against bacterial endocarditis in patients with congenital heart disease or rheumatic, or other acquired valvular heart disease when they undergo dental procedures and surgical procedures of the upper respiratory tract.1 Since it may happen that alpha hemolytic streptococci relatively resistant to penicillin may be found when patients are receiving continuous oral penicillin for secondary prevention of rheumatic fever, prophylactic agents other than penicillin may be chosen for these patients and prescribed in addition to their continuous rheumatic fever prophylactic regimen. NOTE: When selecting antibiotics for the prevention of bacterial endocarditis, the physician or dentist should read the full joint statement of the American Heart Association and the American Dental Association.1 To reduce the development of drug-resistant bacteria and maintain effectiveness of Pfizerpen (penicillin g potassium) and other antibacterial drugs, Pfizerpen (penicillin g potassium) 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 Severe infections due to Susceptible Strains of Streptococci, Pneumococci, and Staphylococci-bacteremia, pneumonia, endocarditis, pericarditis, empyema, meningitis, and other severe infections-a minimum of 5 million units daily. Syphilis - Aqueous penicillin G may be used in the treatment of acquired and congenital syphilis, but because of the necessity of frequent dosage, hospitalization is recommended. Dosage and duration of therapy will be determined by age of patient and stage of the disease. Gonorrheal endocarditis - a minimum of 5 million units daily. Meningococcic meningitis - 1-2 million units intramuscularly every 2 hours, or continuous IV drip of 20-30 million units/day. Actinomycosis - 1-6 million units/day for cervicofacial cases; 10-20 million units/day for thoracic and abdominal disease. Clostridial infections - 20 million units/day; penicillin is adjunctive therapy to antitoxin. Fusospirochetal infections - severe infections of oropharynx, lower respiratory tract, and genital area-5-10 million units/day. Rat-bite fever (Spirillum minus or Streptobacillus moniliformis) - 12-15 million units/day for 3-4 weeks. Listeria infections (Listeria monocytogenes) Neonates - 500,000 to 1 million units/day Adults with meningitis - 15-20 million units/day for 2 weeks. Adults with endocarditis - 15-20 million units/day for 4 weeks. Pasteurella infections (Pasteurella multocida) Bacteremia and meningitis - 4-6 million units/day for 2 weeks. Erysipeloid (Erysipelothrix insidiosa) Endocarditis - 2-20 million units/day for 4-6 weeks. Gram-negative bacillary infections (E. coli, Enterobacter aerogenes, A. faecalis, Salmonella, Shigella and Proteus mirabilis) Bacteremia - 20-80 million units/day. Diphtheria (carrier state) - 300,000-400,000 units of penicillin/day in divided doses for 10-12 days. Anthrax - A minimum of 5 million units of penicillin/day in divided doses until cure is effected. For prophylaxis against bacterial endocarditis1 in patients with congenital heart disease or rheumatic or other acquired valvular heart disease, when undergoing dental procedures or surgical procedures of the upper respiratory tract, use a combined parenteral-oral regimen. One million units of aqueous crystalline penicillin G (30,000 units/kg in children) intramuscularly, mixed with 600,000 units procaine penicillin G (600,000 units for children) should be given one-half to one hour before the procedure. Oral penicillin V (phenoxymethyl penicillin), 500 mg for adults or 250 mg for children less than 60 lb, should be given every 6 hours for 8 doses. Doses for children should not exceed recommendations for adults for a single dose or for a 24 hour period. Reconstitution The following table shows the amount of solvent required for solution of various concentrations: Approx. Desired Concentration (units/mL) Approx. Volume (mL) 1,000,000 units Solvent for Vial of 5,000,000 units Infusion Only 20,000,000 units 50,000 20.0 - - 100,000 10.0 - - 250,000 4.0 18.2 75.0 500,000 1.8 8.2 33.0 750,000 - 4.8 - 1,000,000 - 3.2 11.5 When the required volume of solvent is greater than the capacity of the vial, the penicillin can be dissolved by first injecting only a portion of the solvent into the vial, then withdrawing the resultant solution and combining it with the remainder of the solvent in a larger sterile container. Buffered Pfizerpen (penicillin g potassium) (penicillin G potassium) for Injection is highly water soluble. It may be dissolved in small amounts of Water for Injection, or Sterile Isotonic Sodium Chloride Solution for Parenteral Use. All solutions should be stored in a refrigerator. When refrigerated, penicillin solutions may be stored for seven days without significant loss of potency. Buffered Pfizerpen (penicillin g potassium) for Injection may be given intramuscularly or by continuous intravenous drip for dosages of 500,000, 1,000,000, or 5,000,000 units. It is also suitable for intrapleural, intraarticular, and other local instillations. THE 20,000,000 UNIT DOSAGE MAY BE ADMINISTERED BY INTRAVENOUS INFUSION ONLY. Intramuscular Injection: Keep total volume of injection small. The intramuscular route is the preferred route of administration. Solutions containing up to 100,000 units of penicillin per mL of diluent may be used with a minimum of discomfort. Greater concentration of penicillin G per mL is physically possible and may be employed where therapy demands. When large dosages are required, it may be advisable to administer aqueous solutions of penicillin by means of continuous intravenous drip. Continuous Intravenous Drip: Determine the volume of fluid and rate of its administration required by the patient in a 24 hour period in the usual manner for fluid therapy, and add the appropriate daily dosage of penicillin to this fluid. For example, if an adult patient requires 2 liters of fluid in 24 hours and a daily dosage of 10 million units of penicillin, add 5 million units to 1 liter and adjust the rate of flow so the liter will be infused in 12 hours. Intrapleural or Other Local Infusion: If fluid is aspirated, give infusion in a volume equal to ¼ or ½ the amount of fluid aspirated, otherwise, prepare as for intramuscular injection. Intrathecal Use: The intrathecal use of penicillin in meningitis must be highly individualized. It should be employed only with full consideration of the possible irritating effects of penicillin when used by this route. The preferred route of therapy in bacterial meningitides is intravenous, supplemented by intramuscular injection. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Sterile solution may be left in refrigerator for one week without significant loss of potency. HOW SUPPLIED Buffered Pfizerpen® (penicillin G potassium) for Injection is available in vials containing respectively 5,000,000 units x10's (NDC 0049-0520-83) and 20,000,000 units x1's (NDC 0049-0530-28); buffered (penicillin g potassium) with sodium citrate and citric acid to an optimum pH. Each million units contains approximately 6.8 milligrams of sodium (0.3 mEq) and 65.6 milligrams of potassium (1.68 mEq). Store the dry powder below 86°F (30°C). REFERENCE 1. American Heart Association, 1977. Prevention of bacterial endocarditis. Circulation. 56:139A-143A. Distributed by: Roerig, Division of Pfizer Inc, NY, NY 10017. Revised December 2005. FDA revision date: 7/14/1994

INDICATIONS Therapy Penicillin G Potassium Injection, USP is indicated in the treatment of serious infections caused by susceptible strains of the designated microorganisms in the conditions listed below. Appropriate culture and susceptibility tests should be done before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to penicillin G. Therapy with Penicillin G Potassium Injection, USP may be initiated before results of such tests are known when there is reason to believe the infection may involve any of the organisms listed below; however, once these results become available, appropriate therapy should be continued. CLINICAL INDICATION INFECTING ORGANISM Septicemia, empyema, pneumonia, pericarditis, endocarditis, meningitis Streptococcus pyogenes (group A β-hemolytic streptococcus), other β-hemolytic streptococci including groups C, H, G, L and M, Streptococcus pneumoniae and Staphylococcus species (non-penicillinase producing strains) Anthrax Bacillus anthracis Actinomycosis (cervico-facial disease and thoracic and abdominal disease) Actinomyces israelii Botulism (adjunctive therapy to antitoxin), gas gangrene, and tetanus (adjunctive therapy to human tetanus immune globulin) Clostridium species Diphtheria (adjunctive therapy to antitoxin and prevention of the carrier state) Corynebacterium diphtheriae Erysipelothrix endocarditis Erysipelothrix rhusiopathiae Fusospirochetosis (severe infections of the oropharynx [Vincent’s], lower respiratory tract and genital area) Fusobacterium species and spirochetes Listeria infections including meningitis and endocarditis Listeria monocytogenes Pasteurella infections including bacteremia and meningitis Pasteurella multocida Haverhill fever Streptobacillus moniliformis Rat bite fever Spirillum minus or Streptobacillus moniliformis Disseminated gonococcal infections Neisseria gonorrhoeae (penicillin-susceptible) Syphilis (congenital and neurosyphilis) Treponema pallidum Meningococcal meningitis and/or septicemia Neisseria meningitidis Gram-negative bacillary infections (bacteremias) Penicillin G is not the drug of choice in the treatment of gram-negative bacillary infections. Gram-negative bacillary organisms (i.e. Enterobacteriaceae) To reduce the development of drug-resistant bacteria and maintain the effectiveness of Penicillin G Potassium Injection, USP and other antibacterial drugs, Penicillin G Potassium 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 Penicillin G Potassium Injection, USP should be administered by intravenous infusion. The usual dose recommendations are as follows: Adult Patients (*) Because of its short half-life, Penicillin G is administered in divided doses, usually every 4-6 hours with the exception of meningococcal meningitis/septicemia, i.e., every 2 hours. CLINICAL INDICATION DOSAGE Serious infections due to susceptible strains of streptococci (including S. pneumoniae) -septicemia, empyema, pneumonia, pericarditis, endocarditis and meningitis 12 to 24 million units/day depending on the infection and its severity administered in equally divided doses every 4-6 hours. Serious infections due to susceptible strains of staphylococci - septicemia, empyema, pneumonia, pericarditis, endocarditis and meningitis 5 to 24 million units/day depending on the infection and its severity administered in equally divided doses every 4-6 hours. Anthrax Minimum of 8 million units/day in divided doses every 6 hours. Higher doses may be required depending on susceptibility of organism. Actinomycosis Cervicofacial disease Thoracic and abdominal disease 1 to 6 million units/day(*) 10 to 20 million units/day(*) Clostridial infections Botulism (adjunctive therapy to antitoxin) Gas gangrene (debridement and/or surgery as indicated) Tetanus (adjunctive therapy to human tetanus immune globulin) 20 million units/day(*) Diphtheria (adjunctive therapy to antitoxin and for the prevention of the carrier state) 2 to 3 million units/day in divided doses for 10-12 days(*) Erysipelothrix endocarditis 12 to 20 million units/day for 4-6 weeks(*) Fusospirochetosis (severe infections of the oropharynx [Vincent’s], lower respiratory tract and genital area) 5 to 10 million units/day(*) Listeria infections Meningitis Endocarditis 15 to 20 million units/day for 2 weeks(*) 15 to 20 million units/day for 4 weeks(*) Pasteurella infections including bacteremia and meningitis 4 to 6 million units/day for 2 weeks(*) Haverhill fever; Rat-bite fever 12 to 20 million units/day for 3-4 weeks(*) Disseminated gonococcal infections, such as meningitis endocarditis, arthritis, etc., caused by penicillin - susceptible organisms 10 million units/day(*); duration depends on the type of infection Syphilis (neurosyphilis) 12 to 24 million units/day, as 2-4 MU every 4 hours for 10-14 days; many experts recommend additional therapy with Benzathine PCN G 2.4 MU IM weekly for 3 doses after completion of IV therapy Meningococcal meningitis and/or septicemia 24 million units/day as 2 million units every 2hours Pediatric Patients This product should not be administered to patients requiring less than one million units per dose (see PRECAUTIONS-Pediatric Use). CLINICAL INDICATION DOSAGE Serious infections, such as pneumonia and endocarditis, due to susceptible strains of streptococci (including S. pneumoniae) and meningococcus 150,000-300,000 units/kg/day divided in equal doses every 4-6 hours; duration depends on infecting organism and type of infection Meningitis caused by susceptible strains of pneumococcus and meningococcus 250,000 units/kg/day divided in equal doses every 4 hours for 7-14 days depending on the infecting organism (maximum dose of 12-20 million units/day) Disseminated Gonococcal Infections (penicillin-susceptible strains) Weight less than 45 kg: Arthritis 100,000 units/kg/day in 4 equally divided doses for 7-10 days Meningitis 250,000 units/kg/day in equal doses every 4 hours for 10-14 days Endocarditis 250,000 units/kg/day in equal doses every 4 hours for 4 weeks Arthritis, meningitis, endocarditis Weight 45 kg or greater: 10 million units/day in 4 equally divided doses with the duration of therapy depending on the type of infection Syphilis (congenital and neurosyphilis) after the newborn period 200,000-300,000 units/kg/day (administered as 50,000 units/kg every 4-6 hours) for 10-14 days Diphtheria (adjunctive therapy to antitoxin and for prevention of the carrier state) 150,000-250,000 units/kg/day in equal doses every 6 hours for 7-10 days Rat-bite fever; Haverhill fever (with endocarditis caused by S. moniliformis) 150,000-250,000 units/kg/day in equal doses every 4 hours for 4 weeks Renal Impairment Penicillin G is relatively nontoxic, and dosage adjustments are generally required only in cases of severe renal impairment. The recommended dosage regimens are as follows: Creatinine clearance less than 10 mL/min/1.73m²; administer a full loading dose (see recommended dosages in the tables above) followed by one-half of the loading dose every 8-10 hours. Uremic patients with a creatinine clearance greater than 10 mL/min/1.73m²; administer a full loading dose (see recommended dosages in the tables above) followed by one-half of the loading dose every 4- 5 hours. Additional dosage modifications should be made in patients with hepatic disease and renal impairment. For most acute infections, treatment should be continued for at least 48 to 72 hours after the patient becomes asymptomatic. Antibiotic therapy for Group A β-hemolytic streptococcal infections should be maintained for at least 10 days to reduce the risk of rheumatic fever. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Directions For Use Of Galaxy Container (PL 2040 Plastic) Penicillin G Potassium Injection, USP in GALAXY Container (PL 2040 Plastic) is for intravenous administration using sterile equipment. Storage Store in a freezer capable of maintaining a temperature of -20°C/-4°F. Thawing Of Plastic Container Thaw frozen container at room temperature (25°C/77°F) or in a refrigerator (5°C/41°F). DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION. Check for minute leaks by squeezing container firmly. If leaks are detected, discard solution as sterility may be impaired. Do not add supplementary medication. Visually inspect the container. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Agitate after solution has reached room temperature. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted, or if any seals are not intact, the container should be discarded. The thawed solution is stable for 14 days under refrigeration (5°C/41°F) or for 24 hours at room temperature (25°C/77°F). Do not refreeze thawed antibiotics. CAUTION: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete. Preparation for Intravenous Administration: Suspend container from eyelet support. Remove protector from outlet port at bottom of container. Attach administration set. Refer to complete directions accompanying set. HOW SUPPLIED Storage And Handling Penicillin G Potassium Injection, USP is supplied as a premixed frozen iso-osmotic solution in 50 mL single dose GALAXY containers (PL 2040 Plastic) as follows: 2G3542 NDC 0338-1021-41 1,000,000 units Penicillin G 2G3543 NDC 0338-1023-41 2,000,000 units Penicillin G 2G3544 NDC-0338-1025-41 3,000,000 units Penicillin G Store at or below -20°C/-4°F. [See Directions for Use of GALAXY Container (PL 2040 Plastic).] Handle frozen product containers with care. Product containers may be fragile in the frozen state. Baxter Healthcare Corporation, Deerfield, IL 60015 USA. Revised: June 2014

PATIENT INFORMATION Patients should be counseled that antibacterial drugs including Pfizerpen (penicillin g potassium) should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Pfizerpen (penicillin g potassium) 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 Pfizerpen (penicillin g potassium) or other antibacterial drugs in the future.

PATIENT INFORMATION Patients should be counseled that antibacterial drugs including Penicillin G Potassium Injection, USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Penicillin G Potassium 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 Penicillin G Potassium 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.

OVERDOSE Neurological adverse reactions, including convulsions, may occur with the attainment of high CSF levels of beta-lactams. In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required. Penicillin G potassium is hemodialyzable. CONTRAINDICATIONS A history of a previous hypersensitivity reaction to any penicillin is a contraindication.

OVERDOSE Dose related toxicity may arise with the use of massive doses of intravenous penicillins (40 to 100 million units per day), particularly in patients with severe renal impairment (see PRECAUTIONS). The manifestations may include agitation, confusion, asterixis, hallucinations, stupor, coma, multifocal myoclonus, seizures and encephalopathy. Hyperkalemia is also possible (see ADVERSE REACTIONS- Metabolic). In case of overdosage, discontinue penicillin, treat symptomatically and institute supportive measures as required. If necessary, hemodialysis may be used to reduce blood levels of Penicillin G, although the degree of effectiveness of this procedure is questionable. CONTRAINDICATIONS A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

SIDE EFFECTS Penicillin is a substance of low toxicity but does have a significant index of sensitization. The following hypersensitivity reactions have been reported: skin rashes ranging from maculopapular eruptions to exfoliative dermatitis; urticaria; and reactions resembling serum sickness, including chills, fever, edema, arthralgia and prostration. Severe and occasionally fatal anaphylaxis has occurred (see WARNINGS). Hemolytic anemia, leucopenia, thrombocytopenia, nephropathy, and neuropathy are rarely observed adverse reactions and are usually associated with high intravenous dosage. Patients given continuous intravenous therapy with penicillin G potassium in high dosage (10 million to 100 million units daily) may suffer severe or even fatal potassium poisoning, particularly if renal insufficiency is present. Hyperreflexia, convulsions, and coma may be indicative of this syndrome. Cardiac arrhythmias and cardiac arrest may also occur. (High dosage of penicillin G sodium may result in congestive heart failure due to high sodium intake.) The Jarisch-Herxheimer reaction has been reported in patients treated for syphilis. DRUG INTERACTIONS Concurrent administration of bacteriostatic antibiotics (e.g., erythromycin, tetracycline) may diminish the bactericidal effects of penicillins by slowing the rate of bacterial growth. Bactericidal agents work most effectively against the immature cell wall of rapidly proliferating microorganisms. This has been demonstrated in vitro; however, the clinical significance of this interaction is not well documented. There are few clinical situations in which the concurrent use of “static” and “cidal” antibiotics are indicated. However, in selected circumstances in which such therapy is appropriate, using adequate doses of antibacterial agents and beginning penicillin therapy first, should minimize the potential for interaction. Penicillin blood levels may be prolonged by concurrent administration of probenecid which blocks the renal tubular secretion of penicillins. Displacement of penicillin from plasma protein binding sites will elevate the level of free penicillin in the serum.

SIDE EFFECTS Body as a whole: The Jarisch-Herxheimer reaction is a systemic reaction, that may occur after the initiation of penicillin therapy in patients with syphilis or other spirochetal infections (i.e., Lyme disease and Relapsing fever). The reaction begins one to two hours after initiation of therapy and disappears within 12 to 24 hours. It is characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing and mild hypotension. The pathogenesis of the Herxheimer reaction may be due to the release from the spirochetes of heat-stable pyrogen. Hypersensitivity reactions : The reported incidence of allergic reactions to all penicillins ranges from 0.7 to 10 percent in different studies (see WARNINGS). Sensitization is usually the result of previous treatment with a penicillin, but some individuals have had immediate reactions when first treated. In such cases, it is postulated that prior exposure to penicillin may have occurred via trace amounts present in milk or vaccines. Two types of allergic reactions to penicillin 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 (see WARNINGS). Such immediate anaphylactic reactions are very rare and usually occur after parenteral therapy, but a few cases of anaphylaxis have been reported following 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, fever and, occasionally, laryngeal edema. Delayed reactions to penicillin therapy usually occur within 1-2 weeks after initiation of therapy. Manifestations include serum sickness-like symptoms, i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain and various skin rashes, ranging from maculopapular eruptions to exfoliative dermatitis. Contact dermatitis has been observed in individuals who prepare penicillin solutions. Gastrointestinal system: Pseudomembranous colitis has been reported with the onset occurring during or after penicillin G treatment. Nausea, vomiting, stomatitis, black or hairy tongue, and other symptoms of gastrointestinal irritation may occur, especially during oral therapy. Hematologic system: Reactions include neutropenia, which resolves after penicillin therapy is discontinued; Coombs-positive hemolytic anemia, an uncommon reaction, occurs in patients treated with intravenous penicillin G in doses greater than 10 million units/day and who have previously received large doses of the drug; and with large doses of penicillin, a bleeding diathesis can occur secondary to platelet dysfunction. Metabolic: Penicillin G Potassium, USP (1 million units contains 1.7 mEq of potassium ion) may cause serious and even fatal electrolyte disturbances, i.e., hyperkalemia, when given intravenously in large doses. Nervous system: Neurotoxic reactions including hyperreflexia, myoclonic twitches, seizures and coma have been reported following the administration of massive intravenous doses, and are more likely in patients with impaired renal function. Urogenital system: Renal tubular damage and interstitial nephritis have been associated with large intravenous doses of penicillin G. Manifestations of this reaction may include fever, rash, eosinophilia, proteinuria, eosinophiluria, hematuria and a rise in serum urea nitrogen. Discontinuation of penicillin G results in resolution in the majority of patients. Local reactions: Phlebitis and thrombophlebitis may occur, and pain at the injection site has been reported with intravenous administration. DRUG INTERACTIONS Bacteriostatic antibacterials (i.e., chloramphenicol, erythromycins, sulfonamides or tetracyclines) may antagonize the bactericidal effect of penicillin, and concurrent use of these drugs should be avoided. This has been documented in vitro; however, the clinical significance of this interaction is not well documented. Penicillin blood levels may be prolonged by concurrent administration of probenecid which blocks the renal tubular secretion of penicillins. Other drugs may compete with penicillin G for renal tubular secretion and thus prolong the serum half-life of penicillin. These drugs include: aspirin, phenylbutazone, sulfonamides, indomethacin, thiazide diuretics, furosemide and ethacrynic acid. Drug/Laboratory Test Interactions After treatment with penicillin G, a false-positive reaction for glucose in the urine may occur with Benedict's solution, Fehling's solution or CLINITEST tablet, but not with the enzyme-based tests, such as CLINISTIX and TES-TAPE. Penicillin G has been associated with pseudoproteinuria by certain test methods.

WARNINGS Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with any penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillin, cephalosporins, or other allergens. If an allergic reaction occurs, the drug should be discontinued and the appropriate therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management including intubation, should also be administered as indicated. PRECAUTIONS General: Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma. Prescribing Pfizerpen (penicillin g potassium) in the absence of 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. Intramuscular Therapy: Care should be taken to avoid intravenous or accidental intraarterial administration, or injection into or near major peripheral nerves or blood vessels, since such injections may produce neurovascular damage. Particular care should be taken with IV administration because of the possibility of thrombophlebitis. In streptococcal infections, therapy must be sufficient to eliminate the organism (10 days minimum), otherwise the sequelae of streptococcal disease may occur. Cultures should be taken following the completion of treatment to determine whether streptococci have been eradicated. The use of antibiotics may result in overgrowth of nonsusceptible organisms. Constant observation of the patient is essential. If new infections due to bacteria or fungi appear during therapy, the drug should be discontinued and appropriate measures taken. 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. Aqueous penicillin G by the intravenous route in high doses (above 10 million units) should be administered slowly because of the adverse effects of electrolyte imbalance from either the potassium or sodium content of the penicillin. Penicillin G potassium contains 1.7 mEq potassium and 0.3 mEq sodium per million units. The patient's renal, cardiac, and vascular status should be evaluated and if impairment of function is suspected or known to exist a reduction in the total dosage should be considered. Frequent evaluation of electrolyte balance, renal and hematopoietic function is recommended during therapy when high doses of intravenous aqueous penicillin G are used. Laboratory Tests: In prolonged therapy with penicillin, periodic evaluation of the renal, hepatic, and hematopoietic systems is recommended for organ system dysfunction. This is particularly important in prematures, neonates and other infants, and when high doses are used. Positive Coomb's tests have been reported after large intravenous doses. Monitor serum potassium and implement corrective measures when necessary. When treating gonococcal infections in which primary and secondary syphilis are suspected, proper diagnostic procedures, including dark field examinations, should be done before receiving penicillin and monthly serological tests made for at least four months. All cases of penicillin treated syphilis should receive clinical and serological examinations every six months for two to three years. In suspected staphylococcal infections, proper laboratory studies, including susceptibility tests, should be performed. In streptococcal infections, cultures should be taken following completion of treatment to determine whether streptococci have been eradicated. Therapy must be sufficient to eliminate the organism (a minimum of 10 days), otherwise the sequelae of streptococcal disease (e.g., endocarditis, rheumatic fever) may occur. Carcinogenesis, Mutagenesis, Impairment of Fertility: No information on long-term studies are available on the carcinogenesis, mutagenesis, or the impairment of fertility with the use of penicillins. Pregnancy Category B - Teratogenic Effects: Reproduction studies performed in the mouse, rat, and rabbit have revealed no evidence of impaired fertility or harm to the fetus due to penicillin G. Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. There are, however, no adequate and 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 human milk. Caution should be exercised when penicillin G is administered to a nursing woman. Pediatric Use: Penicillins are excreted largely unchanged by the kidney. Because of incompletely developed renal function in infants, the rate of elimination will be slow. Use caution in administering to newborns and evaluate organ system function frequently.

WARNINGS Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with penicillin G, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, penicillin G should be discontinued and appropriate therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should also be administered as indicated. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Penicillin G Potassium 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. PRECAUTIONS General Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma (see WARNINGS). 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. Penicillin G Potassium, USP by the intravenous route in high doses (above 10 million units) should be administered slowly because of the potential adverse effects of electrolyte imbalance from the potassium content of the penicillin. Penicillin G Potassium Injection, USP contains 1.7 mEq potassium and 1.02 mEq of sodium per million units. The use of antibiotics may promote overgrowth of nonsusceptible organisms, including fungi. Indwelling intravenous catheters encourage superinfections.  Should superinfection occur, appropriate measures should be taken. When indicated, incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy. Prescribing Penicillin G Potassium 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 Periodic assessment of organ system function, including frequent evaluation of electrolyte balance, hepatic, renal and hematopoietic systems, and cardiac and vascular status should be performed during prolonged therapy with high doses of intravenous penicillin G (see ADVERSE REACTIONS). If any impairment of function is suspected or known to exist, a reduction in the total dosage should be considered (see DOSAGE AND ADMINISTRATION). In suspected staphylococcal infections, proper laboratory studies, including susceptibility tests should be performed. All infections due to Group A betahemolytic streptococci should be treated for at least 10 days. Patients being treated for gonococcal infection should have a serologic test for syphilis before receiving penicillin. All cases of penicillin treated syphilis should receive adequate follow-up including clinical and serological examinations. The recommended follow-up varies with the stage of syphilis being treated. Carcinogenesis, Mutagenesis, Impairment Of Fertility No long term animal studies have been conducted with this drug. 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 penicillin G. Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. There are, however, no adequate and 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 human milk. Caution should be exercised when penicillins are administered to a nursing woman. Pediatric Use Incompletely developed renal function in newborns may delay elimination of penicillin; therefore, appropriate reductions in the dosage and frequency of administration should be made in these patients. All newborns treated with penicillins should be monitored closely for clinical and laboratory evidence of toxic or adverse effects (see PRECAUTIONS). Pediatric doses are generally determined on a weight basis and should be calculated for each patient individually. Recommended guidelines for pediatric dosages are presented in Dosage and Administration. The potential for toxic effects in children from chemicals that may leach from the single dose premixed intravenous preparation in plastic containers has not been evaluated. Geriatric Use Clinical studies of Penicillin G Injection did not include sufficient numbers 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. Penicillin G Injection contains 23.5 mg (1.02 mEq) of sodium per million units. At the usual recommended doses, patients would receive between 23.5 and 564 mg/day (1.02 and 24.5 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.