AMPICILLIN- ampicillin_injection, powder, for solution

CLINICAL PHARMACOLOGY
Ampicillin for Injection, USP diffuses readily into most body tissues and fluids. However, penetration into the cerebrospinal fluid and brain occurs only when the meninges are inflamed. Ampicillin is excreted largely unchanged in the urine and its excretion can be delayed by concurrent administration of probenecid. Due to maturational changes in renal function, ampicillin half-life decreases as postmenstrual age (a sum of gestational age and postnatal age) increases for infants with postnatal age of less than 28 days. The active form appears in the bile in higher concentrations than those found in serum. Ampicillin is the least serum-bound of all the penicillins, averaging about 20% compared to approximately 60 to 90% for other penicillins. Ampicillin for Injection, USP is well tolerated by most patients and has been given in doses of 2 grams daily for many weeks without adverse reactions. While in vitro INDICATIONS AND USAGE Antibacterial Activity: The following bacteria have been shown in in vitro Gram-positive Bacteria Hemolytic and nonhemolytic streptococci Streptococcus pneumoniae Nonpenicillinase-producing staphylococci Clostridium B. anthracis Listeria monocytogenes Most strains of enterococci. Gram-negative Bacteria H. influenzae N. gonorrhoeae N. meningitidis Proteus mirabilis Many strains of Salmonella, Shigella E. coli AMPICILLIN does not resist destruction by penicillinase. 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.
Microbiology:
While in vitro INDICATIONS AND USAGE Antibacterial Activity: The following bacteria have been shown in in vitro Gram-positive Bacteria Hemolytic and nonhemolytic streptococci Streptococcus pneumoniae Nonpenicillinase-producing staphylococci Clostridium B. anthracis Listeria monocytogenes Most strains of enterococci. Gram-negative Bacteria H. influenzae N. gonorrhoeae N. meningitidis Proteus mirabilis Many strains of Salmonella, Shigella E. coli AMPICILLIN does not resist destruction by penicillinase. 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.

INDICATIONS AND USAGE
Ampicillin for Injection, USP is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the following conditions: Respiratory Tract Infections S. pneumoniae, Staphylococcus aureus H. influenzae Bacterial Meningitis E. coli, Listeria monocytogenes, N. meningitidis Septicemia and Endocarditis Streptococcus E. coli, Proteus mirabilis Salmonella Urinary Tract Infections E. coli Proteus mirabilis Gastrointestinal Infections Salmonella typhi Salmonella Shigella Bacteriology studies to determine the causative organisms and their susceptibility to ampicillin should be performed. Therapy may be instituted prior to obtaining results of susceptibility testing. It is advisable to reserve the parenteral form of this drug for moderately severe and severe infections and for patients who are unable to take the oral forms. A change to oral ampicillin may be made as soon as appropriate. Indicated surgical procedures should be performed. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Ampicillin for Injection, USP and other antibacterial drugs, Ampicillin 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.
Urethritis in males due to
Adults: Treatment may be repeated if necessary or extended if required. In the treatment of complications of gonorrheal urethritis, such as prostatitis and epididymitis, prolonged and intensive therapy is recommended. Cases of gonorrhea with a suspected primary lesion of syphilis should have darkfield examinations before receiving treatment. In all other cases where concomitant syphilis is suspected, monthly serological tests should be made for a minimum of four months. The doses for the preceding infections may be given by either the intramuscular or intravenous route. A change to oral ampicillin may be made when appropriate.
Bacterial Meningitis.
Adults and children: Neonates (less than or equal to 28 days of postnatal age): Table 1: Dosage in Neonates (less than or equal to 28 days of postnatal age) for Bacterial Meningitis and Septicemia Gestational age (weeks) Postnatal age (days) Dosage less than or equal to 34 less than or equal to 7 100 mg/kg/day in equally divided doses every 12 hours less than or equal to 34 greater than or equal to 8 and less than 28 150 mg/kg/day in equally divided doses every 12 hours greater than 34 less than or equal to 28 150 mg/kg/day in equally divided doses every 8 hours
Septicemia.
Adults and children: Neonates (less than or equal to 28 days of postnatal age): Treatment of all infections should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. A minimum of 10 days treatment is recommended for any infection caused by Group A beta-hemolytic streptococci to help prevent the occurrence of acute rheumatic fever or acute glomerulonephritis. DIRECTIONS FOR USE Use only freshly prepared solutions. Intramuscular and intravenous injections should be administered within one hour after preparation, since the potency may decrease significantly after this period. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. For Intramuscular Use: NDC Label Claim Recommended Amount of Diluent Withdrawable Volume Concentration (in mg/mL) 44567-105-10 125 mg 1.2 mL 1 mL 125 mg 44567-100-10 250 mg 1 mL 1 mL 250 mg 44567-101-10 500 mg 1.8 mL 2 mL 250 mg 44567-102-10 1 gram 3.5 mL 4 mL 250 mg 44567-103-10 2 grams 6.8 mL 8 mL 250 mg While Ampicillin for Injection, USP 1 g and 2 g, are primarily for intravenous use, they may be administered intramuscularly when the 250 mg or 500 mg vials are unavailable. In such instances, dissolve in 3.5 or 6.8 mL Sterile Water for Injection, USP or Bacteriostatic Water for Injection, USP, respectively. The resulting solution will provide a concentration of 250 mg per mL. Ampicillin for Injection, USP 125 mg, is intended primarily for pediatric use. It also serves as a convenient dosage form when small parenteral doses of the antibiotic are required. Note: Bacteriostatic Water for Injection, USP is not to be used as a diluent when the product will be used in newborns. For Direct Intravenous Use Add 5 mL Sterile Water for Injection, USP, or Bacteriostatic Water for Injection, USP to the 125 mg, 250 mg, and 500 mg vials and administer slowly over a 3 to 5 minute period. Ampicillin for Injection, USP 1 g or 2 g, may also be given by direct intravenous administration. Dissolve in 7.4 or 14.8 mL Sterile Water for Injection, USP, or Bacteriostatic Water for Injection, USP, respectively, and administer slowly over at least 10 to 15 minutes. CAUTION: More rapid administration may result in convulsive seizures. For Administration by Intravenous Drip: Reconstitute as directed above ( For Direct Intravenous Use) Room Temperature (25°C) Diluent Concentrations Stability Periods Sterile Water for Injection up to 30 mg/mL 8 hours 0.9% Sodium Chloride Injection, USP up to 30 mg/mL 8 hours 5% Dextrose Injection, USP 10 to 20 mg/mL 1 hour 5% Dextrose Injection, USP up to 2 mg/mL 2 hours 5% Dextrose and 0.45% Sodium Chloride Injection, USP up to 2 mg/mL 2 hours Lactated Ringer’s Injection, USP up to 30 mg/mL 8 hours Refrigerated (4°C) Sterile Water for Injection 30 mg/mL 48 hours Sterile Water for Injection up to 20 mg/mL 72 hours 0.9% Sodium Chloride Injection, USP 30 mg/mL 24 hours 0.9% Sodium Chloride Injection, USP up to 20 mg/mL 48 hours Lactated Ringer’s Injection, USP up to 30 mg/mL 24 hours 5% Dextrose Injection, USP up to 20 mg/mL 1 hour 5% Dextrose and 0.45% Sodium Chloride Injection, USP up to 10 mg/mL 1 hour Only those solutions listed above should be used for the intravenous infusion of Ampicillin for Injection, USP. The concentrations 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 ampicillin is administered before the drug loses its stability in the solution in use. Piggyback IV Package:

DOSAGE AND ADMINISTRATION
Patients weighing 40 kg (88 lbs) or more: 250 mg to 500 mg every 6 hours. Patients weighing less than 40 kg (88 lbs): 25 to 50 mg/kg/day in equally divided doses at 6- to 8-hour intervals. Patients weighing 40 kg (88 lbs) or more: 500 mg every 6 hours. Patients weighing less than 40 kg (88 lbs): 50 mg/kg/day in equally divided doses at 6- to 8-hour intervals. In the treatment of chronic urinary tract and intestinal infections, frequent bacteriological and clinical appraisal is necessary. Smaller doses than those recommended above should not be used. Higher doses should be used for stubborn or severe infections. In stubborn infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy. Adults: Treatment may be repeated if necessary or extended if required. In the treatment of complications of gonorrheal urethritis, such as prostatitis and epididymitis, prolonged and intensive therapy is recommended. Cases of gonorrhea with a suspected primary lesion of syphilis should have darkfield examinations before receiving treatment. In all other cases where concomitant syphilis is suspected, monthly serological tests should be made for a minimum of four months. The doses for the preceding infections may be given by either the intramuscular or intravenous route. A change to oral ampicillin may be made when appropriate. Adults and children: Neonates (less than or equal to 28 days of postnatal age): Table 1: Dosage in Neonates (less than or equal to 28 days of postnatal age) for Bacterial Meningitis and Septicemia Gestational age (weeks) Postnatal age (days) Dosage less than or equal to 34 less than or equal to 7 100 mg/kg/day in equally divided doses every 12 hours less than or equal to 34 greater than or equal to 8 and less than 28 150 mg/kg/day in equally divided doses every 12 hours greater than 34 less than or equal to 28 150 mg/kg/day in equally divided doses every 8 hours Adults and children: Neonates (less than or equal to 28 days of postnatal age): Treatment of all infections should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. A minimum of 10 days treatment is recommended for any infection caused by Group A beta-hemolytic streptococci to help prevent the occurrence of acute rheumatic fever or acute glomerulonephritis. DIRECTIONS FOR USE Use only freshly prepared solutions. Intramuscular and intravenous injections should be administered within one hour after preparation, since the potency may decrease significantly after this period. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. For Intramuscular Use: NDC Label Claim Recommended Amount of Diluent Withdrawable Volume Concentration (in mg/mL) 44567-105-10 125 mg 1. 2 mL 1 mL 125 mg 44567-100-10 250 mg 1 mL 1 mL 250 mg 44567-101-10 500 mg 1. 8 mL 2 mL 250 mg 44567-102-10 1 gram 3. 5 mL 4 mL 250 mg 44567-103-10 2 grams 6. 8 mL 8 mL 250 mg While Ampicillin for Injection, USP 1 g and 2 g, are primarily for intravenous use, they may be administered intramuscularly when the 250 mg or 500 mg vials are unavailable. In such instances, dissolve in 3. 8 mL Sterile Water for Injection, USP or Bacteriostatic Water for Injection, USP, respectively. The resulting solution will provide a concentration of 250 mg per mL. Ampicillin for Injection, USP 125 mg, is intended primarily for pediatric use. It also serves as a convenient dosage form when small parenteral doses of the antibiotic are required. Note: Bacteriostatic Water for Injection, USP is not to be used as a diluent when the product will be used in newborns. For Direct Intravenous Use Add 5 mL Sterile Water for Injection, USP, or Bacteriostatic Water for Injection, USP to the 125 mg, 250 mg, and 500 mg vials and administer slowly over a 3 to 5 minute period. Ampicillin for Injection, USP 1 g or 2 g, may also be given by direct intravenous administration. Dissolve in 7. 8 mL Sterile Water for Injection, USP, or Bacteriostatic Water for Injection, USP, respectively, and administer slowly over at least 10 to 15 minutes. CAUTION: More rapid administration may result in convulsive seizures. For Administration by Intravenous Drip: Reconstitute as directed above ( For Direct Intravenous Use) Room Temperature (25°C) Diluent Concentrations Stability Periods Sterile Water for Injection up to 30 mg/mL 8 hours 0. 9% Sodium Chloride Injection, USP up to 30 mg/mL 8 hours 5% Dextrose Injection, USP 10 to 20 mg/mL 1 hour 5% Dextrose Injection, USP up to 2 mg/mL 2 hours 5% Dextrose and 0. 45% Sodium Chloride Injection, USP up to 2 mg/mL 2 hours Lactated Ringer’s Injection, USP up to 30 mg/mL 8 hours Refrigerated (4°C) Sterile Water for Injection 30 mg/mL 48 hours Sterile Water for Injection up to 20 mg/mL 72 hours 0. 9% Sodium Chloride Injection, USP 30 mg/mL 24 hours 0. 9% Sodium Chloride Injection, USP up to 20 mg/mL 48 hours Lactated Ringer’s Injection, USP up to 30 mg/mL 24 hours 5% Dextrose Injection, USP up to 20 mg/mL 1 hour 5% Dextrose and 0. 45% Sodium Chloride Injection, USP up to 10 mg/mL 1 hour Only those solutions listed above should be used for the intravenous infusion of Ampicillin for Injection, USP. The concentrations 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 ampicillin is administered before the drug loses its stability in the solution in use. Piggyback IV Package:.
Infections of the respiratory tract and soft tissues.
Patients weighing 40 kg (88 lbs) or more: 250 mg to 500 mg every 6 hours. Patients weighing less than 40 kg (88 lbs): 25 to 50 mg/kg/day in equally divided doses at 6- to 8-hour intervals.
Infections of the gastrointestinal and genitourinary tracts (including those caused by
Patients weighing 40 kg (88 lbs) or more: 500 mg every 6 hours. Patients weighing less than 40 kg (88 lbs): 50 mg/kg/day in equally divided doses at 6- to 8-hour intervals. In the treatment of chronic urinary tract and intestinal infections, frequent bacteriological and clinical appraisal is necessary. Smaller doses than those recommended above should not be used. Higher doses should be used for stubborn or severe infections. In stubborn infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy.

As with other penicillins, it may be expected that untoward reactions will be essentially limited to sensitivity phenomena. They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillins and in those with a history of allergy, asthma, hay fever or urticaria. The following adverse reactions have been reported as associated with the use of ampicillin: Gastrointestinal Glossitis, stomatitis, black “hairy” tongue, nausea, vomiting, enterocolitis, pseudomembranous colitis, and diarrhea. (These reactions are usually associated with oral dosage forms.) Hypersensitivity Reactions Skin rashes and urticaria have been reported frequently. A few cases of exfoliative dermatitis and erythema multiforme have been reported. Linear IgA bullous dermatosis has been reported. Note: Whenever such reactions occur, ampicillin should be discontinued, unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to ampicillin therapy. Serious anaphylactic reactions require the immediate use of epinephrine, oxygen, and intravenous steroids. Liver A moderate rise in serum glutamic oxaloacetic transaminase (SGOT) has been noted, particularly in infants, but the significance of this finding is unknown. Mild transitory SGOT elevations have been observed in individuals receiving larger (two to four times) than usual and oft-repeated intramuscular injections. Evidence indicates that glutamic oxaloacetic transaminase (GOT) is released at the site of intramuscular injection of Ampicillin for Injection and that the presence of increased amounts of this enzyme in the blood does not necessarily indicate liver involvement. Hemic and Lymphatic Systems Anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during therapy with the penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Central Nervous System Seizures.

A history of a previous hypersensitivity reaction to any of the penicillins is a contraindication.

Pregnancy Category B:
Reproduction studies have been performed in laboratory animals at doses several times the human dose and have revealed no evidence of adverse effects due to ampicillin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers
Ampicillin is excreted in trace amounts in human milk. Therefore, caution should be exercised when ampicillin-class antibacterials are administered to a nursing woman.
Pediatric Use
Guidelines for the administration of these drugs to children, including neonates are presented in DOSAGE AND ADMINISTRATION

Drug Interactions
The concurrent administration of allopurinol and ampicillin increases substantially the incidence of skin rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients.
Drug/Laboratory Test Interactions
With high urine concentrations of ampicillin, false-positive glucose reactions may occur if Clinitest, Benedict’s Solution, or Fehling’s Solution are used. Therefore, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix or Tes-Tape) be used.

WARNINGS
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been well-documented reports of individuals with a history of penicillin hypersensitivity reactions who have experienced severe hypersensitivity reactions when treated with a cephalosporin. Before initiating therapy with a penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, and other allergens. If an allergic reaction occurs, the drug should be discontinued and 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. Clostridium difficile C. difficile. C. difficile C. difficile If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile C. difficile
Carcinogenesis,Mutagenesis, and Impairment of Fertility
No long-term animal studies have been conducted with this drug.
Labor and Delivery
Oral ampicillin-class antibacterials are poorly absorbed during labor. Studies in guinea pigs showed that intravenous administration of ampicillin slightly decreased the uterine tone and frequency of contractions, but moderately increased the height and duration of contractions. However, it is not known whether use of these drugs in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary.
OVERDOSAGE
In cases of overdose, discontinue medication, treat symptomatically and institute supportive measures as required. In patients with renal function impairment, ampicillin-class antibacterials can be removed by hemodialysis but not peritoneal dialysis.

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AMPICILLIN- ampicillin_injection, powder, for solution Product manual source documgent