NDC 66794-208 Ampicillin And Sulbactam

Ampicillin And Sulbactam

NDC Product Code 66794-208

NDC 66794-208-15

Package Description: 1 BOTTLE in 1 CARTON > 100 mL in 1 BOTTLE

NDC Product Information

Ampicillin And Sulbactam with NDC 66794-208 is a a human prescription drug product labeled by Piramal Critical Care Inc. The generic name of Ampicillin And Sulbactam is ampicillin and sulbactam. The product's dosage form is injection, powder, for solution and is administered via intravenous form.

Labeler Name: Piramal Critical Care Inc

Dosage Form: Injection, Powder, For Solution - A sterile preparation intended for reconstitution to form a solution for parenteral use.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Ampicillin And Sulbactam Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • SULBACTAM SODIUM 50 mg/mL
  • AMPICILLIN SODIUM 100 mg/mL

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravenous - Administration within or into a vein or veins.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • beta Lactamase Inhibitor - [EPC] (Established Pharmacologic Class)
  • beta Lactamase Inhibitors - [MoA] (Mechanism of Action)
  • Penicillin-class Antibacterial - [EPC] (Established Pharmacologic Class)
  • Penicillins - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Piramal Critical Care Inc
Labeler Code: 66794
FDA Application Number: ANDA090578 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 05-20-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Ampicillin And Sulbactam Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Description

Ampicillin and Sulbactam for Injection, USP is an injectable antibacterial combination consisting of the semisynthetic antibacterial ampicillin sodium and the beta-lactamase inhibitor sulbactam sodium for intravenous administration.Ampicillin sodium is derived from the penicillin nucleus, 6-aminopenicillanic acid. Chemically, it is monosodium (2S,5R,6R)-6-[(R)-2-amino-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate and has a molecular weight of 371.39. Its chemical formula is C
16H
18N
3NaO
4S. The structural formula is:
Sulbactam sodium is a derivative of the basic penicillin nucleus. Chemically, sulbactam sodium is sodium penicillinate sulfone; sodium (2S, 5R)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 4,4-dioxide. Its chemical formula is C
8H
10NNaO
5S with a molecular weight of 255.22. The structural formula is:
Ampicillin and Sulbactam for Injection, USP, ampicillin sodium/sulbactam sodium parenteral combination, is available as a white to off-white dry powder for reconstitution. Ampicillin and Sulbactam for Injection, USP dry powder is freely soluble in aqueous diluents to yield pale yellow to yellow solutions containing ampicillin sodium and sulbactam sodium equivalent to 250 mg ampicillin per mL and 125 mg sulbactam per mL. The pH of the solutions is between 8.0 and 10.0.Dilute solutions (up to 30 mg ampicillin and 15 mg sulbactam per mL) are essentially colorless to pale yellow. The pH of dilute solutions remains the same.Ampicillin and Sulbactam for Injection, USP pharmacy bulk package is a bottle containing a sterile preparation of ampicillin sodium and sulbactam sodium for parenteral use that contains many single doses. The Pharmacy Bulk Package is for use in a pharmacy admixture setting; it provides many single doses of Ampicillin and Sulbactam for Injection, USP for addition to suitable parenteral fluids in the preparation of admixtures for intravenous infusion (see
DIRECTIONS FOR USE, Directions for Proper Use of Pharmacy Bulk Package).
Each 15 gram Ampicillin and Sulbactam for Injection Pharmacy Bulk Package bottle contains ampicillin sodium and sulbactam sodium equivalent to 10 grams ampicillin plus 5 grams sulbactam. The sodium content per 1.5 gram is 115.1 mg (5.0 mEq). The sodium content is approximately 1,151 mg (50 mEq) sodium per bottle.

Clinical Pharmacology

GeneralImmediately after completion of a 15-minute intravenous infusion of ampicillin and sulbactam for injection peak serum concentrations of ampicillin and sulbactam are attained. Ampicillin serum levels are similar to those produced by the administration of equivalent amounts of ampicillin alone. Peak ampicillin serum levels ranging from 109 to 150 mcg/mL are attained after administration of 2000 mg of ampicillin plus 1000 mg sulbactam and 40 to 71 mcg/mL after administration of 1000 mg ampicillin plus 500 mg sulbactam. The corresponding mean peak serum levels for sulbactam range from 48 to 88 mcg/mL and 21 to 40 mcg/mL, respectively. After an intramuscular injection of 1000 mg ampicillin plus 500 mg sulbactam, peak ampicillin serum levels ranging from 8 to 37 mcg/mL and peak sulbactam serum levels ranging from 6 to 24 mcg/mL are attained.The mean serum half-life of both drugs is approximately 1 hour in healthy volunteers.Approximately 75 to 85% of both ampicillin and sulbactam are excreted unchanged in the urine during the first 8 hours after administration of ampicillin and sulbactam for injection to individuals with normal renal function. Somewhat higher and more prolonged serum levels of ampicillin and sulbactam can be achieved with the concurrent administration of probenecid.In patients with impaired renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function. The dose of ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin (see
DOSAGE AND ADMINISTRATION section).
Ampicillin has been found to be approximately 28% reversibly bound to human serum protein and sulbactam approximately 38% reversibly bound.The following average levels of ampicillin and sulbactam were measured in the tissues and fluids listed:TABLE 1Concentration of Ampicillin and Sulbactam for Injection in Various Body Tissues and FluidsDoseConcentrationFluid or Tissue(grams)Ampicillin/Sulbactam(mcg/mL or mcg/g)Ampicillin/SulbactamPeritoneal Fluid0.5/0.5 IV7/14Blister Fluid (Cantharides)0.5/0.5 IV8/20Tissue Fluid1/0.5 IV8/4Intestinal Mucosa0.5/0.5 IV11/18Appendix2/1 IV3/40Penetration of both ampicillin and sulbactam into cerebrospinal fluid in the presence of inflamed meninges has been demonstrated after IV administration of ampicillin and sulbactam for injection.The pharmacokinetics of ampicillin and sulbactam in pediatric patients receiving ampicillin and sulbactam for injection are similar to those observed in adults. Immediately after a 15-minute infusion of 50 to 75 mg ampicillin and sulbactam for injection/kg body weight, peak serum and plasma concentrations of 82 to 446 mcg ampicillin/mL and 44 to 203 mcg sulbactam/mL were obtained. Mean half-life values were approximately 1 hour.MICROBIOLOGYAmpicillin is similar to benzyl penicillin in its bactericidal action against susceptible organisms during the stage of active multiplication. It acts through the inhibition of cell wall mucopeptide biosynthesis. Ampicillin has a broad spectrum of bactericidal activity against many gram-positive and gram-negative aerobic and anaerobic bacteria. (Ampicillin is, however, degraded by beta-lactamases and therefore the spectrum of activity does not normally include organisms which produce these enzymes.)A wide range of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins have been shown in biochemical studies with cell free bacterial systems to be irreversibly inhibited by sulbactam. Although sulbactam alone possesses little useful antibacterial activity except against the
Neisseriaceae, whole
particular, sulbactam has good inhibitory activity against the clinically important plasmid mediated beta-lactamases most frequently responsible for transferred drug resistance. Sulbactam has no effect on the activity of ampicillin against ampicillin susceptible strains.The presence of sulbactam in the ampicillin and sulbactam for injection formulation effectively extends the antibacterial spectrum of ampicillin to include many bacteria normally resistant to it and to other beta-lactam antibacterials. Thus, ampicillin and sulbactam for injection possesses the properties of a broad-spectrum antibacterial and a beta-lactamase inhibitor.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.
organism studies have shown that sulbactam restores ampicillin activity against beta-lactamase producing strains. InGram-Positive BacteriaStaphylococcus aureus (beta-lactamase and non-beta-lactamase producing),
Staphylococcus epidermidis (beta-lactamase and non-beta-lactamase producing),
Staphylococcus saprophyticus (beta-lactamase and non-beta-lactamase producing),
Streptococcus faecalis† (Enterococcus),
Streptococcus pneumoniae† (formerly
D. pneumoniae),
Streptococcus pyogenes†,
Streptococcus viridans†.Gram-Negative BacteriaHaemophilus influenzae (beta-lactamase and non-beta-lactamase producing),
Moraxella (Branhamella) catarrhalis (beta-lactamase and non-beta-lactamase producing),
Escherichia coli (beta-lactamase and non-beta-lactamase producing),
Klebsiella species (all known strains are beta-lactamase producing),
Proteus mirabilis (beta-lactamase and non-beta-lactamase producing),
Proteus vulgaris,
Providencia rettgeri,
Providencia stuartii,
Morganella morganii, and
Neisseria gonorrhoeae (beta-lactamase and non-beta-lactamase producing).
AnaerobesClostridium species†, Peptococcus species†, Peptostreptococcus species, Bacteroides species, including B. fragilis.† These are not beta-lactamase producing strains and, therefore, are susceptible to ampicillin alone.Susceptibility TestingFor 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 and sulbactam for injection, USP is indicated for the treatment of infections due to susceptible strains of the designated microorganisms in the conditions listed below.Skin and Skin Structure Infections caused by beta-lactamase producing strains of
Staphylococcus aureus,
Escherichia coli*,
Klebsiella spp.* (including
K. pneumoniae*),
Proteus mirabilis*,
Bacteroides fragilis*,
Enterobacter spp.*, and
Acinetobacter calcoaceticus*.NOTE: For information on use in pediatric patients see
PRECAUTIONS, Pediatric Useand
CLINICAL STUDIES sections.
Intra-Abdominal Infections caused by beta-lactamase producing strains of
Escherichia coli,
Klebsiella spp. (including
K. pneumoniae*),
Bacteroides spp. (including
B. fragilis), and
Enterobacter spp.*
Gynecological Infections caused by beta-lactamase producing strains of
Escherichia coli*, and
Bacteroides spp.* (including
B. fragilis*)
.* Efficacy for this organism in this organ system was studied in fewer than 10 infections.While ampicillin and sulbactam for injection, USP is indicated only for the conditions listed above, infections caused by ampicillin-susceptible organisms are also amenable to treatment with ampicillin and sulbactam for injection, USP due to its ampicillin content. Therefore, mixed infections caused by ampicillin-susceptible organisms and beta-lactamase producing organisms susceptible to ampicillin and sulbactam for injection, USP should not require the addition of another antibacterial.Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify the organisms causing infection and to determine their susceptibility to ampicillin and sulbactam for injection, USP.Therapy may be instituted prior to obtaining the results from bacteriological and susceptibility studies when there is reason to believe the infection may involve any of the beta-lactamase producing organisms listed above in the indicated organ systems. Once the results are known, therapy should be adjusted if appropriate.To reduce the development of drug-resistant bacteria and maintain effectiveness of ampicillin and sulbactam for injection, USP and other antibacterial drugs, ampicillin and sulbactam for injection, USP should be used only to treat 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.

Contraindications

The use of ampicillin and sulbactam for injection is contraindicated in individuals with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to ampicillin, sulbactam or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins).Ampicillin and sulbactam for injection is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with ampicillin and sulbactam for injection.

Warnings

HypersensitivitySerious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or hypersensitivity reactions 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 therapy with a penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, and other allergens. If an allergic reaction occurs, ampicillin and sulbactam for injection should be discontinued and the appropriate therapy instituted.HepatotoxicityHepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of ampicillin and sulbactam for injection. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.Severe Cutaneous Adverse ReactionsAmpicillin and sulbactam may cause severe skin reactions, such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), dermatitis exfoliative, erythema multiforme, and acute generalized exanthematous pustulosis (AGEP). If patients develop a skin rash they should be monitored closely and ampicillin and sulbactam discontinued if lesions progress (see
CONTRAINDICATIONSand
ADVERSE REACTIONSsections).
Clostridium difficile-Associated Diarrhea
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ampicillin and sulbactam for injection, 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 antibacterial drug 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 antibacterial
drug use not directed against
C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of
C. difficile, and surgical evaluation should be instituted as clinically indicated.

Precautions

GeneralA high percentage of patients with mononucleosis who receive ampicillin develop a skin rash. Thus, ampicillin class antibacterials should not be administered to patients with mononucleosis. In patients treated with ampicillin and sulbactam for injection the possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving
Pseudomonas or
Candida), the drug should be discontinued and/or appropriate therapy instituted.
Prescribing ampicillin and sulbactam for injection 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.Information for PatientsPatients should be counseled that antibacterial drugs including ampicillin and sulbactam for injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection or other antibacterial drugs in the future.Diarrhea is a common problem caused by antibacterials which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, 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 antibacterial. If this occurs, patients should contact their physician as soon as possible.Drug InteractionsProbenecid decreases the renal tubular secretion of ampicillin and sulbactam. Concurrent use of probenecid with ampicillin and sulbactam for injection may result in increased and prolonged blood levels of ampicillin and sulbactam. The concurrent administration of allopurinol and ampicillin increases substantially the incidence of 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. There are no data with ampicillin and sulbactam for injection and allopurinol administered concurrently. Ampicillin and sulbactam for injection and aminoglycosides should not be reconstituted together due to the
in vitro inactivation of aminoglycosides by the ampicillin component of ampicillin and sulbactam for injection.
Drug/Laboratory Test InteractionsAdministration of ampicillin and sulbactam for injection will result in high urine concentration of ampicillin. High urine concentrations of ampicillin may result in false positive reactions when testing for the presence of glucose in urine using Clinitest™, Benedict’s Solution or Fehling’s Solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix™ or Testape™) be used. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone and estradiol has been noted. This effect may also occur with ampicillin and sulbactam for injection.Carcinogenesis, Mutagenesis, Impairment of FertilityLong-term studies in animals have not been performed to evaluate carcinogenic or mutagenic potential.PregnancyReproduction studies have been performed in mice, rats, and rabbits at doses up to ten (10) times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to ampicillin and sulbactam for injection. 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 (see
PRECAUTIONS, Drug/Laboratory Test Interactionssection).
Labor and DeliveryStudies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions. However, it is not known whether the use of ampicillin and sulbactam for injection 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.Nursing MothersLow concentrations of ampicillin and sulbactam are excreted in the milk; therefore, caution should be exercised when ampicillin and sulbactam for injection is administered to a nursing woman.Pediatric UseThe safety and effectiveness of ampicillin and sulbactam for injection have been established for pediatric patients one year of age and older for skin and skin structure infections as approved in adults. Use of ampicillin and sulbactam in pediatric patients is supported by evidence from adequate and well-controlled studies in adults with additional data from pediatric pharmacokinetic studies, a controlled clinical trial conducted in pediatric patients and post-marketing adverse events surveillance (see
CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE, ADVERSE REACTIONS, DOSAGE AND ADMINISTRATION, and
CLINICAL STUDIESsections).
The safety and effectiveness of ampicillin and sulbactam for injection have not been established for pediatric patients for intra-abdominal infections.

Adverse Reactions

Adult PatientsAmpicillin and sulbactam for injection is generally well tolerated. The following adverse reactions have been reported in clinical trials.Local Adverse ReactionsPain at IM injection site – 16%Pain at IV injection site – 3%Thrombophlebitis – 3%Phlebitis – 1.2%Systemic Adverse ReactionsThe most frequently reported adverse reactions were diarrhea in 3% of the patients and rash in less than 2% of the patients.Additional systemic reactions reported in less than 1% of the patients were: itching, nausea, vomiting, candidiasis, fatigue, malaise, headache, chest pain, flatulence, abdominal distension, glossitis, urine retention, dysuria, edema, facial swelling, erythema, chills, tightness in throat, substernal pain, epistaxis and mucosal bleeding.Pediatric PatientsAvailable safety data for pediatric patients treated with ampicillin and sulbactam for injection demonstrate a similar adverse events profile to those observed in adult patients. Additionally, atypical lymphocytosis has been observed in one pediatric patient receiving ampicillin and sulbactam for injection.Adverse Laboratory ChangesAdverse laboratory changes without regard to drug relationship that were reported during clinical trials were:Hepatic: Increased AST (SGOT), ALT (SGPT), alkaline phosphatase, and LDH.
Hematologic: Decreased hemoglobin, hematocrit, RBC, WBC, neutrophils, lymphocytes, platelets and increased lymphocytes, monocytes, basophils, eosinophils, and platelets.
Blood Chemistry: Decreased serum albumin and total proteins.
Renal: Increased BUN and creatinine.
Urinalysis: Presence of RBC’s and hyaline casts in urine.
Postmarketing ExperienceIn addition to adverse reactions reported from clinical trials, the following have been identified during post-marketing use of ampicillin sodium/sulbactam sodium or other products containing ampicillin. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency, or potential causal connection to ampicillin sodium/sulbactam sodium.Blood and Lymphatic System DisordersHemolytic anemia, thrombocytopenic purpura, and agranulocytosis have been reported. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Some individuals have developed positive direct Coombs Tests during treatment with ampicillin and sulbactam for injection, as with other beta-lactam antibacterials.Gastrointestinal DisordersAbdominal pain, cholestatic hepatitis, cholestasis, hyperbilirubinemia, jaundice, abnormal hepatic function, melena, gastritis, stomatitis, dyspepsia, black “hairy” tongue, and
Clostridium difficile associated diarrhea (see
CONTRAINDICATIONSand
WARNINGSsections).
General Disorders and Administration Site ConditionsInjection site reactionImmune System DisordersSerious and fatal hypersensitivity (anaphylactic) reactions (see
WARNINGSsection).
Nervous System DisordersConvulsion and dizzinessRenal and Urinary DisordersTubulointerstitial nephritisRespiratory, Thoracic and Mediastinal DisordersDyspneaSkin and Subcutaneous Tissue DisordersToxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, acute generalized exanthematous pustulosis (AGEP), erythema multiforme, exfoliative dermatitis, and urticaria (see
CONTRAINDICATIONSand
WARNINGSsections).
To report SUSPECTED ADVERSE REACTIONS, contact Piramal Critical Care at 1-888-822-8431or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.

Overdosage

Neurological adverse reactions, including convulsions, may occur with the attainment of high CSF levels of beta-lactams. Ampicillin may be removed from circulation by hemodialysis. The molecular weight, degree of protein binding and pharmacokinetics profile of sulbactam suggest that this compound may also be removed by hemodialysis.

Clinical Studies

Skin and Skin Structure Infections in Pediatric PatientsData from a controlled clinical trial conducted in pediatric patients provided evidence supporting the safety and efficacy of ampicillin and sulbactam for injection for the treatment of skin and skin structure infections. Of 99 pediatric patients evaluable for clinical efficacy, 60 patients received a regimen containing intravenous ampicillin and sulbactam for injection, and 39 patients received a regimen containing intravenous cefuroxime. This trial demonstrated similar outcomes (assessed at an appropriate interval after discontinuation of all antimicrobial therapy) for ampicillin and sulbactam- and cefuroxime-treated patients:TABLE 4Therapeutic RegimenClinical SuccessClinical FailureAmpicillin and Sulbactam for Injection51/60 (85%)9/60 (15%)Cefuroxime34/39 (87%)5/39 (13%)Most patients received a course of oral antimicrobials following initial treatment with intravenous administration of parenteral antimicrobials. The study protocol required that the following three criteria be met prior to transition from intravenous to oral antimicrobial therapy: (1) receipt of a minimum of 72 hours of intravenous therapy; (2) no documented fever for prior 24 hours; and (3) improvement or resolution of the signs and symptoms of infection.The choice of oral antimicrobial agent used in this trial was determined by susceptibility testing of the original pathogen, if isolated, to oral agents available. The course of oral antimicrobial therapy should not routinely exceed 14 days.

Dosage And Administration

The pharmacy bulk package is for preparation of solutions for IV infusion only. Ampicillin and sulbactam for injection should be administered by slow intravenous injection over at least 10 to 15 minutes or can also be delivered in greater dilutions with 50 to 100 mL of a compatible diluent as an intravenous infusion over 15 to 30 minutes.The recommended adult dosage of ampicillin and sulbactam for injection is 1.5 grams (1 gram ampicillin as the sodium salt plus 0.5 gram sulbactam as the sodium salt) to 3 grams (2 grams ampicillin as the sodium salt plus 1 gram sulbactam as the sodium salt) every six hours. This 1.5 to 3 gram range represents the total of ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to a range of 1 gram ampicillin/0.5 gram sulbactam to 2 grams ampicillin/1 gram sulbactam. The total dose of sulbactam should not exceed 4 grams per day.Pediatric Patients 1 Year of Age or OlderThe recommended daily dose of ampicillin and sulbactam for injection in pediatric patients is 300 mg per kg of body weight administered via intravenous infusion in equally divided doses every 6 hours. This 300 mg/kg/day dosage represents the total ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection administered via intramuscular injection in pediatric patients have not been established. Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations, and the total dose of sulbactam should not exceed 4 grams per day. The course of intravenous therapy should not routinely exceed 14 days. In clinical trials, most children received a course of oral antimicrobials following initial treatment with intravenous ampicillin and sulbactam for injection (see
CLINICAL STUDIES section).
Impaired Renal FunctionIn patients with impairment of renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function. The dose of ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:TABLE 5Ampicillin and Sulbactam for InjectionDosage Guide for Patients with Renal ImpairmentCreatinine Clearance

(mL/min/1.73m
2)
Ampicillin/Sulbactam

Half-Life (Hours)
Recommended

Ampicillin and Sulbactam

for Injection Dosage
≥3011.5 g to 3 g q6h to q8h15 to 2951.5 g to 3 g q12h5 to 1491.5 g to 3 g q24hWhen only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.Males (weight (kg) x (140 - age)) / (72 x serum creatinine)Females 0.85 x above valueCOMPATIBILITY, RECONSTITUTION AND STABILITYWhen concomitant therapy with aminoglycosides is indicated, ampicillin and sulbactam for injection and aminoglycosides should be reconstituted and administered separately, due to the
in vitro inactivation of aminoglycosides by any of the aminopenicillins.
DIRECTIONS FOR USEIntravenous AdministrationDirections for Proper Use of Pharmacy Bulk PackageAmpicillin and sulbactam for injection sterile powder for intravenous use may be reconstituted with any of the compatible diluents described in this insert. Solutions should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization. Ampicillin and sulbactam for injection concentrations between 3 and 45 mg (2 to 30 mg ampicillin/1 to 15 mg sulbactam/mL) are recommended for intravenous use.

The 15 gram bottle may be reconstituted with either 92 mL Sterile Water for Injection or 0.9% Sodium Chloride Injection. The diluent should be added in two separate aliquots in a suitable work area, such as a laminar flow hood. Add 50 mL of solution, shake to dissolve. Then add an additional 42 mL and shake. The solution should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization. The resultant solution will have a final concentration of approximately 100 mg/mL ampicillin and 50 mg/mL sulbactam. The closure may be penetrated only one time after reconstitution, if needed, using a suitable sterile transfer device or dispensing set that allows for measured dispensing of the contents.

After reconstitution, use within two hours if stored at room temperature, or within four hours if stored under refrigeration.
Reconstituted Bulk Solution Should Not be Used For Direct InfusionIf the reconstituted bulk solution is stored for less than one hour at room temperature (20°C/68°F) prior to further dilution, the use periods indicated in Table 6 apply for the diluted solutions.If the bulk solution is stored for one to two hours at room temperature (20°C/68°F) and then diluted with Sterile Water for Injection or 0.9% Sodium Chloride Injection to the following concentrations, the use periods indicated in Table 7 apply.Any unused portions of solution that remain after the indicated time periods should be discarded.TABLE 6DiluentMaximum Concentration (mg/mL)(Ampicillin and Sulbactam for Injection)Use PeriodsSterile Water for Injection45 (30/15)8 hrs at 21°C45 (30/15)48 hrs at 4°C30 (20/10)72 hrs at 4°C0.9% Sodium Chloride Injection45 (30/15)8 hrs at 21°C45 (30/15)48 hrs at 4°C30 (20/10)72 hrs at 4°C5% Dextrose Injection30 (20/10)2 hrs at 21°C30 (20/10)4 hrs at 4°C3 (2/1)2 hrs at 21°CLactated Ringer’s Injection45 (30/15)8 hrs at 21°C45 (30/15)24 hrs at 4°CM/6 Sodium Lactate Injection45 (30/15)8 hrs at 21°C45 (30/15)12 hrs at 4°C5% Dextrose in 0.45% Saline3 (2/1)4 hrs at 21°C15 (10/5)4 hrs at 4°C10% Invert Sugar3 (2/1)4 hrs at 21°C30 (20/10)3 hrs at 4°CTABLE 7IV SolutionMaximum Concentration (mg/mL)(Ampicillin and Sulbactam for Injection)Use PeriodsSterile Water for Injection, USP45 (30/15)4 hrs at 21°C45 (30/15)24 hrs at 4°C0.9% Sodium Chloride Injection, USP45 (30/15)4 hrs at 21°C45 (30/15)24 hrs at 4°CAnimal PharmacologyWhile reversible glycogenosis was observed in laboratory animals, this phenomenon was dose- and time-dependent and is not expected to develop at the therapeutic doses and corresponding plasma levels attained during the relatively short periods of combined ampicillin/sulbactam therapy in man.

How Supplied

Ampicillin and Sulbactam for Injection, USP is available as follows:NDC Ampicillin and Sulbactam for Injection, USPPackage Factor66794-206-021.5 grams per vial1 vial66794-206-411.5 grams per vial10 vials per carton(1 gram ampicillin as the sodium salt plus 0.5 gram sulbactam as the sodium salt) 66794-207-023 grams per vial1 vial66794-207-413 grams per vial10 vials per carton(2 grams ampicillin as the sodium salt plus 1 gram sulbactam as the sodium salt)Ampicillin and Sulbactam for Injection, USP is also available in a Pharmacy Bulk Package supplied as follows:NDC Ampicillin and Sulbactam for Injection, USPPackage Factor66794-208-1515 grams per Pharmacy Bulk Package Bottle1 bottle per carton(10 grams ampicillin as the sodium salt plus 5 grams sulbactam as the sodium salt)Storage ConditionsPrior to reconstitution store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F). [See USP Controlled Room Temperature.]Sterile, Nonpyrogenic, Preservative-free.The container closure is not made with natural rubber latex.Brands listed are the trademarks of their respective owners.Piramal Critical CareBethlehem, PA 18017, USAMade in India©2019 Piramal Critical CareRevised: February 2019

* Please review the disclaimer below.