PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Principal Display Panel – Ampicillin and Sulbactam for Injection, USP 3 gram

Vial Label

NDC 72603-335-01
Rx only

Ampicillin and Sulbactam for Injection, USP

3 grams per vial*

For Intramuscular or Intravenous Use

Single-Dose Vial

NorthStar

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DESCRIPTION SECTION

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 and intramuscular 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 C16H18N3NaO4S. 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 C8H10NNaO5S 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.

1.5 g of Ampicillin and Sulbactam for Injection, USP (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) parenteral contains approximately 115 mg (5 mEq) of sodium.

3 g of Ampicillin and Sulbactam for Injection, USP (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) parenteral contains approximately 230 mg (10 mEq) of sodium.

MICROBIOLOGY SECTION

MICROBIOLOGY

Ampicillin 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 organism studies have shown that sulbactam restores ampicillin activity against beta-lactamase producing strains. In 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 theINDICATIONS and USAGE section has not been documented.

**Gram-Positive Bacteria:**Staphylococcus 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 Bacteria:**Hemophilus 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).

**Anaerobes:**Clostridium 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 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.

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INDICATIONS & USAGE SECTION

INDICATIONS AND USAGE

Ampicillin and sulbactam for injection 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 (seePRECAUTIONS - Pediatric Use andCLINICAL 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 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 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 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.

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 and other antibacterial drugs, ampicillin and sulbactam for injection 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.

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CONTRAINDICATIONS SECTION

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 SECTION

WARNINGS

Hypersensitivity

Serious 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.

Hepatotoxicity

Hepatic 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 Reactions

Ampicillin and sulbactam for injection 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 for injection discontinued if lesions progress (seeCONTRAINDICATIONS andADVERSE REACTIONS sections).

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.

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ADVERSE REACTIONS SECTION

ADVERSE REACTIONS

Adult Patients: Ampicillin and sulbactam for injection is generally well tolerated. The following adverse reactions have been reported in clinical trials.

Local Adverse Reactions

Pain at IM injection site – 16%
Pain at IV injection site – 3%Thrombophlebitis – 3%Phlebitis – 1.2%

Systemic Adverse Reactions

The 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 Patients: Available 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 Changes

Adverse 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 Experience

In 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 Disorders: Hemolytic 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 Disorders: Abdominal pain, cholestatic hepatitis, cholestasis, hyperbilirubinemia, jaundice, abnormal hepatic function, melena, gastritis, stomatitis, dyspepsia, black “hairy” tongue, and Clostridium difficile associated diarrhea (seeCONTRAINDICATIONS andWARNINGS sections).

**General Disorders and Administration Site Conditions:**Injection site reaction

Immune System Disorders:Serious and fatal hypersensitivity (anaphylactic) reactions (seeWARNINGS section)

**Nervous System Disorders:**Convulsion and dizziness

**Renal and Urinary Disorders:**Tubulointerstitial nephritis

**Respiratory, Thoracic and Mediastinal Disorders:**Dyspnea

Skin and Subcutaneous Tissue Disorders:Toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, Acute generalized exanthematous pustulosis (AGEP), erythema multiforme, exfoliative dermatitis, and urticaria (seeCONTRAINDICATIONS andWARNINGS sections).

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OVERDOSAGE SECTION

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.

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HOW SUPPLIED SECTION

HOW SUPPLIED

Ampicillin and Sulbactam for Injection, USP is supplied as follows:

Ampicillin and Sulbactam for Injection, USP powder should be stored at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature], prior to reconstitution.

Sterile, Nonpyrogenic, Preservative-free.
The container closure is not made with natural rubber latex.

To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx, LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.

Brands listed are the trademarks of their respective owners.

Manufactured for:
Northstar Rx LLC,
Memphis, TN 38141.
Toll-free: 1-800-206-7821

Manufactured by:
Istituto Biochimico Italiano Giovanni Lorenzini S.p.A.
Via Fossignano 2, 04011 Aprilia (LT), Italy
Issued November 2023

860613

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