Piperacillin and Tazobactam: Package Insert and Label Information (Page 5 of 5)

12.4 Microbiology

Mechanism of Action

Piperacillin sodium exerts bactericidal activity by inhibiting septum formation and cell wall synthesis of susceptible bacteria. I n vitro , piperacillin is active against a variety of gram-positive and gram-negative aerobic and anaerobic bacteria. Tazobactam sodium has little clinically relevant in vitro activity against bacteria due to its reduced affinity to penicillin-binding proteins. It is, however, a beta-lactamase inhibitor of the Molecular class A enzymes, including Richmond- Sykes class III (Bush class 2b & 2b’) penicillinases and cephalosporinases. It varies in its ability to inhibit class II and IV (2a & 4) penicillinases. Tazobactam does not induce chromosomally-mediated beta-lactamases at tazobactam concentrations achieved with the recommended dosage regimen.

Antimicrobial Activity

Piperacillin/tazobactam has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections [see Indications and Usage (1)].

Aerobic Bacteria

Gram-positive bacteria

Staphylococcus aureus (methicillin susceptible isolates only)

Gram-negative bacteria

Acinetobacter baumannii

Escherichia coli

Haemophilus influenzae (excluding beta-lactamase negative, ampicillin-resistant isolates)

Klebsiella pneumoniae

Pseudomonas aeruginosa (given in combination with an aminoglycoside to which the isolate is susceptible)

Anaerobic Bacteria

Bacteroides fragilis group (B. fragilis, B. ovatus, B. thetaiotaomicron, and B. vulgatus)

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for piperacillin/tazobactam against isolates of similar genus or organism group. However, the efficacy of piperacillin/tazobactam in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials.

Aerobic Bacteria

Gram-positive bacteria

Enterococcus faecalis (ampicillin or penicillin-susceptible isolates only)

Staphylococcus epidermidis (methicillin susceptible isolates only)

Streptococcus agalactiae

Streptococcus pneumoniae (penicillin-susceptible isolates only)

Streptococcus pyogenes

Viridans group streptococci

Gram-negative bacteria

Citrobacter koseri

Moraxella catarrhalis

Morganella morganii

Neisseria gonorrhoeae

Proteus mirabilis

Proteus vulgaris

Serratia marcescens

Providencia stuartii

Providencia rettgeri

Salmonella enterica

Anaerobic Bacteria

Clostridium perfringens

Bacteroides distasonis

Prevotella melaninogenica

† These are not beta-lactamase producing bacteria and, therefore, are susceptible to piperacillin 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.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term carcinogenicity studies in animals have not been conducted with piperacillin/tazobactam, piperacillin, or tazobactam.

Mutagenesis

Piperacillin/tazobactam was negative in microbial mutagenicity assays, the unscheduled DNA synthesis (UDS) test, a mammalian point mutation (Chinese hamster ovary cell HPRT) assay, and a mammalian cell (BALB/c-3T3) transformation assay. In vivo , piperacillin/tazobactam did not induce chromosomal aberrations in rats.

Fertility

Reproduction studies have been performed in rats and have revealed no evidence of impaired fertility when piperacillin/tazobactam is administered intravenously up to a dose of 1280/320 mg/kg piperacillin/tazobactam, which is similar to the maximum recommended human daily dose based on body-surface area (mg/m2).

15 REFERENCES

1.
Jensen J-US, Hein L, Lundgren B, et al. BMJ Open 2012; 2:e000635. doi:10.1136.

16 HOW SUPPLIED/STORAGE AND HANDLING

Piperacillin and tazobactam for injection, USP is supplied as a powder in the pharmacy bulk bottle as follows:

Piperacillin and tazobactam for injection, USP 13.5 g pharmacy bulk bottle containing piperacillin sodium equivalent to 12 grams of piperacillin, tazobactam sodium equivalent to 1.5 grams tazobactam and 28.2 mEq (648 mg) of sodium.

Supplied as 1 pharmacy bulk package bottle per box – NDC 0409-2999-14

Piperacillin and tazobactam for injection, USP pharmacy bulk bottles should be stored at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature] prior to reconstitution.

17 PATIENT COUNSELING INFORMATION

Serious Hypersensitivity Reactions

Advise patients, their families, or caregivers that serious hypersensitivity reactions, including serious allergic cutaneous reactions, could occur with use of piperacillin and tazobactam that require immediate treatment. Ask them about any previous hypersensitivity reactions to piperacillin and tazobactam for injection, other beta-lactams (including cephalosporins), or other allergens [see Warnings and Precautions (5.2)].

Hemophagocytic Lymphohistiocytosis

Prior to initiation of treatment with piperacillin and tazobactam for injection, inform patients that excessive immune activation may occur with piperacillin and tazobactam for injection and that they should report signs or symptoms such as fever, rash, or lymphadenopathy to a healthcare provider immediately [see Warnings and Precautions (5.3)].

Diarrhea

Advise patients, their families, or caregivers that diarrhea is a common problem caused by antibacterial drugs, including piperacillin and tazobactam which usually ends when the drug is discontinued. Sometimes after starting treatment with antibacterial drugs, 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 drug. If this occurs, patients should contact their physician as soon as possible [see Warnings and Precautions ( 5.8)].

Antibacterial Resistance

Patients should be counseled that antibacterial drugs including piperacillin and tazobactam for injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When piperacillin and tazobactam 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 piperacillin and tazobactam for injection or other antibacterial drugs in the future.

Pregnancy and Lactation

Patients should be counseled that piperacillin and tazobactam can cross the placenta in humans and is excreted in human milk [see Use in Specific Populations (8.1, 8.2)].

CLINITEST® is a registered trademark of Siemens Healthcare Diagnostics Inc.

Manufactured by Sandoz GmbH for Hospira, Inc.

Lake Forest, IL 60045, USA.

46303068

13.5 grams Carton

carton
(click image for full-size original)

NDC 0409-2999-14

Piperacillin and

Tazobactam for

Injection, USP

13.5 grams per Pharmacy Bulk Package

PHARMACY BULK PACKAGE –

NOT FOR DIRECT INFUSION

Rx Only

RECONSTITUTED STOCK

SOLUTION MUST BE

TRANSFERRED AND FURTHER

DILUTED FOR I.V. INFUSION

1 Bottle

Hospira

PIPERACILLIN AND TAZOBACTAM piperacillin and tazobactam injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0409-2999
Route of Administration INTRAVENOUS, PARENTERAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
PIPERACILLIN SODIUM (PIPERACILLIN ANHYDROUS) PIPERACILLIN ANHYDROUS 12 g in 60 mL
TAZOBACTAM SODIUM (TAZOBACTAM) TAZOBACTAM 1.5 g in 60 mL
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0409-2999-14 1 VIAL, PHARMACY BULK PACKAGE in 1 CARTON contains a VIAL, PHARMACY BULK PACKAGE
1 60 mL in 1 VIAL, PHARMACY BULK PACKAGE This package is contained within the CARTON (0409-2999-14)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA203557 12/14/2016
Labeler — Hospira, Inc (141588017)

Revised: 05/2022 Hospira, Inc

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