Piperacillin and Tazobactam (Page 6 of 6)

12.4 Microbiology

Mechanism of Action

Piperacillin sodium exerts bactericidal activity by inhibiting septum formation and cell wall synthesis of susceptible bacteria. In 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.

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

16 HOW SUPPLIED/STORAGE AND HANDLING

Piperacillin and tazobactam for injection, USP are supplied as single-dose vials in the following sizes:

Each piperacillin and tazobactam for injection, USP 2.25 g vial provides piperacillin sodium equivalent to 2 grams of piperacillin and tazobactam sodium equivalent to 0.25 g of tazobactam. Each vial contains 4.87 mEq (112 mg) of sodium.

Supplied 10 per box — NDC 64679-034-01

Each piperacillin and tazobactam for injection, USP 3.375 g vial provides piperacillin sodium equivalent to 3 grams of piperacillin and tazobactam sodium equivalent to 0.375 g of tazobactam. Each vial contains 7.30 mEq (168 mg) of sodium.

Supplied 10 per box — NDC 64679-056-01

Each piperacillin and tazobactam for injection, USP 4.5 g vial provides piperacillin sodium equivalent to 4 grams of piperacillin and tazobactam sodium equivalent to 0.5 g of tazobactam. Each vial contains 9.74 mEq (224 mg) of sodium.

Supplied 10 per box — NDC 64679-012-01

Piperacillin and tazobactam for injection vials should be stored at controlled room temperature (20°C to 25°C [68°F to 77°F]) 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 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)].

Diarrhea

Advise patients, their families, or caregivers that diarrhea is a common problem caused by antibacterial drugs 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.

Antibacterial Resistance

Counsel patients 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.

Counsel patients that piperacillin and tazobactam for injection can cross the placenta in humans and is excreted in human milk.

This product’s labeling may have been updated. For the most recent prescribing information, please call at 1-800-346-6854.

Manufactured by:

Mitim S.r.l.

Via Cacciamali n°34-36-38

25125 Brescia (BS), Italy.

Distributed by:

Wockhardt USA LLC.

20 Waterview Blvd.

Parsippany, NJ 07054

USA.

Rev.020720

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

DRUG: Piperacillin and Tazobactam

GENERIC: Piperacillin and Tazobactam

DOSAGE: Injection

ADMINSTRATION: Intravenous

NDC: 64679-034-02

STRENGTH: 2.25 gram per vial

QTY: 2.25 gram Single Use Vial Label

Label 2.25 g
(click image for full-size original)

DRUG: Piperacillin and Tazobactam

GENERIC: Piperacillin and Tazobactam

DOSAGE: Injection

ADMINSTRATION: Intravenous

NDC: 64679-056-02

STRENGTH: 3.375 gram per vial

QTY: 3.375 gram Single Use Vial Label

Label -- 3.375 g

DRUG: Piperacillin and Tazobactam

GENERIC: Piperacillin and Tazobactam

DOSAGE: Injection

ADMINSTRATION: Intravenous

NDC: 64679-012-02

STRENGTH: 4.5 gram per vial

QTY: 4.5 gram Single Use Vial Label

Label-4.5 gLabel 2.25 gLabel — 3.375 gLabel-4.5 g
PIPERACILLIN AND TAZOBACTAM piperacillin sodium and tazobactam sodium injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:64679-034
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
PIPERACILLIN SODIUM (PIPERACILLIN ANHYDROUS) PIPERACILLIN ANHYDROUS 2 g in 10 mL
TAZOBACTAM SODIUM (TAZOBACTAM) TAZOBACTAM 0.25 g in 10 mL
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:64679-034-01 10 VIAL, SINGLE-USE in 1 CARTON contains a VIAL, SINGLE-USE (64679-034-02)
1 NDC:64679-034-02 10 mL in 1 VIAL, SINGLE-USE This package is contained within the CARTON (64679-034-01)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA206996 03/22/2017
PIPERACILLIN AND TAZOBACTAM piperacillin sodium and tazobactam sodium injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:64679-056
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
PIPERACILLIN SODIUM (PIPERACILLIN ANHYDROUS) PIPERACILLIN ANHYDROUS 3 g in 15 mL
TAZOBACTAM SODIUM (TAZOBACTAM) TAZOBACTAM 0.375 g in 15 mL
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:64679-056-01 10 VIAL, SINGLE-USE in 1 CARTON contains a VIAL, SINGLE-USE (64679-056-02)
1 NDC:64679-056-02 15 mL in 1 VIAL, SINGLE-USE This package is contained within the CARTON (64679-056-01)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA206996 03/22/2017
PIPERACILLIN AND TAZOBACTAM piperacillin sodium and tazobactam sodium injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:64679-012
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
PIPERACILLIN SODIUM (PIPERACILLIN ANHYDROUS) PIPERACILLIN ANHYDROUS 4 g in 20 mL
TAZOBACTAM SODIUM (TAZOBACTAM) TAZOBACTAM 0.5 g in 20 mL
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:64679-012-01 10 VIAL, SINGLE-USE in 1 CARTON contains a VIAL, SINGLE-USE (64679-012-02)
1 NDC:64679-012-02 20 mL in 1 VIAL, SINGLE-USE This package is contained within the CARTON (64679-012-01)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA206996 03/22/2017
Labeler — Wockhardt USA LLC. (170508365)
Registrant — Wockhardt Limited (650069115)
Establishment
Name Address ID/FEI Operations
Mitim S.r.l. 438137085 ANALYSIS (64679-034), ANALYSIS (64679-056), ANALYSIS (64679-012), LABEL (64679-034), LABEL (64679-056), LABEL (64679-012), MANUFACTURE (64679-034), MANUFACTURE (64679-056), MANUFACTURE (64679-012), PACK (64679-034), PACK (64679-056), PACK (64679-012)

Revised: 12/2020 Wockhardt USA LLC.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2021. All Rights Reserved.