Piperacillin and Tazobactam

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

The following clinically significant adverse reactions are described elsewhere in the labeling: • Hypersensitivity Adverse Reactions [see Warnings and Precautions (5.1)] • Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.2)] • Hemophagocytic Lymphohistiocytosis [see Warnings and Precautions (5.3)] • Rhabdomyolysis [see Warnings and Precautions (5.4)] • Hematologic Adverse Reactions [see Warnings and Precautions (5.5)] • Central Nervous System Adverse Reactions [see Warnings and Precautions (5.6)] • Nephrotoxicity in Critically Ill Patients [see Warnings and Precautions (5.7)] • Clostridioides difficile-Associated Diarrhea [see Warnings and Precautions (5.9)]

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

10 OVERDOSAGE

OVERDOSAGE SECTION

There have been postmarketing reports of overdose with piperacillin and tazobactam. The majority of those events experienced, including nausea, vomiting, and diarrhea, have also been reported with the usual recommended dosages. Patients may experience neuromuscular excitability or seizures if higher than recommended doses are given intravenously (particularly in the presence of renal failure) [ see Warnings and Precautions (5.6) ] . Treatment should be supportive and symptomatic according the patient's clinical presentation. Excessive serum concentrations of either piperacillin or tazobactam may be reduced by hemodialysis. Following a single 3.375 g dose of piperacillin and tazobactam, the percentage of the piperacillin and tazobactam dose removed by hemodialysis was approximately 31% and 39%, respectively [ see Clinical Pharmacology (12) ] .

11 DESCRIPTION

DESCRIPTION SECTION

Piperacillin and Tazobactam for Injection, USP is an injectable antibacterial combination product consisting of the semisynthetic antibacterial piperacillin sodium and the beta-lactamase inhibitor tazobactam sodium for intravenous administration. Piperacillin sodium is derived from D(-)-α-aminobenzyl-penicillin. The chemical name of piperacillin sodium is sodium (2 S ,5 R ,6 R )-6-[( R )-2-(4-ethyl-2,3-dioxo-1-piperazine-carboxamido)-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate. The chemical formula is C 23 H 26 N 5 NaO 7 S and the molecular weight is 539.5. The chemical structure of piperacillin sodium is: Tazobactam sodium, a derivative of the penicillin nucleus, is a penicillanic acid sulfone. Its chemical name is sodium (2 S ,3 S ,5 R )-3-methyl-7-oxo-3-(1 H -1,2,3-triazol-1-ylmethyl)-4-thia-1-azabicyclo[3.2.0] heptane-2-carboxylate-4,4-dioxide. The chemical formula is C 10 H 11 N 4 NaO 5 S and the molecular weight is 322.3. The chemical structure of tazobactam sodium is: Piperacillin and Tazobactam for Injection, USP contains a total of 2.35 mEq (54 mg) of sodium (Na + ) per gram of piperacillin in the combination product. Piperacillin and Tazobactam for Injection, USP is a white to off white sterile powder consisting of piperacillin and tazobactam as their sodium salts packaged in glass vials. The product does not contain excipients or preservatives. Each Piperacillin and Tazobactam for Injection, USP 2.25 g single dose vial contains an amount of drug sufficient for withdrawal of piperacillin sodium equivalent to 2 grams of piperacillin and tazobactam sodium equivalent to 0.25 g of tazobactam. Each Piperacillin and Tazobactam for Injection, USP 3.375 g single dose vial contains an amount of drug sufficient for withdrawal of piperacillin sodium equivalent to 3 grams of piperacillin and tazobactam sodium equivalent to 0.375 g of tazobactam. Each Piperacillin and Tazobactam for Injection, USP 4.5 g single dose vial contains an amount of drug sufficient for withdrawal of piperacillin sodium equivalent to 4 grams of piperacillin and tazobactam sodium equivalent to 0.5 g of tazobactam. Meets USP Organic Impurities Procedure 3.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

15 REFERENCES

REFERENCES SECTION

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

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

Piperacillin and Tazobactam for Injection, USP is supplied as white or almost-white sterile powder in single-dose vials in the following sizes: 4.5 g (piperacillin sodium equivalent to 4 grams piperacillin and tazobactam sodium equivalent to 0.5g tazobactam). Each vial contains has 9.39 mEq (216 mg) of sodium. Supplied 10 per box — NDC 72485-404-10 Piperacillin and Tazobactam for Injection, USP vials should be stored at controlled room temperature (20° to 25°C [68° to 77°F]) prior to reconstitution.

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

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 for Injection 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 for Injection 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 (5.9)]. 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 for Injection can cross the placenta in humans and is excreted in human milk [see Use in Specific Populations (8.1, 8.2)]. Manufactured by: STERISCIENCE SPECIALTIES PRIVATE LIMITED Beta Lactam Division, Bangalore India Distributed by: Armas Pharmaceuticals, Inc. Freehold, NJ 07728 (USA) Rev. 09/2024

Package label 4.5g/vial

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL