Piperacillin, Tazobactam

RECENT MAJOR CHANGES SECTION

RECENT MAJOR CHANGES SECTION

Warnings and Precautions, Rhabdomyolysis ( 5.4 ) 8/2024

SPL UNCLASSIFIED SECTION

SPL UNCLASSIFIED SECTION

PHARMACY BULK PACKAGE – NOT FOR DIRECT INFUSION

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

Piperacillin and Tazobactam for Injection, USP is a white to off-white powder in pharmacy bulk package bottles: 40.5 gram pharmacy bulk bottle (piperacillin sodium equivalent to 36 grams of piperacillin and tazobactam sodium equivalent to 4.5 grams of tazobactam).

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

Piperacillin and tazobactam is contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins, or beta-lactamase inhibitors.

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 to the patient's clinical presentation. Excessive serum concentrations of either piperacillin or tazobactam may be reduced by hemodialysis. Following a single 3.375 gram 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, is a white to off-white sterile, cryodesiccated powder consisting of piperacillin and tazobactam as their sodium salts packaged in glass bottles. Each Piperacillin and Tazobactam for Injection, USP 40.5 gram pharmacy bulk package bottle contains piperacillin sodium equivalent to 36 grams of piperacillin and tazobactam sodium equivalent to 4.5 grams of tazobactam sufficient for delivery of multiple doses. 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. Meets the USP Organic Impurities modified Test Procedure 1.

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 in a Pharmacy Bulk Package as follows: Piperacillin and Tazobactam NDC for Injection, USP Package Factor 25021-181-99 Each 40.5 gram bottle provides piperacillin sodium equivalent to 36 grams of piperacillin and tazobactam sodium equivalent to 4.5 grams of tazobactam. Each bottle contains 84.6 mEq (1,944 mg) of sodium. 1 bottle per carton

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Bottle Label

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 25021-181-99 Rx only Piperacillin and Tazobactam for Injection, USP 40.5 grams per Pharmacy Bulk Package PHARMACY BULK PACKAGE NOT FOR DIRECT INFUSION RECONSTITUTED STOCK SOLUTION MUST BE TRANSFERRED AND FURTHER DILUTED FOR INTRAVENOUS INFUSION