Piperacillin Sodium And Tazobactam Sodium

FDA Drug Information • Also known as: Piperacillin And Tazobactam, Zosyn

Brand Names: Piperacillin And Tazobactam, Zosyn
Route: INTRAVENOUS
Dosage Form: INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

PHARMACY BULK PACKAGE – NOT FOR DIRECT INFUSION PHARMACY BULK PACKAGE – NOT FOR DIRECT INFUSION

Description

11 DESCRIPTION Piperacillin and Tazobactam for Injection 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-piperazinecarboxamido)-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 contains a total of 2.84 mEq (65 mg) of sodium (Na + ) per gram of piperacillin in the combination product. Piperacillin and Tazobactam for Injection is a white to off-white sterile powder consisting of piperacillin and tazobactam as their sodium salts packaged in a glass bottles. Each Piperacillin and Tazobactam for Injection 13.5 g pharmacy bulk bottle contains piperacillin sodium equivalent to 12 grams of piperacillin and tazobactam sodium equivalent to 1.5 g of tazobactam sufficient for delivery of multiple doses. Each Piperacillin and Tazobactam for Injection 40.5 g pharmacy bulk bottle contains piperacillin sodium equivalent to 36 grams of piperacillin and tazobactam sodium equivalent to 4.5 g of tazobactam sufficient for delivery of multiple doses. pip1 taz2

What Is Piperacillin Sodium And Tazobactam Sodium Used For?

1 INDICATIONS AND USAGE Piperacillin and tazobactam for injection is a combination of piperacillin, a penicillin-class antibacterial and tazobactam, a beta-lactamase inhibitor, indicated for treatment of: Intra-abdominal infections in adult and pediatric patients 2 months of age and older ( 1.1 ) Nosocomial pneumonia in adult and pediatric patients 2 months of age and older ( 1.2 ) Skin and skin structure infections in adults ( 1.3 ) Female pelvic infections in adults ( 1.4 ) Community-acquired pneumonia in adults ( 1.5 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of piperacillin and tazobactam for injection and other antibacterial drugs, piperacillin and tazobactam for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1.6 ) 1.1 Intra-abdominal Infections Piperacillin and tazobactam for injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of appendicitis (complicated by rupture or abscess) and peritonitis caused by beta-lactamase producing isolates of Escherichia coli or the following members of the Bacteroides fragilis group: B. fragilis , B. ovatus , B. thetaiotaomicron , or B. vulgatus . 1.2 Nosocomial Pneumonia Piperacillin and tazobactam for injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of nosocomial pneumonia (moderate to severe) caused by beta lactamase producing isolates of Staphylococcus aureus and by piperacillin/tazobactam-susceptible Acinetobacter baumannii , Haemophilus influenzae , Klebsiella pneumoniae , and Pseudomonas aeruginosa (Nosocomial pneumonia caused by P. aeruginosa should be treated in combination with an aminoglycoside) [see Dosage and Administration ( 2 )] . 1.3 Skin and Skin Structure Infections Piperacillin and tazobactam for injection is indicated in adults for the treatment of uncomplicated and complicated skin and skin structure infections, including cellulitis, cutaneous abscesses and ischemic/diabetic foot infections caused by beta-lactamase producing isolates of Staphylococcus aureus . 1.4 Female Pelvic Infections Piperacillin and tazobactam for injection is indicated in adults for the treatment of postpartum endometritis or pelvic inflammatory disease caused by beta-lactamase producing isolates of Escherichia coli . 1.5 Community-acquired Pneumonia Piperacillin and tazobactam for injection is indicated in adults for the treatment of community-acquired pneumonia (moderate severity only) caused by beta-lactamase producing isolates of Haemophilus influenzae . 1.6 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of piperacillin and tazobactam for injection and other antibacterial drugs, piperacillin and tazobactam for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. When culture...

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Adult Patients With Indications Other Than Nosocomial Pneumonia; The usual daily dosage of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12.0 g piperacillin/1.5 g tazobactam). ( 2.2 ) Adult Patients With Nosocomial Pneumonia: Initial presumptive treatment of patients with nosocomial pneumonia should start with piperacillin and tazobactam for injection at a dosage of 4.5 g every six hours plus an aminoglycoside, totaling 18.0 g (16.0 g piperacillin/2.0 g tazobactam). ( 2.3 ) Adult Patients With Renal Impairment: Dosage in patients with renal impairment (creatinine clearance ≤40 mL/min) and dialysis patients should be reduced, based on the degree of renal impairment. ( 2.4 ) Pediatric Patients by Indication and Age: See Table below ( 2.5 ) Recommended Dosage of Piperacillin and Tazobactam for Injection for Pediatric Patients 2 months of Age and Older,Weighing up to 40 Kg and With Normal Renal Function Age Appendicitis and/or Peritonitis Nosocomial Pneumonia 2 months to 9 months 90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 8 (eight) hours 90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 6 (six) hours Older than 9 months 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 8 (eight) hours 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 6 (six) hours Administer piperacillin and tazobactam for injection by intravenous infusion over 30 minutes to both adult and pediatric patients ( 2.2 , 2.3 , 2.4 , 2.5 ). Piperacillin and tazobactam for injection and aminoglycosides should be reconstituted, diluted, and administered separately. Co-administration via Y-site can be done under certain conditions. ( 2.8 ). See the full prescribing information for the preparation and administration instructions for piperacillin and tazobactam for injection pharmacy bulk bottles. 2.2 Dosage in Adult Patients With Indications Other Than Nosocomial Pneumonia The usual total daily dosage of piperacillin and tazobactam for injection for adult patients with indications other than nosocomial pneumonia is 3.375 g every six hours [totaling 13.5 g (12.0 g piperacillin/1.5 g tazobactam)], to be administered by intravenous infusion over 30 minutes. The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days. 2.3 Dosage in Adult Patients With Nosocomial Pneumonia Initial presumptive treatment of adult patients with nosocomial pneumonia should start with piperacillin and tazobactam for injection at a dosage of 4.5 g every six hours plus an aminoglycoside, [totaling 18.0 g (16.0 g piperacillin/2.0 g tazobactam)], administered by intravenous infusion over 30 minutes. The recommended duration of piperacillin and tazobactam for injection treatment for nosocomial pneumonia is 7 to 14 days. Treatment with the aminoglycoside should be continued in patients from whom P. aeruginosa is isolated. 2.4 Dosage in Adult Patients With Renal Impairment In adult...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS 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 )] The most common adverse reactions (incidence >5%) are diarrhea, constipation, nausea, headache, and insomnia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Provepharm Inc., at 1–833-727-6556 or [email protected] or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials in Adult Patients During the initial clinical investigations, 2621 patients worldwide were treated with piperacillin and tazobactam for injection in phase 3 trials. In the key North American monotherapy clinical trials (n=830 patients), 90% of the adverse events reported were mild to moderate in severity and transient in nature. However, in 3.2% of the patients treated worldwide, piperacillin and tazobactam for injection was discontinued because of adverse events primarily involving the skin (1.3%), including rash and pruritus; the gastrointestinal system (0.9%), including diarrhea, nausea, and vomiting; and allergic reactions (0.5%). Table 5: Adverse Reactions from Piperacillin and Tazobactam for Injection Monotherapy Clinical Trials System Organ Class Adverse Reaction Gastrointestinal disorders Diarrhea (11.3%) Constipation (7.7%) Nausea (6.9%) Vomiting (3.3%) Dyspepsia (3.3%) Abdominal pain (1.3%) General disorders and administration site conditions Fever (2.4%) Injection site reaction (≤1%) Rigors (≤1%) Immune system disorders Anaphylaxis (≤1%) Infections and infestations Candidiasis (1.6%) Pseudomembranous colitis (≤1%) Metabolism and nutrition disorders Hypoglycemia (≤1%) Musculoskeletal and connective tissue disorders Myalgia (≤1%) Arthralgia (≤1%) Nervous system disorders Headache (7.7%) Psychiatric disorders Insomnia (6.6%) Skin and subcutaneous tissue disorders Rash (4.2%, including maculopapular, bullous, and urticarial) Pruritus (3.1%) Purpura (≤1%) Vascular disorders Phlebitis (1.3%) Thrombophlebitis (≤1%) Hypotension (≤1%) Flushing (≤1%) Respiratory, thoracic and mediastinal disorders Epistaxis (≤1%) Nosocomial Pneumonia Trials Two trials of nosocomial lower respiratory tract infections were conducted. In one study, 222 patients were treated with piperacillin and tazobactam for injection in a dosing regimen of 4.5 g every 6 hours in combination with an aminoglycoside and 215 patients were treated with imipenem/cilastatin (500 mg/500 mg every 6 hours) in combination with an aminoglycoside. In this trial, treatment-emergent adverse events were reported by 402 patients, 204 (91.9%) in the piperacillin/tazobactam group and 198 (92.1%) in the imipenem/cilastatin group. Twenty-five (11.0%) patients in the piperacillin/tazobactam group and 14 (6.5%) in the imipenem/cilastatin group (p > 0.05) discontinued treatment due to an adverse event. The second trial used a dosing regimen of 3.375 g given every 4 hours with an aminoglycoside. Table 6: Adverse Reactions from Piperacillin and Tazobactam for Injection Plus Aminoglycoside Clinical Trials a a For adverse drug reactions that appeared in both studies the higher frequency is...

Drug Interactions

7 DRUG INTERACTIONS Piperacillin and tazobactam for injection administration can significantly reduce tobramycin concentrations in hemodialysis patients. Monitor tobramycin concentrations in these patients. ( 7.1 ) Probenecid prolongs the half-lives of piperacillin and tazobactam and should not be co-administered with piperacillin and tazobactam for injection unless the benefit outweighs the risk. ( 7.2 ) Co-administration of piperacillin and tazobactam for injection with vancomycin may increase the incidence of acute kidney injury. Monitor kidney function in patients receiving piperacillin and tazobactam for injection and vancomycin. ( 7.3 ) Monitor coagulation parameters in patients receiving piperacillin and tazobactam for injection and heparin or oral anticoagulants. ( 7.4 ) Piperacillin and tazobactam for injection may prolong the neuromuscular blockade of vecuronium and other non-depolarizing neuromuscular blockers. Monitor for adverse reactions related to neuromuscular blockade. ( 7.5 ) 7.1 Aminoglycosides Piperacillin may inactivate aminoglycosides by converting them to microbiologically inert amides. In vivo inactivation: When aminoglycosides are administered in conjunction with piperacillin to patients with end-stage renal disease requiring hemodialysis, the concentrations of the aminoglycosides (especially tobramycin) may be significantly reduced and should be monitored. Sequential administration of piperacillin and tazobactam for injection and tobramycin to patients with either normal renal function or mild to moderate renal impairment has been shown to modestly decrease serum concentrations of tobramycin but no dosage adjustment is considered necessary. In vitro inactivation: Due to the in vitro inactivation of aminoglycosides by piperacillin, piperacillin and tazobactam for injection and aminoglycosides are recommended for separate administration. Piperacillin and tazobactam for injection and aminoglycosides should be reconstituted, diluted, and administered separately when concomitant therapy with aminoglycosides is indicated. Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous Y-site infusion [ see Dosage and Administration ( 2.8 ) ] . 7.2 Probenecid Probenecid administered concomitantly with piperacillin and tazobactam for injection prolongs the half-life of piperacillin by 21% and that of tazobactam by 71% because probenecid inhibits tubular renal secretion of both piperacillin and tazobactam. Probenecid should not be co-administered with piperacillin and tazobactam for injection unless the benefit outweighs the risk. 7.3 Vancomycin Studies have detected an increased incidence of acute kidney injury in patients concomitantly administered piperacillin/tazobactam and vancomycin as compared to vancomycin alone [ see Warnings and Precautions ( 5.7 ) ] . Monitor kidney function in patients concomitantly administered with piperacillin/tazobactam and vancomycin. No pharmacokinetic interactions...

Contraindications

4 CONTRAINDICATIONS Piperacillin and tazobactam for injection is contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins, or beta-lactamase inhibitors. Patients with a history of allergic reactions to any of the penicillins, cephalosporins, or beta-lactamase inhibitors. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Piperacillin and tazobactam cross the placenta in humans. However, there are insufficient data with piperacillin and/or tazobactam in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. No fetal structural abnormalities were observed in rats or mice when piperacillin/tazobactam was administered intravenously during organogenesis at doses 1 to 2 times and 2 to 3 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area (mg/m 2 ). However, fetotoxicity in the presence of maternal toxicity was observed in developmental toxicity and peri/postnatal studies conducted in rats (intraperitoneal administration prior to mating and throughout gestation or from gestation day 17 through lactation day 21) at doses less than the maximum recommended human daily dose based on body-surface area (mg/m 2 ) [ see Data ]. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In embryo-fetal development studies in mice and rats, pregnant animals received intravenous doses of piperacillin/tazobactam up to 3000/750 mg/kg/day during the period of organogenesis. There was no evidence of teratogenicity up to the highest dose evaluated, which is 1 to 2 times and 2 to 3 times the human dose of piperacillin and tazobactam, in mice and rats respectively, based on body-surface area (mg/m 2 ). Fetal body weights were reduced in rats at maternally toxic doses at or above 500/62.5 mg/kg/day, minimally representing 0.4 times the human dose of both piperacillin and tazobactam based on body-surface area (mg/m 2 ). A fertility and general reproduction study in rats using intraperitoneal administration of tazobactam or the combination piperacillin/tazobactam prior to mating and...

Overdosage

10 OVERDOSAGE There have been postmarketing reports of overdose with piperacillin/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 ( 5.5 ) ] . 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/tazobactam, the percentage of the piperacillin and tazobactam dose removed by hemodialysis was approximately 31% and 39%, respectively [see Clinical Pharmacology ( 12 )] .

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Piperacillin and Tazobactam for Injection, USP are supplied as pharmacy bulk bottles in the following size: Each Piperacillin and Tazobactam for Injection, USP 13.5 g pharmacy bulk bottle provides piperacillin sodium equivalent to 12 grams of piperacillin and tazobactam sodium equivalent to 1.5 g tazobactam. Each bottle contains 29.16 mEq (672 mg) of sodium. Supplied as singles-NDC 81284-154-01 or 10 per box-NDC 81284-154-10. Each Piperacillin and Tazobactam for Injection, USP 40.5 g pharmacy bulk bottle provides piperacillin sodium equivalent to 36 grams of piperacillin and tazobactam sodium equivalent to 4.5 grams of tazobactam. Each pharmacy bulk bottle contains 87.48 mEq (2016 mg) of sodium. NDC 81284-155-01. Piperacillin and Tazobactam for Injection, USP pharmacy bulk bottles should be stored at controlled room temperature (20°C to 25°C [68°F to 77°F]) prior to reconstitution.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.