Piperacillin And Tazobactam

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose 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).  The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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).  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.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment.  The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

Table 1:  Recommended Dosing of Piperacillin and Tazobactam for Injection in Patients with Normal Renal Function and Renal Impairment (As total grams piperacillin/tazobactam)

Renal Function

(creatinine clearance,

All Indications

Nosocomial

mL/min)

(except nosocomial pneumonia)

Pneumonia

>40 mL/min

3.375 q6h

4.5 q6h

20-40 mL/min*

2.25 q6h

3.375 q6h

<20 mL/min*

2.25 q8h

2.25 q6h

Hemodialysis**

2.25 q12h

2.25 q8h

CAPD

2.25 q12h

2.25 q8h

*Creatinine clearance for patients not receiving hemodialysis
**0.75 g (0.67 g piperacillin/0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis days

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia.  Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days.  No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours.  For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)].  Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.  It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Single Dose Vials

Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.

2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively.  Swirl until dissolved.

Compatible Reconstitution Diluents for Single Dose Vials
0.9% Sodium chloride for injection
Sterile water for injection‡
Dextrose 5%
Bacteriostatic saline/parabens
Bacteriostatic water/parabens
Bacteriostatic saline/benzyl alcohol
Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solution should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below.  Administer by infusion over a period of at least 30 minutes.  During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Solutions for Single Dose Vials
0.9% Sodium chloride for injection
Sterile water for injection‡
Dextran 6% in saline
Dextrose 5%

LACTATED RINGER’S SOLUTION IS NOT COMPATIBILE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.
‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates.

Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection reconstituted from single vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.  Discard unused portions after storage for 24 hours at room temperature or after storage for 48 hours at refrigerated temperature 2°C to 8°C (36°F to 46°F).

Single dose vials should be used immediately after reconstitution.  Discard any unused portion after 24 hours if stored at room temperature 20°C to 25°C (68°F to 77°F), or after 48 hours if stored at refrigerated temperature 2°C to 8°C (36°F to 46°F).  Vials should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature.  Piperacillin and tazobactam for injection contains no preservatives.  Appropriate consideration of aseptic technique should be used.

Piperacillin and tazobactam for injection reconstituted from single vials can be used in ambulatory intravenous infusion pumps.  Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature.  Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL.  One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge).  The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions.  Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam for injection is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:

Table 2: Compatibility with Aminoglycosides

Aminoglycoside

Piperacillin and Tazobactam
Dose
(grams)

Piperacillin and Tazobactam Diluent Volume (mL)

Aminoglycoside Concentration Range a
(mg/mL)

Acceptable Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 – 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25, 3.375, 4.5

50, 100 150

0.7 – 3.32

0.9% sodium chloride or 5% dextrose

aThe concentration ranges in Table 2 are based on administration of the aminoglycoside in divided doses (10-15 mg/kg/day in two daily doses for amikacin and 3-5 mg/kg/day in three daily doses for gentamicin).  Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with piperacillin and tazobactam has not been evaluated.  See package insert for each aminoglycoside for complete Dosage and Administration instructions.

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion.  Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion.  Compatibility of piperacillin and tazobactam with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose 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).  The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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).  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.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment.  The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

Table 1:  Recommended Dosing of Piperacillin and Tazobactam for Injection in Patients with Normal Renal Function and Renal Impairment (As total grams piperacillin/tazobactam)

Renal Function

(creatinine clearance,

All Indications

Nosocomial

mL/min)

(except nosocomial pneumonia)

Pneumonia

>40 mL/min

3.375 q6h

4.5 q6h

20-40 mL/min*

2.25 q6h

3.375 q6h

<20 mL/min*

2.25 q8h

2.25 q6h

Hemodialysis**

2.25 q12h

2.25 q8h

CAPD

2.25 q12h

2.25 q8h

*Creatinine clearance for patients not receiving hemodialysis
**0.75 g (0.67 g piperacillin/0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis days

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia.  Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days.  No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours.  For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)].  Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.  It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Pharmacy Bulk Package Bottles

Reconstituted stock solution must be transferred and further diluted for intravenous infusion.

The pharmacy bulk package bottle is for use in a hospital pharmacy admixture service only under a laminar flow hood.  After reconstitution, entry into the vial must be made with a sterile transfer set or other sterile dispensing device, and contents should be dispensed as aliquots into intravenous solution using aseptic technique.  Use entire contents of pharmacy bulk package bottle promptly.  Discard unused portion after 24 hours if stored at room temperature 20°C to 25°C (68°F to 77°F), or after 48 hours if stored at refrigerated temperature 2°C to 8°C (36°F to 46°F).

Reconstitute the pharmacy bulk package bottle with exactly 152 mL of a compatible reconstitution diluent, listed below, to a concentration of 200 mg/mL of piperacillin and 25 mg/mL of tazobactam.  Shake well until dissolved.  Parenteral drug products should be inspected visually for particulate matter and discoloration prior to and during administration whenever solution and container permit.

Compatible Reconstitution Diluents for Pharmacy Bulk Bottles
0.9% Sodium chloride for injection
Sterile water for injection‡
Dextrose 5%
Bacteriostatic saline/parabens
Bacteriostatic water/parabens
Bacteriostatic saline/benzyl alcohol
Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solution should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below.  Administer by infusion over a period of at least 30 minutes.  During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Solutions for Pharmacy Bulk Package Bottles and Single Dose Vials
0.9% Sodium chloride for injection
Sterile water for injection‡
Dextran 6% in saline
Dextrose 5%

LACTATED RINGER’S SOLUTION IS NOT COMPATIBILE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.

‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates.

Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection reconstituted from pharmacy bulk package bottles is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.  The pharmacy bulk package bottle should NOT be frozen after reconstitution.  Discard unused portions after storage for 24 hours at room temperature or after storage for 48 hours at refrigerated temperature 2°C to 8°C (36°F to 46°F).

Pharmacy bulk package bottles should be used immediately after reconstitution.  Discard any unused portion after 24 hours if stored at room temperature 20°C to 25°C (68°F to 77°F),  or after 48 hours if stored at refrigerated temperature 2°C to 8°C (36°F to 46°F).  Pharmacy bulk package bottles should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature.  Piperacillin and tazobactam for injection contains no preservatives.  Appropriate consideration of aseptic technique should be used.

Piperacillin and tazobactam for injection reconstituted from bulk package bottles can be used in ambulatory intravenous infusion pumps.  Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature.  Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL.  One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge).  The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions.  Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:

Table 2: Compatibility with Aminoglycosides

Aminoglycoside

Piperacillin and Tazobactam
Dose
(grams)

Piperacillin and Tazobactam Diluent Volume (mL)

Aminoglycoside Concentration Rangea
(mg/mL)

Acceptable Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 – 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25, 3.375, 4.5

50, 100 150

0.7 – 3.32

0.9% sodium chloride or 5% dextrose

aThe concentration ranges in Table 2 are based on administration of the aminoglycoside in divided doses (10-15 mg/kg/day in two daily doses for amikacin and 3-5 mg/kg/day in three daily doses for gentamicin).  Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with piperacillin and tazobactam has not been evaluated.  See package insert for each aminoglycoside for complete Dosage and Administration instructions.

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion.  Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam.

Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion.  Compatibility of piperacillin and tazobactam with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose 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).  The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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).  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.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment.  The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

Table 1:  Recommended Dosing of Piperacillin and Tazobactam for Injection in Patients with Normal Renal Function and Renal Impairment (As total grams piperacillin/tazobactam)

Renal Function

(creatinine clearance,

All Indications

Nosocomial

mL/min)

(except nosocomial pneumonia)

Pneumonia

>40 mL/min

3.375 q6h

4.5 q6h

20-40 mL/min*

2.25 q6h

3.375 q6h

<20 mL/min*

2.25 q8h

2.25 q6h

Hemodialysis**

2.25 q12h

2.25 q8h

CAPD

2.25 q12h

2.25 q8h

*Creatinine clearance for patients not receiving hemodialysis
**0.75 g (0.67 g piperacillin/0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis days

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia.  Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days.  No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours.  For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)].  Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.  It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Pharmacy Bulk Package Bottles

Reconstituted stock solution must be transferred and further diluted for intravenous infusion.

The pharmacy bulk package bottle is for use in a hospital pharmacy admixture service only under a laminar flow hood.  After reconstitution, entry into the vial must be made with a sterile transfer set or other sterile dispensing device, and contents should be dispensed as aliquots into intravenous solution using aseptic technique.  Use entire contents of pharmacy bulk package bottle promptly.  Discard unused portion after 24 hours if stored at room temperature 20°C to 25°C (68°F to 77°F), or after 48 hours if stored at refrigerated temperature 2°C to 8°C (36°F to 46°F).

Reconstitute the pharmacy bulk package bottle with exactly 152 mL of a compatible reconstitution diluent, listed below, to a concentration of 200 mg/mL of piperacillin and 25 mg/mL of tazobactam.  Shake well until dissolved.  Parenteral drug products should be inspected visually for particulate matter and discoloration prior to and during administration whenever solution and container permit.

Compatible Reconstitution Diluents for Pharmacy Bulk Bottles
0.9% Sodium chloride for injection
Sterile water for injection‡
Dextrose 5%
Bacteriostatic saline/parabens
Bacteriostatic water/parabens
Bacteriostatic saline/benzyl alcohol
Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solution should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below.  Administer by infusion over a period of at least 30 minutes.  During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Solutions for Pharmacy Bulk Package Bottles and Single Dose Vials
0.9% Sodium chloride for injection
Sterile water for injection‡
Dextran 6% in saline
Dextrose 5%

LACTATED RINGER’S SOLUTION IS NOT COMPATIBILE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.

‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates.

Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection reconstituted from pharmacy bulk package bottles is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.  The pharmacy bulk package bottle should NOT be frozen after reconstitution.  Discard unused portions after storage for 24 hours at room temperature or after storage for 48 hours at refrigerated temperature 2°C to 8°C (36°F to 46°F).

Pharmacy bulk package bottles should be used immediately after reconstitution.  Discard any unused portion after 24 hours if stored at room temperature 20°C to 25°C (68°F to 77°F),  or after 48 hours if stored at refrigerated temperature 2°C to 8°C (36°F to 46°F).  Pharmacy bulk package bottles should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature.  Piperacillin and tazobactam for injection contains no preservatives.  Appropriate consideration of aseptic technique should be used.

Piperacillin and tazobactam for injection reconstituted from bulk package bottles can be used in ambulatory intravenous infusion pumps.  Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature.  Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL.  One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge).  The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions.  Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:

Table 2: Compatibility with Aminoglycosides

Aminoglycoside

Piperacillin and Tazobactam
Dose
(grams)

Piperacillin and Tazobactam Diluent Volume (mL)

Aminoglycoside Concentration Rangea
(mg/mL)

Acceptable Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 – 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25, 3.375, 4.5

50, 100 150

0.7 – 3.32

0.9% sodium chloride or 5% dextrose

aThe concentration ranges in Table 2 are based on administration of the aminoglycoside in divided doses (10-15 mg/kg/day in two daily doses for amikacin and 3-5 mg/kg/day in three daily doses for gentamicin).  Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with piperacillin and tazobactam has not been evaluated.  See package insert for each aminoglycoside for complete Dosage and Administration instructions.

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion.  Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam.

Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion.  Compatibility of piperacillin and tazobactam with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Weeks 1 to 6

Weeks 7 to 9

Weeks 10 to 12

1 piece every

1 to 2 hours

1 piece every

2 to 4 hours

1 piece every

4 to 8 hours

adults and children 12 years and older

children under 12 years

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose 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).  The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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).  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.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment.  The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

Table 1:  Recommended Dosing of Piperacillin and Tazobactam for Injection in Patients with Normal Renal Function and Renal Impairment (As total grams piperacillin/tazobactam)

Renal Function

(creatinine clearance,

All Indications

Nosocomial

mL/min)

(except nosocomial pneumonia)

Pneumonia

>40 mL/min

3.375 q6h

4.5 q6h

20-40 mL/min*

2.25 q6h

3.375 q6h

<20 mL/min*

2.25 q8h

2.25 q6h

Hemodialysis**

2.25 q12h

2.25 q8h

CAPD

2.25 q12h

2.25 q8h

*Creatinine clearance for patients not receiving hemodialysis
**0.75 g (0.67 g piperacillin/0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis days

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia.  Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days.  No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours.  For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)].  Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.  It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Single Dose Vials

Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.

2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively.  Swirl until dissolved.

Compatible Reconstitution Diluents for Single Dose Vials
0.9% Sodium chloride for injection
Sterile water for injection‡
Dextrose 5%
Bacteriostatic saline/parabens
Bacteriostatic water/parabens
Bacteriostatic saline/benzyl alcohol
Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solution should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below.  Administer by infusion over a period of at least 30 minutes.  During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Solutions for Single Dose Vials
0.9% Sodium chloride for injection
Sterile water for injection‡
Dextran 6% in saline
Dextrose 5%

LACTATED RINGER’S SOLUTION IS NOT COMPATIBILE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.
‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates.

Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection reconstituted from single vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.  Discard unused portions after storage for 24 hours at room temperature or after storage for 48 hours at refrigerated temperature 2°C to 8°C (36°F to 46°F).

Single dose vials should be used immediately after reconstitution.  Discard any unused portion after 24 hours if stored at room temperature 20°C to 25°C (68°F to 77°F), or after 48 hours if stored at refrigerated temperature 2°C to 8°C (36°F to 46°F).  Vials should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature.  Piperacillin and tazobactam for injection contains no preservatives.  Appropriate consideration of aseptic technique should be used.

Piperacillin and tazobactam for injection reconstituted from single vials can be used in ambulatory intravenous infusion pumps.  Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature.  Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL.  One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge).  The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions.  Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam for injection is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:

Table 2: Compatibility with Aminoglycosides

Aminoglycoside

Piperacillin and Tazobactam
Dose
(grams)

Piperacillin and Tazobactam Diluent Volume (mL)

Aminoglycoside Concentration Range a
(mg/mL)

Acceptable Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 – 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25, 3.375, 4.5

50, 100 150

0.7 – 3.32

0.9% sodium chloride or 5% dextrose

aThe concentration ranges in Table 2 are based on administration of the aminoglycoside in divided doses (10-15 mg/kg/day in two daily doses for amikacin and 3-5 mg/kg/day in three daily doses for gentamicin).  Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with piperacillin and tazobactam has not been evaluated.  See package insert for each aminoglycoside for complete Dosage and Administration instructions.

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion.  Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion.  Compatibility of piperacillin and tazobactam with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose 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).  The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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).  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.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment.  The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

Table 1:  Recommended Dosing of Piperacillin and Tazobactam for Injection in Patients with Normal Renal Function and Renal Impairment (As total grams piperacillin/tazobactam)

Renal Function

(creatinine clearance,

All Indications

Nosocomial

mL/min)

(except nosocomial pneumonia)

Pneumonia

>40 mL/min

3.375 q6h

4.5 q6h

20-40 mL/min*

2.25 q6h

3.375 q6h

<20 mL/min*

2.25 q8h

2.25 q6h

Hemodialysis**

2.25 q12h

2.25 q8h

CAPD

2.25 q12h

2.25 q8h

*Creatinine clearance for patients not receiving hemodialysis
**0.75 g (0.67 g piperacillin/0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis days

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia.  Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days.  No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours.  For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)].  Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.  It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Pharmacy Bulk Package Bottles

Reconstituted stock solution must be transferred and further diluted for intravenous infusion.

The pharmacy bulk package bottle is for use in a hospital pharmacy admixture service only under a laminar flow hood.  After reconstitution, entry into the vial must be made with a sterile transfer set or other sterile dispensing device, and contents should be dispensed as aliquots into intravenous solution using aseptic technique.  Use entire contents of pharmacy bulk package bottle promptly.  Discard unused portion after 24 hours if stored at room temperature 20°C to 25°C (68°F to 77°F), or after 48 hours if stored at refrigerated temperature 2°C to 8°C (36°F to 46°F).

Reconstitute the pharmacy bulk package bottle with exactly 152 mL of a compatible reconstitution diluent, listed below, to a concentration of 200 mg/mL of piperacillin and 25 mg/mL of tazobactam.  Shake well until dissolved.  Parenteral drug products should be inspected visually for particulate matter and discoloration prior to and during administration whenever solution and container permit.

Compatible Reconstitution Diluents for Pharmacy Bulk Bottles
0.9% Sodium chloride for injection
Sterile water for injection‡
Dextrose 5%
Bacteriostatic saline/parabens
Bacteriostatic water/parabens
Bacteriostatic saline/benzyl alcohol
Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solution should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below.  Administer by infusion over a period of at least 30 minutes.  During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Solutions for Pharmacy Bulk Package Bottles and Single Dose Vials
0.9% Sodium chloride for injection
Sterile water for injection‡
Dextran 6% in saline
Dextrose 5%

LACTATED RINGER’S SOLUTION IS NOT COMPATIBILE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.

‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates.

Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection reconstituted from pharmacy bulk package bottles is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.  The pharmacy bulk package bottle should NOT be frozen after reconstitution.  Discard unused portions after storage for 24 hours at room temperature or after storage for 48 hours at refrigerated temperature 2°C to 8°C (36°F to 46°F).

Pharmacy bulk package bottles should be used immediately after reconstitution.  Discard any unused portion after 24 hours if stored at room temperature 20°C to 25°C (68°F to 77°F),  or after 48 hours if stored at refrigerated temperature 2°C to 8°C (36°F to 46°F).  Pharmacy bulk package bottles should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature.  Piperacillin and tazobactam for injection contains no preservatives.  Appropriate consideration of aseptic technique should be used.

Piperacillin and tazobactam for injection reconstituted from bulk package bottles can be used in ambulatory intravenous infusion pumps.  Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature.  Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL.  One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge).  The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions.  Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:

Table 2: Compatibility with Aminoglycosides

Aminoglycoside

Piperacillin and Tazobactam
Dose
(grams)

Piperacillin and Tazobactam Diluent Volume (mL)

Aminoglycoside Concentration Rangea
(mg/mL)

Acceptable Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 – 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25, 3.375, 4.5

50, 100 150

0.7 – 3.32

0.9% sodium chloride or 5% dextrose

aThe concentration ranges in Table 2 are based on administration of the aminoglycoside in divided doses (10-15 mg/kg/day in two daily doses for amikacin and 3-5 mg/kg/day in three daily doses for gentamicin).  Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with piperacillin and tazobactam has not been evaluated.  See package insert for each aminoglycoside for complete Dosage and Administration instructions.

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion.  Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam.

Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion.  Compatibility of piperacillin and tazobactam with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam).

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 g (16 g piperacillin/2 g tazobactam).  Treatment with the aminoglycoside should be continued in patients from whom Pseudomonas aeruginosa is isolated.  If Pseudomonas aeruginosa is not isolated, the aminoglycoside may be discontinued at the discretion of the treating physician.

Due to the in vitro inactivation of the aminoglycoside by beta-lactam antibiotics, piperacillin and tazobactam and the aminoglycoside are recommended for separate administration.  Piperacillin and tazobactam and the aminoglycoside should be reconstituted, diluted, and administered separately when concomitant therapy with aminoglycosides is indicated (see PRECAUTIONS, Drug Interactions).

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam is compatible for simultaneous co-administration via Y-site infusion only with the following aminoglycosides under the following conditions:

                                                                                              TABLE 4

Aminoglycoside

Piperacillin

and Tazobactam Dose (grams)

Piperacillin and Tazobactam Diluent Volume (mL)

Aminoglycoside Concentration Range* (mg/mL)

Acceptable Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 to 7.5

0.9%Sodium Chloride or 5% Dextrose

Gentamicin

2.25, 3.375, 4.5

100, 150

0.7 to 3.32

0.9% Sodium Chloride

*The concentration ranges in Table 4 are based on administration of the aminoglycoside in divided doses (10 to 15 mg/kg/day in two daily doses for amikacin and 3 to 5 mg/kg/day in three daily doses for gentamicin).  Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with piperacillin and tazobactam has not been evaluated.  See package insert for each aminoglycoside for complete dosage and administration instructions.

Piperacillin and tazobactam is not compatible with tobramycin for simultaneous co-administration via Y-site infusion.  Compatibility of piperacillin and tazobactam with other aminoglycosides has not been established.  Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam listed above have been established as compatible for co-administration via Y-site infusion.  Simultaneous co-administration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam.

In patients with renal insufficiency (Creatinine Clearance ≤ 40 mL/min), the intravenous dose of piperacillin and tazobactam for injection should be adjusted to the degree of actual renal function impairment.  In patients with nosocomial pneumonia receiving concomitant aminoglycoside therapy, the aminoglycoside dosage should be adjusted according to the recommendations of the manufacturer.  The recommended daily doses of piperacillin and tazobactam for injection for patients with renal insufficiency are as follows:

Recommended Dosing of Piperacillin and Tazobactam for injection in Patients with Normal Renal Function and Renal Insufficiency (As total grams piperacillin/tazobactam)

Renal Function

(Creatinine Clearance,

mL/min)

All Indications

(except nosocomial pneumonia)

Nosocomial Pneumonia

>40 mL/min

3.375 q 6 h

4.5 q 6 h

20 to 40 mL/min*

2.25 q 6 h

3.375 q 6 h

<20 mL/min*

2.25 q 8 h

2.25 q 6 h

Hemodialysis**

2.25 q 12 h

2.25 q 8 h

CAPD

2.25 q 12 h

2.25 q 8 h

* Creatinine clearance for patients not receiving hemodialysis

** 0.75 g should be administered following each hemodialysis session on hemodialysis days

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia.  Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection should be administered following each dialysis period on hemodialysis days.  No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

The usual duration of piperacillin and tazobactam for injection treatment is from seven to ten days.  However, the recommended duration of piperacillin and tazobactam for injection treatment of nosocomial pneumonia is 7 to 14 days.  In all conditions, the duration of therapy should be guided by the severity of the infection and the patient's clinical and bacteriological progress.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours (see PRECAUTIONS, General, Pediatric Use and CLINICAL PHARMACOLOGY).  Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.  There are no dosage recommendations for piperacillin and tazobactam for injection in pediatric patients with impaired renal function.

Intravenous Administration

For conventional vials, reconstitute piperacillin and tazobactam for injection per gram of piperacillin with 5 mL of a compatible reconstitution diluent from the list provided below.

2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively.  Swirl until dissolved.

Pharmacy vials should be used immediately after reconstitution.  Discard any unused portion after 24 hours if stored at room temperature 20° to 25°C (68° to 77°F), or after 48 hours if stored at refrigerated temperature 2° to 8°C (36° to 46°F).

Compatible Reconstitution Diluents

0.9% Sodium Chloride for Injection

Sterile Water for Injection‡

Dextrose 5%

Bacteriostatic Saline/Parabens

Bacteriostatic Water/Parabens

Bacteriostatic Saline/Benzyl Alcohol

Bacteriostatic Water/Benzyl Alcohol

Reconstituted piperacillin and tazobactam for injection solution should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous diluent solution listed below.  Administer by infusion over a period of at least 30 minutes.  During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Diluent Solutions

0.9% Sodium Chloride for Injection

Sterile Water for Injection‡

Dextrose 5%

Dextran 6% in Saline

LACTATED RINGER’S SOLUTION IS NOT COMPATIBLE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.

‡ Maximum recommended volume per dose of Sterile Water for Injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates.

Piperacillin and tazobactam for injection can be used in ambulatory intravenous infusion pumps.

Stability of Piperacillin and Tazobactam for Injection Following Reconstitution

Piperacillin and tazobactam for injection is stable in glass and plastic containers (plastic syringes, IV bags and tubing) when used with compatible diluents.

Pharmacy vials should be used immediately after reconstitution.  Discard any unused portion after 24 hours if stored at room temperature 20° to 25°C (68° to 77°F), or after 48 hours if stored at refrigerated temperature 2° to 8°C (36° to 46°F).  Vials should not be frozen after reconstitution.

Stability studies in the IV bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature.  Piperacillin and tazobactam for injection contains no preservatives.  Appropriate consideration of aseptic technique should be used.

Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature.  Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL.  One-day supplies of dosing solution were aseptically transferred into the medication reservoir (IV bags or cartridge).  The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer’s instructions.  Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

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 g (16 g piperacillin/2 g tazobactam).  Treatment with the aminoglycoside should be continued in patients from whom Pseudomonas aeruginosa is isolated.  If Pseudomonas aeruginosa is not isolated, the aminoglycoside may be discontinued at the discretion of the treating physician.

Due to the in vitro inactivation of the aminoglycoside by beta-lactam antibiotics, piperacillin and tazobactam and the aminoglycoside are recommended for separate administration.  Piperacillin and tazobactam and the aminoglycoside should be reconstituted, diluted, and administered separately when concomitant therapy with aminoglycosides is indicated (see PRECAUTIONS, Drug Interactions).

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam is compatible for simultaneous co-administration via Y-site infusion only with the following aminoglycosides under the following conditions:

                                                                                              TABLE 4

Aminoglycoside

Piperacillin

and Tazobactam Dose (grams)

Piperacillin and Tazobactam Diluent Volume (mL)

Aminoglycoside Concentration Range* (mg/mL)

Acceptable Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 to 7.5

0.9%Sodium Chloride or 5% Dextrose

Gentamicin

2.25, 3.375, 4.5

100, 150

0.7 to 3.32

0.9% Sodium Chloride

*The concentration ranges in Table 4 are based on administration of the aminoglycoside in divided doses (10 to 15 mg/kg/day in two daily doses for amikacin and 3 to 5 mg/kg/day in three daily doses for gentamicin).  Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with piperacillin and tazobactam has not been evaluated.  See package insert for each aminoglycoside for complete dosage and administration instructions.

Piperacillin and tazobactam is not compatible with tobramycin for simultaneous co-administration via Y-site infusion.  Compatibility of piperacillin and tazobactam with other aminoglycosides has not been established.  Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam listed above have been established as compatible for co-administration via Y-site infusion.  Simultaneous co-administration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam.

In patients with renal insufficiency (Creatinine Clearance ≤ 40 mL/min), the intravenous dose of piperacillin and tazobactam for injection should be adjusted to the degree of actual renal function impairment.  In patients with nosocomial pneumonia receiving concomitant aminoglycoside therapy, the aminoglycoside dosage should be adjusted according to the recommendations of the manufacturer.  The recommended daily doses of piperacillin and tazobactam for injection for patients with renal insufficiency are as follows:

Recommended Dosing of Piperacillin and Tazobactam for injection in Patients with Normal Renal Function and Renal Insufficiency (As total grams piperacillin/tazobactam)

Renal Function

(Creatinine Clearance,

mL/min)

All Indications

(except nosocomial pneumonia)

Nosocomial Pneumonia

>40 mL/min

3.375 q 6 h

4.5 q 6 h

20 to 40 mL/min*

2.25 q 6 h

3.375 q 6 h

<20 mL/min*

2.25 q 8 h

2.25 q 6 h

Hemodialysis**

2.25 q 12 h

2.25 q 8 h

CAPD

2.25 q 12 h

2.25 q 8 h

* Creatinine clearance for patients not receiving hemodialysis

** 0.75 g should be administered following each hemodialysis session on hemodialysis days

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia.  Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection should be administered following each dialysis period on hemodialysis days.  No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

The usual duration of piperacillin and tazobactam for injection treatment is from seven to ten days.  However, the recommended duration of piperacillin and tazobactam for injection treatment of nosocomial pneumonia is 7 to 14 days.  In all conditions, the duration of therapy should be guided by the severity of the infection and the patient's clinical and bacteriological progress.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours (see PRECAUTIONS, General, Pediatric Use and CLINICAL PHARMACOLOGY).  Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.  There are no dosage recommendations for piperacillin and tazobactam for injection in pediatric patients with impaired renal function.

Intravenous Administration

For conventional vials, reconstitute piperacillin and tazobactam for injection per gram of piperacillin with 5 mL of a compatible reconstitution diluent from the list provided below.

2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively.  Swirl until dissolved.

Pharmacy vials should be used immediately after reconstitution.  Discard any unused portion after 24 hours if stored at room temperature 20° to 25°C (68° to 77°F), or after 48 hours if stored at refrigerated temperature 2° to 8°C (36° to 46°F).

Compatible Reconstitution Diluents

0.9% Sodium Chloride for Injection

Sterile Water for Injection‡

Dextrose 5%

Bacteriostatic Saline/Parabens

Bacteriostatic Water/Parabens

Bacteriostatic Saline/Benzyl Alcohol

Bacteriostatic Water/Benzyl Alcohol

Reconstituted piperacillin and tazobactam for injection solution should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous diluent solution listed below.  Administer by infusion over a period of at least 30 minutes.  During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Diluent Solutions

0.9% Sodium Chloride for Injection

Sterile Water for Injection‡

Dextrose 5%

Dextran 6% in Saline

LACTATED RINGER’S SOLUTION IS NOT COMPATIBLE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.

‡ Maximum recommended volume per dose of Sterile Water for Injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates.

Piperacillin and tazobactam for injection can be used in ambulatory intravenous infusion pumps.

Stability of Piperacillin and Tazobactam for Injection Following Reconstitution

Piperacillin and tazobactam for injection is stable in glass and plastic containers (plastic syringes, IV bags and tubing) when used with compatible diluents.

Pharmacy vials should be used immediately after reconstitution.  Discard any unused portion after 24 hours if stored at room temperature 20° to 25°C (68° to 77°F), or after 48 hours if stored at refrigerated temperature 2° to 8°C (36° to 46°F).  Vials should not be frozen after reconstitution.

Stability studies in the IV bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature.  Piperacillin and tazobactam for injection contains no preservatives.  Appropriate consideration of aseptic technique should be used.

Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature.  Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL.  One-day supplies of dosing solution were aseptically transferred into the medication reservoir (IV bags or cartridge).  The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer’s instructions.  Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam). The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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 g (16 g piperacillin/2 g tazobactam). 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.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment. The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows: 

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)]. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose. It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Single dose vials

Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.

2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively. Swirl until dissolved.

Compatible Reconstitution Diluents for Single Dose Vials

0.9% sodium chloride for injection
Sterile water for injection
Dextrose 5%
Bacteriostatic saline/parabens
Bacteriostatic water/parabens
Bacteriostatic saline/benzyl alcohol
Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solutions for single dose vials should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below. Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Solutions for Single Dose Vials

0.9% sodium chloride for injection
sterile water for injection‡
Dextran 6% in salineDextrose 5%

LACTATED RINGER'S SOLUTION IS NOT COMPATIBLE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.

‡Maximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and tazobactam should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam Powder Formulation Following Reconstitution

Piperacillin and tazobactam for injection reconstituted from single vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.

Single dose vials should be used immediately after reconstitution. Discard any unused portion after 24 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]), or after 48 hours if stored at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Vials should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature. Piperacillin and tazobactam for injection contains no preservatives. Appropriate consideration of aseptic technique should be used.

Piperacillin and tazobactam for injection reconstituted from single vials can be used in ambulatory intravenous infusion pumps. Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature. Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL. One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge). The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions. Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

Due to the in vitro inactivation of aminoglycosides by piperacillin, piperacillin and tazobactam and aminoglycosides are recommended for separate administration. Piperacillin and tazobactam and aminoglycosides should be reconstituted, diluted, and administered separately when concomitant therapy with aminoglycosides is indicated [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam.

Piperacillin and tazobactam is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam). The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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 g (16 g piperacillin/2 g tazobactam). 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.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment. The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

>40 mL/min

3.375 q 6 h

4.5 q 6 h

20-40 mL/min*

2.25 q 6 h

3.375 q 6 h

<20 mL/min*

2.25 q 8 h

2.25 q 6 h

Hemodialysis†

2.25 q 12 h

2.25 q 8 h

CAPD

2.25 q 12 h

2.25 q 8 h

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)]. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.

It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

ADD-Vantage® System Admixtures

Dextrose 5% in Water (50 or 100 mL)

0.9% Sodium Chloride (50 or 100 mL)

For ADD-Vantage® vials reconstitution directions see Instructions for Use of the ADD-Vantage® System

LACTATED RINGER’S SOLUTION IS NOT COMPATIBLE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.

Stability studies with the admixed ADD-Vantage® system have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature. (Note: The admixed ADD-Vantage® should not be refrigerated or frozen after reconstitution.). Piperacillin and tazobactam for injection contains no preservatives. Appropriate consideration of aseptic technique should be used.

To Open Diluent Container:

Peel overwrap from the corner and remove container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

To Assemble Vial and Flexible Diluent Container (Use Aseptic Technique):

To Prepare Admixture:

Preparation for Administration (Use Aseptic Technique):

WARNING: Do not use flexible container in series connections.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, Y-site infusion only with the following aminoglycosides under the following conditions:

Aminoglycoside

Piperacillin and
Tazobactam for
Injection Dose
(grams)

Piperacillin and
Tazobactam for
Injection Diluent
Volume (mL)

Aminoglycoside
Concentration
Range*
(mg/mL)

Acceptable
Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 – 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25, 3.375, 4.5

50, 100, 150

0.7 – 3.32

0.9% sodium chloride or 5% dextrose

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam). The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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 g (16 g piperacillin/2 g tazobactam). 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. aeruginosais isolated.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment. The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

>40 mL/min

3.375 q 6 h

4.5 q 6 h

20-40 mL/min*

2.25 q 6 h

3.375 q 6 h

<20 mL/min*

2.25 q 8 h

2.25 q 6 h

Hemodialysis†

2.25 q 12 h

2.25 q 8 h

CAPD

2.25 q 12 h

2.25 q 8 h

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)]. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.

It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Single dose vials

Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.

2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively. Swirl until dissolved.

Compatible Reconstitution Diluents for Single Dose Vials

0.9% sodium chloride for injection

Sterile water for injection

Dextrose 5%

Bacteriostatic saline/parabens

Bacteriostatic water/parabens

Bacteriostatic saline/benzyl alcohol

Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solutions for single dose vials should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below. Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Solutions for Single Dose Vials

0.9% sodium chloride for injection

sterile water for injection‡

Dextran 6% in saline

Dextrose 5%

LACTATED RINGER’S SOLUTION IS NOT COMPATIBLE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.

‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection reconstituted from single dose vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.

Single dose vials should be used immediately after reconstitution. Discard any unused portion after 24 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]), or after 48 hours if stored at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Vials should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature. Piperacillin and tazobactam for injection contains no preservatives. Appropriate consideration of aseptic technique should be used.

Piperacillin and tazobactam for injection reconstituted from single dose vials can be used in ambulatory intravenous infusion pumps. Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature. Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL. One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge). The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions. Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, Y-site infusion only with the following aminoglycosides under the following conditions:

Aminoglycoside

Piperacillin and
Tazobactam for
Injection Dose
(grams)

Piperacillin and
Tazobactam for
Injection Diluent
Volume* (mL)

Aminoglycoside
Concentration
Range†
(mg/mL)

Acceptable
Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 – 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25, 3.375, 4.5

50, 100, 150

0.7 – 3.32

0.9% sodium chloride or 5% dextrose

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam). The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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 g (16 g piperacillin/2 g tazobactam). 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.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment. The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

>40 mL/min

3.375 q 6 h

4.5 q 6 h

20-40 mL/min*

2.25 q 6 h

3.375 q 6 h

<20 mL/min*

2.25 q 8 h

2.25 q 6 h

Hemodialysis†

2.25 q 12 h

2.25 q 8 h

CAPD

2.25 q 12 h

2.25 q 8 h

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)]. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.

It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

ADD-Vantage® System Admixtures

Dextrose 5% in Water (50 or 100 mL)

0.9% Sodium Chloride (50 or 100 mL)

For ADD-Vantage® vials reconstitution directions see Instructions for Use of the ADD-Vantage® System

LACTATED RINGER’S SOLUTION IS NOT COMPATIBLE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.

Stability studies with the admixed ADD-Vantage® system have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature. (Note: The admixed ADD-Vantage® should not be refrigerated or frozen after reconstitution.). Piperacillin and tazobactam for injection contains no preservatives. Appropriate consideration of aseptic technique should be used.

To Open Diluent Container:

Peel overwrap from the corner and remove container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

To Assemble Vial and Flexible Diluent Container (Use Aseptic Technique):

To Prepare Admixture:

Preparation for Administration (Use Aseptic Technique):

WARNING: Do not use flexible container in series connections.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, Y-site infusion only with the following aminoglycosides under the following conditions:

Aminoglycoside

Piperacillin and
Tazobactam for
Injection Dose
(grams)

Piperacillin and
Tazobactam for
Injection Diluent
Volume (mL)

Aminoglycoside
Concentration
Range*
(mg/mL)

Acceptable
Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 – 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25, 3.375, 4.5

50, 100, 150

0.7 – 3.32

0.9% sodium chloride or 5% dextrose

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam). The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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 g (16 g piperacillin/2 g tazobactam). 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. aeruginosais isolated.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment. The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

>40 mL/min

3.375 q 6 h

4.5 q 6 h

20-40 mL/min*

2.25 q 6 h

3.375 q 6 h

<20 mL/min*

2.25 q 8 h

2.25 q 6 h

Hemodialysis†

2.25 q 12 h

2.25 q 8 h

CAPD

2.25 q 12 h

2.25 q 8 h

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)]. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.

It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Single dose vials

Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.

2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively. Swirl until dissolved.

Compatible Reconstitution Diluents for Single Dose Vials

0.9% sodium chloride for injection

Sterile water for injection

Dextrose 5%

Bacteriostatic saline/parabens

Bacteriostatic water/parabens

Bacteriostatic saline/benzyl alcohol

Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solutions for single dose vials should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below. Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Solutions for Single Dose Vials

0.9% sodium chloride for injection

sterile water for injection‡

Dextran 6% in saline

Dextrose 5%

LACTATED RINGER’S SOLUTION IS NOT COMPATIBLE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.

‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection reconstituted from single dose vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.

Single dose vials should be used immediately after reconstitution. Discard any unused portion after 24 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]), or after 48 hours if stored at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Vials should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature. Piperacillin and tazobactam for injection contains no preservatives. Appropriate consideration of aseptic technique should be used.

Piperacillin and tazobactam for injection reconstituted from single dose vials can be used in ambulatory intravenous infusion pumps. Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature. Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL. One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge). The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions. Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, Y-site infusion only with the following aminoglycosides under the following conditions:

Aminoglycoside

Piperacillin and
Tazobactam for
Injection Dose
(grams)

Piperacillin and
Tazobactam for
Injection Diluent
Volume* (mL)

Aminoglycoside
Concentration
Range†
(mg/mL)

Acceptable
Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 – 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25, 3.375, 4.5

50, 100, 150

0.7 – 3.32

0.9% sodium chloride or 5% dextrose

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam). The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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 g (16 g piperacillin/2 g tazobactam). 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. aeruginosais isolated.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment. The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

>40 mL/min

3.375 q 6 h

4.5 q 6 h

20-40 mL/min*

2.25 q 6 h

3.375 q 6 h

<20 mL/min*

2.25 q 8 h

2.25 q 6 h

Hemodialysis†

2.25 q 12 h

2.25 q 8 h

CAPD

2.25 q 12 h

2.25 q 8 h

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)]. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.

It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Single dose vials

Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.

2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively. Swirl until dissolved.

Compatible Reconstitution Diluents for Single Dose Vials

0.9% sodium chloride for injection

Sterile water for injection

Dextrose 5%

Bacteriostatic saline/parabens

Bacteriostatic water/parabens

Bacteriostatic saline/benzyl alcohol

Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solutions for single dose vials should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below. Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Solutions for Single Dose Vials

0.9% sodium chloride for injection

sterile water for injection‡

Dextran 6% in saline

Dextrose 5%

LACTATED RINGER’S SOLUTION IS NOT COMPATIBLE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.

‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection reconstituted from single dose vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.

Single dose vials should be used immediately after reconstitution. Discard any unused portion after 24 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]), or after 48 hours if stored at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Vials should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature. Piperacillin and tazobactam for injection contains no preservatives. Appropriate consideration of aseptic technique should be used.

Piperacillin and tazobactam for injection reconstituted from single dose vials can be used in ambulatory intravenous infusion pumps. Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature. Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL. One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge). The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions. Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, Y-site infusion only with the following aminoglycosides under the following conditions:

Aminoglycoside

Piperacillin and
Tazobactam for
Injection Dose
(grams)

Piperacillin and
Tazobactam for
Injection Diluent
Volume* (mL)

Aminoglycoside
Concentration
Range†
(mg/mL)

Acceptable
Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 – 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25, 3.375, 4.5

50, 100, 150

0.7 – 3.32

0.9% sodium chloride or 5% dextrose

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose 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).  The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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).  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.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment.  The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

Table 1:  Recommended Dosing of Piperacillin and Tazobactam for Injection in Patients with Normal Renal Function and Renal Impairment (As total grams piperacillin/tazobactam)

(creatinine clearance,

All Indications

Nosocomial

mL/min)

(except nosocomial pneumonia)

Pneumonia

>40 mL/min

3.375 q6h

4.5 q6h

20-40 mL/min*

2.25 q6h

3.375 q6h

<20 mL/min*

2.25 q8h

2.25 q6h

Hemodialysis**

2.25 q12h

2.25 q8h

CAPD

2.25 q12h

2.25 q8h

*Creatinine clearance for patients not receiving hemodialysis
**0.75 g (0.67 g piperacillin/0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis days

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia.  Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days.  No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours.  For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)].  Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.  It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Single Dose Vials

Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.

2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively.  Swirl until dissolved.

Compatible Reconstitution Diluents for Single Dose Vials
0.9% Sodium chloride for injection
Sterile water for injection‡
Dextrose 5%
Bacteriostatic saline/parabens
Bacteriostatic water/parabens
Bacteriostatic saline/benzyl alcohol
Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solution should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below.  Administer by infusion over a period of at least 30 minutes.  During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Solutions for Pharmacy Bulk Package Bottles and Single Dose Vials
0.9% Sodium chloride for injection
Sterile water for injection‡
Dextran 6% in saline
Dextrose 5%

LACTATED RINGER’S SOLUTION IS NOT COMPATIBILE WITH PIPERACILLIN AND TAZOBACTAM FOR INJECTION.
‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates.

Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection reconstituted from single vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.  Discard unused portions after storage for 24 hours at room temperature or after storage for 48 hours at refrigerated temperature 2°C to 8°C (36°F to 46°F).

Single dose vials should be used immediately after reconstitution.  Discard any unused portion after 24 hours if stored at room temperature 20°C to 25°C (68°F to 77°F), or after 48 hours if stored at refrigerated temperature 2°C to 8°C (36°F to 46°F).  Vials should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature.  Piperacillin and tazobactam for injection contains no preservatives.  Appropriate consideration of aseptic technique should be used.

Piperacillin and tazobactam for injection reconstituted from single vials can be used in ambulatory intravenous infusion pumps.  Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature.  Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL.  One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge).  The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions.  Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam for injection is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:

Table 2: Compatibility with Aminoglycosides

Aminoglycoside

Piperacillin and Tazobactam
Dose
(grams)

Piperacillin and Tazobactam Diluent Volume (mL)

Aminoglycoside Concentration Range a
(mg/mL)

Acceptable Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 – 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25, 3.375, 4.5

50, 100, 150

0.7 – 3.32

0.9% sodium chloride or 5% dextrose

aThe concentration ranges in Table 2 are based on administration of the aminoglycoside in divided doses (10-15 mg/kg/day in two daily doses for amikacin and 3-5 mg/kg/day in three daily doses for gentamicin).  Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with piperacillin and tazobactam has not been evaluated.  See package insert for each aminoglycoside for complete Dosage and Administration instructions.

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion.  Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion.  Compatibility of piperacillin and tazobactam with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and Tazobactam for Injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam). The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and Tazobactam for Injection should be administered by intravenous infusion over 30 minutes.

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 g (16 g piperacillin/2 g tazobactam). 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.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment. The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

Renal Function
(creatinine clearance,
mL/min)

All Indications (except nosocomial
pneumonia)

Nosocomial
Pneumonia

>40 mL/min

3.375 q 6 h

4.5 q 6 h

20 to 40 mL/min*

2.25 q 6 h

3.375 q 6 h

<20 mL/min*

2.25 q 8 h

2.25 q 6 h

Hemodialysis**

2.25 q 12 h

2.25 q 8 h

CAPD

2.25 q 12 h

2.25 q 8 h

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)]. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose. It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.

2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively. Swirl until dissolved.

0.9% sodium chloride for injection
Sterile water for injection
Dextrose 5%
Bacteriostatic saline/parabens
Bacteriostatic water/parabens
Bacteriostatic saline/benzyl alcohol
Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solution for single dose vials should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below. Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.

0.9% sodium chloride for injection
sterile water for injection‡
Dextran 6% in saline
Dextrose 5%
Lactated Ringer’s Solution is not compatible with piperacillin and tazobactam for injection

‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and Tazobactam for Injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and Tazobactam for Injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and Tazobactam for Injection should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and Tazobactam for Injection reconstituted from single vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents. Discard unused portions after storage for 24 hours at room temperature or after storage for 48 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).

Single dose vials should be used immediately after reconstitution. Discard any unused portion after 24 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]), or after 48 hours if stored at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Vials should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature. Piperacillin and Tazobactam for injection contains no preservatives. Appropriate consideration of aseptic technique should be used.

Piperacillin and Tazobactam for Injection reconstituted from single vials can be used in ambulatory intravenous infusion pumps. Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature. Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL. One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge). The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer’s instructions. Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam for injection is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:

Aminoglycoside

Piperacillin and Tazobactam for Injection Dose (grams)

Piperacillin and Tazobactam for Injection Diluent Volumea(mL)

Aminoglycoside Concentration Rangeb
(mg/mL)

Acceptable Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 to 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25
3.375
4.5

100
150

0.7 to 3.32

0.9% sodium chloride

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and Tazobactam for Injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and Tazobactam for Injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam). The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and Tazobactam for Injection should be administered by intravenous infusion over 30 minutes.

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 g (16 g piperacillin/2 g tazobactam). 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.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment. The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

Renal Function
(creatinine clearance,

All Indications (except nosocomial

Nosocomial

mL/min)

pneumonia)

Pneumonia

>40 mL/min

3.375 q 6 h

4.5 q 6 h

20 to 40 mL/min*

2.25 q 6 h

3.375 q 6 h

<20 mL/min*

2.25 q 8 h

2.25 q 6 h

Hemodialysis**

2.25 q 12 h

2.25 q 8 h

CAPD

2.25 q 12 h

2.25 q 8 h

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)]. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose. It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Reconstituted stock solution must be transferred and further diluted for intravenous infusion.

The pharmacy bulk vial is for use in a hospital pharmacy admixture service only under a laminar flow hood. After reconstitution, entry into the vial must be made with a sterile transfer set or other sterile dispensing device, and contents should be dispensed as aliquots into intravenous solution using aseptic technique. Use entire contents of pharmacy bulk vial promptly. Discard unused portion after 4 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]).

Reconstitute the pharmacy bulk vial with exactly 152 mL of a compatible reconstitution diluent, listed below, to a concentration of 200 mg/mL of piperacillin and 25 mg/mL of tazobactam. Shake well until dissolved. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to and during administration whenever solution and container permit.

Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.

0.9% sodium chloride for injection
Sterile water for injection
Dextrose 5%
Bacteriostatic saline/parabens
Bacteriostatic water/parabens
Bacteriostatic saline/benzyl alcohol
Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solution for bulk vials should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below. Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.

0.9% sodium chloride for injection
sterile water for injection‡
Dextran 6% in saline
Dextrose 5%
Lactated Ringer’s Solution is not compatible with piperacillin and tazobactam for injection

‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and Tazobactam for Injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and Tazobactam for Injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and Tazobactam for Injection should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution

Piperacillin and Tazobactam for Injection reconstituted from bulk vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents. The pharmacy bulk vial should NOT be frozen after reconstitution. Discard unused portions after storage for 4 hours at room temperature.

Pharmacy vials should be used immediately after reconstitution. Discard any unused portion after 4 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]). Vials should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature. Piperacillin and Tazobactam for injection contains no preservatives. Appropriate consideration of aseptic technique should be used.

Piperacillin and Tazobactam for Injection reconstituted from bulk vials can be used in ambulatory intravenous infusion pumps. Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature. Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL. One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge). The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer’s instructions. Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam for injection is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:

Aminoglycoside

Piperacillin and Tazobactam for Injection
Dose (grams)

Piperacillin and Tazobactam for Injection Diluent Volumea(mL)

Aminoglycoside Concentration Rangeb
(mg/mL)

Acceptable
Diluents

Amikacin

2.25, 3.375, 4.5

50, 100, 150

1.75 to 7.5

0.9% sodium chloride or 5% dextrose

Gentamicin

2.25
3.375
4.5

100
150

0.7 to 3.32

0.9% sodium chloride

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and Tazobactam for Injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam). The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

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 g (16 g piperacillin/2 g tazobactam). 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.

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment. The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:

For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)]. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.

It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

Single dose vials

Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.

2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively. Swirl until dissolved.

Compatible Reconstitution Diluents for Single Dose Vials

0.9% sodium chloride for injection

Sterile water for injection

Dextrose 5%

Bacteriostatic saline/parabens

Bacteriostatic water/parabens

Bacteriostatic saline/benzyl alcohol

Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solutions for single dose vials should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below. Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Solutions for Single Dose Vials

0.9% sodium chloride for injection

sterile water for injectiona

Dextran 6% in saline

Dextrose 5%

Lactated Ringer's Solution is not compatible with Piperacillin and Tazobactam for Injection.

aMaximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates.

Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Stability of piperacillin and tazobactam for injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection reconstituted from single vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.

Single dose vials should be used immediately after reconstitution. Discard any unused portion after 24 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]), or after 48 hours if stored at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Vials should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature. Piperacillin and tazobactam for injection contains no preservatives. Appropriate consideration of aseptic technique should be used.

Piperacillin and tazobactam for injection reconstituted from single vials can be used in ambulatory intravenous infusion pumps. Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature. Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL. One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge). The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions. Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

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 [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and tazobactam is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

Adult or child: Take three pills daily. Leaving a gap of 30 minutes after any food or as advised by your physician.