Piperacillin and Tazobactam: Package Insert and Label Information

PIPERACILLIN AND TAZOBACTAM- piperacillin sodium and tazobactam sodium injection, powder, lyophilized, for solution
Hospira, Inc

PHARMACY BULK PACKAGE – NOT FOR DIRECT INFUSION

1 INDICATIONS AND USAGE

1.1 Intra-abdominal Infections

Piperacillin and tazobactam for injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of appendicitis (complicated by rupture or abscess) and peritonitis caused by beta-lactamase producing isolates of Escherichia coli or the following members of the Bacteroides fragilis group: B. fragilis, B. ovatus, B. thetaiotaomicron , or B. vulgatus.

1.2 Nosocomial Pneumonia

Piperacillin and tazobactam for injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of nosocomial pneumonia (moderate to severe) caused by beta-lactamase producing isolates of Staphylococcus aureus and by piperacillin/tazobactam-susceptible Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae , and Pseudomonas aeruginosa (Nosocomial pneumonia caused by P. aeruginosa should be treated in combination with an aminoglycoside) [see Dosage and Administration (2) ].

1.3 Skin and Skin Structure Infections

Piperacillin and tazobactam for injection is indicated in adults for the treatment of uncomplicated and complicated skin and skin structure infections, including cellulitis, cutaneous abscesses and ischemic/diabetic foot infections caused by beta-lactamase producing isolates of Staphylococcus aureus.

1.4 Female Pelvic Infections

Piperacillin and tazobactam for injection is indicated in adults for the treatment of postpartum endometritis or pelvic inflammatory disease caused by beta-lactamase producing isolates of Escherichia coli.

1.5 Community-acquired Pneumonia

Piperacillin and tazobactam for injection is indicated in adults for the treatment of community-acquired pneumonia (moderate severity only) caused by beta-lactamase producing isolates of Haemophilus influenzae.

1.6 Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of piperacillin and tazobactam for injection and other antibacterial drugs, piperacillin and tazobactam for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

2 DOSAGE AND ADMINISTRATION

2.2 Dosage in Adult Patients with Indications Other Than Nosocomial Pneumonia

The usual total daily dosage of piperacillin and tazobactam for injection for adult patients with indications other than nosocomial pneumonia is 3.375 g every six hours [totaling 13.5 g (12 g piperacillin/1.5 g tazobactam)], to be administered by intravenous infusion over 30 minutes. The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

2.3 Dosage in Adult Patients with Nosocomial Pneumonia

Initial presumptive treatment of adult patients with nosocomial pneumonia should start with piperacillin and tazobactam for injection at a dosage of 4.5 g every six hours plus an aminoglycoside, [totaling 18 g (16 g piperacillin/2 g tazobactam)], administered by intravenous infusion over 30 minutes. The recommended duration of piperacillin and tazobactam for injection treatment for nosocomial pneumonia is 7 to 14 days. Treatment with the aminoglycoside should be continued in patients from whom P. aeruginosa is isolated.

2.4 Dosage in Adult Patients with Renal Impairment

In adult 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 based on the degree of renal impairment. The recommended daily dosage of piperacillin and tazobactam for injection for patients with renal impairment administered by intravenous infusion over 30 minutes is described in Table 1.

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

Creatinine Clearance,mL/min All Indications(except nosocomialpneumonia) NosocomialPneumonia

Greater than 40 mL/min

3.375 every 6 hours

4.5 every 6 hours

20 to 40 mL/min

2.25 every 6 hours

3.375 every 6 hours

Less than 20 mL/min

2.25 every 8 hours

2.25 every 6 hours

Hemodialysis

2.25 every 12 hours

2.25 every 8 hours

CAPD

2.25 every 12 hours

2.25 every 8 hours

* Administer piperacillin and tazobactam for injection by intravenous infusion over 30 minutes

† 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.

2.5 Dosage in Pediatric Patients with Appendicitis/Peritonitis or Nosocomial Pneumonia

The recommended dosage for pediatric patients with appendicitis and/or peritonitis or nosocomial pneumonia aged 2 months of age and older, weighing up to 40 kg, and with normal renal function, is described in Table 2 [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)].

Table 2: Recommended Dosage of Piperacillin and Tazobactam for Injection in Pediatric Patients 2 Months of Age and Older, Weighing up to 40 kg and With Normal Renal Function*

Age

Appendicitis and /or Peritonitis

Nosocomial Pneumonia

2 months to 9 months

90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 8 (eight) hours

90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 6 (six) hours

Older than 9 months of age

112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 8 (eight) hours

112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 6 (six) hours

* Administer piperacillin and tazobactam for injection by intravenous infusion over 30 minutes.

Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose [see Dosage and Administration (2.2, 2.3)].

Dosage of piperacillin and tazobactam for injection in pediatric patients with renal impairment has not been determined.

2.6 Reconstitution and Dilution of Piperacillin and Tazobactam for Injection

Reconstitution of Piperacillin and Tazobactam for Injection for Adult Patients and Pediatric Patients Weighing Over 40 kg

Pharmacy Bulk Bottles

Reconstituted pharmacy bulk bottle solution must be transferred and further diluted for intravenous infusion.

The pharmacy bulk bottle is for use in a hospital pharmacy admixture service only under a laminar flow hood. After reconstitution, entry into the bottle 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 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 bottle with exactly 51 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

Dilution of the Reconstituted Piperacillin and Tazobactam Solution for Adult Patients and Pediatric Patients Weighing Over 40 kg

Reconstituted piperacillin and tazobactam for injection solutions for pharmacy bulk bottles 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 Bottles

0.9% sodium chloride for injection

Sterile water for injection (Maximum recommended volume per dose of sterile water for injection is 50 mL)

Dextran 6% in saline

Dextrose 5%

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.

Dilution of the Reconstituted Piperacillin and Tazobactam Solution for Pediatric Patients Weighing up to 40 kg

The volume of reconstituted solution required to deliver the dose of piperacillin and tazobactam is dependent on the weight of the child [see Dosage and Administration ( 2.5 )] . Reconstituted piperacillin and tazobactam solutions for bulk bottles should be further diluted in a compatible intravenous solution listed above.

1.
Calculate patient dose as described in Table 2 above [see Dosage and Administration ( 2.5 )] .
2.
Reconstitute bottle with a compatible reconstitution diluent, as listed above under the subheading “Compatible Reconstitution Diluents for Pharmacy Bulk Bottles,” using the appropriate volume of diluent, as listed in Table 4 below. Following the addition of the diluent, shake the pharmacy bulk bottle until the powder is completely dissolved.

Table 4: Reconstitution of Pharmacy Bulk Bottle and Resulting Concentration

Strength per Pharmacy Bulk Bottle

Volume of Diluent to be Added to the Bottle

Concentration of the Reconstituted Product

13.5 g (12 g piperacillin /1.5 g tazobactam)

51 mL

225 mg/mL (200 mg/mL piperacillin/ 25 mg/mL tazobactam)

3.
Calculate the required volume (mL) of reconstituted piperacillin and tazobactam solution based on the required dose.
4.
Aseptically withdraw the required volume of reconstituted piperacillin and tazobactam solution from pharmacy bulk bottle. It should be further diluted to a final piperacillin concentration of between 20 mg/mL to 80 mg/mL (tazobactam between 2.5 mg/mL to 10 mg/mL) in a compatible intravenous solution (as listed above) in an appropriately sized syringe or IV bag.
5.
Administer the diluted piperacillin and tazobactam solution by infusion over a period of at least 30 minutes (a programmable syringe or infusion pump is recommended). During the infusion it is desirable to discontinue the primary infusion solution.

Stability of Piperacillin and Tazobactam for Injection Following Reconstitution and Dilution

Piperacillin and tazobactam for injection reconstituted from pharmacy bulk bottles is stable in glass and plastic containers (plastic syringes, IV bags and tubing) when used with compatible diluents. The pharmacy bulk bottle should NOT be frozen after reconstitution.

Pharmacy bulk bottles should be used immediately after reconstitution. Discard any unused portion after storage for 24 hours at room temperature (20°C to 25°C [68°F to 77°F]), or after storage for 48 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).

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.

Piperacillin and tazobactam for injection reconstituted from pharmacy bulk 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 supply 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.

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