Piperacillin And Tazobactam

•  Warnings and Precautions, Rhabdomyolysis (
  5.4 Rhabdomyolysis

  Rhabdomyolysis has been reported with the use of Piperacillin and tazobactam for injection [

  see Adverse Reactions (

  6.2

  )

  ]. If signs or symptoms of rhabdomyolysis such as muscle pain, tenderness or weakness, dark urine, or elevated creatine phosphokinase are observed, discontinue Piperacillin and tazobactam for injection and initiate appropriate therapy.
  ) 08/2024

Piperacillin and tazobactam for injection is a combination of piperacillin, a penicillin-class antibacterial and tazobactam, a beta-lactamase inhibitor, indicated for the treatment of:

• •Intra-abdominal infections in adult and pediatric patients 2 months of age and older (
  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

  .
  )
• •Nosocomial pneumonia in adult and pediatric patients 2 months of age and older (
  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 and 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

  ].
  )
• •Skin and skin structure infections in adults (
  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

  .
  )
• •Female pelvic infections in adults (
  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

  .
  )
• •Community-acquired pneumonia in adults (
  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.
  )

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. (

• •
  Adult Patients with Indications Other Than Nosocomial Pneumonia:
  The usual daily dosage of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin and 1.5 g tazobactam). (
  2.1 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 and 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.
  )
• •
  Adult Patients with Nosocomial Pneumonia:
  Initial presumptive treatment of patients with nosocomial pneumonia should start with piperacillin and tazobactam for injection at a dosage of 4.5 g every six hours plus an aminoglycoside, totaling 18 g (16 g piperacillin and 2 g tazobactam). (
  2.2 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 and 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.
  )
• •
  Adult Patients with Renal Impairment:
  Dosage in patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients should be reduced, based on the degree of renal impairment. (
  2.3 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 and tazobactam)*

  Creatinine Clearance, mL/min	All Indications (except nosocomial pneumonia)	Nosocomial Pneumonia
  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 and 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 and 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.
  )
• •
  Pediatric Patients by Indication and Age:
  See Table below. (
  2.4 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 and Clinical Pharmacology

  ].

  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 and 10 mg tazobactam) every 8 ( eight ) hours	90 mg/kg (80 mg piperacillin and 10 mg tazobactam) every 6 ( six ) hours
  Older than 9 months of age	112.5 mg/kg (100 mg piperacillin and 12.5 mg tazobactam) every 8 ( eight ) hours	112.5 mg/kg (100 mg piperacillin and 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 (

  2.1

  ,

  2.2

  )

  ].

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

• •Administer piperacillin and tazobactam for injection by intravenous infusion over 30 minutes to both adult and pediatric patients. (
  2.1 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 and 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.
  ,
  2.2 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 and 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.
  ,
  2.3 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 and tazobactam)*

  Creatinine Clearance, mL/min	All Indications (except nosocomial pneumonia)	Nosocomial Pneumonia
  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 and 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 and 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.
  ,
  2.4 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 and Clinical Pharmacology

  ].

  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 and 10 mg tazobactam) every 8 ( eight ) hours	90 mg/kg (80 mg piperacillin and 10 mg tazobactam) every 6 ( six ) hours
  Older than 9 months of age	112.5 mg/kg (100 mg piperacillin and 12.5 mg tazobactam) every 8 ( eight ) hours	112.5 mg/kg (100 mg piperacillin and 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 (

  2.1

  ,

  2.2

  )

  ].

  Dosage of piperacillin and tazobactam for injection in pediatric patients with renal impairment has not been determined.
  )
• •Piperacillin and tazobactam for injection and aminoglycosides should be reconstituted, diluted, and administered separately. Co-administration via Y-site can be done under certain conditions. (
  2.6 Compatibility with Aminoglycosides

  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 ]

  .

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

  Table 5: Compatibility with Aminoglycosides

  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

  * Diluent volumes apply only to single vials and bulk pharmacy containers.

  † The concentration ranges in

  Table 5

  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 for injection 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 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 for injection.

  Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous co-administration 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.
  )
• •See the full prescribing information for the preparation and administration instructions for piperacillin and tazobactam for injection single-dose vials.

Piperacillin and tazobactam for injection, USP is supplied as a white to yellowish powder in vials of the following sizes:

Each piperacillin and tazobactam for injection, USP 2.25 g vial provides piperacillin sodium equivalent to 2 grams of piperacillin and tazobactam sodium equivalent to 0.25 g of tazobactam.

Each piperacillin and tazobactam for injection, USP 3.375 g vial provides piperacillin sodium equivalent to 3 grams of piperacillin and tazobactam sodium equivalent to 0.375 g of tazobactam.

Each piperacillin and tazobactam for injection, USP 4.5 g vial provides piperacillin sodium equivalent to 4 grams of piperacillin and tazobactam sodium equivalent to 0.5 g of tazobactam.

• •Dosage in patients with renal impairment (creatinine clearance ≤ 40 mL/min) should be reduced based on the degree of renal impairment. (
  2.3 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 and tazobactam)*

  Creatinine Clearance, mL/min	All Indications (except nosocomial pneumonia)	Nosocomial Pneumonia
  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 and 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 and 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.
  ,
  8.6 Renal Impairment

  In patients with 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 renal function impairment

  [see Dosage and Administration ]

  .
  )