Pharmacokinetics in children

The following pharmacokinetic parameters were found: [Li 2013, SmPC, Reed 1994]

Age	t½ PIP	t½ PIP-TAZO	V	Cl PIP	Cl PIP-TAZO
< 2 months				0.13 l/kg/hour	0.15 l/kg/hour
2-5 months	1.4 hours	1.6 hours	0.24 l/kg
6-23 months	0.9 hours	1.0 hours	0.24 l/kg
2-12 yrs	0.7 hours	0.8-0.9 hours	0.24 l/kg		0.27 l/kg/hour

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Febrile neutropenia, complicated infections of urinary tract, abdomen or skin/soft tissue; severe pneumonia (including HAP and ventilator associated pneumonia, and pulmonary infections in CF)

Intravenous 1 month up to 18 years [5] [6] [7] [8] [9] [10] [11] [13] [14] 320/40 mg/kg/day in 4 doses. Maximum for febrile neutropenia and CF: 18/2.25 g/day. Maximum for abdominal infections: 16/2 g/day. Alternative: administer as a continuous infusion: 300/37.5 mg/kg/day, maximum of 18/2.25 g/day Duration of treatment: The length of treatment should be guided by the severity of the infection and the clinical and bacteriological process. A course of treatment of at least 5 and at most 14 days is recommended, taking into account a continuing administration during 48 hours after solving clinical signals and symptoms. CF: preferably use in combination with an aminoglycoside or another antibiotic with an anti-Pseudomonas effect.

Infections (without clinical suspicion of meningitis) caused by microorganisms susceptible at increased exposure ('I')
Intravenous 1 month up to 18 years [18] [19] 400 / 50 mg/kg/day in 4 doses, max 4 g / 0,5 g per dose.  Extended infusion time in 3 hours.

Renal impaiment in children > 3 months

Adjustment in renal impairment as specified:

GFR 50-80 ml/min/1.73 m2

Dose adjustment is not required

GFR 30-50 ml/min/1.73 m2

100 percentage of single dose and dosing interval : 8 uur

GFR 10-30 ml/min/1.73 m2

100 percentage of single dose and dosing interval : 12 uur

GFR < 10 ml/min/1.73 m2

50 percentage of single dose and dosing interval : 8 uur

Clinical consequences

Neurotoxicity can occur (for example convulsions) at high parenteral doses.

Patients on dialysis

The manufacturer says that dialysis patients can use 50% of the normal dose each time, dosage interval 8 hours between 2 dosages. After each dialysis an extra dose of 50% of the normal dosage each time can be administered.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Thrombophlebitis and pain at the injection site, disturbance of the thrombocyte aggregation, diarrhoea, vomiting, nausea, rash, erythema, itching, urticaria and allergic reactions of an anaphylactoid nature. Piperacillin is associated with an increased incidence of fever and rash in cystic fibrosis patients.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

The serum galactomannan indication (Aspergillus antigen) can give a false positive reaction. There can be crossover sensitivity with other penicillins and cephalosporin. Severe and persistent diarrhoea during or after a treatment can be signs of colitis as a result of an antibiotic. The treatment must immediately be stopped in such cases.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

• ANTIINFECTIVES FOR SYSTEMIC USE
• ANTIBACTERIALS FOR SYSTEMIC USE

BETA-LACTAM ANTIBACTERIALS, PENICILLINS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Penicillins with extended spectrum
	Amoxicillin Related Medicines Menu">	J01CA04
	Ampicillin Related Medicines Menu">	J01CA01

Beta-lactamase sensitive penicillins
	Benzathine benzylpenicillin Related Medicines Menu">	J01CE08
	Benzylpenicillin Related Medicines Menu">	J01CE01
	Phenoxymethylpenicillin Related Medicines Menu">	J01CE02

Beta-lactamase resistant penicillins
	Kloksacillin Related Medicines Menu">	J01CF02

Combinations of penicillins, incl. beta-lactamase inhibitors
	Amoxicillin + clavulanic acid Related Medicines Menu">	J01CR02

References

1. Sulahian A, et al, False positive test for aspergillus antigenemia related to concomitant administration of piperacillin and tazobactam, N Engl J Med, 2003, Dec 11;349(24), 2366-7
2. Steinbach WJ, et al, Prospective Aspergillus galactomannan antigen testing in pediatric hematopoietic stem cell transplant recipients, Pediatr Infect Dis J, 2007, Jul;26(7), 558-64
3. Penack O, et al, False-positive Aspergillus antigen testing due to application of piperacillin/tazobactam--is it still an issue?, Diagn Microbiol Infect Dis., 2008, Jan;60(1), 117-20
4. CBO, Richtlijn Diagnostiek en behandeling Cystic Fibrosis, www.cbo.nl, 2007
5. Corapcioglu F, et al, Monotherapy with piperacillin/tazobactam versus cefepime as empirical therapy for febrile neutropenia in pediatric cancer patients: a randomized comparison, Pediatr Hematol Oncol, 2006, 23, 177-86
6. Nadler EP, et al, Monotherapy versus multi-drug therapy for the treatment of perforated appendicitis in children, Surg Infect (Larchmt)., 2003, 4, 327-33
7. Nürnberger W, et al, Tolerability of piperacillin/tazobactam in children and adolescents after high dose radio-/chemotherapy and autologous stem cell transplantation, Infection, 1998, 26, 65-7
8. Reed MD, et al, Single-dose pharmacokinetics of piperacillin and tazobactam in infants and children, Antimicrob Agents Chemother, 1994, 38, 2817-26
9. Simon A, et al, Piperacillin-tazobactam in pediatric cancer patients younger than 25 months: a retrospective multicenter survey, Eur J Clin Microbiol Infect Dis, 2007, 26, 801-6
10. Tornøe CW, et al, Optimising piperacillin/tazobactam dosing in paediatrics, Int J Antimicrob Agents, 2007, 30, 320-4
11. Viscoli C, et al, Piperacillin-tazobactam monotherapy in high-risk febrile and neutropenic cancer patients, Clin Microbiol Infect., 2006, 12, 212-6
12. Aronoff GR et al., Drug prescribing in renal failure. Dosing guidelines for children. , 2007, Fifth edition
13. Li Z et al, Population pharmacokinetics of piperacillin/tazobactam in neonates and young infants., 2013, Jun;69(6), 1223-33
14. Accord Healthcare B.V., SmPC Piperacilline-tazobactam (RVG 131844) 29-05-2024, www.geneesmiddeleninformatiebank.nl
15. UpToDate® Pediatric Drug information, Piperacillin/Tazobactam Lexicomp® Version 154.0, accessed 08/2018
16. Fresenius Kabi, SmPC Piperacillin/Tazobactam Kabi 4g/0,5g Pulver zur Herstellung einer Infusionslösung (67720.00.00), 04/2017
17. Fresenius Kabi, SmPC Piperacillin/Tazobactam Kabi 2g/0,25g Pulver zur Herstellung einer Infusionslösung (67719.00.00), 04/2017
18. European Committee on Antimicrobial Susceptibility Testing - EUCAST, Clinical breakpoints - breakpoints and guidance, https://www.eucast.org/clinical_breakpoints, Jan 2, 2023
19. Dutch Working Party on Antibiotic Policy (SWAB) - Special Interest Group Pediatrics, Expert opinion on high dosing for infections caused by microorganisms susceptible to increased doses., Dec 6, 2022

Changes

Therapeutic Drug Monitoring

Overdose