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Piperacillin + enzyme inhibitor

Classification: A

Drug products: Piperacillin and Tazobactam, Piperacillin Tazobactam, Piperacillin/Tazobactam, Piperacillin/Tazobactam Actavis, Piperacillin/Tazobactam Fresenius Kabi, Piperacillin/Tazobactam IBISQUS, Piperacillin/Tazobactam Kabi, Piperacillin/Tazobactam Mylan, Piperacillin/Tazobactam Pfizer, Piperacillin/Tazobactam Reig Jofre, Piperacillin/Tazobactam Sandoz, Piperacillin/Tazobactam Stragen, Piperacillin/Tazobaktam AB Unimedic Vial Mate, Piperacillina e Tazobactam Kabi, Pipitaz, Tazocin®, Tazopenil

ATC code: J01CR05

Summary

Published controlled studies on differences between men and women regarding piperacillin efficacy in adults are lacking. One study in children with febrile neutropenia showed no sex difference in treatment success of piperacillin-tazobactam.
 
In our opinion, the present evidence does not motivate differentiation in dosing or treatment between men and women.

Additional information

Pharmacokinetics and dosing

Studies show conflicting results whether pharmacokinetics is altered during pregnancy or not. In one study, eight parturient pregnant women and five non-pregnant women received 4 g piperacillin i.v.. The total clearance was faster in pregnant women, and the authors suggest that pregnant women may require higher doses for effective treatment of serious infections [2]. However, another study did not observe any difference between pharmacokinetics in pregnant versus non-pregnant women [3]. A study in puerperal 12 women observed a lower serum levels of piperacillin during pregnancy than 6 months after pregnancy [4].

Effects

A randomized study compared imipenem-cilastatin (60 mg/kg/day) and piperacillin-tazobactam (360 mg/kg/day) for treatment of febrile neutropenia in children with malignant diseases (41 boys, 22 girls). The authors reported that treatment success was not correlated with the patient’s sex or primary disease [1].

Adverse effects

A retrospective cohort study evaluated the risk of developing neutropenia in children <18 years old exposed to piperacillin-tazobactam (42 boys, 23 girls) compared to children exposed to ticarcillin-clavulanic acid (110 boys, 124 girls). There was an increased risk of neutropenia in the group receiving piperacillin-tazobactam and the risk was correlated with age, treatment duration, and total use, but not with the patient’s sex [5].

The risk of acute kidney injury was compared in hospitalized patients receiving combination of vancomycin and piperacillin-tazobactam or monotherapy with either drug in a retrospective study (148 men, 80 women). Multivariate analysis showed that monotherapy of each drug was associated with lower odds of acute kidney injury than the combination of the two drugs. Overall, women had higher odds of developing acute kidney injury during treatment with these drugs, but no sex-specific odds ratios were reported for each drug [6].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Updated: 2019-02-26

Date of litterature search: 2016-10-03

References

  1. Vural S, Erdem E, Gulec SG, Yildirmak Y, Kebudi R. Imipenem-cilastatin versus piperacillin-tazobactam as monotherapy in febrile neutropenia. Pediatr Int. 2010;52:262-7. PubMed
  2. Heikkilä A, Erkkola R. Pharmacokinetics of piperacillin during pregnancy. J Antimicrob Chemother. 1991;28:419-23. PubMed
  3. Voigt R, Schröder S, Peiker G. Pharmacokinetic studies of azlocillin and piperacillin during late pregnancy. Chemotherapy. 1985;31:417-24. PubMed
  4. Charles D, Larsen B. Pharmacokinetics of piperacillin in the postpartum patient. Gynecol Obstet Invest. 1985;20:194-8. PubMed
  5. Lemieux P, Grégoire JP, Thibeault R, Bergeron L. Higher risk of neutropenia associated with piperacillin-tazobactam compared with ticarcillin-clavulanate in children. Clin Infect Dis. 2015;60:203-7. PubMed
  6. Kim T, Kandiah S, Patel M, Rab S, Wong J, Xue W et al. Risk factors for kidney injury during vancomycin and piperacillin/tazobactam administration, including increased odds of injury with combination therapy. BMC Res Notes. 2015;8:579. PubMed
  7. Conicse. Stockholm: eHälsomyndigheten. 2015 [cited 2016-03-23.] länk

Authors: Linnéa Karlsson Lind

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson