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Imipenem

Classification: A

Drug products: Imipenem/Cilastatin Actavis, Imipenem/Cilastatin Fresenius Kabi, Imipenem/Cilastatin Pfizer, Tienam®

ATC code: J01DH51

Substances: imipenem, imipenem monohydrate

Summary

Controlled studies on differences between men and women regarding imipenem efficacy in adults are lacking. One study in children with febrile neutropenia showed no sex difference in treatment success.
 
In our opinion, the described differences do not motivate differentiated dosing or treatment in men and women.

Additional information

Pharmacokinetics and dosing

No studies with a clinically relevant sex analysis regarding imipenem pharmacokinetics in healthy volunteers have been found. In a study of imipenem in burn patients (25 men, 12 women), sex was tested as a covariate but did not influence clearance [2].

During pregnancy, plasma clearance of imipenem was found to be 2.2 times faster but renal clearance was unchanged (adjusted for body weight). The volume of distribution was 3.3 times higher and AUC was reduced with 44%. Half-life was unchanged. The authors suggests that dose adjustment may be necessary when treating pregnant women with serious infections [3].

Effects

In a randomized double-blind trial conducted by the manufacturer, adult patients (in total 1037) with complicated skin and skin structure infections received 500 mg meropenem IV every 8 h or 500 mg imipenem-cilastatin IV every 8 h. Percent of patients with satisfactory clinical response at the follow-up visit were similar in men and women receiving imipenem-cilastatin (80% and 88%, respectively) [4]. 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]. Resistance patterns for pathogens often differ between populations and ages. A Spanish study (73914 isolates from women, 29978 isolates from men) found higher percentages of imipenem resistance in E. coliisolate from men in the age group 0-54 years. In patients 55 years and older, the percentage of resistance were similar in men and women [5]. In a Turkish retrospective case-control study investigating risk factors for nosocomial imipenem-resistant Acinetobacter baumanniiinfections (83 men, 40 women), univariate analysis showed that that female sex was a significant risk factor [6]. Male sex was identified as a risk factor (OR 8.01, 95%CI 1.7-38.5) associated with hospital-acquired pneumonia caused by imipenem-resistant Pseudomonas aeruginosain a Brazilian retrospective case-control study (202 men, 140 women).

Adverse effects

No studies with a clinically relevant sex analysis regarding adverse effects of imipenem have been found.

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: 2016-08-22

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. Dailly E, Kergueris MF, Pannier M, Jolliet P, Bourin M. Population pharmacokinetics of imipenem in burn patients. Fundam Clin Pharmacol. 2003;17:645-50. PubMed
  3. Heikkilä A, Renkonen OV, Erkkola R. Pharmacokinetics and transplacental passage of imipenem during pregnancy. Antimicrob Agents Chemother. 1992;36:2652-5. PubMed
  4. Merrem IV (meropenem). DailyMed [www]. US National Library of Medicine. [updated 2016-07-27, cited 2016-08-17]. länk
  5. Sahuquillo-Arce JM, Selva M, Perpiñán H, Gobernado M, Armero C, López-Quílez A et al. Antimicrobial resistance in more than 100,000 Escherichia coli isolates according to culture site and patient age, gender, and location. Antimicrob Agents Chemother. 2011;55:1222-8. PubMed
  6. Baran G, Erbay A, Bodur H, Ongürü P, Akinci E, Balaban N et al. Risk factors for nosocomial imipenem-resistant Acinetobacter baumannii infections. Int J Infect Dis. 2008;12:16-21. 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