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Lee, Kim, Joo, and Kwon: Seven Cases of Decreased Serum Valproic Acid Concentration During Concomitant Use of Carbapenem Antibiotics
Original Article

Korean J Leg Med 2007;27(5):338-343.

Published online: 14 February 2007

DOI: https://doi.org/10.3343/kjlm.2007.27.5.338

Seven Cases of Decreased Serum Valproic Acid Concentration During Concomitant Use of Carbapenem Antibiotics

Sang-Guk Lee, M.D.1, Jeong-Ho Kim, M.D.1, Jin Yang Joo, M.D.2, Oh Hun Kwon, M.D.3

1Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

2Department of Neurosurgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

3Yongdong Severance Hospital, Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

Received 6 June 200727 July 2007       Accepted 5 August 2007

Copyright © 2007 by the Korean Society for Legal Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Valproic acid (VPA) is a commonly prescribed anticonvulsant drug for the treatment of various forms of epilepsy. Concomitant administration of VPA and carbapenem antibiotics such as panipenem/betamipron and meropenem has been reported to decrease the serum level of VPA. We observed seven cases which showed a decrease in serum levels of VPA due to concomitant use of VPA and carbapenem from January 2002 to October 2006 in a 750-bed university hospital, the average decrease of 70.4% was observed. Carbapenem antibiotics administrated concomitantly with VPA were panipenem (1 case), meropenem (3 cases), and imipenem (2 cases), and in one other case imipenem and meropenem were used sequentially. We found the VPA serum levels were significantly decreased with meropenem (n=4) more than with other carbapenem antibiotics (n=4, 89.3% vs. 51.5% decrease, P=0.03). Clinicians should be aware of this potential interaction, pay attention to the failure of seizure control due to decreased serum VPA levels with concomitant use of carbapenem antibiotics, and monitor VPA serum levels for those cases.

Keywords: Valproic acid, Carbapenem, Meropenem, Imipenem, Panipenem, Drug interaction, Therapeutic drug monitoring

REFERENCES

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Table 1.
Summary of seven cases of decreased serum valproic acid levels with concomitant use of carbapenem antibiotics
Case Age Sex Diagnosis Carbapenem antibiotic VPA dose Effect on VPA concentration Clinical outcome
1 57 M Left MCA infarction Panipenem 900 mg/day ↓by 74% Seizure attak at the 9th day of panipenem
2 56 M Intracranial hemorrhage Meropenem 900 mg/day ↓by 91% No seizure attack
3 65 M Intracranial hemorrhage Imipenem 1,200 mg/day ↓by 70% No seizure attack
4 79 M Meningioma Meropenem 1,200 mg/day ↓by 88% No seizure attack
5 80 F Epidural hemorrhage Meropenem 1,080 mg/day ↓by 88% No seizure attack
6 51 M subdural hemorrhage Imipenem 1,000 mg/day ↓by 29% No seizure attack
7 28 M Chordoma Imipenem 1,200 mg/day ↓by 34% No seizure attack
        Meropenem 1,200 mg/day ↓by 89% No seizure attack
Table 2.
Reports of valproic acid-carbapenem antibiotics interactions
Case report (Publication year, author, reference number) Patient Carbapenem antibiotic VPA dose Effect on VPA concentration Clinical outcome
Age Gender
1997 Nagai et al. [8] 10 M Panipenem 8.3 mg/kg q8h ↓by 93% Seizure (day 16)
    8 F Panipenem 500 mg/day ↓by 95% No seizure
    10 F Panipenem 5 mg/kg q12h ↓Not described Seizure (day 2)
1998 De Turck et al.[15] 65 F Meropenem 1,200 mg/day ↓by 60% No seizure
    57 F Meropenem 1,200 mg/day ↓by 89% No seizure
1998 Yamagata et al.[7] 3 F Panipenem 35 mg/kg/day ↓by 65% Seizure (day 3)
    22 M Panipenem 32 mg/kg/day ↓by 74% Seizure (day 2)
    4 F Panipenem 25 mg/kg/day ↓by 58% No seizure
2002 Roe et al.[19] 26 M Meropenem 1,500 mg/day ↓by 77% Seizure (day 5)
    32 F Meropenem 1,080 mg/day ↓by 87% No seizure
    50 F Meropenem 900 mg/day ↓by 93% No seizure
2003 Llinares et al.[14] 28 M Imipenem 1,600 mg/day ↓by 45% No seizure
    71 F Meropenem 1,500 mg/day ↓by 75% Seizure (day 9)
    24 F Meropenem 1,000 mg/day ↓by 95% No seizure
2004 Nacarkucuk et al.[13] 14 M Meropenem 50 mg/kg/day ↓by 79% No seizure
    7M F Meropenem 75 mg/kg/day ↓by 80% No seizure
    14 M Meropenem 75 mg/kg/day ↓by 88% No seizure
2005 Covert-Orts et al.[11] 21 F Meropenem 1,920 mg/day ↓by 87% Seizure (day 2)
2005 Clause et al.[12] 30 M Meropenem 150 mg/hr ↓by 72% No seizure
    77 M Meropenem 130 mg/hr ↓by 49% No seizure
2006 Fudio et al.[9] 50 F Meropenem 1,500 mg/day ↓by 85% Seizure (day 5)
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