Valproic acid/carbapenems interaction
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Valproic acid/carbapenems interaction Decreased valproic acid concentration and seizures (first report for valproic acid/imipenem interaction): 6 case reports Concomitant therapy with intermittent divided-dose IV infusions of valproic acid and a carbapenem antibiotic led to decreased valproic acid plasma concentrations and/or seizures in six ICU patients [see table for patient characteristics]. The patients were all critically ill and had been receiving valproic acid for unknown durations when carbapenem antibiotics were started; two patients had a remote seizure history, and one patient had poorly-controlled epilepsy. All except patient 1 developed subtherapeutic plasma valproic acid concentrations within 24–72 hours of initiation of carbapenem antibiotics. Four patients developed seizures within 24–48 hours [time to onset not stated for patient 2], and patient 1 experienced seizures < 4 hours after her first dose of IV meropenem; patient 3 was seizure-free.
Patient characteristics Pt/sex/ age (y)
Valproic acid dosage therapeutic (mg/kg/day) indication
1/F/54
13.5
2/M/61
22
3/M/47
14
Bipolar disorder Bipolar disorder Prophylaxis
4/M/67
15
Seizure
5/M/49
7.5
Epilepsy
6/M/28
25
Prophylaxis
Carbapenem drug and dosage
therapeutic indication
Meropenem Meningitis 500 mg/24h Meropenem Bacteraemia 1 g/12h Meropenem Bacteraemia 1 g/24h Meropenem Bacteraemia 1 g/18h Ertapenem Prophylaxis 1 g/24h Imipenem Pneumonia 500 mg/6h
Patient 1 received an IV valproic acid bolus, and her daily valproic acid dose was increased; however, her plasma valproic acid concentration remained largely unchanged. This patient had therapeutic valproic acid concentrations after meropenem withdrawal. Treatments for the other patients were not stated. One patient was subsequently discharged home, three to a long-term nursing facility, one to a hospice and one patient died; in the latter patient, intractable seizures were considered contributory to the cause of death. Tobin JK, et al. Valproic acid-carbapenem interaction: Report of six cases and a review of the literature. Drug Metabolism and Drug Interactions 24: 153-182, No. 803023659 2-4, 2009 - USA
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Editorial comment: A search of AdisBase, Medline and Embase did not reveal any previous case reports of an interaction between valproic acid and imipenem. The WHO ADR database contained no reports regarding the concomitant use of valproic acid and imipenem.
0114-9954/10/1308-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved
Reactions 3 Jul 2010 No. 1308
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