[Seven cases of decreased serum valproic acid concentration during concomitant use of carbapenem antibiotics].

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.

[1]  M. Hirata-Koizumi,et al.  Adverse events caused by drug interactions involving glucuronoconjugates of zidovudine, valproic acid and lamotrigine, and analysis of how such potential events are discussed in package inserts of Japan, UK and USA , 2007, Journal of clinical pharmacy and therapeutics.

[2]  A. Carcas,et al.  Epileptic seizures caused by low valproic acid levels from an interaction with meropenem , 2006, Journal of clinical pharmacy and therapeutics.

[3]  P. Hantson,et al.  Pharmacokinetic interaction between valproic acid and meropenem , 2005, Intensive Care Medicine.

[4]  R. Riva,et al.  Seizure Worsening Caused by Decreased Serum Valproate During Meropenem Therapy , 2005, Journal of child neurology.

[5]  J. Borrás-Blasco,et al.  Acute Seizures Due to a Probable Interaction between Valproic Acid and Meropenem , 2005, The Annals of pharmacotherapy.

[6]  Masahiro Nakamura,et al.  MECHANISM OF THE DRUG INTERACTION BETWEEN VALPROIC ACID AND CARBAPENEM ANTIBIOTICS IN MONKEYS AND RATS , 2004, Drug Metabolism and Disposition.

[7]  H. Sağlam,et al.  Meropenem decreases serum level of valproic acid. , 2004, Pediatric neurology.

[8]  F. L. Tello,et al.  Interacción farmacocinética entre ácido valproico y antibióticos carbapenémicos: descripción de tres casos , 2003 .

[9]  J. P. Ordovás Baines,et al.  [Pharmacokinetic interaction between valproic acid and carbapenem-like antibiotics: a discussion of three cases]. , 2003, Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria.

[10]  Y. Takiguchi,et al.  Inhibition by carbapenem antibiotic imipenem of intestinal absorption of valproic acid in rats , 2001, The Journal of pharmacy and pharmacology.

[11]  H. Naganuma,et al.  Panipenem, a carbapenem antibiotic, enhances the glucuronidation of intravenously administered valproic acid in rats. , 1999, Drug metabolism and disposition: the biological fate of chemicals.

[12]  T. Hasegawa,et al.  Possible Mechanism by Which the Carbapenem Antibiotic Panipenem Decreases the Concentration of Valproic Acid in Plasma in Rats , 1998, Antimicrobial Agents and Chemotherapy.

[13]  F. Camu,et al.  Lowering of plasma valproic acid concentrations during concomitant therapy with meropenem and amikacin. , 1998, The Journal of antimicrobial chemotherapy.

[14]  A. Fujimura,et al.  Panipenem-betamipron and decreases in serum valproic acid concentration. , 1998, Therapeutic drug monitoring.

[15]  T. Matsuishi,et al.  Decrease in serum levels of valproic acid during treatment with a new carbapenem, panipenem/betamipron. , 1997, The Journal of antimicrobial chemotherapy.

[16]  M. Contin,et al.  Pharmacokinetic Interactions Between Antiepileptic Drugs , 1996, Clinical pharmacokinetics.

[17]  S. Norrby,et al.  Safety profile of meropenem: international clinical experience based on the first 3125 patients treated with meropenem. , 1995, The Journal of antimicrobial chemotherapy.

[18]  B. Pfausler,et al.  A randomised comparison of meropenem with cefotaxime or ceftriaxone for the treatment of bacterial meningitis in adults. Meropenem Meningitis Study Group. , 1995, The Journal of antimicrobial chemotherapy.

[19]  K. Shimada [最新の抗菌薬XLVI] Panipenem/Betamipron , 1994 .

[20]  K. Shimada [New antimicrobial agent series XLVI: panipenem/betamipron]. , 1994, The Japanese Journal of Antibiotics.

[21]  Y. Sugiyama,et al.  Drug interaction. Effects of salicylate on pharmacokinetics of valproic acid in rats. , 1990, Drug Metabolism And Disposition.

[22]  G. Zaccara,et al.  Clinical Pharmacokinetics of Valproic Acid — 1988 , 1988, Clinical pharmacokinetics.

[23]  J. Sackellares,et al.  Reduction of Steady‐State Valproate Levels by Other Antiepileptic Drugs , 1981, Epilepsia.

[24]  R. Cutler,et al.  Effects of carbamazepine on valproic acid kinetics in normal subjects , 1979, Clinical pharmacology and therapeutics.

[25]  J. Cramer,et al.  Valproic acid in epilepsy: Clinical and pharmacological effects , 1978, Annals of neurology.