Interactions between depacon(valproic acid) and Doripenem (doripenem)
valproic acid and doripenem (Major Drug-Drug)
MONITOR CLOSELY: Coadministration with carbapenem antibiotics may substantially decrease the serum concentrations of valproic acid (VPA). The exact mechanism of interaction is unknown. In vitro and animal studies suggest that carbapenems may increase the metabolism of VPA to VPA glucuronide; inhibit the hydrolysis of VPA glucuronide in the liver; increase the renal clearance of VPA glucuronide; and inhibit the intestinal absorption of VPA. Clinically, the interaction has been reported with imipenem, meropenem and panipenem, often resulting in subtherapeutic levels of VPA promptly following initiation of the carbapenem and despite increases in the VPA dosage. Seizures have been reported in several cases. VPA levels typically begin to increase soon after discontinuation of the carbapenem.
MANAGEMENT: Caution is advised if valproic acid must be used concomitantly with a carbapenem. Pharmacologic response and serum valproate levels should be monitored more closely whenever a carbapenem is added to or withdrawn from therapy, and the dosage of valproic acid adjusted as necessary. Use of alternative antibiotic or antiepileptic therapy should be considered if serum valproate levels cannot be maintained in the therapeutic range or if seizures develop.
