Interacting drugs | Effects (probable mechanism) | Management |
Valproate, with: | ||
Carbamazepine | Decreased valproate effect and possible increased toxicity (increased metabolism by CYP 2C9, 2C19, glucuronidation, and formation of toxic metabolite) | Monitor clinical status and valproate concentrations |
Carbamazepine toxicity (increased concentration of active epoxide metabolite¶ and displacement from binding sites) | Monitor clinical status and carbamazepine and carbamazepine epoxide concentrations; carbamazepine dose may need to be adjusted | |
Ethosuximide | Possible ethosuximide toxicity (decreased metabolism) | Monitor clinical status and ethosuximide concentrations |
Possible decreased valproate effect (mechanism not established) | Monitor clinical status and valproate concentrations | |
Felbamate | Possible decreased felbamate effect (mechanism unknown) | Monitor clinical status |
Possible valproate toxicity (decreased metabolism by CYP2C19) | Monitor clinical status and valproate concentrations. A reduction in valproate dose is recommended when initiating felbamate. Specific dose adjustment recommendations are provided in the drug monograph included within UpToDate. | |
Lamotrigine | Lamotrigine toxicity (decreased metabolism; glucuronidation) | Decrease lamotrigine dose by approximately 50%; monitor clinical status and lamotrigine concentrations. Specific lamotrigine dose adjustment recommendations for use with valproate are provided in the drug monograph included within UpToDate. |
Oxcarbazepine | Possible decreased oxcarbazepine effect (increased metabolism) | Monitor clinical status and oxcarbazepine concentrations |
Phenobarbital | Possible phenobarbital toxicity (decreased metabolism by CYP2C9 and glucuronidation) | Monitor clinical status and phenobarbital concentrations |
Possible decreased valproate effect (increased metabolism by glucuronidation and CYP oxidation) | Monitor clinical status and valproate concentrations | |
Phenytoin | Possible phenytoin toxicity (displacement from binding sites and decreased metabolism; complex time course) | Monitor clinical status and phenytoin concentrations (unbound concentrations may be more helpful than total) |
Possible decreased valproate effect and increased toxicity (increased metabolism and formation of toxic valproate metabolites) | Monitor clinical status and valproate serum concentrations | |
Rufinamide | Possible increased rufinamide toxicity (decreased metabolism) | Monitor clinical status; a decrease in initial rufinamide dose is recommended. Specific rufinamide dose adjustment recommendations for use with valproate are provided in the drug monograph included within UpToDate. |
Topiramate | Possible increased hepatotoxic effect of valproate and increased risk for hypothermia (mechanism not established) | Monitor clinical status |
CYP: cytochrome P450.
* Not all potential interactions are listed. Additional interactions of antiseizure medications and management suggestions may be determined using the drug interactions program included within UpToDate.
¶ Routine carbamazepine serum measurements do not assess for accumulation of the active carbamazepine-epoxide metabolite, but this metabolite can be measured as a separate test; refer to accompanying text.Adapted from: Drugs for Epilepsy. Treatment guidelines from The Medical Letter 2008; 6(70):37-46. Copyright © 2008 The Medical Letter.
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