Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI5UHND0R)
  Drug Name Trimethadione Drug Info Sodium oxybate Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Anticonvulsants Anxiolytics/Sedatives/Hypnotics
  Structure

 Mechanism of Trimethadione-Sodium oxybate Interaction (Severity Level: Major)
     Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Trimethadione Sodium oxybate
      Mechanism 1 GHB dehydrogenase inhibitor GHB dehydrogenase substrate
      Key Mechanism Factor 1
Factor Name Hydroxyacid-oxoacid transhydrogenase
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Structure Sequence
MAAAARARVAYLLRQLQRAACQCPTHSHTYSQAPGLSPSGKTTDYAFEMAVSNIRYGAAVTKEVGMDLKNMGAKNVCLMTDKNLSKLPPVQVAMDSLVKNGIPFTVYDNVRVEPTDSSFMEAIEFAQKGAFDAYVAVGGGSTMDTCKAANLYASSPHSDFLDYVSAPIGKGKPVSVPLKPLIAVPTTSGTGSETTGVAIFDYEHLKVKIGITSRAIKPTLGLIDPLHTLHMPARVVANSGFDVLCHALESYTTLPYHLRSPCPSNPITRPAYQGSNPISDIWAIHALRIVAKYLKRAVRNPDDLEARSHMHLASAFAGIGFGNAGVHLCHGMSYPISGLVKMYKAKDYNVDHPLVPHGLSVVLTSPAVFTFTAQMFPERHLEMAEILGADTRTARIQDAGLVLADTLRKFLFDLDVDDGLAAVGYSKADIPALVKGTLPQERVTKLAPCPQSEEDLAALFEASMKLY
Gene Name ADHFE1
Uniprot ID HOT_HUMAN
KEGG Pathway hsa:137872
Protein Family Iron-containing alcohol dehydrogenase family
Protein Function
Catalyzes the cofactor-independent reversible oxidation of gamma-hydroxybutyrate (GHB) to succinic semialdehyde (SSA) coupled to reduction of 2-ketoglutarate (2-KG) to D-2-hydroxyglutarate (D-2-HG). D,L-3-hydroxyisobutyrate and L-3-hydroxybutyrate (L-3-OHB) are also substrates for HOT with 10-fold lower activities.
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      Mechanism Description
  • Decreased metabolism of Sodium oxybate caused by Trimethadione mediated inhibition of non-CYP450 enzyme
     Additive CNS depression effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Trimethadione Sodium oxybate
      Mechanism 2 CNS depression effects CNS depression effects
      Key Mechanism Factor 2
Factor Name CNS depression effects
Factor Description CNS depressants are drugs that inhibit or suppress brain activity and can reduce mental and physical processes. Excessive CNS depression can lead to decreased heart rate, slow breathing (less than 10 breaths per minute), extreme confusion or loss of memory, nausea and vomiting, poor judgment, blue lips or fingertips, irritability and aggression, and clammy or cold skin.
      Mechanism Description
  • Additive CNS depression effects by the combination of Trimethadione and Sodium oxybate 

Recommended Action
      Management Concomitant use of sodium oxybate with other CNS depressants should be avoided whenever possible. Otherwise, close monitoring and/or dosage reductions should be considered. For patients already stabilized on sodium oxybate who are prescribed divalproex sodium, the manufacturer recommends that the nightly dosage of sodium oxybate be reduced initially by at least 20%. Conversely, for patients already taking divalproex sodium, it is recommended that prescribers use a lower starting dosage of sodium oxybate upon initiation of treatment. Further dosage adjustments should be made according to patient response and tolerance. No specific dosage recommendations are available for use with other anticonvulsants.

References
1 Product Information. Xyrem (sodium oxybate). Orphan Medical, Minnetonka, MN.
2 Product Information. Xywav (calcium/magnesium/potass/sodium oxybates). Jazz Pharmaceuticals, Palo Alto, CA.
3 Cerner Multum, Inc. "UK Summary of Product Characteristics.".