Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIJO0BTM7)
  Drug Name Haloperidol Drug Info Ethotoin Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antipsychotic Agents Anticonvulsants
  Structure

 Mechanism of Haloperidol-Ethotoin Interaction (Severity Level: Moderate)
     CYP450 enzyme induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Haloperidol Ethotoin
      Mechanism 1 CYP450 substrate CYP450 inducer
      Key Mechanism Factor 1
Factor Name Cytochrome P450 Structure Sequence
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:20702771, PubMed:19965576, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:2732228, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:21576599, PubMed:21490593). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:14559847, PubMed:12865317). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:2732228, PubMed:15373842, PubMed:15764715, PubMed:22773874). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:2732228, PubMed:15373842, PubMed:15764715). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981).
    Click to Show/Hide
      Mechanism Description
  • Increased metabolism of Haloperidol caused by Ethotoin mediated induction of CYP450 enzyme
     Antagonize the effect of antiepileptic agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Haloperidol Ethotoin
      Mechanism 2 Lower seizure threshold Antiepileptic agent
      Key Mechanism Factor 2
Factor Name Antiepileptic agents
Factor Description The beneficial effects of antiepileptic drugs may be reduced, leading to an increase in seizure frequency or duration.
      Mechanism Description
  • Antagonize the effect of Ethotoin when combined with Haloperidol 

Recommended Action
      Management Close observation for decreased neuroleptic effect is indicated during concurrent use and for increased or adverse effects after the hydantoin is discontinued. Patients should be monitored for loss of seizure control.

References
1 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2 Linnoila M, Viukari M, Vaisanen K, Auvinen J "Effect of anticonvulsants on plasma haloperidol and thioridazine levels." Am J Psychiatry 137 (1980): 819-21. [PMID: 6770696]
3 Product Information. Haldol (haloperidol). McNeil Pharmaceutical, Raritan, NJ.
4 Product Information. Peganone (ethotoin) Abbott Pharmaceutical, Abbott Park, IL.