Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIA3SEQGR)
  Drug Name Doxepin Drug Info Propafenone Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Antiarrhythmic Agents
  Structure

 Mechanism of Doxepin-Propafenone Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Doxepin Propafenone
      Mechanism 1 CYP450 2D6 substrate CYP450 2D6 inhibitor
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2D6
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Structure Sequence
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQLRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKVLRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAFLVSPSPYELCAVPR
Gene Name CYP2D6
Uniprot ID CP2D6_HUMAN
KEGG Pathway hsa:1565
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, 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) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Doxepin caused by Propafenone mediated inhibition of CYP450 enzyme
     Increased risk of prolong QT interval Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Doxepin Propafenone
      Mechanism 2 Prolong QT interval Prolong QT interval
      Key Mechanism Factor 2
Factor Name QT interval
Factor Description Long QT syndrome is a heart signaling disorder that can cause a fast, chaotic heartbeat (arrhythmia). Many people may not exhibit symptoms, and usually the condition is detected during routine medical tests. In others, the most common symptoms include: sudden fainting, palpitations, dizziness, seizures, sudden death.
      Mechanism Description
  • Increased risk of prolong QT interval by the combination of Doxepin and Propafenone 

Recommended Action
      Management Caution and clinical monitoring are recommended if a class IC antiarrhythmic agent is prescribed in combination with a tricyclic antidepressant. Pharmacologic response and serum TCA levels should be monitored more closely whenever a class IC antiarrhythmic agent is added to or withdrawn from therapy, and the TCA dosage adjusted as necessary. Patients should be advised to notify their physician if they experience possible signs and symptoms of TCA toxicity such as excessive sedation, dry mouth, blurred vision, urinary retention, constipation, tachycardia, arrhythmia, and seizures. Patients should seek medical attention if they experience symptoms that could indicate the occurrence of torsades de pointes such as dizziness, palpitations, or syncope.

References
1 Katz MR "Raised serum levels of desipramine with the antiarrhythmic propafenone ." J Clin Psychiatry 52 (1991): 432-3. [PMID: 1938981]
2 Product Information. Sinequan (doxepin). Roerig Division, New York, NY.
3 Witchel HJ, Hancox JC, Nutt DJ "Psychotropic drugs, cardiac arrhythmia, and sudden death." J Clin Psychopharmacol 23 (2003): 58-77. [PMID: 12544377]