Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDICZPEX6D)
  Drug Name Tramadol Drug Info Abiraterone Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Antineoplastics
  Structure

 Mechanism of Tramadol-Abiraterone Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tramadol Abiraterone
      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 Tramadol caused by Abiraterone mediated inhibition of CYP450 enzyme
     Increased risk of prolong QT interval Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tramadol Abiraterone
      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 Tramadol and Abiraterone 

Recommended Action
      Management Concomitant use of abiraterone and tramadol should generally be avoided. If coadministration is required, careful consideration of the effects on tramadol and M1 is required. Patients should be monitored for opioid withdrawal, seizures, and serotonin syndrome, and care should be exercised in patients suspected to be at an increased risk of torsade de pointes. If abiraterone is discontinued, consider reducing the tramadol dose until stable drug effects are achieved and monitor for respiratory depression and sedation. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References
1 Cerner Multum, Inc. "Australian Product Information.".
2 Cerner Multum, Inc. "Canadian Product Information.".
3 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
4 Product Information. Eligard (leuprolide). Sanofi Winthrop Pharmaceuticals, New York, NY.
5 Product Information. Firmagon (degarelix). Ferring Pharmaceuticals Inc, Tarrytown, NY.
6 Product Information. Lupron (leuprolide). TAP Pharmaceuticals Inc, Deerfield, IL.
7 Product Information. Plenaxis (abarelix). Praecis Pharmaceuticals Inc, Waltham, MA.
8 Product Information. Trelstar (triptorelin) Pharmacia and Upjohn, Kalamazoo, MI.
9 Product Information. Ultram (tramadol). McNeil Pharmaceutical, Raritan, NJ.
10 Product Information. Vantas (histrelin). Endo Pharmaceuticals (formally Indevus Pharmaceuticals Inc), Lexington, MA.
11 Product Information. Zoladex (goserelin). Zeneca Pharmaceuticals, Wilmington, DE.
12 Product Information. Zytiga (abiraterone). Centocor Inc, Malvern, PA.
13 European Medicines Agency Pharmacovigilance Risk Assessment Committee "PRAC recommendations on signals. Adopted at the PRAC meeting of 8-11 September 2014".