Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI4SJBPRE)
  Drug Name Bupropion Drug Info Metamfetamine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Cns Stimulants
  Structure

 Mechanism of Bupropion-Metamfetamine Interaction (Severity Level: Major)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Bupropion Metamfetamine
      Mechanism 1 CYP450 2D6 inhibitor CYP450 2D6 substrate
      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 Metamfetamine caused by Bupropion mediated inhibition of CYP450 enzyme
     Increased risk of lowers seizure threshold Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Bupropion Metamfetamine
      Mechanism 2 Lower seizure threshold Lower seizure threshold
      Key Mechanism Factor 2
Factor Name Lowers seizure threshold
Factor Description The combination of medications that lower the seizure threshold is a factor that makes people with epilepsy more likely to have seizures. A seizure is a sudden, uncontrolled electrical disturbance in the brain that can cause changes in your behavior, movements or sensations, and level of consciousness.
      Mechanism Description
  • Increased risk of lowers seizure threshold by the combination of Bupropion and Metamfetamine 

Recommended Action
      Management Extreme caution is advised if bupropion is administered with any substance that can reduce the seizure threshold, particularly in the elderly and in patients with a history of seizures or other risk factors for seizures (e.g., head trauma brain tumor severe hepatic cirrhosis metabolic disorders CNS infections excessive use of alcohol or sedatives addiction to opiates, cocaine, or stimulants diabetes treated with oral hypoglycemic agents or insulin). Bupropion as well as concomitant medications should be initiated at the lower end of the dosage range and titrated gradually as needed and as tolerated. The maximum recommended dosage for the specific bupropion formulation should not be exceeded.

References
1 James WA, Lippmann S "Bupropion: overview and prescribing guidelines in depression." South Med J 84 (1991): 222-4. [PMID: 1899294]
2 Johnston JA, Lineberry CG, Ascher JA, et al. "A 102-center prospective study of seizure in association with bupropion." J Clin Psychiatry 52 (1991): 450-6. [PMID: 1744061]
3 Shin YW, Erm TM, Choi EJ, Kim SY "A Case of Prolonged Seizure Activity After Combined Use of Bupropion and Clomipramine." Clin Neuropharmacol 27 (2004): 192-194. [PMID: 15319707]