Details of Drug-Drug Interaction
| Drug General Information (ID: DDIBSXM9KP) | |||||||||
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| Drug Name | Aripiprazole | Drug Info | Dacomitinib | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antipsychotic Agents | Antineoplastics/Her2 Inhibitors | |||||||
| Structure | |||||||||
| Mechanism of Aripiprazole-Dacomitinib Interaction (Severity Level: Moderate) | |||||||||
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| CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Aripiprazole | Dacomitinib | |||||||
| Mechanism | CYP450 2D6 substrate | CYP450 2D6 inhibitor | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Cytochrome P450 2D6 |
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Structure
Sequence
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQLRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKVLRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAFLVSPSPYELCAVPR
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| 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.
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | Pharmacologic response to aripiprazole should be monitored more closely whenever quinidine or other potent inhibitors of CYP450 2D6 (e.g., fluoxetine, paroxetine, cinacalcet) are added to or withdrawn from therapy. The manufacturer recommends that aripiprazole dosage be reduced to one-half the normal dosage during concomitant administration with quinidine, and additional dosage adjustments be made based on clinical evaluation. Although clinical data are lacking, similar dosage adjustments may be appropriate during coadministration with other potent CYP450 2D6 inhibitors. Aripiprazole dosage should be increased accordingly if these agents are discontinued. | ||||||||
| References | |||||||||||||||||||
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| 1 | Product Information. Abilify (aripiprazole). Bristol-Myers Squibb, Princeton, NJ. | ||||||||||||||||||