CYP450

CYP2D6

Cytochrome P450 2D6

Also known as: CYP2D6

What it is

Cytochrome P450 enzyme that metabolises about 20-25% of drugs, including many psychotropics, opioids and antiarrhythmics. It is highly polymorphic: there are poor, intermediate, extensive and ultrarapid metabolisers.

Role in interactions

CYP2D6 inhibition (e.g. fluoxetine, paroxetine) can double concentrations of substrates such as codeine, tramadol and metoprolol; in poor metabolisers, prodrugs activated by this enzyme (codeine → morphine) may have reduced effect.

Common substrates31

amitriptylineamphetamineatomoxetinecarvedilolchlorpheniramineclomipraminecodeinedebrisoquinedesipraminedeutetrabenazinedextromethorphandoxepinduloxetineeliglustatencainideescitalopram fluoxetinefluvoxaminehaloperidolmephedronemethoxyamphetaminemetoclopramide metoprololmexiletinenebivololnortriptylineoxycodoneparoxetineperhexilineperphenazinepropafenone

Strong evidenceModerate evidence

Inhibitors14

abirateronebupropioncinacalcetdoxepindronedaroneduloxetine fluoxetinehalofantrinemirabegronmoclobemideparoxetineperhexilinequinidineterbinafine (oral)

Strong evidenceModerate evidence

Inducers

Inducers (lista em revisão)

Clinical notes

Important in pain: codeine and tramadol depend on CYP2D6 to produce the active metabolite (morphine / O-desmethyltramadol); in poor metabolisers analgesia fails, in ultrarapid metabolisers there is a risk of opioid toxicity.