Opioids and NSAIDs

Genes of Interest

• Opioids —> (4)

• NSAIDs —> (2)

• CYP2D6, CYP2B6, OPRM1, COMT

• CYP2C8, CYP2C9

Which antidepressants are:

1. STRONG inhibitors of CYP2D6 —> (3)

   • AS x ______

2. moderate inhibitors of CYP2D6 —>

   • AS x ______

• bupropion, fluoxetine, paroxetine

• 0

• duloxetine

• 0.5

What are the metabolites (CYP2D6) of these opioids? 

• Codeine ———> ______

• Tramadol ———> ______

• Hydrocodone ———> ______

• Oxycodone ———> ______

• Morphine

• O-desmethyl-tramadol (M1)

• Hydromorphone

• Oxymorphone

CPIC Guidelines for Opioids — CYP2D6

• Codeine —> (2) 

• Tramadol —> (2)

• Hydrocodone —>

• UM + PM —> avoid + consider a non-tramadol opioid 

• UM + PM —> avoid + consider a non-codeine opioid

• UM —> no recommendation

Which opioid has no CPIC guidelines?

Oxycodone

CPIC Guidelines – Methadone and CYP2B6

• ______ dosing for all phenotypes

• CYP2B6 poor metabolizers (PMs) have increased __________ concentrations

  • may raise the risk of __________ side effects, such as QT prolongation or cardiac arrhythmia.

• standard

• s-methadone

• toxic/adverse

What are the two pharmacodynamic genes that do not have CPIC guidelines?

OPRM1 + COMT

NSAIDs that have CPIC Guidelines

• Non-selective NSAIDs —> (4)

• COX-2 Selective NSAIDs —>

• flurbiprofen, ibuprofen, meloxicam, piroxicam

• celecoxib

CYP2C9

• inhibitors —> (2)

• inducers —> (3)

• AS based phenotype:

  • PM —> ______

  • IM —> ______

  • NM —> ______

• amiodarone, fluconazole

• rifampin, carbamazepine, aprepitant

• 0, 0.5

• 1, 1.5

• 2

CYP2C9 CPIC Guidelines

• Meloxicam —>

• Piroxicam —>

• Celecoxib, Flurbiprofen, Ibuprofen —>

• IM (1) —> 50% of lowest recommended starting dose, PM (0, 0.5) —> alternative

• IM (1) + PM —> choose an alternative

• IM (1) —> lowest recommended starting dose, PM —> 25-50% of the lowest recommended starting dose

A patient has a CYP2C9 activity score of 1 (intermediate metabolizer). You are considering prescribing meloxicam.
What would be the most appropriate recommendation?

Initiate therapy with 50% of the lowest recommended starting dose or consider alternatives.

Ibuprofen is metabolized by ______ and ______.

CYP2C8 + CYP2C9