Cytochrome P-450 2D6 Isoenzyme

See Pharmacogenetics
Populations with CYP2D6 deficiency (poor metabolizers)
1. Occurs in 7% of white persons
Consequences of CYP2D6 Deficiency
1. Exaggerated physiologic response to substrate medications listed below
2. No response to Codeine or Tramadol (not metabolized to active form)
3. Fluoxetine and Nortriptyline risk of toxicity
4. Amitriptyline, Nortriptyline, Paroxetine risk of toxicity (reduce starting dose by 50%)
5. Aripiprazole (Abilify) risk of toxicity (reduce starting dose)
6. Atomoxetine (Strattera) risk of toxicity (reduce starting dose)
References
1. Ingelman-Sundberg (2005) Pharmacogenomics J 5:6-13 [PubMed]

See Pharmacogenetics
Populations with CYP2D6 ultrarapid metabolization (fast metabolizers)
1. Occurs in 5% of caucasians and african americans
2. Occurs in 30% of arabs or North Africans
Consequences of CYP2D6 ultrarapid metabolization
1. Amitriptyline, Nortriptyline, Paroxetine with reduced response (consider other agents)
2. Increased Codeine metabolization to Morphine
  1. Also effects Hydrocodone, Oxycodone and Tramadol
  2. Risk of Opioid induced respiratory depression and other Overdose adverse effects
  3. Children are especially susceptible (deaths have occurred)
  4. Deaths in children have occurred with codeine Analgesics following Tonsillectomy and adenoidectomy
  5. Resulted in FDA black box warning in 2013
References
1. (2013) Presc Lett 20(4): 21
2. FDA Drug Safety Communication
  1. http://www.fda.gov/Drugs/DrugSafety/ucm339112.htm