II. Background

  1. Accounts for 2-5% of hepatic P-450 isoenzymes

III. Precautions: CYP2D6 Deficiency or poor metabolizers (5-10%)

  1. See Pharmacogenetics
  2. Populations with CYP2D6 deficiency (poor metabolizers)
    1. Occurs in 7% of white persons
  3. 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)
  4. References
    1. Ingelman-Sundberg (2005) Pharmacogenomics J 5:6-13 [PubMed]

IV. Precautions: CYP2D6 Ultrarapid metabolizers (1-2%)

  1. See Pharmacogenetics
  2. 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
  3. 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
  4. References
    1. (2013) Presc Lett 20(4): 21
    2. FDA Drug Safety Communication
      1. http://www.fda.gov/Drugs/DrugSafety/ucm339112.htm

V. Interactions: Metabolized by CYP2D6 (Substrates)

  1. Neuropsychiatric drugs
    1. Tricyclics
      1. Amitriptyline (Elavil)
      2. Desipramine (Norpramin)
      3. Imipramine
      4. Paroxetine (Paxil)
      5. Nortriptyline (Pamelor)
      6. Trimipramine (Surmontil)
    2. Antipsychotics
      1. Perphenazine (Trilafon)
      2. Risperidone (Risperdal)
      3. Haloperidol (Haldol)
      4. Thioridazine (Mellaril)
    3. Neurologic
      1. Donepezil (Aricept)
  2. Cardiopulmonary Drugs
    1. Beta Blockers
      1. Carvedilol (Coreg)
      2. Metoprolol (Lopressor)
      3. Propranolol (Inderal)
      4. Timolol
      5. Water soluble Beta-Blockers not hepatic metabolized
        1. May not be affected by CYP2D6 system
        2. Examples: Sotalol, Nadolol, Atenolol
    2. 1C Antiarrhythmics
      1. Encainide
      2. Flecainide
      3. Mexiletine
      4. Propafenone
  3. Analgesics
    1. Codeine
    2. Dextromethorphan
    3. Oxycodone
    4. Hydrocodone
    5. Tramadol (Ultram)

VI. Interactions: Inhibitor of CYP2D6

  1. Neuropsychiatric drugs
    1. Haloperidol (Haldol)
    2. Thioridazine (Mellaril)
    3. Fluoxetine (Prozac)
    4. Paroxetine (Paxil)
  2. Cardiopulmonary Drugs
    1. Amiodarone
    2. Quinidine
  3. Antibiotics
    1. Ritonavir
    2. Terbinafine (Lamisil)
  4. Miscellaneous
    1. Celecoxib (Celebrex)
    2. Cimetidine
    3. Diphenhydramine (Benadryl)

VII. Interactions: Inducer of CYP2D6

  1. Neuropsychiatric drugs
    1. Fluoxetine (Prozac)
    2. Paroxetine (Paxil)
  2. Cardiopulmonary Drugs
    1. Quinidine
    2. Amiodarone
  3. Antibiotics
    1. Ritonavir
  4. Miscellaneous
    1. Cimetidine

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Ontology: Cytochrome P-450 CYP2D6 (C0057223)

Definition (NCI) Cytochrome P450 2D6 (497 aa, ~56 kDa) is encoded by the human CYP2D6 gene. This protein plays a role in flavoprotein metabolism.
Definition (MSH) A cytochrome P450 enzyme that catalyzes the hydroxylation of many drugs and environmental chemicals, such as DEBRISOQUINE; ADRENERGIC RECEPTOR ANTAGONISTS; and TRICYCLIC ANTIDEPRESSANTS. This enzyme is deficient in up to 10 percent of the Caucasian population.
Concepts Amino Acid, Peptide, or Protein (T116) , Enzyme (T126)
MSH D019389
SnomedCT 425292000
English CYP2D6, 2-Hydroxylase, Imipramine, 4-Hydroxylase, Debrisoquine, 4-Monooxygenase, Debrisoquine, CYP 2D6, CYP2D6, Cytochrome P-450, Cytochrome P 450 CYP2D6, Cytochrome P450 2D6, Debrisoquine 4 Hydroxylase, Debrisoquine 4 Monooxygenase, Debrisoquine 4-Hydroxylase, Debrisoquine 4-Monooxygenase, Debrisoquine Hydroxylase, Hydroxylase, Debrisoquine, Imipramine 2 Hydroxylase, Imipramine 2-Hydroxylase, Monooxygenase, Sparteine, P-450 CYP2D6, Cytochrome, P450 2D6, Cytochrome, Sparteine Monooxygenase, Cytochrome p450 CYP2D6 enzyme (substance), Cytochrome p450 CYP2D6 enzyme, CYTOCHROME P 450 CYP 002 D 006, CYP 002 D 006, DEBRISOQUINE HYDROXYLASE 04, Cytochrome P-450 CYP2D6 [Chemical/Ingredient], p450 2d6, cyp2d6, Cytochrome P450-DB1, Cytochrome P-450 CYP2D6, Flavoprotein-Linked Monooxygenase, P450-2D6, P450-DB1, Cytochrome P450 Subfamily IID Polypeptide 6, Cytochrome P450, Subfamily IID-Like 1, Cytochrome P450, Subfamily IID, EC 1.14.14.1, Microsomal Monooxygenase, P450DB1, Xenobiotic Monooxygenase, CYPIID6
Swedish Cytokrom P-450 CYP2D6
Spanish enzima CYP2D6 de citocromo p450, enzima CYP2D6 de citocromo p450 (sustancia), CYP2D6, Citocromo P-450 CYP2D6, Debrisoquina 4-Hidroxilasa, Debrisoquina Hidroxilasa
Czech cytochrom P-450 CYP2D6
Finnish Sytokromi P-450 CYP2D6
Russian DEBRIZOKHIN-4-GIDROKSILAZA, DEBRIZOKHINGIDROKSILAZA, TSITOKHROM P-450 CYP2D6, ДЕБРИЗОХИН-4-ГИДРОКСИЛАЗА, ДЕБРИЗОХИНГИДРОКСИЛАЗА, ЦИТОХРОМ P-450 CYP2D6
Japanese イミプラン2-ヒドロキシラーゼ, シトクロムP-450CYP2D6, チトクロームP-450CYP2D6, デブリソキン4-ヒドロキシラーゼ, デブリソキンヒドロキシラーゼ
Italian CYP 2D6, Debrisochina 4-idrossilasi, Debrisochina idrossilasi, Sparteina monoossigenasi, Imipramina 2-idrossilasi, Citocromo P450 2D6, CYP2D6, Citocromo P-450 CYP2D6
German CYTOCHROM P 450 CYP 002 D 006, CYP 002 D 006, DEBRISOQUIN HYDROXYLASE 04, CYP2D6, Cytochrom P-450 CYP2D6, Debrisoquin-4-Hydroxylase, Debrisoquin-Hydroxylase
French CYP 2D6, Cytochrome P450 2D6, CYP2D6, Cytochrome P-450 CYP2D6, Débrisoquine 4-hydroxylase, Débrisoquine hydroxylase
Polish Cytochrom P-450 CYP2D6
Norwegian Cytokrom P-450 CYP2D6, CYP2D6, Cytokrom P450 2D6, Debrisoquine-hydroksylase, Sparteine monooxygenase, Debrisoquine-4-hydroksylase, Imipramine 2-hydroxylase, Debrisoquine-4-monooksygenase
Portuguese CYP2D6, Citocromo P-450 CYP2D6, Debrisoquina 4-Hidroxilase, Debrisoquina Hidroxilase