Pharmacogenomics (PGx) Flashcards
Based on the drug and indication, identify the gene/CYP enzyme affected and recommendations for different genotypes.
Substrates (5) and inhibitors (1) of:
Sertaline
Substrates: CYP3A4 (major), CYP2B6 (minor), CYP2C19 (minor), CYP2D6 (minor), CYP2C9 (minor)
Inhibitor: CYP2D6 (weak)
Abacavir
anti-HIV
HLA-B*5701
HLA-B5701 (-): Use abacavir per standard dosing guidelines
HLA-B5701 (+): Abacavir is not recommended
Substrates and inhibitors of:
Hydrocodone
Substrates: CYP2D6 (minor, active > Hydromorphone) CYP3A4 (major)
Tramadol
Pain
CYP2D6
URM (AS > 2.25): Avoid tramadol. Consider non-codeine opioid
NM/IM (0 < AS < 2.25): Use tramadol as per normal
PM (AS = 0): Avoid tramadol use because of diminished analgesia
Substrates (7) and inhibitors (2) of:
Fluoxetine
Substrates: CYP1A2 (minor), CYP2B6 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP2E1 (minor), CYP3A4 (minor)
Inhibitor: CYP2D6 (strong), CYP2C19 (moderate)
Substrates (2) and inhibitors (0) of:
Oxycodone
Substrates: CYP2D6 (minor), CYP3A4 (major)
Substrates (2) and inducers (8) of:
Carbamazepine
Substrates: CYP2C8 (minor), CYP3A4 (major)
Inducer: BCRP/ABCG2, CYP1A2 (weak), CYP2B6 (moderate), CYP2C9 (weak), CYP3A4 (strong), SLCO1B1/1B3, P-glycoprotein, UGT1A1
Statins
Hyperlipidemia
SLCO1B1
↑ /Normal func: Prescribe desired starting dose
↓ func: Prescribe ≤40mg (starting dose)
Poor func: Prescribe ≤20mg (starting dose)
Vortioxetine
SSRI
CYP2D6
URM: Select alternative antidepressant, else initiate at standard dose and consider increasing maintenance dose by 50%
NM/IM: Initiate therapy at recommended starting dose
PM: Initiate 50% of starting dose, else consider alternative antidepressant
Substrates (7) and inhibitors (1) of:
Bupropion
Substrates: CYP2B6 (major), CYP1A2 (minor), CYP2A6 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP2E1 (minor), CYP3A4 (minor)
Inhibitor: CYP2D6 (strong)
Sertraline
SSRI
CYP2C19
UM/RM/NM: Initiate therapy with recommended starting dose
IM: Initiate with recommended starting dose, but consider a slower titration schedule and lower maintenance dose
PM: Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose
CYP2B6
UM/RM/NM: Initiate therapy with recommended starting dose
IM: Initiate therapy with recommended starting dose, but lower maintenance dose and slowly titrate.
PM: Consider a lower starting dose, slower titration schedule and 25% of standard maintenance dose
Substrates (3) and inducers (6) of:
Phenytoin
Substrates: CYP2C19 (major), CYP2C9 (major), CYP3A4 (minor)
Inducer: CYP1A2 (weak), CYP2B6 (weak), CYP3A4 (strong), P-GP/ABCB1, UGT1A1, UGT1A4
Paroxetine
SSRI
CYP2D6
UM (AS > 2.25): Select alternative drug not predominantly metabolized by CYP2D6.
NM (1.25<AS<2.25): Initiate therapy with recommended starting dose.
IM (0<AS<1.25): Consider a lower starting dose and slower titration schedule as compared to normal metabolizer
PM: Select an alternative drug not predominantly metabolized by CYP2D6/ If paroxetine use is warranted, consider a 50% reduction in recommended starting dose, slower titration schedule, and a 50% lower maintenance dose as compared to normal metabolizers.
Phenytoin
Antipsychosis
HLA-B *15:02
HLA-B15:02 (-): Use at standard dosings.
HLA-B15:02 (+): If the patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Also avoid carbamazepine/ oxcarbamazepine.
If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future.
CYP2C9
Norm. (AS 2)/ Inter. (AS 1.5) Metab.: No adjustments needed from typical dosing strategies.
Inter. Metab. (AS 1): For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose.
Poor Metab.: For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose.
Substrates (4) and inhibitors (0) of:
Venlafaxine
Substrates: CYP3A4 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (minor > Active metabolite [Desvenlafaxine])
Substrates (4) and inhibitors (0) of:
Nortriptyline
Substrate: CYP1A2 (minor), CYP2C19 (minor), CYP2D6 (major), CYP3A4 (minor)
Substrates (3) and inhibitors (1) of:
Escitalopram/ citalopram
Substrates: CYP2C19 (major), CYP2D6 (minor), CYP3A4 (minor)
Inhibitor: CYP2D6 (weak)
Substrates (4) and inhibitors (0) of:
Rosuvastatin
Substrates: BCRP/ABCG2, CYP2C9 (minor), CYP3A4 (minor), OATP1B1/1B3 (SLCO1B1/1B3)
Substrates (4) and inhibitors (0) of:
Codeine
Substrates: CYP2D6 (major, active > Morphine), UGT2B7 and UGT2B4, CYP3A4 (major)
Substrates (1) and inhibitors (1) of:
Abacavir
Substrate: BCRP/ABCG2
Inhibitor: MRP2
Clopidogrel
Cardiovascular
CYP2C19
URM/RM/NM: Use at standard dose (75 mg/day)
IM/PM: Avoid standard dose clopidogrel (75 mg) if possible. Use prasugrel or ticagrelor at standard dose if no contraindication.
Substrates (5) and inhibitors (2) of:
Omeprazole
Substrates: CYP2C19 (major), CYP2A6 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (minor)
Inhibitors: CYP2C19 (weak), OAT1/3
Clopidogrel
Neurovascular
CYP2C19
URM/RM: No recommendation
NM: If considering clopidogrel, use at standard dose (75 mg/day)
IM: Consider an alternative P2Y12 inhibitor at standard dose if clinically indicated and no contraindication.
PM: Avoid clopidogrel if possible. Consider an alternative P2Y12 inhibitor at standard dose if clinically indicated and no contraindication.
Escitalopram / Citalopram
SSRI
Generally: Consider alternatives not predominantly metabolized by CYP2C19.
URM: If adequate efficacy is not achieved at standard maintenance dosing, consider titrating to a higher maintenance dose.
RM: Initiate therapy with recommended starting dose. If inadequate response, consider titrating to a higher maintenance dose.
NM: Initiate therapy with recommended starting dose.
IM: Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.
PM: Consider a lower starting dose, slower titration schedule and 50% reduction of the standard maintenance dose as compared to normal metabolizers.
Substrates (3) and inhibitors (0) of:
Morphine
Substrates: OCT, P-GP/ABCB1 (major), UGT1A
Codeine
Cough
CYP2D6
[DWG] UR: If presenting with CYP3A4 inhibitors, and/or reduced eGFR: Dose Codeine less than 20 mg q6h for adults or 10 mg q6h for children. Else, dose normally.
[DWG] IM/PM: No action is required
Oxycodone
Pain
CYP2D6
COMT, OPRM1
No recommedations
Substrates (2) and inhibitors (1) of:
Duloxetine
Substrate: CYP1A2 (major), CYP2D6 (major)
Inhibitor: CYP2D6 (mod.)
Substrates (2) and inhibitors (3) of:
Clopidogrel
Substrates: CYP2C19 (major, active), CYP3A4 (minor, active)
Inhibitors: BCRP/ABCG2, CYP2B6 (weak), CYP2C8 (moderate)
Omeprazole
PPI
CYP2C19
URM: Increase starting daily dose by 100% (given in divided doses)
RM/NM: Initiate standard starting daily dose (given in divided doses). Consider increasing the dose by 50-100%.
IM/PM: Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.
Substrates (3) and inhibitors (0) of:
Tramadol
Substrates: CYP2B6 (minor), CYP2D6 (major, active), CYP3A4 (major, inactive)
What is phenoconversion?
Phenotype clinically deviates from the genotype, and can be due to many factors such as drug interactions, organ functions and nutrition.
Codeine
Pain
CYP2D6
UM (AS > 2.25): Avoid use of codeine due to toxicity. If opioid use is warranted, consider a non-tramadol opioid.
NM/IM (0 < AS < 2.25): Use codeine as per label
PM (AS = 0): Avoid codeine due to possible diminished analgesia
Substrates (2) and inhibitors (1) of:
Paroxetine
Substrates: CYP2D6 (major), CYP3A4 (major)
Inhibitor: ABCB1
Fluvoxamine
SSRI
CYP2D6
UM: No recommendation due to lack of evidence
NM/IM: Recommended starting dose
PM: Consider a 25–50% lower starting dose and slower titration schedule or consider an alternative antidepressant not predominantly metabolized by CYP2D6
Substrates (4) and inhibitors (0) of:
Mirtazapine
Substrate: CYP1A2 (minor), CYP2C19 (minor), CYP2D6 (minor), CYP3A4 (major)
Substrates (4) and inhibitors (0) of:
Other Statins
Substrates: BCRP/ABCG2, CYP3A4 (major), SLCO1B1, P-glycoprotein (minor)
Amitriptyline / Nortriptyline / Desipramine / Clomipramine
TCA
CYP2D6 (Amitriptyline/Nortriptyline/Desipramine/Clomipramine)
URM: Avoid TCA due to potential lack of efficacy. Consider alternative drug not metabolised by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose.
NM: Initiate therapy with recommended starting dose.
IM: Consider a 25% reduction of recommended starting dose.
PM: Avoid TCA use due to potential for side effects. Consider alternative drug not metabolised by CYP2D6. If a TCA is warranted, consider a 50% reduction of recommended starting dose.
CYP2C19 (Amitriptyline/Clomipramine)
URM/RM: Consider alternative drug not metabolised by CYP2C19. TCAs without major CYP2C19 include nortriptyline and desipramine.
NM/IM: Initiate therapy with recommended starting dose.
PM: Consider alternative drug not metabolised by CYP2C19. TCAs without major CYP2C19 include nortriptyline and desipramine. For tertiary amines, consider 50% reduction of recommended starting dose
Carbamazepine
Anti-epileptic
HLA-B*15:02
HLA-B15:02 (-): Use carbamazepine per standard dosing guidelines
HLA-B15:02 (+): If patient is carbamazepine-naive, do not use carbamazepine.
If the patient has previously used carbamazepine consistently for longer than 3 months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine in the future.
HLA-A*31:01
HLA-A*31:01 (-): Use carbamazepine per standard dosing guidelines
HLA-A*31:01 (+): If patient is carbamazepine-naive and alternative agents are available, do not use carbamazepine.
If patient is carbamazepine-naive and alternative agents are not available, consider the use of carbamazepine with increased frequency of clinical monitoring. Discontinue therapy at first evidence of a cutaneous adverse reaction.
If patient has previously used carbamazepine for > 3 months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine.
Substrates (6) and inhibitors (0) of:
Amitriptyline
Substrate: CYP1A2 (minor), CYP2B6 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP3A4 (minor), CYP2D6 (major > Nortriptyline [active])
Substrates (2) and inhibitors (5) of:
Fluvoxamine
Substrates: CYP1A2 (minor), CYP2D6 (minor)
Inhibitor: CYP1A2 (strong), CYP2C19 (mod.), CYP2C9 (weak), CYP2D6 (weak), CYP3A4 (weak)
Allopurinol
Gout
HLA-B *58:01
HLA-B*58:01 (-): Use allopurinol per standard dosing guidelines
HLA-B*58:01 (+): Allopurinol is contraindicated
ABCG2
G/G: Normal genotype. Dosing schedule of 100, 200, 300 and 400 mg/day.
G/T: Use 1.25X the standard dose. Dosing schedule of 100, 200, 400 and 500 mg/day
T/T: Use 1.4X the standard dose. Dosing schedule of 100, 300, 400, 600 and 700 mg/day
Substrates (1) and inhibitors (0) of:
Desvenlafaxine
Substrate: CYP3A4 (minor)
Venlafaxine
SNRI
CYP2D6
UM/NM/IM (0< AS< 2.25): Initiate therapy with recommended starting dose
PM: Consider alternative antidepressant
