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PR4152 CA1 > CPIC recommendations > Flashcards

CPIC recommendations Flashcards

(85 cards)

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1
Q

abacavir HSR what are the symptoms (and onset)

A

fever, rash, GI (n/v/d), fatigue, malaise, respiratory sx (cough, dyspnea)

within 6 weeks of therapy
median time 8 days

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2
Q

what genotype affects abacavir

A

HLA-B*57:01

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3
Q

what happens when HLAB 5701 positive (abacavir)

A

significant risk of HSR
DO NOT RECOMMEND

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4
Q

what happens when HLAB 5701 NEGATIVE (abacavir)

A

LOW OR reduced risk of HSR
use per standard dosing guidelines

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5
Q

when to test for abacavir (locally)

A

screen only for Malay and Indian patients with late stage HIV
(CD4 < 200 cells/mm3)

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6
Q

what is the positive and negative predictive value for abacavir HSR.
what are the implications

A

ppv = around 50%
npv = >99%
= only 99/100 people will test negative, but 1 will still test positive,
therefore even a negative test result ≠ zero risk of HSR.

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7
Q

allopurinol scar reactions s/sx + onset

A

SJSTEN = fever, mucotaneous lesions (necrosis and sloughing of epidermis)

DRESS = fever, rash, multi organ failure (liver, heart , kidney, lungs)

ONSET weeks to months

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8
Q

what genotype affects allopurinol

A

HLA B 5801

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9
Q

what happens when HLAB 5801 positive (ALLOPURINOL)

stabilised?

A

significantly increased SCAR risk

CONTRAINDICATED

UNLESS patient has been stabilised and on target dose - continue taking despite being a carrier

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10
Q

what happens when HLAB 5801 NEGATIVE (ALLOPURINOL)

A

LOW OR REDUCED risk of SCAR

use standard dosing

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11
Q

when to test for allopurinol (locally)

A

locally only if patient has risk factors
- renal impairment
- old age

high prevalence among Chinese population

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12
Q

what other factors increase risk of allopurinol scar

A

antibiotics e.g. penicillin, ampicillin, cephalosporin; cyclophosphamide; thiazide diuretics; thiopurines e.g. azathioprine, mercaptopurine).

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13
Q

CBZ hypersx reactions s/sx + onset

A

SJS TENS (1502)
DRESS (hla3101)
MPE (hla3101)

MPE = mild HYPERSX reaction with only rash without mucosal or organ involvement, or systemic features

ONSET 4-28 days

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14
Q

what genotype affects CBZ

A

HLAB3101
HLAB1502

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15
Q

when to test for CBZ locally

A

STANDARD OF CARE TO TEST ALL patients for HLAB 1502
- 1502 common in asian ancestry, HLAB3101 more common in EU and JAP only

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16
Q

what happens when HLAB1502 negative AND 3101negative (CBZ)

A

normal risk = standard dosing

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17
Q

what happens when HLAB1502 negative AND 3101 positive (CBZ)

A

greater risk = if naive = do not use

if no alt agents = increase freq of monitoring and discontinue at first sign of cutaneous reaction

caution with other aromatic anticonvulsants unless severe hypersx

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18
Q

what happens when HLAB1502 positive AND 3101negative/positive (CBZ)

A

greater risk = if naive = do not use

caution with other aromatic anticonvulsants

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19
Q

if long term CBZ? but still carrier?

A

if >3 months
= continue taking

because onset is short at 4-28 days

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20
Q

phenytoin toxicity reactions s/sx + onset

A

dose related side effects: sedation, ataxia, dizziness, nystagmus, nausea, cognitive impairment

phenytoin induced SJS/TEN

usually 4-28 day onset

may also cause hematologic and hepatic toxicity

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21
Q

what genotype affects phenytoin

A

cyp2c9 polymorphism
hlab1502

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22
Q

when to test for phenytoin locally

A

no indication

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23
Q

what happens when HLAB1502 positive (phenytoin)

A

regardless of phenotype for 2c9

there is increased risk of phenytoin induced SJS TEN

DO NOT START IS PHENYTOIN NAIVE

IF already using for 3 months without incidence for cutaneous reactions, may consider continuing (with caution)

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24
Q

what happens when HLAB1502 negative + cyp2c9 NM (phenytoin)

A

NO CHANGE

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25
what happens when HLAB1502 negative + cyp2c9 IM (AS 1.5) (phenytoin)
SLIGHLTY REDUCED phenytoin metabolism may increase side effect risk but no evidence for dosing change need
26
what happens when HLAB1502 negative + cyp2c9 IM (as 1.0) (phenytoin)
reduced phenytoin metabolism - increased risk of toxicity first dose: initial loading dose subsequent doses: 25% less than typical maintenance dose adjust to TDM
27
what happens when HLAB1502 negative + cyp2c9 pm (phenytoin)
reduced phenytoin metabolism - increased risk of toxicity first dose: initial loading dose subsequent doses: 50% less than typical maintenance dose adjust to TDM
28
what genotype affects clopidogrel
2c19
29
what happens with 2c19 and clopidogrel
it affects the conversion of clopidogrel to the active metabolite = increases risk of MACE due to decreased action (reduced platelet inhibition)
30
local recommendations for testing pgx clopidogrel?
no indication/?
31
what happens when cyp2c19 UM(clopidogrel)
increased metabolite formation no change use standard dose 75mg OD
32
what happens when cyp2c19 RM (clopidogrel)
increased metabolite formation no change use standard dose 75mg OD
33
what happens when cyp2c19 NM (clopidogrel)
increased metabolite formation no change use standard dose 75mg OD
34
what happens when cyp2c19 IM (clopidogrel)
avoid standard dose use prasugrel or tica reduce active metabolite formation = increased MACE risk.
35
what happens when cyp2c19 PM (clopidogrel)
avoid standard dose use prasugrel or tica reduce active metabolite formation = increased MACE risk.
36
what genotypes affect nsaids (and which main ones affected)
2c9 with ibuprofen, celecoxib
37
what happens when 2c9 polymorphism with nsaids
ibuprofen, celecoxib increased irsk of serious GI renal and cardio ADR 2C9 main route of clearance = REDUCED FUNCTION = prolonged half life.
38
what happens when 2c9 NM for ibuprofen./ celecoxib
initiate recommended starting dose lowest effecrtive dose, shortest duration
39
what happens when 2c9 IM AS1.5 for ibuprofen./ celecoxib
initiate recommended starting dose lowest effecrtive dose, shortest duration (MILDLY reduced metabolism)
40
what happens when 2c9 IM AS1.0 for ibuprofen./ celecoxib
initiate with lowest recommended starting dose and titrate upward with caution lowest effective dose for shortest duration
40
what happens when 2c9 PM for ibuprofen./ celecoxib
25 - 50 % of starting dose titrate to 25-50% of max dose (do not dose titrate until steady state is reached = 5 and 8 days respectively) OR CHOOSE ALTERNATIVE not metabolised by 2c9
41
relevant cyp genotypes for opioids in cpic and their mechanism
codeine and tramadol metabolised by 2D6 to more active metahbolites reduced function = risk of diminished response increased function = risk of toxicity
42
what other genotypes affect opioids
OPRM1 COMT also associated with opioid clinical effec.t
43
what happens if UM 2D6 for tramadol and codeine
avoid use increased active metabolite = increased toxicity
44
what happens if IM 2D6 for tramadol and codeine
reduced morphine formation can continue using age specific or weight specific dosing
45
what happens if PM 2D6 for tramadol and codeine
avoid possible diminished anlageisa
45
relevant cyp genotypes for ppi in cpic and their mechanism
2c19 reduced function = more plasma concentration = more toxicity
46
what happens if UM 2C19 for ppi
Increase starting dose by 100 percent decreased plasma conc = risk of therapeutic failure
47
what happens if RM 2C19 for ppi
decreased plasma conc but same dosing as normal monitor
48
what happens if IM 2C19 for ppi
increase plasma conc = increased toxicity initiate at starting dose for chronic therapy >12 weeks and efficacy achieved, consider 50% reduction in daily dose
48
what happens if PM 2C19 for ppi
increase plasma conc = increased toxicity initiate at starting dose for chronic therapy >12 weeks and efficacy achieved, consider 50% reduction in daily dose
49
if 2d6 UM and fluvoxamine
no data
49
paroxetine metabolised by what enzyme and mechanism
2d6 less active
49
if 2d6 im and paroxetine
reduced metabolism = higher plasma conc = more side effects lOWER STARTING DOSE slower titration
49
if 2d6 UM and paroxetine
increased metabolism = less active compounds CHOOSE ALTERNATIVE AGENT
49
if 2d6 pM and paroxetine
reduced metabolism = higher plasma conc = more side effects 50% starting dose slower titration 50% maintenance dose
49
fluvoxamine metabolised by what enzyme and mechanism
2d6
50
if 2d6 PM and fluvoxamine
reduced metabolism = more conc = more side effects 25-50% starting slow titration OR CHOOSE ALTERNATIVE
50
if 2d6 IM and fluvoxamine
reduced metabolism = more conc = more side effects NO CHANGE
51
venlafaxine metabolised by what enzyme and mechanism
2d6 active metabolite
52
if 2d6 UM and venlafaxine
increased metabolism NO CHANGE?
53
if 2d6 IM and VENLAFAXINE
decreased metabolism to active NO CHANGE
54
vortioxetine metabolised by what enzyme and mechanism
2d6 iless active
54
if 2d6 PM and VENLAFAXINE
DECREASEd metbaolism CHOOSE ALTENRATIVE
54
if 2d6 UM and vortioxetine
increased metabolism to inactive = less clinical benefit CHOOSE ALTERNATIVE or start at normal starting dose but maintenance dose increase by 50%
55
if 2d6 IM and vortioxetine
reudced metbaolism = more side effects NO CHANGE
56
if 2d6 PM and vortioxetine
reduced metabolism = more side effects 50% OF STARTING DOSE or ALTENRATIVE
57
citalopram/escitalopram metabolised by what enzyme and mechanism
2c19 metabolise to less active
58
2c19 um and citalopram
incraease metabolism = less clinical benefit ALTERNATIVE or normal starting dose, higher maintenance dose
59
2c19 im and citalopram
reduced metabolism = more SE recommended starting dose slower titration lower maintenance dose
60
2c19 PM and citalopram
reduced metabolism = more SE ALTERNATIVE OR lower starting dose slower titration 50% maintenance dose
60
sertraline is metabolised by what enzyme and mechanism
2c19 2b6 less active metabolite 2c19 more relevant, if IM or PM lower starting dose, 50% maintenance dose OR choose alternative 2b6 = just 25% if IM or PM
60
what genotypes for statins
SLCO1B1 = metabolises ALL statins ABCG2 = rosuva 2c9 = fluvastatin
60
recommendations for statins prescribing
if slcob1 decreased or poor function, if mod sams risk + stable statin dose ≥4 weeks = continue long term if high sams risk + stable statin dose ≥1 year = continue long term OTHERWISE = CHANGE
61
slco1b1 phenotypes
transporter increased normal decreased poor function
61
rosuva + slco1b1 decreased function
increased exposure starting dose but monitor for SAMS
62
rosuva + slco1b1 poor function
<20 mg starting dose if >20 consider combination therapy
62
atorva + slco1b1 decreased function
<40mg starting dose if >40 consider combination therapy
63
atorva + slco1b1 poor function
<40mg starting dose if >40 consider combination therapy
64
simva + slco1b1 decreased function
<20mg starting dose OR CHOOSE ALT
65
simva + slco1b1 poor function
<20mg starting dose OR CHOOSE ALT
65
rosuva + abcg2 decreased function
increased exposure <20 mg starting dose if >20 consider combination therapy or alternative
66
rosuva + abcg2 POOR function
increased exposure <20 mg starting dose if >20 consider combination therapy or alternative
67
fluva 2c9 IM
<40mg starting dose if >40 = alternative
68
fluva 2c9 PM
<20mg starting dose if >20 = alternativ

PR4152 CA1 (5 decks)

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