. Author manuscript; available in PMC: 2019 Apr 1.

Published in final edited form as: Clin Pharmacol Ther. 2017 Oct 10;103(4):599–618. doi: 10.1002/cpt.762

Table 4.

Gene-drug pairs and dose recommendations by CPIC and the DPWG (differences in dosing recommendations of ≥20% are marked bold)

Gene	Drug	Gene-drug Interaction	Phenotype	Action Required?	Therapeutic Recommendations + Classification of Evidence		Cat.	Ref.
CYP2C9	Phenytoin	CPIC: Yes	IM	Yes	Consider 25% reduction of recommended starting maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring and response.	M		(19)
		CPIC: Yes	PM	Yes	Consider 50% reduction of recommended starting maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring and response.	S		(19)
		DPWG: Yes	IM	Yes	Standard loading dose. Reduce maintenance dose by 25%. Evaluate response and serum concentration after 7–10 days. Be alert to ADEs (e.g., ataxia, nystagmus, dysarthria, sedation).	4D		(5–7)
		DPWG: Yes	PM	Yes	Standard loading dose. Reduce maintenance dose by 50–60%. Evaluate response and serum concentration after 7–10 days. Be alert to ADEs (e.g., ataxia, nystagmus, dysarthria, sedation).	4D		(5–7)
CYP2C9	Warfarin	CPIC: Yes	1/2	Yes	Calculate dose based on validated published pharmacogenetic algorithm	S	V	(17;18)
			1/3	Yes	Calculate dose based on validated published pharmacogenetic algorithm	S	V
			2/2	Yes	Calculate dose based on validated published pharmacogenetic algorithm	S	V
			2/3	Yes	Calculate dose based on validated published pharmacogenetic algorithm	S	V
			3/3	Yes	Calculate dose based on validated published pharmacogenetic algorithm	S	V
		DPWG: Yes	1/2	Yes	Initiate therapy with recommended starting dose	4A	V	(7)
			1/3	Yes	Consider a reduction to 65% of the normal starting dose	4D	V
			2/2	Yes	Consider a reduction to 65% of the normal starting dose	4A	V
			2/3	Yes	Consider a reduction to 45% of the normal starting dose	4A	V
			3/3	Yes	Consider a reduction to 45% of the normal starting dose	4C	V
CYP2C19	Amitriptyline	CPIC: Yes	IM	No	Initiate therapy with recommended starting dose	S		(24;25)
			PM	Yes	1) Avoid amitriptyline use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include nortriptyline and desipramine. 2) Consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	M	III
			UM or RM	Yes	1) Avoid amitriptyline use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include nortriptyline and desipramine. 2) If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	O	III
		DPWG: Yes	IM	No	Initiate therapy with recommended starting dose.	IN		(7)
			PM	No	Initiate therapy with recommended starting dose.	IN	III
			UM	No	Initiate therapy with recommended starting dose.	IN	III
CYP2C19	Citalopram / Escitalopram	CPIC: Yes	IM	No	Initiate therapy with recommended starting dose.	S	III	(26)
			PM	Yes	1) Consider a 50% reduction of recommended starting dose and titrate to response. 2) Select alternative drug not predominantly metabolized by CYP2C19.	M
			UM	Yes	Consider an alternative drug not predominantly metabolized by CYP2C19.	M	III
		DPWG: Yes	IM	Yes	1) Consider a maximum daily dose of 20 mg for age < 65 or 10 mg for ≥ 65 years. 2) Consider a 50% reduction in starting dose and raise to normal dose under monitoring of ECG to 40 mg for age < 65 or 20 mg for ≥ 65 years.	4A	III	(6;7)
			PM	Yes	Consider a maximum daily dose of 20 mg for age < 65 or 10 mg for ≥ 65 years.	4A
			UM	No	Initiate therapy with recommended starting dose.	3AA	III
CYP2C19	Clopidogrel	CPIC: Yes	IM	Yes	Consider alternative drug not metabolized by CYP2C19.	M		(20;21)
			PM	Yes	Consider alternative drug not metabolized by CYP2C19.	S
			UM	No	Initiate therapy with recommended starting dose.	S
		DPWG: Yes	IM	Yes	Consider alternative drug not metabolized by CYP2C19.	4F		(6;7)
			PM	Yes	Consider alternative drug not metabolized by CYP2C19.	4F
			UM	No	Initiate therapy with recommended starting dose.	4A
CYP2C19	Clomipramine	CPIC: Yes	IM	No	Initiate therapy with recommended starting dose.	O		(24;25)
			PM	Yes	1) Avoid clomipramine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include nortriptyline and desipramine. 2) Consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	O	III
			UM or RM	Yes	1) Avoid clomipramine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include nortriptyline and desipramine. 2) If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	O	III
		DPWG: Yes	IM	No	Initiate therapy with recommended starting dose.	IN		(7)
			PM	No	Initiate therapy with recommended starting dose.	IN	III
			UM	No	Initiate therapy with recommended starting dose.	IN	III
CYP2C19	Doxepin	CPIC: Yes	IM	No	Initiate therapy with recommended starting dose	O		(24;25)
			PM	Yes	1) Avoid doxepin use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include nortriptyline and desipramine. 2) Consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	O	III
			UM or RM	Yes	1) Avoid doxepin use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include nortriptyline and desipramine. 2) If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	O	III
		DPWG: No	IM	No	Initiate therapy with recommended starting dose.	IN		(7)
			PM	No	Initiate therapy with recommended starting dose.	IN	III
			UM	No	Initiate therapy with recommended starting dose.	IN	III
CYP2C19	Imipramine	CPIC: Yes	IM	No	Initiate therapy with recommended starting dose.	O		(24;25)
			PM	Yes	1) Avoid imipramine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include nortriptyline and desipramine. 2) Consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	O	III
			UM or RM	Yes	1) Avoid imipramine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include nortriptyline and desipramine. 2) If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	O	III
		DPWG: Yes	IM	No	Initiate therapy with recommended starting dose.	4A		(6;7)
			PM	Yes	1) Consider a 30% reduction of recommended starting dose and utilize therapeutic drug monitoring of imipramine and desipramine. 2) Consider alternative drug not metabolized by CYP2C19.	4A	III
			UM	No	Initiate therapy with recommended starting dose	4A	III
CYP2C19	Sertraline	CPIC: Yes	IM	No	Initiate therapy with recommended starting dose.	S	III	(26)
			PM	Yes	1) Consider a 50% reduction of recommended starting dose and titrate to response. 2) Select alternative drug not predominantly metabolized by CYP2C19.	O	III
			UM	Yes	Initiate therapy with recommended starting dose. If patient does not respond to recommended maintenance dosing, consider alternative drug not predominantly metabolized by CYP2C19.	O
		DPWG: Yes	IM	Yes	Consider a maximum daily dose of 100 mg and utilize clinical monitoring on response/side effects or therapeutic drug monitoring of sertraline + desmethylsertraline to guide dose adjustments.	4A	III	(6;7)
			PM	Yes	Consider a maximum daily dose of 50 mg and utilize clinical monitoring on response/side effects or therapeutic drug monitoring of sertraline + desmethylsertraline to guide dose adjustments.	4C	III
			UM	No	Initiate therapy with recommended starting dose.	4AA
CYP2C19	Voriconazole	CPIC: Yes	IM	No	Initiate therapy with recommended starting dose.	M	V	(32)
			PM	Yes	Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole	M	V
			RM	Yes	Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole	M	II
			UM	Yes	Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole	M	V
		DPWG: Yes	IM	Yes	Monitor serum concentration	4A	V	(5–7)
			PM	Yes	Monitor serum concentration	4A	V
			UM	Yes	Monitor serum concentration	4A	V
CYP2D6	Amitriptyline	CPIC: Yes	IM	Yes	Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	M	III	(24;25)
			PM	Yes	1) Avoid amitriptyline use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. 2) If amitriptyline is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	S
			UM	Yes	1) Avoid amitriptyline use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. 2) If amitriptyline is warranted, consider titrating to a higher target dose (compared to normal metabolizers). . Utilize therapeutic drug monitoring to guide dose adjustments	S
		DPWG: Yes	IM	Yes	1) Consider alternative drug not metabolized by CYP2D6. 2) If an alternative is not possible consider a decrease of up to 60% of the recommended dose under therapeutic drug monitoring of amitriptyline and nortriptyline.	3C	III	(6;7)
			PM	Yes	1) Consider alternative drug not metabolized by CYP2D6. 2) If an alternative is not possible consider a decrease of up to 50% of the recommended dose under therapeutic drug monitoring of amitriptyline and nortriptyline.	3A
			UM	Yes	1) Consider alternative drug not metabolized by CYP2D6. 2) If an alternative is not possible consider an increase of up to 125% of the recommended dose under therapeutic drug monitoring of amitriptyline and nortriptyline. Be alert of a possible decrease in therapeutic levels and an increase of active cardiotoxic hydroxymetabolites.	3C
CYP2D6	Clomipramine	CPIC: Yes	IM	Yes	Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	O		(24;25)
			PM	Yes	1) Avoid clomipramine use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. 2) If clomipramine is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	O	III
			UM	Yes	1) Avoid clomipramine use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. 2) If clomipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	O
		DPWG: Yes	IM	Yes	1) Consider 30% reduction of recommended starting dose. 2) Utilize therapeutic drug monitoring of clomipramine and desmethylclomipramine.	4C		(5–7)
			PM	Yes	Depression: 1) Consider 60% reduction of recommended starting dose. 2) Utilize therapeutic drug monitoring of clomipramine and desmethylclomipramine. Anxiety: 1) Consider alternative drug not metabolized by CYP2D6. 2) If an alternative is not possible consider a decrease of up to 50% of the recommended dose under therapeutic drug monitoring of clomipramine and desmethylclomipramine.	4C	III
			UM	Yes	1) Consider alternative drug not metabolized by CYP2D6. 2) If an alternative is not possible consider an increase of up to 150% of the recommended dose under therapeutic drug monitoring of amitriptyline and nortriptyline. Be alert of a possible decrease in therapeutic levels and an increase of cardiotoxic active hydroxymetabolites.	3C
CYP2D6	Codeine	CPIC: Yes	IM	Yes	Use label-recommended age- or weight-specific dosing. If no response, consider alternative analgesics such as morphine or a non-opioid.	M		(15;16)
			PM	Yes	Avoid codeine use due to lack of efficacy.	S
			UM	Yes	Avoid codeine use due to potential for toxicity.	S
		DPWG: Yes	IM	Yes	Cough: no action required Pain: Be on alert for a lack of clinical effect. In case of a lack of clinical effect consider a raise in daily dose or consider an alternative drug	3A		(5–7)
			PM	Yes	Cough: no action required / Pain: Consider an alternative drug	4B
			UM	Yes	Contraindicated	3F
CYP2D6	Doxepin	CPIC: Yes	IM	Yes	Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	O		(24;25)
			PM	Yes	1) Avoid doxepin use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. 2) If doxepin is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	O
			UM	Yes	1) Avoid doxepin use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. 2) If doxepin is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	O
		DPWG: Yes	IM	Yes	Consider a 20% reduction of recommended starting dose. Utilize therapeutic drug monitoring to monitor doxepin and nordoxepin to guide dose adjustments.	3A		(6;7)
			PM	Yes	Consider a 60% reduction of recommended starting dose. Utilize therapeutic drug monitoring to monitor doxepin and nordoxepin to guide dose adjustments.	3F
			UM	Yes	1) Consider alternative drug not metabolized by CYP2D6. 2) If an alternative is not possible consider an increase of up to 200% of the recommended dose under therapeutic drug monitoring of doxepin and nordoxepin.	3A
CYP2D6	Fluvoxamine	CPIC: Yes	IM	No	Initiate therapy with recommended starting dose.	M		(26)
			PM	No	1) Consider a 25–50% reduction of recommended starting dose and titrate to response. 2) Use an alternative drug not metabolized by CYP2D6.	O	IV
			UM	No	No recommendation due to lack of evidence.	O
		DPWG: No	IM	No	Initiate therapy with recommended starting dose	IN		(7)
			PM	No	Initiate therapy with recommended starting dose	3AA	IV
			UM	No	Initiate therapy with recommended starting dose	IN
CYP2D6	Imipramine	CPIC: Yes	IM	Yes	Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	O		(24;25)
			PM	Yes	1) Avoid imipramine use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. 2) If imipramine is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	O	III
			UM	Yes	1) Avoid imipramine use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. 2) If imipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	O
		DPWG: Yes	IM	Yes	Consider 30% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	4A		(5–7)
			PM	Yes	Consider 70% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	4C	III
			UM	Yes	1) Consider alternative drug not metabolized by CYP2D6. 2) If an alternative is not possible consider an increase of up to 170% of the recommended dose under therapeutic drug monitoring of imipramine and desipramine.	4A
CYP2D6	Nortriptyline	CPIC: Yes	IM	Yes	Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	M		(24;25)
			PM	Yes	1) Avoid nortriptyline use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. 2) If nortriptyline is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	S
			UM	Yes	1) Avoid nortriptyline use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. 2) If nortriptyline is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	S
		DPWG: Yes	IM	Yes	Consider a 40% reduction of recommended starting dose. Utilize therapeutic drug monitoring of nortriptyline and 10-hydroxytriptyline to guide dose adjustments	4C		(5–7)
			PM	Yes	Consider a 60% reduction of recommended starting dose. Utilize therapeutic drug monitoring of nortriptyline and 10-hydroxytriptyline to guide dose adjustments	3C
			UM	Yes	1) Consider alternative drug not metabolized by CYP2D6 2) If an alternative is not possible consider an increase of up to 60% of the recommended dose. Utilize therapeutic drug monitoring of nortriptyline and 10-hydroxytriptyline to guide dose adjustments.	3C
CYP2D6	Paroxetine	CPIC: Yes	IM	No	Initiate therapy with recommended starting dose.	M		(26)
			PM	Yes	1) Consider alternative drug not predominantly metabolized by CYP2D6. 2) If paroxetine use warranted, consider a 50% reduction of recommended starting dose and titrate to response.	O	III
			UM	Yes	Consider alternative drug not predominantly metabolized by CYP2D6.	S
		DPWG: Yes	IM	No	Initiate therapy with recommended starting dose	4A		(5–7)
			PM	No	Initiate therapy with recommended starting dose	4A	III
			UM	Yes	Consider alternative drug not metabolized by CYP2D6	4C
CYP3A5	Tacrolimus	CPIC: Yes	IM (heterozygous expressor)	Yes	Increase starting dose 1.5 to 2 times recommended starting dose. Total starting dose should not exceed 0.3 mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments.	S		(30)
		CPIC: Yes	NM (homozygous expressor)	Yes	Increase starting dose 1.5 to 2 times recommended starting dose. Total starting dose should not exceed 0.3 mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments.	S	III	(30)
		DPWG: Yes	Heterozygous expressor	Yes	Increase starting dose 1.75 times recommended starting dose. Total starting dose should not exceed 0.3 mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments.	4E		(6;7)
		DPWG: Yes	Homozygous expressor	Yes	Increase starting dose 2.5 times recommended starting dose. Total starting dose should not exceed 0.3 mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments.	4E	III	(6;7)
DPYD	Capecitabine/5-Fluorouracil	CPIC: Yes	IM	Yes	Start with at least a 50% reduction in starting dose followed by titration of dose based on toxicity or pharmacokinetic test (if available).	M		(14)
		CPIC: Yes	PM	Yes	Select alternate drug.	S		(14)
		DPWG: Yes	1.5	Yes	Start with at least a 75% reduction in star ting dose followed by titration of dose based on toxicity and efficacy.	4F	II	(6;7;51)
			1.0	Yes	Start with at least a 50% reduction in starting dose followed by titration of dose based on toxicity and efficacy.	4F
			0.5	Yes	Start with at least a 25% reduction in starting dose followed by titration of dose based on toxicity and efficacy.	4F	II
			0.0	Yes	Select alternate drug.	4F
DPYD	Tegafur	CPIC: Yes	IM	Yes	Start with at least a 50% reduction in starting dose followed by titration of dose based on toxicity or pharmacokinetic test (if available).	M	III	(14)
		CPIC: Yes	PM	Yes	Select alternate drug.	S		(14)
		DPWG: Yes	1.5	Yes	Select alternate drug.	2E		(6;7;51)
			1.0	Yes	Select alternate drug.	2D	III
			0.5	Yes	Select alternate drug.	0E
			0.0	Yes	Select alternate drug.	0E
HLA-B	Abacavir	CPIC: Yes	57:01/ X; 57:01/57:01	Yes	Abacavir is not recommended.	S		(12;13)
HLA-B	Abacavir	DPWG: Yes	57:01/ X; 57:01/57:01	Yes	Abacavir is contraindicated.	4E		(6;7)
HLA-B	Carbamazepine	CPIC: Yes	15:02/ X; 15:02/15:02	Yes	A. If patient is carbamazepine-naive, do not use carbamazepine B. If patient has previously used carbamazepine for longer than 3 months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine	S(A) O(B)		(11)
HLA-B	Carbamazepine	DPWG: Yes	15:02/ X; 15:02/15:02 15:11/ X; 15:11/15:11 31:01/ X; 31:01/31:01	Yes	For HLA-B1502, the recommendation is to choose an alternative. If an alternative is possible, choosing an alternative is also recommended for HLA-A3101 and HLA-B*151	4E (ALL		(7)
SLCO1B1	Simvastatin	CPIC: Yes	Decreased Function (521TC)	Yes	1) Prescribe a lower dose. 2) Consider an alternative statin (e.g., pravastatin or rosuvastatin). 3) Consider routine CK surveillance.	S		(22;23)
		CPIC: Yes	Poor Function (521CC)	Yes	1) Prescribe a lower dose. 2) Consider an alternative statin (e.g., pravastatin or rosuvastatin). 3) Consider routine CK surveillance.	S		(22;23)
		DPWG: Yes	521TC	Yes	1) Consider alternative drug. 2) If simvastatin is warranted, prescribe a maximum dose of 40 mg/day.	4D		(7)
		DPWG: Yes	521CC	Yes	Select alternative drug.	4D		(7)
TPMT	Azathioprine/mercaptopurine	CPIC: Yes	IM	Yes	If disease treatment normally starts at the “full dose”, consider starting at 30–70% of target dose (e.g., 1–1.5 mg/kg/d), and titrate based on tolerance. Allow 2–4 weeks to reach steady state after each dose adjustment.	S		(8;9)
		CPIC: Yes	PM	Yes	1) Consider alternative agents. 2) If using azathioprine start with drastically reduced doses (reduce daily dose by 10-fold and dose thrice weekly instead of daily) and adjust doses of azathioprine based on degree of myelosuppression and disease-specific guidelines. Allow 4–6 weeks to reach steady state after each dose adjustment. Azathioprine is the likely cause of myelosuppression.	S		(8;9)
		DPWG: Yes	IM	Yes	1) Select alternative drug. 2) Reduce dose by 50%. Increase dose in response of hematologic monitoring and efficacy.	4E		(6;7)
		DPWG: Yes	PM	Yes	1) Select alternative drug. 2) Reduce dose by 90%. Increase dose in response of hematologic monitoring and efficacy.	4F		(6;7)
TPMT	Thioguanine	CPIC: Yes	IM	Yes	Start with reduced doses (reduce by 30–50%) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 2–4 weeks to reach steady state after each dose adjustment. In setting of myelosuppression, and depending on other therapy, emphasis should be on reducing thioguanine over other agents.	M	V	(8;9)
		CPIC: Yes	PM	Yes	Start with drastically reduced doses (reduce daily dose by 10-fold and dose thrice weekly instead of daily) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 4–6 weeks to reach steady state after each dose adjustment. In setting of myelosuppression, emphasis should be on reducing thioguanine over other agents. For nonmalignant conditions, consider alternative nonthiopurine immunosuppressant therapy.	S		(8;9)
		DPWG: Yes	IM	Yes	1) Select alternative drug, 2) Reduce dose by 25%. Increase dose in response of hematologic monitoring and efficacy.	3E	V	(6;7)
		DPWG: Yes	PM	Yes	1) Select alternative drug. 2) Reduce dose to 6–7% of starting dose. Increase dose in response of hematologic monitoring and efficacy.	2F		(6;7)
VKORC1	Warfarin	CPIC: Yes	-1639GA	Yes	Calculate dose based on validated published pharmacogenetic algorithm	S	V	(17;18)
		CPIC: Yes	-1639AA	Yes	Calculate dose based on validated published pharmacogenetic algorithm	S	V	(17;18)
		DPWG: Yes	-1639GA	Yes	Initiate therapy with recommended starting dose	4A	V	(7)
		DPWG: Yes	-1639AA	Yes	Consider a reduction to 60% of the normal starting dose	4A	V	(7)

IM = intermediate metabolizer; NM = normal metabolizer; PM = poor metabolizer; RM = rapid metabolizer; UM = ultra-rapid metabolizer; ADE = adverse drug event; M = moderate; S = strong; O = Optional; IN = Insufficient evidence; 0 = data on file; 1 = published incomplete case reports; 2 = well documented case reports / case series; 3 = published controlled studies of moderate quality; 4 = published controlled studies of good quality; A = minor clinical effect; B = clinical effect : short-lived discomfort (<48 h) without permanent injury; C = clinical effect: long-standing discomfort (48–168 h) without permanent injury; D = clinical effect: long-standing effect (>168) and permanent symptom or invalidating injury; E = Increased risk of failure of lifesaving therapy / expected bone marrow depression; F = death, arrhythmia, unexpected bone marrow depression

Category of discordance: I = discordance in allele classification, II = discordance in genotype to phenotype translation, III = discordance in therapeutic recommendation attributed to a difference in methodology of the two consortia, IV = discordance in therapeutic recommendation attributed to a time-effect, V = discordance in therapeutic recommendation attributed to a difference in clinical practice.