Estimated nationwide impact of implementing a preemptive pharmacogenetic panel approach to guide drug prescribing in primary care in The Netherlands

P. C. D. Bank; J. J. Swen; H. J. Guchelaar

doi:10.1186/s12916-019-1342-5

Table 2 Overview of inferred gene-drug pairs sorted per gene. An overview of the estimates of the occurrences of gene-drug pairs among 45 drugs frequently prescribed in primary care

From: Estimated nationwide impact of implementing a preemptive pharmacogenetic panel approach to guide drug prescribing in primary care in The Netherlands

Drug	Count incident prescriptions (total)	Actionable phenotype	Count incident prescriptions	Type of therapeutic recommendation
CYP2C9
PHENYTOIN*	828	EM	518	No action
		IM	294	Lower dose required at start therapy
		PM	17	Lower dose required at start therapy
CYP2C19
CITALOPRAM < 65 years^*	41,338	EM	29,557	No action
		IM	8,888	Guard maximum daily dose
		PM	1240	Guard maximum daily dose
		UM	1654	No action
CITALOPRAM ≥ 65 years^*	15,242	EM	10,898	No action
		IM	3277	Guard maximum daily dose
		PM	457	Guard maximum daily dose
		UM	610	No action
CLOPIDOGREL^*	98,709	EM	70,577	No action
		IM	21,222	Switch to alternate drug at start therapy
		PM	2961	Switch to alternate drug at start therapy
		UM	3948	Observe status of patient carefully
ESCITALOPRAM < 65 years^*	21,427	EM	15,320	No action
		IM	4607	Guard maximum daily dose
		PM	643	Guard maximum daily dose
		UM	857	No action
ESCITALOPRAM ≥ 65 years^*	3027	EM	2164	No action
		IM	651	Guard maximum daily dose
		PM	91	Guard maximum daily dose
		UM	121	No action
ESOMEPRAZOLE	65,370	EM	46,740	No action
		IM	14,055	No action
		PM	1961	No action
		UM	2615	Optional increase of dose
ESOMEPRAZOLE AND NAPROXEN	673	EM	481	No action
		IM	145	No action
		PM	20	No action
		UM	27	Optional increase of dose
LANSOPRAZOLE	1536	EM	1098	No action
		IM	330	No action
		PM	46	No action
		UM	61	Optional increase of dose
OMEPRAZOLE	575,353	EM	411,377	No action
		IM	123,701	No action
		PM	17,261	No action
		UM	23,014	Optional increase of dose
PANTOPRAZOLE	361,741	EM	258,645	No action
		IM	77,774	No action
		PM	10,852	No action
		UM	14,470	Optional increase of dose
PANTOPAC	21,768	EM	15,564	No action
		IM	4680	No action
		PM	653	No action
		UM	871	Higher dose required at start therapy
SERTRALINE^*	28,861	EM	20,636	No action
		IM	6205	Guard maximum daily dose
		PM	866	Guard maximum daily dose
		UM	1154	No action
VORICONAZOLE^*	891	EM	637	No action
		IM	192	Observe status of patient carefully
		PM	27	Observe status of patient carefully
		UM	36	Higher dose required at start therapy
CYP2D6
AMITRIPTYLINE^*	98,750	EM	52,338	No action
		IM	39,994	Switch to alternate drug at start therapy
		PM	4938	Switch to alternate drug at start therapy
		UM	1481	Switch to alternate drug at start therapy
ARIPIPRAZOLE	13,869	EM	7351	No action
		IM	5617	No action
		PM	693	Guard maximum daily dose
		UM	208	No action
ATOMOXETINE^*	1987	EM	1053	No action
		IM	805	Optional decrease of dose
		PM	99	Optional decrease of dose
		UM	30	Observe status of patient carefully
CLOMIPRAMINE^*	7079	EM	3752	No action
		IM	2867	Lower dose required at start therapy
		PM	354	Lower dose required at start therapy
		UM	106	Switch to alternate drug at start therapy
CODEINE^*	519,728	EM	275,456	No action
		IM	210,490	No action
		PM	25,986	No action
		UM	7796	Switch to alternate drug at start therapy
CODEINE AND PARACETAMOL^*	69,300	EM	36,729	No action
		IM	28,067	Optional increase of dose
		PM	3465	Switch to alternate drug at start therapy
		UM	1040	Switch to alternate drug at start therapy
DOXEPIN^*	270	EM	143	No action
		IM	109	Lower dose required at start therapy
		PM	14	Lower dose required at start therapy
		UM	4	Switch to alternate drug at start therapy
FLECAINIDE	13,605	EM	7211	No action
		IM	5510	Lower dose required at start therapy
		PM	680	Lower dose required at start therapy
		UM	204	Observe status of patient carefully
HALOPERIDOL	51,217	EM	27,145	No action
		IM	20,743	No action
		PM	2561	Lower dose required at start therapy
		UM	768	Optional increase of dose
IMIPRAMINE (TOTAL)	988
IMIPRAMINE (CYP2C19 EM, IM, UM)^*	958	EM	508	No action
		IM	388	Lower dose required at start therapy
		PM	48	Lower dose required at start therapy
		UM	14	Switch to alternate drug at start therapy
IMIPRAMINE (CYP2C19 PM) ^*	30	EM	16	Lower dose required at start therapy
		IM	12	Lower dose required at start therapy
		PM	2	Lower dose required at start therapy
		UM	0	Switch to alternate drug at start therapy
METOPROLOL	194,724	EM	103,204	No action
		IM	78,863	Optional decrease of dose
		PM	9736	Optional decrease of dose
		UM	2921	Optional increase of dose
METOPROLOL AND THIAZIDE	1908	EM	1011	No action
		IM	773	Optional decrease of dose
		PM	95	Optional decrease of dose
		UM	29	Optional increase of dose
NORTRIPTYLINE^*	20,717	EM	10,980	No action
		IM	8390	Lower dose required at start therapy
		PM	1036	Lower dose required at start therapy
		UM	311	Switch to alternate drug at start therapy
OXYCODONE	464,799	EM	246,343	No action
		IM	188,244	Observe status of patient carefully
		PM	23,240	Observe status of patient carefully
		UM	6972	Observe status of patient carefully
OXYCODONE AND NALOXONE	82	EM	43	No action
		IM	33	Observe status of patient carefully
		PM	4	Observe status of patient carefully
		UM	1	Observe status of patient carefully
PAROXETINE^*	27,018	EM	14,320	No action
		IM	10,942	No action
		PM	1351	No action
		UM	405	Switch to alternate drug at start therapy
PIMOZIDE	1060	EM	562	No action
		IM	429	Lower dose required at start therapy
		PM	53	Lower dose required at start therapy
		UM	16	No action
PROPAFENON	409	EM	217	No action
		IM	166	Optional decrease of dose
		PM	20	Lower dose required at start therapy
		UM	6	Observe status of patient carefully
TAMOXIFEN^*	10,807	EM	5728	No action
		IM	4377	Switch to alternate drug at start therapy
		PM	540	Switch to alternate drug at start therapy
		UM	162	No action
TRAMADOL^*	357,389	EM	189,416	No action
		IM	144,743	Optional increase of dose
		PM	17,869	Optional increase of dose
		UM	5361	Lower dose required at start therapy
TRAMADOL AND PARACETAMOL^*	124,951	EM	66,224	No action
		IM	50,605	Optional increase of dose
		PM	6248	Optional increase of dose
		UM	1874	Lower dose required at start therapy
VENLAFAXINE	26,603	EM	14,100	No action
		IM	10,774	Switch to alternate drug at start therapy
		PM	1330	Switch to alternate drug at start therapy
		UM	399	Optional increase of dose
ZUCLOPENTHIXOL	1873	EM	993	No action
		IM	759	Lower dose required at start therapy
		PM	94	Lower dose required at start therapy
		UM	28	Optional increase of dose
CYP3A5
TACROLIMUS^*	2722	Non-Ex	2314	No action
		Het-Ex	395	Higher dose required at start therapy
		Homo-Ex	14	Higher dose required at start therapy
SLCO1B1
ATORVASTATIN (TOTAL)	111,840
ATORVASTATIN (WITHOUT CYP3A4 INHIBITOR)	108,400	NT (521TT)	80,758	No action
		PT (521TC)	25,474	Observe status of patient carefully
		PT (521CC)	2168	Observe status of patient carefully
ATORVASTATIN (WITH CYP3A4 INHIBITOR)	3440	NT (521TT)	2563	No action
		PT (521TC)	808	Switch to alternate drug at start therapy
		PT (521CC)	69	Switch to alternate drug at start therapy
ATORVASTATIN AND EZETIMIBE	1909
ATORVASTATIN AND EZETIMIBE (WITHOUT CYP3A4 INHIBITOR)	1739	NT (521TT)	1296	No action
		PT (521TC)	409	Observe status of patient carefully
		PT (521CC)	35	Observe status of patient carefully
ATORVASTATIN AND EZETIMIBE (WITH CYP3A4 INHIBITOR)	170	NT (521TT)	127	No action
		PT (521TC)	40	Switch to alternate drug at start therapy
		PT (521CC)	3	Switch to alternate drug at start therapy
SIMVASTATIN^*	187,362	NT (521TT)	139,585	No action
		PT (521TC)	44,030	Switch to alternate drug at start therapy
		PT (521CC)	3747	Switch to alternate drug at start therapy
SIMVASTATIN AND EZETIMIBE^*	4888	NT (521TT)	3642	No action
		PT (521TC)	1149	Switch to alternate drug at start therapy
		PT (521CC)	98	Switch to alternate drug at start therapy
TPMT
AZATHIOPRINE^*	6943	EM	5867	No action
		IM	1041	Lower dose required at start therapy
		PM	35	Switch to alternate drug at start therapy
MERCAPTOPURINE^*	2598	EM	2195	No action
		IM	390	Lower dose required at start therapy
		PM	13	Switch to alternate drug at start therapy
TIOGUANINE^*	1888	EM	1591	No action
		IM	282	Lower dose required at start therapy
		PM	9	Switch to alternate drug at start therapy
VKORC1
ACENOCOUMAROL	49,934	NS (1173CC)	16,478	No action
		NS (1173CT)	25,217	No action
		HS (1173TT)	8239	Lower dose required at start therapy
FENPROCOUMON	12,621	NS (1173CC)	4165	No action
		NS (1173CT)	6374	No action
		HS (1173TT)	2082	Lower dose required at start therapy

^*Gene-drug interactions with a recommendation both by the DPWG and CPIC
EM extensive/normal metabolizer, IM intermediate metabolizer, PM poor metabolizer, UM ultra-metabolizer, Non-Ex non-expressor, Het heterozygous expressor, HOM homozygous expressor, NT normal transport activity, PT poor transport activity, NS normal sensitivity, HS high sensitivity

Back to article page