Utilization of Drugs with Pharmacogenetic Dosing Recommendations in Switzerland: A Descriptive Study Using the Helsana Database

Figures & data

Table 1 PGx Drugs with Their Corresponding Genes

Gene	Gene Name	Drug
CACNA1S	Calcium voltage-gated channel subunit alpha1 S	Desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane, succinylcholine
CFTR	Cystic fibrosis transmembrane conductance regulator	Ivacaftor
CYP2B6	Cytochrome P450 2B6	Efavirenz
CYP2C9	Cytochrome P450 2C9	Acenocoumarol, celecoxib, fluindione, flurbiprofen, fosphenytoin, ibuprofen, lornoxicam, meloxicam, phenytoin, piroxicam, siponimod, tenoxicam, warfarin
CYP2C19	Cytochrome P450 2C19	Amitriptyline, citalopram, clomipramine, clopidogrel, dexlansoprazole, doxepin, escitalopram, imipramine, lansoprazole, omeprazole, pantoprazole, sertraline, trimipramine, voriconazole
CYP2D6	Cytochrome P450 2D6	Amitriptyline, aripiprazole, atomoxetine, brexipiprazole, clomipramine, codeine, desipramine, doxepin, eliglustat, flecainide, fluvoxamine, haloperidol, hydrocodone, imipramine, metoprolol, nortriptyline, ondansetron, paroxetine, pimozide, propafenone, risperidone, tamoxifen, tramadol, tropisetron, venlafaxine, zuclopenthixol
CYP3A4	Cytochrome P450 3A4	Tacrolimus
CYP3A5	Cytochrome P450 3A5	Tacrolimus
CYP4F2	Cytochrome P450 4F2	Warfarin
DPYD	Dihydropyrimidine dehydrogenase	Capecitabine, flucytosine, fluorouracil, tegafur
G6PD	Glucose-6-phosphate dehydrogenase	Rasburicase
HLA-A	Human leukocyte antigen A	Carbamazepine
HLA-B	Human leukocyte antigen B	Abacavir, allopurinol, carbamazepine, flucloxacillin, fosphenytoin, oxcarbazepine
IFNL3	Interferon lambda 3	Peginterferon alfa-2a, peginterferon alfa-2b, ribavirin
MT-RNR1	Mitochondrially encoded 12S RNA	Amikacin, gentamicin, kanamycin, paromomycin, plazomicin, streptomycin, tobramycin
NUDT15	Nudix hydrolase 15	Azathioprine, mercaptopurine, thioguanine
RARG	Retinoic acid receptor gamma	Daunorubicin, doxorubicin
RYR1	Ryanodine receptor 1	Enflurane, halothane, isoflurane, methoxyflurane, sevoflurane, succinylcholine
SLC8A3	Solute carrier family 8 member A3	Daunorubicin, doxorubicin
SLCO1B1	Solute carrier organic anion transporter family member 1B1	Atorvastatin, simvastatin
TPMT	Thiopurine S-methyltransferase	Azathioprine, cisplatin, mercaptopurine, thioguanine
UGT1A1	UDP glucuronosyltransferase 1 family, polypeptide A1	Atazanavir, irinotecan
UGT1A6	UDP glucuronosyltransferase 1 family, polypeptide A6	Daunorubicin, doxorubicin
VKORC1	Vitamin K epoxide reductase complex subunit 1	Acenocoumarol, fluindione, phenprocoumon, warfarin

Table 2 Characteristics of the Study Population

Prescribing Period	1-Year Periods					5-Year Period
	2016	2017	2018	2019	2020	2016–2020
Persons	Number of persons [N, %]
All	1,169,302	1,105,027	1,138,659	1,198,081	1,315,606	885,866
Women	602,403, 51.5	571,944, 51.8	588,495, 51.7	617,015, 51.5	673,540, 51.2	464,064, 52.4
Men	566,899, 48.5	533,083, 48.2	550,164, 48.3	581,066, 48.5	642,066, 48.8	421,802, 47.6
Age	Number of persons [N, %]
0–19 years	237,016, 20.3	220,720, 20.0	227,884, 20.0	242,712, 20.3	268,821, 20.4	140,200, 15.8
20–39 years	285,437, 24.4	258,500, 23.4	273,961, 24.1	297,492, 24.8	342,892, 26.1	177,612, 20.0
40–59 years	310,533, 26.6	292,866, 26.5	301,233, 26.5	317,953, 26.5	353,191, 26.8	244,634, 27.6
60–79 years	247,648, 21.2	243,628, 22.0	245,240, 21.5	248,473, 20.7	257,420, 19.6	233,076, 26.3
80–99 years	88,200, 7.5	88,858, 8.0	89,864, 7.9	90,963, 7.6	92,709, 7.0	89,779, 10.1
100–119 years	468, <0.1	455, <0.1	477, <0.1	488, <0.1	573, <0.1	565, 0.1
Persons with drug claims	Number of persons [N, %]
Any drug	884,947, 75.7	839,290, 76.0	865,916, 76.0	908,307, 75.8	966,705, 73.5	841,491, 95.0
≥1 PGx drug	504,327, 43.1	480,033, 43.4	493,608, 43.3	517,873, 43.2	522,726, 39.7	662,157, 74.7
≥2 PGx drugs	234,601, 20.1	225,871, 20.4	230,863, 20.3	241,062, 20.1	239,530, 18.2	441,140, 49.8
≥3 PGx drugs	107,381, 9.2	103,207, 9.3	104,304, 9.2	108,384, 9.0	105,641, 8.0	281,862, 31.8
≥4 PGx drugs	45,679, 3.9	44,023, 4.0	43,663, 3.8	45,506, 3.8	43,308, 3.3	175,802, 19.8
≥5 PGx drugs	17,938, 1.5	16,997, 1.5	16,838, 1.5	17,647, 1.5	16,229, 1.2	106,255, 12.0
≥10 PGx drugs	85, <0.1	86, <0.1	79, <0.1	83, <0.1	56, <0.1	5960, 0.7
	Mean per person ± sd
Drugs	6.2±7.3	6.4±7.4	6.4±7.4	6.3±7.3	5.8±7.0	19.8±16.8
PGx drugs	0.8±1.1	0.8±1.2	0.8±1.2	0.8±1.2	0.7±1.1	2.0±2.1

Abbreviations: N, number of persons; %, percentage of all persons present in the respective observation period; sd, standard deviation; PGx, pharmacogenetic.

Table 3 Top 15 PGx Drugs Stratified by Prescribing Periods 2016–2020

Drug	1-Year Periods					5-Year Period
	2016	2017	2018	2019	2020	2016–2020
Number of persons [N, %]
Ibuprofen	206,159, 17.6	195,631, 17.7	210,627, 18.5	231,131, 19.3	220,863, 16.8	423,442, 47.8
Pantoprazole	160,042, 13.7	153,933, 13.9	159,591, 14.0	167,148, 14.0	173,956, 13.2	313,206, 35.4
Tramadol	50,396, 4.3	46,230, 4.2	45,027, 4.0	45,015, 3.8	44,768, 3.4	129,217, 14.6
Codeine	34,778, 3.0	31,906, 2.9	32,137, 2.8	36,777, 3.1	29,379, 2.2	100,312, 11.3
Atorvastatin	60,349, 5.2	60,752, 5.5	61,474, 5.4	63,140, 5.3	66,423, 5.0	88,948, 10.0
Omeprazole	27,361, 2.3	23,862, 2.2	22,337, 2.0	21,675, 1.8	21,398, 1.6	50,206, 5.7
Metoprolol	38,042, 3.3	36,872, 3.3	36,727, 3.2	36,764, 3.1	37,456, 2.8	49,893, 5.6
Escitalopram	25,322, 2.2	24,589, 2.2	25,579, 2.2	26,654, 2.2	27,874, 2.1	46,775, 5.3
Ondansetron	12,915, 1.1	13,566, 1.2	14,152, 1.2	16,965, 1.4	15,358, 1.2	44,673, 5.0
Tobramycin	9131, 0.8	9170, 0.8	8939, 0.8	10,009, 0.8	8138, 0.6	29,799, 3.4
Allopurinol	18,021, 1.5	17,775, 1.6	18,037, 1.6	18,258, 1.5	18,806, 1.4	26,433, 3.0
Simvastatin	23,139, 2.0	20,853, 1.9	18,869, 1.7	17,250, 1.4	16,425, 1.2	25,038, 2.8
Celecoxib	8793, 0.8	8478, 0.8	8449, 0.7	8534, 0.7	8627, 0.7	24,480, 2.8
Clopidogrel	12,629, 1.1	12,301, 1.1	12,423, 1.1	12,586, 1.1	12,563, 1.0	23,359, 2.6
Trimipramine	8381, 0.7	7488, 0.7	7352, 0.6	7344, 0.6	7660, 0.6	17,121, 1.9

Note: The drugs are ranked by the number of exposed persons in the 5-year period 2016–2020.

Abbreviations: N, number of persons in the respective observation period; %, percentage of all persons present in the respective observation period; PGx, pharmacogenetic.

Figure 1 Percentage of persons with PGx drug claims stratified by anatomical groups for the five-year period 2016–2020 and stratified by year. The anatomical groups are ranked by the proportion of persons with PGx drug claims in the 5-year period 2016–2020.

Notes: Anatomical groups excluded, because ≤1.0%: antineoplastic and immunomodulating agents, dermatologicals, antiinfectives for systemic use, various, genitourinary system and sex hormones, systemic hormonal preparations, excl. sex hormones and insulins and antiparasitic products, insecticides and repellents. As persons may use multiple drugs, they can appear in several groups.

Abbreviation: PGx, pharmacogenetic.

Table 4 Genes Associated with PGx Drugs

Gene	1-Year Periods					5-Year Period
	2016	2017	2018	2019	2020	2016–2020
Number of persons [N, %]
CYP2C9	223,029, 44.2	210,415, 43.8	224,331, 45.4	243,763, 47.1	231,868, 44.0	442,352, 97.6
CYP2C19	227,805, 45.2	216,496, 45.1	221,405, 44.9	229,097, 44.2	236,603, 45.3	379,656, 83.8
CYP2D6	144,502, 28.7	137,438, 28.6	137,843, 27.9	145,186, 28.0	139,557, 26.7	271,755, 60.0
SLCO1B1	82,288, 16.3	79,884, 16.6	78,470, 15.9	78,392, 15.1	80,662, 15.4	103,334, 22.8
HLA-B	21,776, 4.3	21,349, 4.4	21,525, 4.4	21,714, 4.2	22,200, 4.2	31,877, 7.0
MT-RNR1	9186, 1.8	9193, 1.9	8970, 1.8	10,035, 1.9	8170, 1.6	29,898, 6.6
VKORC1	20,087, 4.0	17,307, 3.6	15,099, 3.1	13,103, 2.5	11,365, 2.2	18,223, 4.0
CYP3A4	5324, 1.1	5256, 1.1	5523, 1.1	6013, 1.2	6341, 1.2	14,986 3.3
CYP3A5	5324, 1.1	5256, 1.1	5523, 1.1	6013, 1.2	6341, 1.2	14,986 3.3
CACNA1S	3975, 0.8	4074, 0.8	4390, 0.9	4380, 0.8	4360, 0.8	14,380, 3.2
RYR1	3783, 0.8	3888, 0.8	4200, 0.9	4167, 0.8	4123, 0.8	13,673, 3.0
DPYD	2452, 0.5	2294, 0.5	2432, 0.5	2541, 0.5	3187, 0.6	7802, 1.7
HLA-A	2356, 0.5	2192, 0.5	2096, 0.4	2076, 0.4	2037, 0.4	3133, 0.7
TPMT	2034, 0.4	1901, 0.4	1914, 0.4	1866, 0.4	1842, 0.4	3088, 0.7
NUDT15	1836, 0.4	1734, 0.4	1750, 0.4	1693, 0.3	1614, 0.3	2589, 0.6
RARG	394, 0.1	358, 0.1	352, 0.1	362, 0.1	427, 0.1	1093, 0.2
SLC8A3	394, 0.1	358, 0.1	352, 0.1	362, 0.1	427, 0.1	1093, 0.2
UGT1A6	394, 0.1	358, 0.1	352, 0.1	362, 0.1	427, 0.1	1093, 0.2
CYP2B6	399, 0.1	321, 0.1	243, <0.1	172, <0.1	129, <0.1	369, 0.1
IFNL3	161, <0.1	120, <0.1	71, <0.1	65, <0.1	71, <0.1	234, 0.1
UGT1A1	185, <0.1	123, <0.1	91, <0.1	70, <0.1	48, <0.1	170, <0.1
CFTR	0, 0.0	0, 0.0	0, 0.0	1, <0.1	18, <0.1	16, <0.1
G6PD	1, <0.1	4, <0.1	4, <0.1	8, <0.1	5, <0.1	6, <0.1
CYP4F2	0, 0.0	0, 0.0	0, 0.0	0, 0.0	0, 0.0	0, 0.0

Notes: The genes are ranked by the highest number of persons with claims for associated drugs in the 5-year period 2016–2020. Percentages can add up to over 100%, as some people were exposed to more than one PGx drug.

Abbreviations: N, number of persons; %, percentage of all persons with PGx drug claims in the respective observation period; PGx, pharmacogenetic.

Figure 2 Proportion of all potential drug-gene interactions, stratified by prescribing periods 2016–2020. The potential drug-gene interactions are ranked by the highest proportion of all potential drug-gene interactions in the 5-year period 2016–2020. Other includes CYP3A4, CYP3A5, CACNA1S, RYR1, DPYD, HLA-A, TPMT, NUDT15, RARG, SLC8A3, UGT1A6, CYP2B6, IFNL3, UGT1A1, CFTR, G6PD, and CYP4F2.