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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

  1. *Gene-drug interactions with a recommendation both by the DPWG and CPIC
  2. 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