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Table 3 Prevalence of the selected DDIs (‘List A’)

From: Countrywide prevalence of critical drug interactions in Hungarian outpatients: a retrospective analysis of pharmacy dispensing data

Drug 1 - Drug 2

Potential adverse consequence of the interaction

Prevalence per 100000 prescriptions (Number of cases)

R2

Change 2013–2016 (%)

Interaction rate*

  

2013

2014

2015

2016

  

2013

2014

2015

2016

Nitratesa - PDE-5 inhibitorsb

Hypotension

0.06 (95)

0.05 (82)

0.06 (97)

0.08 (135)

LP

LP

0.04, 1.03

0.04, 0.81

0.05, 0.71

0.07, 0.90

MAO inhibitorsc - SSRIsd

Serotonin toxicity

4.09 (7118)

4.21 (7365)

4.19 (7382)

3.96 (6980)

0.07

DNF

44.92, 3.74

46.96, 3.92

49.51, 3.93

46.03, 3.72

MAO inhibitorsc - Tricyclic antidepressantse

Serotonin toxicity

0.32 (551)

0.26 (446)

0.36 (631)

0.53 (933)

0.67

DNF

3.48, 3.51

2.84, 2.94

4.23, 4.13

6.15, 5.52

MAO inhibitorsc - Narcotic analgesicsf

Serotonin toxicity

2.02 (3516)

2.16 (3770)

2.41 (4245)

2.41 (4252)

0.90

+ 21

22.19, 2.50

24.04, 2.52

28.47, 2.89

28.04, 2.90

MAO inhibitorsc - Triptansg

Serotonin toxicity

0.01 (22)

0.01 (13)

0.01 (13)

0.01 (16)

LP

LP

0.14, 0.38

0.08, 0.21

0.08, 0.18

0.10, 0.21

MAO inhibitorsc - Amphetamine derivativesh

Serotonin toxicity

0.00 (0)

0.00 (0)

0.00 (0)

0.00 (0)

LP

LP

0.00, 0.00

0.00, 0.00

0.00, 0.00

0.00, 0.00

QT prolonging agentsi - QT prolonging agentsi

Potentially lethal ventricular arrhythmia

6.50 (11301)

6.52 (11401)

6.23 (10963)

5.63 (9925)

0.76

−12

NA

NA

NA

NA

Vitamin K antagonistsj - NSAIDsk

Bleeding

44.53 (77442)

49.46 (86478)

57.10 (100563)

54.42 (95977)

0.77

+ 24

41.38, 11.23

46.66, 12.28

55.36, 13.75

53.94, 12.95

Vitamin K antagonistsj - Fibric acid derivativesl

Bleeding

16.02 (27854)

15.67 (27395)

15.13 (26639)

14.56 (25677)

0.98

−8

14.88, 38.12

14.78, 38.88

14.66, 38.54

14.43, 37.29

Vitamin K antagonistsj - Barbituratesm

Reduced anticoagulant effect

0.47 (823)

0.62 (1079)

0.58 (1020)

0.78 (1376)

0.81

+ 67

0.44, 15.54

0.58, 21.81

0.56, 16.73

0.77, 17.72

Simvastatin - CYP3A4 inhibitorsn

Statin toxicity (e.g. rhabdomyolysis)

13.81 (24013)

11.14 (19471)

8.96 (15774)

7.33 (12921)

0.99

−46

18.89, 20.39

18.87, 16.49

18.95, 13.57

18.07, 12.52

Theophylline - Ciprofloxacin

Theophylline toxicity (e.g. seizures, hypotension)

2.81(4884)

2.65 (4626)

2.62 (4620)

2.19 (3870)

0.81

−21

5.33, 8.86

5.14, 8.24

5.25, 8.47

4.64, 7.80

Theophylline - Fluvoxamine

Theophylline toxicity (e.g. seizures, hypotension)

0.15 (261)

0.12 (200)

0.06 (111)

0.24 (414)

0.14

DNF

0.25, 7.97

0.20, 6.88

0.11, 4.49

0.45, 19.10

Tizanidine - CYP1A2 inhibitorso

Tizanidine toxicity (e.g. hypotension, drowsiness)

0.73 (1262)

0.70 (1228)

0.67 (1172)

0.72 (1262)

0.03

DNF

8.55, 1.23

8.57, 1.21

8.53, 1.19

7.87, 1.36

Alprazolam - Azole antifungalsp

Benzodiazepine toxicity

2.15 (3739)

2.48 (4335)

2.42 (4260)

2.33 (4110)

0.26

DNF

0.71, 13.35

0.79, 14.61

0.80, 13.97

0.78, 13.98

Ergot alkaloidsq - CYP3A4 inhibitorsr

Ergot toxicity

0.14 (244)

0.15 (260)

0.13 (224)

0.11 (196)

0.70

−19

2.95, 0.34

3.27, 0.35

2.96, 0.30

2.67, 0.30

Thiopuriness - Xanthine oxidase inhibitorst

Thiopurine toxicity (e.g. bone marrow suppression)

0.17 (297)

0.21 (365)

0.27 (472)

0.31 (546)

0.99

+ 84

5.46, 0.13

6.36, 0.15

7.97, 0.18

8.75, 0.20

Methotrexate - Trimethoprim

Methotrexate toxicity (e.g. bone marrow suppression)

0.00 (6)

0.00 (7)

0.01 (11)

0.01 (9)

LP

LP

0.19, 0.02

0.23, 0.03

0.32, 0.04

0.27, 0.03

Digoxin - Clarithromycin

Digoxin toxicity

0.07 (115)

0.05 (83)

0.03 (56)

0.04 (65)

LP

LP

0.60, 0.27

0.49, 0.19

0.36, 0.12

0.47, 0.19

 

Total

99.28 (172673)

101.84 (178055)

105.79 (186309)

100.18 (176686)

0.21

DNF

    
  1. LP – not calculated because of low prevalence (< 100 cases/year), DNF – not calculated because the linear model does not fit (R2 < 0.7)
  2. *number of interaction cases per 1000 prescriptions of Drug 1 and Drug 2, respectively
  3. aglyceryl trinitrate, isosorbide mononitrate
  4. bavanafil, sildenafil, tadalafil, vardenafil
  5. cselegiline, rasagiline, moclobemide
  6. dcitalopram, escitalopram, fluoxetine, paroxetine, sertraline, venlafaxine (not SSRI but similar pharmacological properties)
  7. eamitriptyline, clomipramine, imipramine, maprotiline, trimipramine
  8. ffentanyl, tramadol
  9. geletriptan, sumatriptan, zolmitriptan
  10. hatomoxetine, methylphenidate
  11. itwelve combinations of the following: amiodarone, ciprofloxacin, citalopram, clarithromycin, domperidone, escitalopram, haloperidol
  12. jacenocoumarol, warfarin
  13. kaceclofenac, acemetacin, dexibuprofen, diclofenac, indometacin, lornoxicam, meloxicam, naproxen, niflumic acid, nimesulide
  14. lbezafibrate, ciprofibrate, fenofibrate, gemfibrozil
  15. mphenobarbital, primidone
  16. namiodarone, clarithromycin, fluconazole, itraconazole, verapamil, diltiazem
  17. ociprofloxacin, fluvoxamine, mexiletine, propafenone, amiodarone, ticlopidine
  18. pfluconazole, itraconazole
  19. qergotamine
  20. rclarithromycin, fluconazole, itraconazole
  21. sazathioprine
  22. tallopurinol, febuxostat