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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