Use of the French Healthcare Insurance Database to Estimate The

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Use of the French healthcare insurance database to estimate the prevalence of exposure to potential drug-drug interactions Cécile Souty, Titouan Launay, Olivier Steichen, Cécile Conte, Clément Turbelin, Marianne Sarazin, Ana-Maria Vilcu, Louise Rossignol, Thierry Blanchon, Maryse Lapeyre-Mestre, Thomas Hanslik. European Journal of Clinical Pharmacology

Table S1. Anatomical Therapeutic and Chemical codes and defined daily dose for the substances selected in the study

Defined Daily Source Susbstance in ATC level Dose for Drug class thesaurus 5 ATC level 5 (DDD) DDD Angiotensin azilsartan C09CA09 azilsartan 40 MG WHO II receptor candesartan cilexetil C09CA06 candesartan 8 MG WHO antagonists candesartan cilexetil C09DA06 candesartan and diuretics 8 MG Expert eprosartan C09CA02 eprosartan 600 MG WHO eprosartan C09DA02 eprosartan and diuretics 600 MG Expert irbesartan C09CA04 irbesartan 150 MG WHO irbesartan C09DA04 irbesartan and diuretics 150 MG Expert losartan C09CA01 losartan 50 MG WHO losartan C09DA01 losartan and diuretics 50 MG Expert olmesartan C09CA08 olmesartan medoxomil 20 MG WHO olmesartan medoxomil and olmesartan C09DA08 diuretics 20 MG Expert olmesartan medoxomil and olmesartan C09DB02 amlodipine 20 MG Expert telmisartan C09CA07 telmisartan 40 MG WHO telmisartan C09DA07 telmisartan and diuretics 40 MG Expert telmisartan C09DB04 telmisartan and amlodipine 40 MG Expert valsartan C09CA03 valsartan 80 MG WHO valsartan C09DA03 valsartan and diuretics 80 MG Expert valsartan C09DB01 valsartan and amlodipine 80 MG Expert valsartan, amlodipine and valsartan C09DX01 hydrochlorothiazide 80 MG Expert valsartan C09DX04 valsartan and sacubitril 80 MG Expert Angiotensin- benazepril C09AA07 benazepril 7.5 MG WHO converting benazepril C09BA07 benazepril and diuretics 7.5 MG Expert enzyme captopril C09AA01 captopril 50 MG WHO inhibitors captopril C09BA01 captopril and diuretics 50 MG Expert cilazapril C09AA08 cilazapril 2.5 MG WHO enalapril C09AA02 enalapril 10 MG WHO enalapril C09BA02 enalapril and diuretics 10 MG Expert enalapril C09BB02 enalapril and lercanidipine 10 MG Expert enalapril C09BB06 enalapril and nitrendipine 10 MG Expert fosinopril C09AA09 fosinopril 15 MG WHO fosinopril C09BA09 fosinopril and diuretics 15 MG Expert lisinopril C09AA03 lisinopril 10 MG WHO lisinopril C09BA03 lisinopril and diuretics 10 MG Expert moexipril C09AA13 moexipril 15 MG WHO

perindopril tert- butylamine C09AA04 perindopril 4 MG WHO perindopril tert- butylamine C09BA04 perindopril and diuretics 4 MG Expert perindopril tert- butylamine C09BB04 perindopril and amlodipine 4 MG Expert perindopril tert- perindopril, amlodipine and butylamine C09BX01 indapamide 4 MG Expert perindopril tert- butylamine C09BX02 perindopril and bisoprolol 4 MG Expert quinapril C09AA06 quinapril 15 MG WHO quinapril C09BA06 quinapril and diuretics 15 MG Expert ramipril C09AA05 ramipril 2.5 MG WHO ramipril C09BA05 ramipril and diuretics 2.5 MG Expert trandolapril C09AA10 trandolapril 2 MG WHO trandolapril C09BB10 trandolapril and verapamil 2 MG Expert zofenopril C09AA15 zofenopril 30 MG WHO zofenopril C09BA15 zofenopril and diuretics 30 MG Expert Antiplatelet clopidogrel B01AC04 clopidogrel 75 MG WHO agents prasugrel B01AC22 prasugrel 10 MG WHO ticagrelor B01AC24 ticagrelor 180 MG WHO ticlopidine B01AC05 ticlopidine 500 MG WHO acetylsalicylic acid B01AC06 acetylsalicylic acid 1 UD WHO acetylsalicylic acid, combinations acetylsalicylic acid B01AC56 with proton pump inhibitors 1 UD WHO acetylsalicylic acid C10BX02 pravastatin and acetylsalicylic acid 1 UD WHO Nonsteroidal aceclofenac M01AB16 aceclofenac 200 MG WHO anti- alminoprofen M01AE16 alminoprofen 600 MG Expert inflammatory celecoxib M01AH01 celecoxib 200 MG WHO drugs dexketoprofen M01AE17 dexketoprofen 75 MG WHO dexketoprofen N02AJ14 tramadol and dexketoprofen 50 MG Expert diclofenac M01AB05 diclofenac 100 MG WHO diclofenac M01AB55 diclofenac, combinations 100 MG WHO etodolac M01AB08 etodolac 400 MG WHO etoricoxib M01AH05 etoricoxib 60 MG WHO fenoprofen M01AE04 fenoprofen 1200 MG WHO flurbiprofen M01AE09 flurbiprofen 200 MG WHO flurbiprofen R02AX01 flurbiprofen 44 MG WHO ibuprofen M01AE01 ibuprofen 1200 MG WHO ibuprofen N02AJ08 codeine and ibuprofen 1200 MG Expert indometacin M01AB01 indometacin 100 MG WHO indometacin M01AB51 indometacin, combinations 100 MG WHO ketoprofen M01AE03 ketoprofen 150 MG WHO mefenamic acid M01AG01 mefenamic acid 1000 MG WHO meloxicam M01AC06 meloxicam 15 MG WHO morniflumate M01AX22 morniflumate 750 MG Expert nabumetone M01AX01 nabumetone 1000 MG WHO naproxen M01AE02 naproxen 500 MG WHO niflumic acid M01AX02 niflumic acid 750 MG WHO nimesulide M01AX17 nimesulide 200 MG WHO parecoxib M01AH04 parecoxib 40 MG WHO piroxicam M01AC01 piroxicam 20 MG WHO rofecoxib M01AH02 rofecoxib 25 MG WHO

sulindac M01AB02 sulindac 400 MG WHO tenoxicam M01AC02 tenoxicam 20 MG WHO tiaprofenic acid M01AE11 tiaprofenic acid 600 MG WHO valdecoxib M01AH03 valdecoxib 10 MG WHO Oral acenocoumarol B01AA07 acenocoumarol 5 MG WHO anticoagulant apixaban B01AF02 apixaban 10 MG WHO dabigatran B01AE07 dabigatran etexilate 300 MG WHO fluindione B01AA12 fluindione 20 MG Expert rivaroxaban B01AF01 rivaroxaban 20 MG WHO phenindione B01AA02 phenindione 100 MG WHO warfarin B01AA03 warfarin 7,5 MG WHO Colchicine Colchicine M04AC01 colchicine 1 MG WHO Serotonergic citalopram N06AB04 citalopram 20 MG WHO drugs dapoxetine G04BX14 dapoxetine 30 MG WHO escitalopram N06AB10 escitalopram 10 MG WHO fluoxetine N06AB03 fluoxetine 20 MG WHO fluvoxamine N06AB08 fluvoxamine 100 MG WHO iproniazide N06AF05 iproniazide 50 MG Expert linezolid J01XX08 linezolid 1200 MG WHO moclobemide N06AG02 moclobemide 300 MG WHO paroxetine N06AB05 paroxetine 20 MG WHO rasagiline N04BD02 rasagiline 1 MG WHO selegiline N04BD01 selegiline 5 MG WHO sertraline N06AB06 sertraline 50 MG WHO venlafaxine N06AX16 venlafaxine 100 MG WHO vortioxetine N06AX26 vortioxetine 10 MG WHO Tramadol tramadol N02AJ14 tramadol and dexketoprofen 150 MG WHO tramadol N02AX02 tramadol 300 MG WHO tramadol N02AJ13 tramadol and paracetamol 150 MG WHO Statins atorvastatin C10AA05 atorvastatin 20 MG WHO atorvastatin C10BX03 atorvastatin and amlodipine 20 MG Expert atorvastatin C10BA05 atorvastatin and ezetimibe 20 MG Expert pravastatin C10AA03 pravastatin 30 MG WHO pravastatin C10BX02 pravastatin and acetylsalicylic acid 40 MG Expert simvastatin C10AA01 simvastatin 30 MG WHO simvastatin C10BA02 simvastatin and ezetimibe 1 UD WHO Macrolides azithromycin J01FA10 azithromycin 300 MG WHO clarithromycin J01FA09 clarithromycin 500 MG WHO erythromycin J01FA01 erythromycin 2000 MG WHO roxithromycin J01FA06 roxithromycin 300 MG WHO telithromycin J01FA15 telithromycin 800 MG WHO Macrolides azithromycin J01FA10 azithromycin 300 MG WHO clarithromycin J01FA09 clarithromycin 500 MG WHO erythromycin J01FA01 erythromycin 2000 MG WHO josamycin J01FA07 josamycin 2000 MG WHO midecamycin J01FA03 midecamycin 1000 MG WHO roxithromycin J01FA06 roxithromycin 300 MG WHO telithromycin J01FA15 telithromycin 800 MG WHO

Figure S1. Prevalence and 95% confidence interval of exposure to six drug-drug interactions between 2006 and 2016 considering the population exposed to the object drug (OD) at denominator, Echantillon généraliste de bénéficiaires - EGB, France. ARBs: angiotensin II Receptor Antagonists; ACEIs: angiotensin-converting enzyme inhibitor(s); NSAIDs: nonsteroidal anti-inflammatory drugs; OAC: oral anticoagulant; AAP: antiplatelet agents; OD: object drug; PD: precipitant drug.

Figure S2. Prevalence and 95% confidence interval of exposure to six drug-drug interactions between 2006 and 2016 considering the population exposed to the precipitant drug (PD) at denominator, Echantillon généraliste de bénéficiaires - EGB, France. ARBs: angiotensin II Receptor Antagonists; ACEIs: angiotensin-converting enzyme inhibitor(s); NSAIDs: nonsteroidal anti-inflammatory drugs; OAC: oral anticoagulant; AAP: antiplatelet agents; OD: object drug; PD: precipitant drug