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Prevalence and Clinical Sig- Nificance of Drug–Drug and Drug–Dietary Supplement Interactions Among Patients Admitted for Cardiothoracic Surgery in Greece

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Prevalence and Clinical Sig- Nificance of Drug–Drug and Drug–Dietary Supplement Interactions Among Patients Admitted for Cardiothoracic Surgery in Greece Supplementary Materials: Prevalence and Clinical Sig- nificance of Drug–Drug and Drug–Dietary Supplement Interactions among Patients Admitted for Cardiothoracic Surgery in Greece Marios Spanakis, Maria Melissourgaki, George Lazopoulos, Athina E. Patelarou and Evridiki Patelarou The supplementary file contains additional information regarding the clinical data that were recorded during the study, the percentages of patients exposed in DDIs during hospitalization, the full list of drug interactions that were identified with relative references that support their clinical significance and the list of drugs that were recorded in each time period of hospitalization in the CTS clinic (admission, pre-opera- tion, post-operation, discharge). Pharmaceutics 2021, 13, 239. https://doi.org/10.3390/pharmaceutics13020239 www.mdpi.com/journal/pharmaceutics Pharmaceutics 2021, 13, 239 2 of 17 Figure S1. Clinical data for patients in the study (HR: Heart Rate (bmp), Cr: Creatinine (μmol/L), Κ: Potas- sium mEq/L, Na: Sodium Chloride mEq/L, INR: International Normalized Ratio, Glu: Blood Glucose mg/dL). Figure S2. Percentages of patients exposed in clinically significant DDIs. Table S1. PK- DDIs -Serious-use alternative. Number of Drugs.co Drug A Drug B Drug categories Pharmacological-Clinical outcome Medscape Refs cases m acenocouma- anti- anticoagu- PK-CYP metabolism inhibition Serious use al- amiodarone 4 Major [1] rol arrhythmic lant acenocoumarol levels ternative antili- PK -CYP3A4 inhibition (statin-rhab- Serious use al- amlodipine simvastatin Ca-blocker 4 Major [2] pidemic domyolisis) ternative PK-Renal clearance (methotrexate Serious use al- aspirin methotrexate NSAIDs chemo-RA 2 Major [3] toxicity) ternative esomepra- anti-plate- Serious use al- cilostazol PPI PK-CYP2C19 inhibition of cilostazol 2 Major [4] zole let ternative esomepra- anti-plate- reduced antiplatelet activity - Serious use al- clopidogrel PPI 11 Moderate [5] zole let CYP2C9 metabolism ternative esomepra- escitalopram PPI SSRI PK-CYP2C19 metabolsim inhibition 1 Monitor closely Moderate [6] zole antipsy- anti- Serious use al- haloperidol amiodarone PK-CYP2D6 inhibition 1 Major [7] chotic arrhythmic ternative ranolazine carvedilol angina β-blocker PK-CYP2D6 metabolism (carvedilol) 3 Monitor closely Moderate PK -renal clearance (metformin) Serious use al- ranolazine metformin angina diabetes II 2 Moderate [8] OCT2 ternative antili- CYP3A4 inhibition (statin-rhabdo- Serious use al- [19- ranolazine simvastatin angina 3 Major pidemic myolysis) ternative 20] Pharmaceutics 2021, 13, 239 3 of 17 Table S2. PK-DDIs Use with caution-Monitor. Num- Pharmacological- Drug A Drug B Drug categories ber of Medscape Drugs.com Refs Clinical outcome cases PK-CYP1A2 inhibi- Serious anticoag- allopurinol acenocoumarol uric acid tion acenocoumarol 1 use alter- Moderate [9-11] ulant levels native anti- antili- PK-bioavailability of Monitor amiodarone atorvastatin arrhyth- 2 Moderate [12] pidemic atorvastatin closely mic anti- PK-CYP2D6 inhibi- Monitor amiodarone metoprolol arrhyth- β-blocker tion for metoprolol 3 closely Moderate [13] mic (bradycardia) anti- PK-CYP2D6 inhibi- Monitor amiodarone tramadol arrhyth- analgesic 1 Major [14] tion for tramadol closely mic antiepi- Monitor aspirin sodium valproate NSAIDs PK-protein binding 2 Moderate [15] leptic closely antili- PK-OATB1 trans- Monitor atorvastatin valsartan ARBs 4 Moderate [16] pidemic porter closely anti- Monitor α,β-block- PK-CYP2D6 inhibi- carvedilol amiodarone arrhyth- 1 closely Moderate [13] ers tion (carvedilol) mic PK-CYP1A2 inhibi- Serious anticoag- ciprofloxacin acenocoumarol antibiotic tion acenocoumarol 2 use alter- Major [10,11] ulant levels native Serious cortico- PK-CYP3A4 inhibi- diltiazem budesonide angina 1 use alter- Moderate [17] steroid tion for budenoside native anticoag- PK-CYP2C9 metabo- Minor esomeprazole acenocoumarol PPI 1 Moderate [10] ulant lism inhibition Monitor PK-CYP2C19 inhibi- esomeprazole citalopram PPI SSNRI 1 closely Major [6] tion of citalopram PK CYP2D6 metabo- antipsy- Monitor haloperidol metoprolol β-blocker lism inhibition 6 Moderate [18] chotic closely (metoprolol) Serious anti-plate-PK CYP2C9 metabo- omeprazole clopidogrel PPI 3 use alter- Major [5] let lism (clopidogrel) native anti-plate- PK-CYP2C19 inhibi- Monitor pantoprazole clopidogrel PPI 1 Moderate [5] let tion of clopidorgrel closely PK- myopathy (P-gp antili- Monitor Major ranolazine atorvastatin angina and OATB1 inhibi- 2 [19,20] pidemic closely tion) antili- PK- myopathy Monitor No inter- ranolazine rosuvastatin angina 2 [19,20] pidemic (OATB1 inhibition) closely action Serious anti-plate- PK-CYP3A4 inhibi- ticagrelor ivabradine angina 1 use alter- moderate [21] let tion (ivabradine) native Pharmaceutics 2021, 13, 239 4 of 17 Table S3. PK- DDIs Moderate-Minor. Pharmaco- Num- logical- Drugs.co Drug A Drug B Drug categories ber of Medscape Refs Clinical m cases outcome PK-CYP2C9 antili- (polymor- Monitor [10,11 acenocoumarol simvastatin anticoagulant 2 Minor pidemic phism de- closely ] pedent) PK- Monitor [14,22 amiodarone codeine antiarrhythmic analgesic CYP2D6 2 Moderate closely ,23] (codeine) PK-protein binding /re- Monitor No inter- amoxicillin aspirin antibiotic NSAIDs 4 [24] nal clear- closely action ance PK- CYP3A4 in- acenocouma- anticoagu- duction me- Monitor [10,11 budesonide corticosteroid 13 Moderate rol lant tabolism of closely ] acenocou- marol PK- CYP3A4 in- Monitor No inter- budesonide alprazolam corticosteroid anxiolytics 6 [25] duction me- closely action tabolism PK- anti- CYP3A4 in- Monitor budesonide amiodarone corticosteroid 6 Moderate [17] arrhythmic duction me- closely tabolism PK- CYP3A4 in- anti-plate- Monitor No inter- budesonide clopidogrel corticosteroid duction me- 5 [17] let closely action tabolism of clopidogrel PK- CYP3A4 in- No inter- budesonide dutasteride corticosteroid BPH duction me- 1 Minor [17] action tabolism of dutasteride PK-metabo- budesonide eplerenone corticosteroid diuretic lism induc- 5 Minor Moderate [17] tion PK- No inter- budesonide finasteride corticosteroid urologicals CYP3A4 in- 2 Minor [17] action duction PK- antipsy- Monitor No inter- budesonide quetiapine corticosteroid CYP3A4 in- 4 [17] chotic closely action duction PK- Serious use al- budesonide ranolazine corticosteroid angina 1 Moderate [17] ranolazine ternative Pharmaceutics 2021, 13, 239 5 of 17 inhibits CYP3A4 PK- antipsy- Monitor carvedilol haloperidol β-blocker CYP2D6 in- 2 Moderate [14] chotic closely hibition PK CYP3A4 metabolism No inter- Minor ciprofloxacin alprazolam antibiotic anxiolytics inhibition 3 action [14] (alprazo- lam) reduce domperi- Not listed Not listed 1,2 and domperidone alprazolam antiemetic anxiolytics 10 done me- [37] tabolism PK CYP3A4 metabolism No inter- Minor esomeprazole alprazolam PPI anxiolytics inhibition 4 action [26] (alprazo- lam) (both oral forms) Monitor esomeprazole cefuroxime PPI antibiotic modulate 2 Moderate [27] closely of pH -ab- sorption PK -duloxe- Monitor esomeprazole duloxetine PPI SSRI tine GI ab- 1 Minor [26] closely sorption ferrous (glu- PK -T4 GI Monitor levothyroxine anaemia thyroid 4 Moderate [28] conate, sulfate) absorption closely PK- CYP3A4 in- acenocouma- anticoagu- duction me- Monitor hydrocortisone corticosteroid 1 Moderate [10] rol lant tabolism of closely acenocou- marol PK-CYP2C9 omeprazole carvedilol PPI β-blocker metabolism 2 Minor Moderate [26] (carvedilol) PK- renal H2-receptor an- ranitidine metformin diabetes II clearance 2 No interaction Moderate [29] tagonist (metform) PK-GI ab- H2-receptor an- vitamin ranitidine vitamin B12 sorption for 15 No interaction Minor [30] tagonist B12 B12 PK- CYP2D6 Monitor ranolazine metoprolol angina β-blocker metabolism 1 Moderate [31] closely (metopro- lol) 1 https://www.mayoclinic.org/drugs-supplements/alprazolam-oral-route/precautions/drg-20061040?p=1 2 https://www.medicines.org.uk/emc/product/556/smpc Pharmaceutics 2021, 13, 239 6 of 17 PK-inhibi- tion Monitor ranolazine morphine angina analgesic CYP2D6 in- 1 Moderate [31] closely crease mor- phine levels PK- antipsy- Monitor tamsulosin haloperidol BPH CYP2D6 in- 1 Moderate [32] chotic closely hibition Table S4. PD- DDIs Serious -use alternative. Pharmacological- Number Drug A Drug B Drug categories Medscape Drugs.com Refs Clinical outcome of cases anxiolyt- antipsy- PD-synergism seda- Monitor alprazolam haloperidol 2 Moderate [33] ics chotic tion closely hypokale- PD-synergism hyper- Serious use amiloride potassium chloride diuretic 3 Major [34] mia kalemia alternative PD-synergism (Sero- Serious use citalopram duloxetine SSNRI SSRI 1 Major [35] tonine syndrome) alternative antili- antili- Serious use fenofibrate pitavastatin PD-synergism 2 Major [36] pidemic pidemic alternative antipsy- anti- Serious use haloperidol amiodarone PD-QT prolangation 1 Major [37] chotic arrhythmic alternative PD-serotonin syn- Serious use morphine escitalopram analgesic SSRI 1 Moderate [38] drome alternative PD-enhance anti- antipsy- antipsy- Monitor quetiapine haloperidol dopaminergic effect - 6 Major [33] chotic chotic closely QT prolangation PD-synergism seda- Serious use tramadol pethidine analgesic analgesic 2 Major tion alternative Table S5. PD-DDIs Use with caution -monitor. Pharmacologi- Number Drug A Drug B Drug categories cal-Clinical Medscape Drugs.com Refs of cases outcome PD-synergism Monitor alprazolam morphine anxiolytics analgesic 16 Major [39] sedation closely PD-synergism Monitor alprazolam quetiapine anxiolytics antipsychotic 4 Major sedation closely PD-antago-
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