Arzneimittelinteraktionen, die man kennen muss!

Arzneimittelinteraktionen (AMI) sind ein häufig unterschätztes Problem der modernen Medizin. Die Zahl älterer, multimorbider Patienten, die mehrere Wirkstoffe gleichzeitig einnehmen, nimmt stetig zu – der damit verbundene exponentielle Anstieg möglicher AMI ist fast unüberschaubar. Diese Übersicht stellt häufige, relevante AMI anhand von Beispielen dar und zeigt Strategien auf, wie sie in der Praxis frühzeitig erkannt und vermieden werden können.

Drug-drug interactions (DDI) represent a significant problem in modern medicine. The number of patients with multi-morbidity, who take multiple drugs, is constantly increasing (polypharmacy). The related exponential increase in potential DDI is almost incomprehensible. In this article, we review pharmacodynamic DDI and provide clinically relevant examples. In addition, we extensively review pharmakokinetic DDI (e. g. through the cytochrome P450-system or p-glycoproteins) that can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. Finally we provide tools, which may help clinicians in their daily practice to identify and avoid potential DDI. In the context of an ageing society receiving polypharmacy, a better awareness of DDI and of strategies to prevent them is expected to reduce mortality and morbidity.

Schlüsselwörter

Arzneimittelinteraktionen - Cytochrom P450 - Polypharmazie - Pharmakokinetik - Pharmakodynamik

Keywords

drug-drug interactions - cytochrome P450 - polypharmacy - pharmacokinetics - pharmacodynamics

• Literatur

• 1 Dechanont S, Maphanta S, Butthum B. et al. Hospital admissions / visits associated with drug-drug interactions: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 2014; 23: 489-497 . doi:10.1002/pds.3592
• 2 Cascorbi I. Drug interactions – principles, examples and clinical consequences. Dtsch Arztebl Int 2012; 109: 546-555 quiz 556. doi:10.3238/arztebl.2012.0546
• 3 Kloner RA, Goldstein I, Kirby MG. et al. Cardiovascular safety of phosphodiesterase type 5 inhibitors after nearly 2 decades on the market. Sex Med Rev 2018 . doi:10.1016/j.sxmr.2018.03.008 [Epub ahead of print]
• 4 Schwartz BG, Kloner RA. Drug interactions with phosphodiesterase- 5 inhibitors used for the treatment of erectile dysfunction or pulmonary hypertension. Circulation 2010; 122: 88-95 . doi:10.1161/CIRCULATIONAHA.110.944603
• 5 Pringle SD, MacEwen CJ. Severe bradycardia due to interaction of timolol eye drops and verapamil. Brit Med J 1987; 294: 155-156
• 6 de Abajo FJ. Effects of selective serotonin reuptake inhibitors on platelet function: mechanisms, clinical outcomes and implications for use in elderly patients. Drugs Aging 2011; 28: 345-367 . doi:10.2165/11589340-000000000-00000
• 7 Hackam DG, Mrkobrada M. Selective serotonin reuptake inhibitors and brain hemorrhage: a meta-analysis. Neurology 2012; 79: 1862-1865 . doi:10.1212/WNL.0b013e318271f848
• 8 Loke YK, Trivedi AN, Singh S. Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2008; 27: 31-40 . doi:10.1111/j.1365-2036.2007.03541.x
• 9 Heijman J, Voigt N, Carlsson LG. et al. Cardiac safety assays. Curr Opin Pharmacol 2014; 15: 16-21 . doi:10.1016/j.coph.2013.11.004
• 10 Drew BJ, Ackerman MJ, Funk M. et al. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. Circulation 2010; 121: 1047-1060 . doi:10.1161/CIRCULATIONAHA.109.192704
• 11 Meid AD, von Medem A, Heider D. et al. Investigating the additive Interaction of QT-prolonging drugs in older people using claims data. Drug Saf 2017; 40: 133-144 . doi:10.1007/s40264-016-0477-y
• 12 Meid AD, Bighelli I, Machler S. et al. Combinations of QTc-prolonging drugs: towards disentangling pharmacokinetic and pharmacodynamic effects in their potentially additive nature. Ther Adv Psychopharmacol 2017; 7: 251-264 . doi:10.1177/2045125317721662
• 13 Hohlfeld T, Saxena A, Schror K. High on treatment platelet reactivity against aspirin by non-steroidal anti-inflammatory drugs – pharmacological mechanisms and clinical relevance. Thromb Haemost 2013; 109: 825-833 . doi:10.1160/TH12-07-0532
• 14 Heidbuchel H, Verhamme P, Alings M. et al. Updated European Heart Rhythm Association Practical Guide on the use of nonvitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015; 17: 1467-1507 . doi:10.1093/europace/euv309
• 15 Benet LZ, Hoener BA. Changes in plasma protein binding have little clinical relevance. Clin Pharmacol Ther 2002; 71: 115-121 . doi:10.1067/mcp.2002.121829
• 16 Shitara Y, Hirano M, Sato H. et al. Gemfibrozil and its glucuronide inhibit the organic anion transporting polypeptide 2 (OATP2 / OATP1B1: SLC21A6)-mediated hepatic uptake and CYP2C8-mediated metabolism of cerivastatin: analysis of the mechanism of the clinically relevant drug-drug interaction between cerivastatin and gemfibrozil. J Pharmacol Exp Ther 2004; 311: 228-236 . doi:10.1124/jpet.104.068536
• 17 Haffner S, Thürmann PA. Which drug interactions the general practitioner should know. Med Klin 2004; 99: 137-146 ; quiz 147. doi:10.1007/s00063-004-1022-9
• 18 Abbas S, Ihle P, Harder S. et al. Risk of bleeding and antibiotic use in patients receiving continuous phenprocoumon therapy. A case-control study nested in a large insurance- and population-based German cohort. Thromb Haemost 2014; 111: 912-922 . doi:10.1160/TH13-09-0723
• 19 Dempfle CE. Pharmacology of the new oral anticoagulants. Herz 2012; 37: 362-368 . doi:10.1007/s00059-012-3616-y
• 20 Wagner J, Suessmair C, Pfister HW. Rhabdomyolysis caused by co-medication with simvastatin and clarithromycin. J Neurol 2009; 256: 1182-1183 . doi:10.1007/s00415-009-5078-6
• 21 Li DQ, Kim R, McArthur E. et al. Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4. CMAJ 2015; 187: 174-180 . doi:10.1503/cmaj.140950
• 22 Cronnolly B, Pegrum H. Fentanyl-clarithromycin interaction. BMJ Case Rep 2012 . doi:10.1136/bcr.02.2012.5936
• 23 Hall SD, Wang Z, Huang SM. et al. The interaction between St John’s wort and an oral contraceptive. Clin Pharmacol Ther 2003; 74: 525-535 . doi:10.1016/j.clpt.2003.08.009
• 24 Walley T, Pirmohamed M, Proudlove C. et al. Interaction of metoprolol and fluoxetine. Lancet 1993; 341: 967-968
• 25 Agewall S, Cattaneo M, Collet JP. et al. Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy. Eur Heart J 2013; 34: 1708-1713, 1713a-1713b . doi:10.1093/eurheartj/eht042