Arzneimittelinteraktionen in der Intensivmedizin

Zusammenfassung

Arzneimittelinteraktionen sind auf Intensivstationen ein häufiges Problem. Dabei spielt die Gesamtmenge der verschriebenen Medikamente bei kritisch kranken Patienten eine große Rolle: Durchschnittlich werden hier 25 – 35 Medikamente pro Patient eingesetzt. Fundierte Kenntnisse über entsprechende pharmakodynamische und pharmakokinetische Mechanismen sind für die Behandlungssicherheit daher essenziell.

Abstract

Drug-drug interactions are common problems in intensive care units. Numerous studies could demonstrate the impact of the total amount of prescribed drugs and the occurrence of potential respectively manifest drug-drug interactions in critically ill patients. The average number of clinically used drugs in this setting is approximately 25 – 35 per patient, thus the profound knowledge of pharmacodynamic and pharmakokinetic mechanisms regarding drug interplay is important for treatment safety. This review aims to summarize the current evidence of drug interactions in intensive care patients. It especially features data regarding pharmacokinetics as main reason for clinically relevant drug-drug interactions. The most important drug classes noted in this context are analgesics and sedatives, antibiotics, antimycotics, antiepileptics, immune suppressive drugs, prokinetics and gastric acid regulating drugs. Furthermore, some pharmacodynamic interactions are described like QTc prolongation or serotonin syndrome. Additionally, a clinical case is demonstrated regarding the malignant impact of rifampin co-medication in a patient suffering from severe hypertension with the use of several antihypertensive drugs.

Schlüsselwörter

Arzneimittelinteraktionen - Intensivmedizin - Pharmakodynamik - Pharmakokinetik - klinische Pharmazie

Key words

drug-drug interactions - intensive care - pharmacodynamics - pharmacokinetics - clinical pharmacy

• Literatur

• 1 Böhm R, Reinecke K, Haen E. et al. Arzneimittelinteraktionen – Verstehen, vermitteln und vermeiden. Deutsche Apotheker Zeitung 2012; 36: 64
• 2 Kane-Gill SL, Kirisci L, Verrico MM. et al. Analysis of risk factors for adverse drug events in critically ill patients. Crit Care Med 2012; 40: 823-828
• 3 Gallagher PF, Barry PJ, Ryan C. et al. Inappropriate prescribing in an acutely ill population of elderly patients as determined by Beersʼ Criteria. Age Ageing 2008; 37: 96-101
• 4 Fialová D, Topinková E, Gambassi G. et al. Potentially inappropriate medication use among elderly home care patients in Europe. JAMA 2005; 293: 1348-1358
• 5 Fitzmaurice MG, Wong A, Akerberg H. et al. Evaluation of Potential Drug-Drug Interactions in Adults in the Intensive Care Unit: A Systematic Review and Meta-Analysis. Drug Saf 2019; 42: 1035-1044
• 6 Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilmanʼs The Pharmacological Basis of Therapeutics. 12th ed. New York: Mcgraw-Hill Professional; 2011: 89-121
• 7 Zagermann-Muncke P. Wenn Arzneistoffe Transportproteine beeinflussen. Pharmazeutische Zeitung 2006; 50 Im Internet: https://www.pharmazeutische-zeitung.de/ausgabe-502006/abda-datenbank-wenn-arzneistoffe-transportproteine-beeinflussen/. Stand: 27.08.2019
• 8 Kämmerer W. Klinisch relevante pharmakokinetische Arzneimittelinteraktionen in der Intensivmedizin. Med Klin Intensivmed Notmed 2011; 107: 128-140
• 9 Liu YT, Hao HP, Liu CX. et al. Drugs as CYP3A probes, inducers, and inhibitors. Drug Metab Rev 2007; 39: 699-721
• 10 Spriet I, Meersseman W, de Hoon J. et al. Mini-series: II. Clinical aspects. Clinically relevant CYP450-mediated drug interactions in the ICU. Intensive Care Med 2009; 35: 603-612
• 11 Cascorbi I. Drug interactions – principles, examples and clinical consequences. Dtsch Arztebl Int 2012; 109: 546-556
• 12 CredibleMeds. Im Internet: http://www.crediblemeds.org. Stand: 25.08.2019
• 13 Wang RZ, Vashistha V, Kaur S. et al. Serotonin syndrome: Preventing, recognizing, and treating it. Cleve Clin J Med 2016; 83: 810-817
• 14 Trescot AM, Datta S, Lee M. et al. Opioid pharmacology. Pain Physician 2008; 11 (2. Suppl): 133-153
• 15 Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI), Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin (DIVI). S3-Leitlinie Analgesie, Sedierung und Delirmanagement in der Intensivmedizin (DAS-Leitlinie 2015). AWMF-Register Nr. 001/012. Im Internet: https://www.awmf.org/leitlinien/detail/ll/001-012.html. Stand: August 2015
• 16 Transformer – Metabolism of Xenobiotics Database. Im Internet: http://bioinformatics.charite.de/transformer/. Stand: 06.08.2019
• 17 Armstrong SC, Cozza KL. Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II. Psychosomatics 2003; 44: 515-520
• 18 Armstrong SC, Cozza KL. Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part I. Psychosomatics 2003; 44: 167-171
• 19 Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM). Rote-Hand-Briefe zu Fentanyl®-Janssen und Durogesic® SMAT (12, 25, 50, 75, 100 µg/h), transdermales Pflaster (Wirkstoff: Fentanyl): Neuer Warnhinweis. Im Internet: http://www.bfarm.de/SharedDocs/Risikoinformationen/Pharmakovigilanz/DE/RHB/2013/rhb-fentanyl-durogesic.html. Stand: 26.08.2019
• 20 Linezolid: Komplexe Interaktion mit serotonergen Substanzen mit der Folge eines Serotonin-Syndroms. [Drug Safety Mail 2019 – 39] Arzneimittelkommission der deutschen Ärzteschaft: s.n., 10. Jul 2019.
• 21 Sahinovic MM, Struys MMRF, Absalom AR. Clinical Pharmacokinetics and Pharmacodynamics of Propofol. Clin Pharmacokinet 2018; 57: 1539-1558
• 22 Dinis-Oliveira RJ. Metabolic Profiles of Propofol and Fospropofol: Clinical and Forensic Interpretative Aspects. Biomed Res Int 2018; 2018: 6852857 doi:10.1155/2018/6852857
• 23 Farrokh S, Tahsili-Fahadan P, Ritzl EK. et al. Antiepileptic drugs in critically ill patients. Crit Care 2018; 22: 153
• 24 Rhabdomyolyse und mehr. Pharmazeutische Zeitung 2012; 56. Im Internet: http://www.pharmazeutische-zeitung.de/ausgabe-052012/rhabdomyolyse-und-mehr/. Stand: 27.08.2019
• 25 Olkkola KT, Ahonen J. Midazolam and other benzodiazepines. Handb Exp Pharmacol 2008; 182: 335-360
• 26 Wedemeyer RS, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf 2014; 37: 201-211
• 27 Uchaipichat V, Suthisisang C, Miners JO. The glucuronidation of R- and S-lorazepam: human liver microsomal kinetics, UDP-glucuronosyltransferase enzyme selectivity, and inhibition by drugs. Drug Metab Dispos 2013; 41: 1273-1284
• 28 Tang JY, Kiang TKL, Ensom MHH. Pharmacokinetic Interactions between Valproic Acid and Lorazepam (PIVOtAL Study): A Review of Site-Specific Practices. Can J Hosp Pharm 2017; 70: 171-178
• 29 Fachinformation Dexdor 100 Mikrogramm/ml Konzentrat zur Herstellung einer Infusionslösung. s.l.: Orion Pharma, Januar 2019.
• 30 Keating GM. Dexmedetomidine: A Review of Its Use for Sedation in the Intensive Care Setting. Drugs 2015; 75: 1119-1130
• 31 Bush K, Bradford PA. β-Lactams and β-Lactamase Inhibitors: An Overview. Cold Spring Harb Perspect Med 2016; 6: pii:a025247 doi:10.1101/cshperspect.a025247
• 32 Bolhuis MS, Panday PN, Pranger AD. et al. Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams. Pharmaceutics 2011; 3: 865-913
• 33 Mori H, Takahashi K, Mizutani T. Interaction between valproic acid and carbapenem antibiotics. Drug Metab Rev 2007; 39: 647-657
• 34 ZYVOXID 2 mg/ml Infusionslösung. s.l.: Pfizer, Januar 2018.
• 35 Sivextro 200 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung. s.l.: MSD, August 2018.
• 36 Dinos GP. The macrolide antibiotic renaissance. Br J Pharmacol 2017; 174: 2967-2983
• 37 Drlica K. Mechanism of fluoroquinolone action. Curr Opin Microbiol 1999; 2: 504-508
• 38 Farr B, Mandell GL. Rifampin. Med Clin North Am 1982; 66: 157-168
• 39 Schäfer-Korting M. New systemic antifungal drugs: mechanisms of action, drug interactions and side effects. Mycoses 2003; 46 (Suppl. 01) 28-31
• 40 Bellmann R, Smuszkiewicz P. Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients. Infection 2017; 45: 737-779
• 41 Patil A, Majumdar S. Echinocandins in antifungal pharmacotherapy. J Pharm Pharmacol 2017; 69: 1635-1660
• 42 Lempers VJ, van den Heuvel JJ, Russel FG. et al. Inhibitory Potential of Antifungal Drugs on ATP-Binding Cassette Transporters P-Glycoprotein, MRP1 to MRP5, BCRP, and BSEP. Antimicrob Agents Chemother 2016; 60: 3372-3379
• 43 Johnson MD, Perfect JR. Caspofungin: first approved agent in a new class of antifungals. Expert Opin Pharmacother 2003; 4: 807-823
• 44 Niwa T, Shiraga T, Takagi A. Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes. Biol Pharm Bull 2005; 28: 1805-1808
• 45 Higashiyama Y, Kohno S. Micafungin: a therapeutic review. Expert Rev Anti Infect Ther 2004; 2: 345-355
• 46 Orinx C, Legro B, Gaspard N. Recent antiseizure medications in the Intensive Care Unit. Minerva Anestesiol 2017; 83: 878-887
• 47 Zaccara G, Perucca E. Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs. Epileptic Disord 2014; 16: 409-431
• 48 Fachinformation Valproat Chrono Winthrop. s.l.: SANOFI, Dezember 2018.
• 49 Fachinformation Keppra^® 100 mg/ml Konzentrat zur Herstellung einer Infusionslösung. s.l.: UCB, März 2019.
• 50 Czock D, Keller F, Rasche FM. et al. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet 2005; 44: 61-98
• 51 Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients. Clin Pharmacokinet 2007; 46: 13-58
• 52 Bullingham RE, Nicholls AJ, Kamm BR. Clinical pharmacokinetics of mycophenolate mofetil. Clin Pharmacokinet 1998; 34: 429-455
• 53 Fachinformation CellCept^® i.v. s.l.: Roche, März 2018.
• 54 Youssef AS, Parkman HP, Nagar S. Drug-drug interactions in pharmacologic management of gastroparesis. Neurogastroenterol Motil 2015; 27: 1528-1541
• 55 Camilleri M, Chedid V, Ford AC. et al. Gastroparesis. Nat Rev Dis Primers 2018; 4: 41
• 56 Fachinformation MCP-ratiopharm SF 10 mg/2 ml Injektionslösung. s.l.: Ratiopharm, November 2018.
• 57 Fachinformation Motilium^® Tropfen 10 mg/ml Suspension. s.l.: Takeda, November 2017.
• 58 Angiolillo DJ, Gibson CM, Cheng S. et al. Differential effects of omeprazole and pantoprazole on the pharmacodynamics and pharmacokinetics of clopidogrel in healthy subjects: randomized, placebo-controlled, crossover comparison studies. Clin Pharmacol Ther 2011; 89: 65-74
• 59 Blume H, Donath F, Warnke A. et al. Pharmacokinetic drug interaction profiles of proton pump inhibitors. Drug Saf 2006; 29: 769-784
• 60 Fachinformation Ranitidin-ratiopharm^® 50 mg/5 ml Injektionslösung. s.l.: Ratiopharm, Juli 2014.