Analjezik İlaçların Diğer İlaçlarla Etkileşmeleri
Özet
Birden fazla ilacın eşzamanlı kullanımıyla ortaya çıkan ilaç etkileşmeleri özellikle yaşlı bireylerde ve kronik hastalığı olanlarda klinik açıdan önemli bir konudur. Dünyada ve ülkemizde analjezik ilaç kullanımı çok yaygındır. Nonsteroid antiinflamatuvar ilaçlar (NSAİİ) ve parasetamol en çok kullanılan analjezik ilaç gruplarıdır. Opioid analjezikler ise şiddetli ağrı tedavisinde tercih edilirler. Analjezik ilaçlarla etkileşmeler en sık görülen ve klinik açıdan en önemli etkileşmeler arasındadır. Özellikle reçetesiz satılan NSAİİ ve parasetamol gibi analjeziklerin yaygın bulunabilirliği ve algılanan güvenliği nedeniyle, bu ilaçlarla kendi kendine tedavi yaygın hale gelmiştir. Potansiyel ilaç etkileşmesinin farkında olmayan hastalar, bu ilaçları önerilenden daha yüksek dozlarda veya kombinasyonlarda kullanabilirler. Bu da ciddi ilaç etkileşmelerine yol açabilir. Saptanan potansiyel ilaç etkileşmelerinin dörtte üçünden fazlasının NSAİİ-NSAİİ ve opioid-benzodiazepin kombinasyonu gibi klinik etkinliğe katkısı düşük, ancak ciddi ilaç etkileşmelerine yol açabilecek kombinasyonlardır ve bu ilaçlar aynı hekim tarafından reçete edilmiştir. İlaçların birlikte reçetelenmesi gerekli olarak düşünülmüş ve tedaviye bilinçli olarak eklenmiş olabilir. Ancak, bu reçeteleme klinisyenlerin yetersiz farmakolojik bilgisinden ya da ilaç etkileşmelerini gözardı etmesinden de kaynaklanabilir. Bunun önlenmesi için eğitim programları yapılarak farkındalık oluşturulabilir. Ayrıca, bilgisayar programları kullanılarak olası ilaç etkileşmelerinin önüne geçilebilir. Hekimler, bu ilaçların doğru kullanımı konusunda danışmanlık sağlayarak, yaygın olarak kullanılan reçetesiz satılan ağrı kesicilerle olası ilaç-ilaç etkileşimlerinden kaçınmalarına yardımcı olabilirler.
Drug interactions arising from the simultaneous use of multiple medications are a clinically significant issue, particularly in elderly individuals and those with chronic diseases. Analgesic drug use is very common worldwide and in our country. Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol are the most commonly used analgesic drug groups. Opioid analgesics are preferred for the treatment of severe pain. Analgesic drug interactions are among the most frequent and clinically significant interactions. Self-treatment with these drugs has become widespread, especially due to the widespread availability and perceived safety of over-the-counter analgesics such as NSAIDs and paracetamol. Patients unaware of potential drug interactions may use these medications in higher doses or combinations than recommended. This can lead to serious drug interactions. More than three-quarters of the identified potential drug interactions are combinations with low clinical efficacy but which can lead to serious drug interactions, such as NSAID-NSAID and opioid-benzodiazepine combinations, and these drugs were prescribed by the same physician. The co-prescription of these drugs may have been considered necessary and consciously added to the treatment. However, this prescribing may also stem from insufficient pharmacological knowledge on the part of clinicians or their disregard for drug interactions. To prevent this, awareness can be raised through educational programs. Furthermore, potential drug interactions can be prevented using computer programs. Physicians can help patients avoid potential drug-drug interactions with commonly used over-the-counter analgesics by providing counseling on the correct use of these drugs.
Referanslar
1.Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA. 2002;287:337–344. doi: 10.1001/jama.287.3.337.
Kardaş P, Urbański F, Lichwierowicz A, et al. The Prevalence of Selected Potential Drug-Drug Interactions of Analgesic Drugs and Possible Methods of Preventing Them: Lessons Learned From the Analysis of the Real-World National Database of 38 Million Citizens of Poland. Front Pharmacol. 2021; Jan 18:11:607852. doi: 10.3389/fphar. 2020.607852. eCollection 2020.
Gagne JJ, Maio V. Rabinowitz C. Prevalence and predictors of potential drug-drug interactions in Regione Emilia-Romagna, Italy. J. Clin. Pharm. Therapeut. 2008. 33, 141–151. 10.1111/j.1365-2710.2007.00891.x
Souty C. Launay T. Steichen O, et al. Use of the French healthcare insurance database to estimate the prevalence of exposure to potential drug-drug interactions. Eur. J. Clin. Pharmacol. 2020; 76, 1675–1682. 10.1007/s00228-020-02952-7
Pergolizzi JV, Ma L, Foster DR, et al. The prevalence of opioid-related major potential drug-drug interactions and their impact on health care costs in chronic pain patients. J. Manag. Care Spec. Pharm. 2014;20, 467–476. 10.18553/jmcp.2014.20.5.467. 61
Tragni E, Casula M, Pieri V, et al. Prevalence of the prescription of potentially interacting drugs. PLoS One. 2013; 8,e78827. 10.1371/journal. pone.0078827
Liew JW, Ward MM, Reveille JD, et al. Nonsteroidal Antiinflammatory Drug Use and Association With Incident Hypertension in Ankylosing Spondylitis. Arthritis Care Res (Hoboken). 2020; 72:1645-52.
Hörl WH. Nonsteroidal Anti-Inflammatory Drugs and the Kidney. Pharmaceuticals (Basel) 2010; 3:2291-321.
Fournier JP, Sommet A, Bourrel R, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) and hypertension treatment intensification: a population-based cohort study. Eur J Clin Pharmacol 2012; 68:1533-40.
Lapi F, Azoulay L, Yin H, et al. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal antiinflammatory drugs and risk of acute kidney injury: nested case-control study. BMJ 2013;346: e8525.
Webster J. Interactions of NSAIDs with diuretics and beta-blockers mechanisms and clinical implications. Drugs. 1985;30(1):32–41.
Moore N, Pollack C, Butkerait P. Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag 2015; 11:1061-75.
Pavlicević I, Glavaski M, Rumboldt M, Rumboldt Z. Prohypertensive effects of non-steroidal anti-inflammatory drugs are mostly due to vasoconstriction. Coll Antropol. 2011;35(3):817–822.
Grover SA, Coupal L, Zowall H. Treating osteoarthritis with cyclooxygenase-2-specific inhibitors: what are the benefits of avoiding blood pressure destabilization? Hypertension. 2005; 45(1):92–97.
Drini M. Peptic ulcer disease and non-steroidal antiinflammatory drugs. Aust Prescr 2017; 40:91-3.
Vazquez SR. Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood 2018; 132:2230-9.
Bakhriansyah M, Souverein PC, de Boer A, et al. Gastrointestinal toxicity among patients taking selective COX-2 inhibitors or conventional NSAIDs, alone or combined with proton pump inhibitors: a case-control study. Pharmacoepidemiol Drug Saf 2017; 26:1141-8
Mendell J, Lee F, Chen S, et al. The effects of the antiplatelet agents, aspirin and naproxen, on pharmacokinetics and pharmacodynamics of the anticoagulant edoxaban, a direct factor Xa inhibitor. J Cardiovasc Pharmacol 2013; 62:212-21.
Hooper L, Brown TJ, Elliott R, et al. The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review. BMJ 2004; 329:948.
Mackenzie IS, Coughtrie MW, MacDonald TM,et al. Antiplatelet drug interactions. J Intern Med. 2010;268(6):516–529.
Saxena A, Balaramnavar VM, Hohlfeld T, et al. Drug/drug interaction of common NSAIDs with antiplatelet effect of aspirin in human platelets. Eur J Pharmacol. 2013;721(1–3):215–224.
Kurth T, Glynn RJ, Walker AM, et al. Inhibition of clinical benefits of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs. Circulation. 2003; 108(10):1191–1195.
MacDonald TM, Wei L. Effect of ibuprofen on cardioprotective effect of aspirin. Lancet. 2003; 361(9357):573–574.
Fischer LM, Schlienger RG, Matter CM, et al. Current use of nonsteroidal antiinflammatory drugs and the risk of acute myocardial infarction. Pharmacotherapy. 2005;25(4):503–510.
MacLeod-Glover N, Mink M, Yarema M, et al. Digoxin
toxicity: Case for retiring its use in elderly patients? Can
Fam Physician 2016; 62:223-8.
Schwartz JI, Agrawal NG, Wehling M, et al. Evaluation
of the pharmacokinetics of digoxin in healthy subjects
receiving etoricoxib. Br J Clin Pharmacol 2008; 24 Eylül; 66(6): 811–817. doi: 10.1111/j.1365-2125.2008.03285.x
Maeda A, Tsuruoka S, Ushijima K, et al. Drug interaction between celecoxib and methotrexate in organic anion transporter 3-transfected renal cells and in rats in vivo. Eur J Pharmacol 2010; 640:168-71.
Pivovarov K, Zipursky JS. Low-dose methotrexate toxicity. CMAJ 2019; 191: E423.
Svanström H, Lund M, Melbye M, et al. Concomitant use of low-dose methotrexate and NSAIDs and the risk of serious adverse events among patients with rheumatoid arthritis. Pharmacoepidemiol Drug Saf 2018; 27: 885-93.
Maeda A, Tsuruoka S, Kanai Y, et al. Evaluation of the interaction between nonsteroidal anti-inflammatory drugs and methotrexate using human organic anion transporter 3-transfected cells. Eur J Pharmacol 2008; 596:166-72.
Anglin R, Yuan Y, Moayyedi P, et al. Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis. Am J Gastroenterol 2014; 109:81.
Halperin D, Reber G. Influence of antidepressants on hemostasis. Dialogues in Clinical Neuroscience. 2007; 9(1): 47-59.
Andrade C, Sandarsh S, Chethan KB, et al. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010; 71(12): 1565-1575
Quinn GR, Hellkamp AS, Hankey GJ, ve diğerleri. Atriyal fibrilasyonlu antikoagüle hastalarda seçici serotonin geri alım inhibitörleri ve kanama riski: ROCKET AF çalışmasından bir analiz. J Am Heart Assoc . 2018; 7(15):1-9. doi:10.1161/jaha.118.008755
Scherf-Clavel M, Treiber S, Deckert J, et al. Drug-Drug Interactions Between Lithium and Cardiovascular as Well as Anti-Inflammatory Drugs. Pharmacopsychiatry 2020; 53:229-3.
Nunes RP. Lithium interactions with non-steroidal anti-inflammatory drugs and diuretics – a review. Arch ClinPsychiatry (Sao Paulo) 2018; 45: 38-40.
Phelan KM, Mosholder AD, Lu S. Lithium interaction with the cyclooxygenase 2 inhibitors rofecoxib and celecoxib and other nonsteroidal anti-inflammatory drugs. J Clin Psychiatry. 2003;64(11): 1328-34.
El-Yazbi AF, Eid AH, El-Mas MM. Cardiovascular and
renal interactions between cyclosporine and NSAIDs:
Underlying mechanisms and clinical relevance. Pharmacol
Res 2018; 129: 251-61
Lee MS, Chang CH, Lin RY, et al. Risks of hypertension
associated with cyclosporine, nonsteroidal anti-inflammatory drugs, and systemic glucocorticoids in patients with psoriasis: a nationwide population-based nested case-control study in Taiwan. Pharmacoepidemiol Drug Saf 2016; 25: 133--40. doi: 10.1002/pds.3890.
Piper JM, Ray WA, Daugherty JR, et al. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991; 114(9):735–740.
Fries JF, Bruce B. Rates of serious gastrointestinal events from low dose use of acetylsalicylic acid, acetaminophen, and ibuprofen in patients with osteoarthritis and rheumatoid arthritis. J Rheumatol. 2003;30(10):2226–2233.
Kataoka H, Horie Y, Koyama R, et al. Interaction between NSAIDs and steroid in rat stomach: safety of nimesulide as a preferential COX-2 inhibitor in the stomach. Dig Dis Sci. 2000; 45(7):1366–1375.
Hunter LJ, Wood DM, Dargan PI. The patterns of toxicity and management of acute nonsteroidal antiinflammatory drug (NSAID) overdose. Open Access Emerg Med 2011; 3:39-48.
Moore N, Pollack C, Butkerait P. Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag 2015; 11:1061-75.
Spence JD, Grosser T, FitzGerald GA. Acetaminophen, Nonsteroidal Anti-Inflammatory Drugs, and Hypertension. Hypertension. 2022; 79: 1922–1926. DOI: 10.1161/HYPERTENSIONAHA.122.19315
Guggenheimer J, Moore PA. The therapeutic applications of and risks associated with acetaminophen use: a review and update. J Am Dent Assoc 2011; 142:38-44.
Caldeira D, Costa J, Barra M, et al. How safe is acetaminophen use in patients treated with vitamin K antagonists? A systematic review and meta-analysis. Thromb Res 2015; 135:58-61.
Lopes RD, Horowitz JD, Garcia DA, et al. Warfarin and acetaminophen interaction: a summary of the evidence and biologic plausibility. Blood. 2011; 118:6269–6273. doi: 10.1182/blood-2011-08-335612
Maideen NMP. Drug interactions of acetaminophen (paracetamol) involving CYP and UGT enzymes. Eur J Med 2019; 7:127-42.
Kotlinska-Lemieszek A, Klepstad P, Haugen DF. Clinically significant drug-drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review. Drug Des Devel Ther 2015; 9:5255-67.
Smith HS. Opioid metabolism. Mayo Clin Proc 2009;84:613-24.
Mercer SL, Coop A. Opioid analgesics and P-glycoprotein efflux transporters: a potential systems-level contribution to analgesic tolerance. Curr Top Med Chem. 2011;11(9):1157–1164. doi: 10.2174/ 156802611795371288.
Park HJ, Shinn HK, Ryu SH, et al. Genetic polymorphisms in the ABCB1 gene and the effects of fentanyl in Koreans. Clin Pharmacol Ther. 2007; 81(4):539–546. doi: 10.1038/sj.clpt.6100046]
Zwisler ST, Enggaard TP, Noehr-Jensen L, et al. The antinociceptive effect and adverse drug reactions of oxycodone in human experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes. Fundam Clin Pharmacol. 2010; 24(4):517–524. doi: 10.1111/j.1472-8206.2009.00781.x.
Tzvetkov MV, dos Santos Pereira JN, Meineke I, et al. Morphine is a substrate of the organic cation transporter OCT1 and polymorphisms in OCT1 gene affect morphine pharmacokinetics after codeine administration. Biochem Pharmacol. 2013; 86(5):666–678. doi: 10.1016/j. bcp.2013.06.019
Li W, Zeng S, Yu LS, et al. Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management. Ther Clin Risk Manag. 2013;9:259–271. doi: 10.2147/TCRM.S43151
Fudin J, Fontenelle DV, Payne A. Rifampin reduces oral morphine absorption: a case of transdermal buprenorphine selection based on morphine pharmacokinetics. J Pain Palliat Care Pharmacother. 2012; 26(4): 362–367. doi: 10.3109/15360288.2012.734903.
Saarikoski T, Saari TI, Hagelberg NM, et al. Rifampicin markedly decreases the exposure to oral and intravenous tramadol. Eur J Clin Pharmacol. 2013;69(6):1293–1301. doi: 10.1007/s00228-012-1460-x.
Nieminen TH, Hagelberg NM, Saari TI, et al. Rifampin greatly reduces the plasma concentrations of intravenous and oral oxycodone. Anesthesiology.2009;110(6):1371–1378.doi:10.1097/ALN.0b013e31819 faa54.
Kharasch ED, Hoffer C, Whittington D,et al. Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone. Clin Pharmacol Ther. 2004;76(3):250–269. doi: 10.1016/j.clpt.2004.05.003.
Kharasch ED, Hoffer C, Whittington D,et al. Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine. Clin Pharmacol Ther. 2003;74(6):543–554. doi: 10.1016/j.clpt.2003.08.011.
Kharasch ED, Hoffer C, Altuntas TG, et al. Quinidine as a probe for the role of p-glycoprotein in the intestinal absorption and clinical effects of fentanyl. J Clin Pharmacol. 2004;44(3):224–233. doi: 10.1177/009127000 3262075.
Heiskanen T, Olkkola KT, Kalso E. Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone. Clin Pharmacol Ther 1998; 64(6):603–611.
Kharasch ED, Hoffer C, Whittington D. The effect of quinidine, used as a probe for the involvement of P-glycoprotein, on the intestinal absorption and pharmacodynamics of methadone. Br J Clin Pharmacol. 2004;57(5):600–610. doi: 10.1111/j.1365-2125.2003.02053.x.
Caraco Y, Sheller J, Wood AJ. Impact of ethnic origin and quinidine coadministration on codeine’s disposition and pharmacodynamic effects. J Pharmacol Exp Ther. 1999;290(1):413–422
Heiskanen T, Backman JT, Neuvonen M,et al. Itraconazole, a potent inhibitor of P-glycoprotein, moderately increases plasma concentrations of oral morphine. Acta Anaesthesiol Scand. 2008;52(10):1319–1326. doi: 10.1111/j.1399-6576.2008.01739.x.
Saari TI, Laine K, Neuvonen M, Neuvonen PJ, Olkkola KT. Effect of voriconazole and fluconazole on the pharmacokinetics of intravenous fentanyl. Eur J Clin Pharmacol. 2008;64(1):25–30. doi: 10.1007/s00228-007-0398-x
Ziesenitz VC, König SK, Mahlke NS, Skopp G, Haefeli WE, Mikus G. Pharmacokinetic interaction of intravenous fentanyl with ketoconazole. J Clin Pharmacol. 2015;55(6):708–717. doi: 10.1002/jcph.469.
Cobb MN, Desai J, Brown LS, Jr, Zannikos PN, Rainey PM. The effect of fluconazole on the clinical pharmacokinetics of methadone. Clin Pharmacol Ther. 1998;63(6):655–662. doi: 10.1016/S0009-9236(98)900 89-3.
Saarikoski T, Saari TI, Hagelberg NM, et al. Effects of terbinafine and itraconazole on the pharmacokinetics of orally administered tramadol. Eur J Clin Pharmacol. 2015;71(3):321–327. doi: 10.1007/s00228-014-1799-2
Hagelberg NM, Nieminen TH, Saari TI, et al. Voriconazole drastically increases exposure to oral oxycodone. Eur J Clin Pharmacol. 2009;65(3):263–271. doi: 10.1007/s00228-008-0568-5.
Liu P, Foster G, Labadie R, et al. Pharmacokinetic interaction between voriconazole and methadone at steady state in patients on methadone therapy. Antimicrob Agents Chemother. 2007;51(1):110–118. doi: 10.1128 /AAC.00559-06
Nieminen TH, Hagelberg NM, Saari TI, et al. Oxycodone concentrations are greatly increased by the concomitant use of ritonavir or lopinavir/ritonavir. Eur J Clin Pharmacol. 2010;66(10):977–985. doi: 10.1007/s00228-010-0879-1.
Olkkola KT, Palkama VJ, Neuvonen PJ. Ritonavir’s role in reducing fentanyl clearance and prolonging its half-life. Anesthesiology. 1999;91(3):681–685. doi: 10.1097/00000542-199909000-00020.
Grün B, Merkel U, Riedel KD, et al. Contribution of CYP2C19 and CYP3A4 to the formation of the active nortilidine from the prodrug tilidine. Br J Clin Pharmacol. 2012;74(5):854–863. doi: 10.1111/j.1365-2125.2012.04261.x.
Laugesen S, Enggaard TP, Pedersen RS,et al. Paroxetine, a cytochrome P450 2D6 inhibitor, diminishes the stereoselective O-demethylation and reduces the hypoalgesic effect of tramadol. Clin Pharmacol Ther. 2005;77(4):312–323. doi: 10.1016/j.clpt.2004.11.002.
Kapil RP, Friedman K, Cipriano A, et al. Effects of paroxetine, a CYP2D6 inhibitor, on the pharmacokinetic properties of hydrocodone after coadministration with a single-entity, once-daily, extended-release hydrocodone tablet. Clin Ther. 2015;37(10):2286–2296. doi: 10.1016/ j.clinthera.2015.08.007.
Grönlund J, Saari TI, Hagelberg NM, et al. Effect of inhibition of cytochrome P450 enzymes 2D6 and 3A4 on the pharmacokinetics of intravenous oxycodone: a randomized, three-phase, crossover, placebo-controlled study. Clin Drug Investig. 2011;31(3):143–153. doi: 10. 2165/ 11539950-000000000-00000.
Noehr-Jensen L, Zwisler ST, Larsen F, et al. Escitalopram is a weak inhibitor of the CYP2D6-catalyzed O-demethylation of (+)-tramadol but does not reduce the hypoalgesic effect in experimental pain. Clin Pharmacol Ther. 2009;86(6):626–633. doi: 10.1038/clpt.2009.154.
Hobl EL, Stimpfl T, Ebner J, et al. Morphine decreases clopidogrel concentrations and effects: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2014;63(7):630–635. doi: 10.1016/j.jacc. 2013. 10.068.
Hobl EL, Reiter B, Schoergenhofer C, et al. Morphine interaction with prasugrel: a double-blind, cross-over trial in healthy volunteers. Clin Res Cardiol. 2016;105(4):349–355. doi: 10.1007/s00392-015-0927-z.
Hobl EL, Reiter B, Schoergenhofer C, et al. Morphine decreases ticagrelor concentrations but not its antiplatelet effects: a randomized trial in healthy volunteers. Eur J Clin Invest. 2016;46(1):7–14. doi: 10.1111/ eci.12550.
Kubica J, Adamski P, Ostrowska M, et al. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J. 2016;37(3):245–252. doi: 10.1093/ eurheartj/ehv547.
Eckhardt K, Ammon S, Hofmann U, et al. Gabapentin enhances the analgesic effect of morphine in healthy volunteers. Anesth Analg. 2000; 91(1):185–191. doi: 10.1097/00000539-200007000-00035.
McCance-Katz EF, Rainey PM, Jatlow P, et al. Methadone effects on zidovudine disposition (AIDS Clinical Trials Group 262) J Acquir Immune Defic Syndr Hum Retrovirol. 1998;18(5):435–443. doi: 10.1097/0004256 -199808150-00004
Witkiewitz K, Vowles KE. Alcohol and Opioid Use, Co- Use, and Chronic Pain in the Context of the Opioid Epidemic: A Critical Review. Alcohol Clin Exp Res 2018; 42:478-88
Nieminen TH, serotonin toxicity: a mechanistic and clinical review. Br J Anaesth 2020; 124:44-62.
Hassamal S, Miotto K, Dale W, et al. Tramadol: Understanding the Risk of Serotonin Syndrome and Seizures. Am J Med 2018;131:1382.e1-6
Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth 2005; 95:434-41.
Gören Z, Demirkapu MJ, Akpinar Aset G, et al. Potential drug–drug interactions among prescriptions for elderly patients in primary health care. Turk. J. Med. Sci. 2017; 47, 47–54. 10.3906/sag-1509-89
