Neželjena dejstva sunitiniba: karakteristike i faktori rizika
Sažetak
Uvod/Cilj. Tumori bubrega čine 2–3% svih tumora. Karcinom bubrežnih ćelija nalazi se na desetom mestu najčešćih maligniteta. Kao prva terapijska linija kod bolesnika sa dobrom i intermedijarnom prognozom koristi se sunitinib. Cilj rada bio je analiza faktora rizika, učestalosti ispoljavljivanja i karakteristika neželjenih dejstava sunitiniba kod bolesnika sa metastatskim karcinomom bubrega. Metode. Retrospektivnom studijom je bilo obuhvaćeno 170 bolesnika lečenih na Klinici za onkologiju Kliničkog centra Crne Gore, Urološkoj klinici Kliničkog centra Srbije i Klinici za onkologiju Kliničkog centra Niš. Kao izvor podataka koristili smo istorije bolesti i/ili elektronske kartone bolesnika. Neželjena dejstva su klasifikovana prema Rawlins and Thompson klasifikaciji, težina prema kriterijumima Svetske zdravstvene organizacije, a uzročno-posledična povezanost korišćenjem Naranjo skale. Rezultati. Neželjena dejstva sunitiniba ispoljila su se kod 152 bolesnika (89,4%). Neželjena dejstva tipa A ispoljila su se kod 89%, a tipa C kod 11% bolesnika. Najčešće su se ispoljili poremećaji krvi i limfnog sistema, gastrointestinalni poremećaji i poremećaji kože i potkožnog tkiva. Uzročno-posledična povezanost između leka i neželjenog dejstva najčešće je klasifikovana kao sigurna (60%). Značajna neželjena dejstva imalo je 4,5% bolesnika. Većina bolesnika se oporavila bez posledica. Najčešća neželjena dejstva bila su: leukopenija, hipotireoza, trombocitopenija, dijareja, stomatitis, astenija i hipertenzija. Sva zabeležena neželjena dejstva bila su očekivana. Najznačajniji faktori rizika od nastanka neželjenih dejstava sunitiniba bila su broj istovremeno korišćenih lekova i trajanje terapije. Zaključak. Naše istraživanje pokazuje da je učestalost neželjenih dejstava sunitiniba kod bolesnika sa karcinomom bubrega visoka. Neželjena dejstva su uglavnom bila umerena i laka po intenzitetu i nastala su kao posledica farmakološkog dejstva leka. Potrebno je sprovesti dodatnu edukaciju medikalnih onkologa iz oblasti praćenja bezbedne primene lekova, a takođe i bolesnika koji su na terapiji sunitinibom, sa ciljem unapređenja njihove informisanosti o neželjenim dejstvima sunitiniba i faktorima rizika koji do njih dovode, kako bi se njihova učestalost smanjila.
Reference
Mathew A, Devesa SS, Fraumeni JF Jr, Chow WH. Global in-creases in kidney cancer incidence, 1973-1992. Eur J Cancer Prev 2002; 11(2): 171‒8.
Ljungberg B, Cowan NC, Hanbury DC, Hora M, Kuczyk MA, Merseburger AS, et al. European Association of Urology Guideline Group. EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol 2010; 58(3): 398‒406.
Summary of product characteristics for sunitinib. CALIMS. Available from: https://www.calims.me/Portal/faces/registar
Humani?_adf.ctrlstate=39jl6fiy3_4&_
afrLoop=1411340127687467. [accessed 2020 October 23].
WHO. Programme for International Monitoring of Adverse Reactions to Drugs: Adverse Reaction Terminology. Uppsala: Uppsala Monitoring Centre; 2002.
Rawlins MD, Thompson JW. Pathogenesis of adverse drug reac-tions. In: Davies DM, editor. Textbook of adverse drug reac-tions. Oxford: Oxford University Press; 1977. p. 224.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30(2): 239−45.
Meyboom RH, Lindquist M, Egberts AC. An ABC of drug-related problems. Drug Saf 2000; 22(6): 415‒23.
Mugoša S, Bukumirić Z, Kovacević A, Bosković A, Protić D, Todo-rović Z. Adverse drug reactions in hospitalized cardiac patients: characteristics and risk factors. Vojnosanit Pregl 2015; 72(11): 975‒81.
Brown EG. Using MedDRA: implications for risk management. Drug Saf 2004; 27(8): 591‒602.
Atta-ur-Rahman., Choudhary MI. Frontiers in Anti-Cancer Drug Discovery, Volume 5. Amsterdam: Bentham Science Publish-ers; 2014.
Brvar M, Fokter N, Bunc M, Mozina M. The frequency of ad-verse drug reaction related admissions according to method of detection, admission urgency and medical department special-ty. BMC Clin Pharmacol 2009; 9: 8.
Mitchell AS, Henry DA, Sanson-Fisher R, O’Connell DL. Pa-tients as a direct source of information on adverse drug reac-tions. BMJ 1988; 297(6653): 891‒3.
van den Bemt PM, Egberts AC, Lenderink AW, Verzijl JM, Si-mons KA, van der Pol WS, et al. Adverse drug events in hospi-talized patients. A comparison of doctors, nurses and patients as sources of reports. Eur J Clin Pharmacol 1999; 55(2): 155‒8.
Chan M, Nicklason F, Vial JH. Adverse drug events as a cause of hospital admission in the elderly. Intern Med J 2001; 31(4): 199‒205.
Hoigné R, Lawson DH, Weber E. Risk factors for adverse drug reactions-epidemiological approaches. Eur J Clin Pharmacol 1990; 39(4): 321‒5.
Mannesse CK, Derkx FH, de Ridder MA, Man in 't Veld AJ, van der Cammen TJ. Adverse drug reactions in elderly patients as contributing factor for hospital admission: cross sectional study. BMJ 1997; 315(7115): 1057‒8.
Roughead EE, Gilbert AL, Primrose JG, Sansom LN. Drug-related hospital admissions: a review of Australian studies published 1988-1996. Med J Aust 1998; 168(8): 405‒8.
Routledge PA, O'Mahony MS, Woodhouse KW. Adverse drug re-actions in elderly patients. Br J Clin Pharmacol 2004; 57(2): 121‒6.
Carbonin P, Pahor M, Bernabei R, Sgadari A. Is age an independ-ent risk factor of adverse drug reactions in hospitalized medi-cal patients? J Am Geriatr Soc 1991; 39(11): 1093‒9.
Classen DC, Pestotnik SL, Evans RS, Burke JP. Computerized surveillance of adverse drug events in hospital patients. JAMA 1991; 266(20): 2847‒51.
Hallas J, Gram LF, Grodum E, Damsbo N, Brøsen K, Haghfelt T, et al. Drug related admissions to medical wards: a population based survey. Br J Clin Pharmacol 1992; 33(1): 61‒8.
Lagnaoui R, Moore N, Fach J, Longy-Boursier M, Bégaud B. Ad-verse drug reactions in a department of systemic diseases-oriented internal medicine: prevalence, incidence, direct costs and avoidability. Eur J Clin Pharmacol 2000; 56(2): 181‒6.
Fattinger K, Roos M, Vergères P, Holenstein C, Kind B, Masche U, et al. Epidemiology of drug exposure and adverse drug reac-tions in two Swiss departments of internal medicine. Br J Clin Pharmacol 2000; 49(2): 158‒67.
Kaur S, Kapoor V, Mahajan R, Lal M, Gupta S. Monitoring of incidence, severity, and causality of adverse drug reactions in hospitalized patients with cardiovascular disease. Indian J Pharmacol 2011; 43(1): 22‒6.
Meibohm B, Beierle I, Derendorf H. How important are gender differences in pharmacokinetics? Clin Pharmacokinet 2002; 41(5): 329‒42.
Beierle I, Meibohm B, Derendorf H. Gender differences in phar-macokinetics and pharmacodynamics. Int J Clin Pharmacol Ther 1999; 37(11): 529‒47.
Dormann H, Muth-Selbach U, Krebs S, Criegee-Rieck M, Tegeder I, Schneider HT, et al. Incidence and costs of adverse drug reac-tions during hospitalisation: computerised monitoring versus stimulated spontaneous reporting. Drug Saf 2000; 22(2): 161‒8.
Somers A, Petrovic M, Robays H, Bogaert M. Reporting adverse drug reactions on a geriatric ward: a pilot project. Eur J Clin Pharmacol 2003; 58(10): 707‒14.
Bowman L, Carlstedt BC, Black CD. Incidence of adverse drug reactions in adult medical inpatients. Can J Hosp Pharm 1994; 47(5): 209‒16.
Grymonpre RE, Mitenko PA, Sitar DS, Aoki FY, Montgomery PR. Drug-associated hospital admissions in older medical patients. J Am Geriatr Soc 1988; 36(12): 1092‒8.
Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. VIGOR Study Group. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000; 343(21): 1520‒8, 2 p following 1528.
Kollmannsberger C, Soulieres D, Wong R, Scalera A, Gaspo R, Bjarnason G. Sunitinib therapy for metastatic renal cell carci-noma: recommendations for management of side effects. Can Urol Assoc J 2007; 1(2 Suppl): S41‒54.
Blackwell SA, Baugh DK, Montgomery MA, Ciborowski GM, Wal-dron CJ, Riley GF. Noncompliance in the use of cardiovascular medications in the Medicare Part D population. Medicare Medicaid Res Rev 2011; 1(4): 001.04.a05.
Malhotra S, Karan RS, Pandhi P, Jain S. Drug related medical emergencies in the elderly: role of adverse drug reactions and non-compliance. Postgrad Med J 2001; 77(913): 703‒7.
Aronson JK, Ferner RE. Preventability of drug-related harms - part II: proposed criteria, based on frameworks that classify adverse drug reactions. Drug Saf 2010; 33(11): 995‒1002.
Hakkarainen KM, Hedna K, Petzold M, Hägg S. Percentage of patients with preventable adverse drug reactions and prevent-ability of adverse drug reactions--a meta-analysis. PLoS One. 2012; 7(3): e33236.
Ducharme MM, Boothby LA. Analysis of adverse drug reactions for preventability. Int J Clin Pract 2007; 61(1): 157‒61.
Ferner RE, Aronson JK. Preventability of drug-related harms part I: A systematic review. Drug Saf 2010; 33(11): 985‒94.
Bates DW, Leape LL, Petrycki S. Incidence and preventability of adverse drug events in hospitalized adults. J Gen Intern Med 1993; 8(6): 289‒94.
Balkrishnan R, Furberg CD. Developing an optimal approach to global drug safety. J Intern Med 2001; 250(4): 271‒9.