Kanser Hastalarında Polifarmasi ve İlaç Etkileşimleri
Year 2022,
Volume: 6 Issue: 1, 31 - 42, 31.01.2022
Metin Deniz Karakoç
Abstract
Amaç: Kanser hastaları, sitotoksik ajanlar başta olmak üzere pek çok ilacın uygulanması nedeniyle ilaç-ilaç etkileşimleri açısından önemli bir risk altındadır. Çalışmada kanser hastalarının polifarmasi ve potansiyel ilaç-ilaç etkileşimleri bakımından mercek altına alınması amaçlanmıştır.
Yöntem: Araştırma, 18 yaşından büyük, kemoterapi tedavisi görmekte olan 202 adet gönüllü kanser hastası ile gerçekleştirildi. Kanser türü, ilaç kullanımı ve demografik bilgiler hasta bilgi formları ile hasta tedavi dosyalarından temin edildi. İlaçlar arasındaki etkileşimler Rx Media Pharma® programı ve www.drugs.com ilaç etkileşimi sorgulama web sitesi kullanılarak belirlendi. p<0.05 istatistiksel olarak anlamlı kabul edildi.
Bulgular: Çalışmada, bir kanser hastasının ortalama olarak sekiz ilaç kullanmakta olduğu ve %82.7’sin de polifarmasi varlığı saptandı. Çalışmada, hasta başına yaklaşık 3.5 ilaç-ilaç etkileşimi tespit edildi. Bu etkileşimlerin %85’inin klinik olarak dikkate alınması gereken orta ve yüksek düzey etkileşimler olduğu belirlendi. Kanser türleri içerisinde toplamda en az ilaç kullanan grubun meme tümörlü hastalar olduğu saptandı ve bunun bir sonucu olarak diğer tümör tiplerine sahip hastalara göre daha az ilaç etkileşimi olduğu belirlendi (p=0.01). Katılımcıların %48’inin kanser haricinde en az bir komorbiditeye sahip olduğu tespit edildi.
Sonuç: Araştırmada kanser hastalarında komorbidite ve polifarmasinin oldukça yaygın olduğu tespit edildi. Polifarmasinin bir sonucu olarak kanser hastaları arasında önemli miktarda ilaç–ilaç etkileşimleri olduğu saptandı. İlaç etkileşimlerinin engellenmesi için tüm paydaşlara önemli sorumluluklar düşmekte ve bu konuda çok merkezli çalışmalara ihtiyaç bulunmaktadır.
Supporting Institution
Hiçbir kişi, kurum ya da kuruluştan hiçbir ayni ya da maddi katkı sağlanmamıştır.
Thanks
Hasta ilaç kullanım bilgilerinin toplanması aşamasındaki katkılarından dolayı Medikal Onkoloji Uzmanı Uz. Dr. Duygu ÇIKMAN’a teşekkür ederim.
References
- 1. Arslan, D., Tural, D., & Akar, E. (2013). Herbal administration and interaction of cancer treatment. Journal of Palliative Medicine, 16(11), 1466-1476.
- 2. Singh, D., Gupta, R., & Saraf, S. A. (2012). Herbs-are they safe enough? an overview. Critical Reviews in Food Science
and Nutrition, 52(10), 876-898.
- 3. Murphy, C. C., Fullington, H. M., Alvarez, C. A., Betts, A. C., Lee, S., Haggstrom, D. A., et al. (2018). Polypharmacy and
patterns of prescription medication use among cancer survivors. Cancer, 124(13), 2850–2857.
- 4. Goodin, S., Griffith, N., Chen, B., Chuk, K., Daouphars, M., Doreau, C., et al. (2011). Safe handling of oral chemotherapeutic
agents in clinical practice: recommendations from an international pharmacy panel. Journal of oncology practice, 7(1),
7–12.
- 5. Chan, A., Tan, S. H., Wong, C. M., Yap, K. Y., & Ko, Y. (2009). Clinically significant drug-drug interactions between oral
anticancer agents and nonanticancer agents: a Delphi survey of oncology pharmacists. Clinical therapeutics, 31 Pt 2,
2379–2386.
- 6. Williams, G. R., Mackenzie, A., Magnuson, A., Olin, R., Chapman, A., Mohile, S., et al. (2016). Comorbidity in older adults
with cancer. Journal of geriatric oncology, 7(4), 249–257.
- 7. Li, D., Soto-Perez-de-Celis, E., & Hurria, A. (2017). Geriatric assessment and tools for predicting treatment toxicity in
older adults with cancer. Cancer journal (Sudbury, Mass.), 23(4), 206–210.
- 8. Gnjidic, D., & Johnell, K. (2013). Clinical implications from drug-drug and drug-disease interactions in older people.
Clinical and experimental pharmacology & physiology, 40(5), 320–325.
- 9. Cresswell, K. M., Fernando, B., McKinstry, B., & Sheikh, A. (2007). Adverse drug events in the elderly. British medical
bulletin, 83, 259–274.
- 10. Tulner, L. R., Kuper, I. M., Frankfort, S. V., van Campen, J. P., Koks, C. H., Brandjes, D. P., et al. (2009). Discrepancies in
reported drug use in geriatric outpatients: relevance to adverse events and drug-drug interactions. The American journal
of geriatric pharmacotherapy, 7(2), 93–104.
- 11. Riechelmann, R. P., & Del Giglio, A. (2009). Drug interactions in oncology: how common are they?. Annals of oncology :
official journal of the European Society for Medical Oncology, 20(12), 1907–1912.
- 12. Miranda, V., Fede, A., Nobuo, M., Ayres, V., Giglio, A., Miranda, M., & Riechelmann, R. P. (2011). Adverse drug reactions and
drug interactions as causes of hospital admission in oncology. Journal of pain and symptom management, 42(3), 342–
353.
- 13. Scripture, C. D., & Figg, W. D. (2006). Drug interactions in cancer therapy. Nature reviews. Cancer, 6(7), 546–558.
- 14. Carcelero, E., Anglada, H., Tuset, M., & Creus, N. (2013). Interactions between oral antineoplastic agents and
concomitant medication: a systematic review. Expert opinion on drug safety, 12(3), 403–420.
- 15. Sharifi, H., Hasanloei, M. A., & Mahmoudi, J. (2014). Polypharmacy-induced drug-drug interactions; threats to patient
safety. Drug research, 64(12), 633–637.
- 16. Shrestha, S., Shrestha, S., & Khanal, S. (2019). Polypharmacy in elderly cancer patients: Challenges and the way clinical
pharmacists can contribute in resource-limited settings. Aging medicine (Milton (N.S.W)), 2(1), 42–49.
- 17. Zheng, W. Y., Richardson, L. C., Li, L., Day, R. O., Westbrook, J. I., & Baysari, M. T. (2018). Drug-drug interactions and their
harmful effects in hospitalised patients: a systematic review and meta-analysis. European journal of clinical
pharmacology, 74(1), 15–27.
- 18. Wang, L., Cao, Y., Ren, M., Chen, A., Cui, J., Sun, D., & et al. (2017). Sex differences in hazard ratio during drug treatment
of non-small-cell lung cancer in major clinical trials: a focused data review and meta-analysis. Clinical therapeutics,
39(1), 34–54.
- 19. Nagini, S. (2017). Breast cancer: Current molecular therapeutic targets and new players. Anti-cancer agents in
medicinal chemistry, 17(2), 152–163.
- 20. Fogli, S., Del Re, M., Curigliano, G., van Schaik, R. H., Lancellotti, P., & Danesi, R. (2019). Drug-drug interactions in breast
cancer patients treated with CDK4/6 inhibitors. Cancer treatment reviews, 74, 21–28.
- 21. Renzi, C., Kaushal, A., Emery, J., Hamilton, W., Neal, R. D., Rachet, B., et al. (2019). Comorbid chronic diseases and cancer
diagnosis: disease-specific effects and underlying mechanisms. Nature reviews. Clinical oncology, 16(12), 746–761.
- 22. Morishima, T., Matsumoto, Y., Koeda, N., Shimada, H., Maruhama, T., Matsuki, D., et al. (2019). Impact of comorbidities on
survival in gastric, colorectal, and lung cancer patients. Journal of epidemiology, 29(3), 110–115.
- 23. Strawson, J. (2018). Nonsteroidal anti-inflammatory drugs and cancer pain. Current opinion in supportive and
palliative care, 12(2), 102–107.
- 24. Karakoç, M. D. (2020). Onkoloji hastalarının tamamlayıcı ve alternatif tedavi yöntemlerini kullanma durumları.
Pamukkale Tıp Dergisi, 13(1), 69-80.
- 25. Chen, N., Cui, D., Wang, Q., Wen, Z., Finkelman, R. D., & Welty, D. (2018). In vitro drug-drug interactions of budesonide:
inhibition and induction of transporters and cytochrome P450 enzymes. Xenobiotica; the fate of foreign compounds in
biological systems, 48(6), 637–646.
- 26. Gattis, W. A., & May, D. B. (1996). Possible interaction involving phenytoin, dexamethasone, and antineoplastic agents:
a case report and review. The Annals of pharmacotherapy, 30(5), 520–526.
- 27. Celio, L., Niger, M., Ricchini, F., & Agustoni, F. (2015). Palonosetron in the prevention of chemotherapy-induced nausea
and vomiting: an evidence-based review of safety, efficacy, and place in therapy. Core evidence, 10, 75–87.
- 28. Patel, P., Leeder, J. S., Piquette-Miller, M., & Dupuis, L. L. (2017). Aprepitant and fosaprepitant drug interactions: a
systematic review. British journal of clinical pharmacology, 83(10), 2148–2162.
- 29. Schnell F. M. (2003). Chemotherapy-induced nausea and vomiting: the importance of acute antiemetic control. The oncologist, 8(2), 187–198.
- 30. Ho, C. L., Su, W. C., Hsieh, R. K., Lin, Z. Z., & Chao, T. Y. (2010). A randomized, double-blind, parallel, comparative study to
evaluate the efficacy and safety of ramosetron plus dexamethasone injection for the prevention of acute chemotherapy-
induced nausea and vomiting. Japanese journal of clinical oncology, 40(4), 294–301.
- 31. Yeh, Y. C., McDonnell, A., Klinger, E., Fowler, B., Matta, L., Voit, D., et al. (2011). Comparison of healthcare resource use
between patients receiving ondansetron or palonosetron as prophylaxis for chemotherapy-induced nausea and
vomiting. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy
Practitioners, 17(3), 179–185.
- 32. Astrand B. (2009). Avoiding drug-drug interactions. Chemotherapy, 55(4), 215–220.
- 33. Riu-Viladoms, G., Carcelero San Martín, E., Martín-Conde, M. T., & Creus, N. (2019). Drug interactions with oral
antineoplastic drugs: The role of the pharmacist. European journal of cancer care, 28(1), e12944.
- 34. Kratz, T., & Diefenbacher, A. (2019). Psychopharmacological treatment in older people: avoiding drug interactions and
polypharmacy. Deutsches Arzteblatt international, 116(29-30), 508–518.
Polypharmacy and Drug Interactions in Cancer Patients
Year 2022,
Volume: 6 Issue: 1, 31 - 42, 31.01.2022
Metin Deniz Karakoç
Abstract
Objective: Cancer patients are under an important risk in terms of drug-drug interactions (DDIs) because administration of many drugs, especially cytotoxic agents. The aim of this study is examine the cancer patients in terms of polypharmacy and potential DDIs.
Methods: The study was conducted with 202 volunteer cancer patients over the age of 18 who were receiving chemotherapy treatment. Cancer type, drug usage and demographic data were obtained by patient information forms and patients' treatment files. Interactions between drugs were determined using the Rx Media Pharma® software and the www.drugs.com DDIs control web page. p<0.05 was considered statistically significant.
Results: It was determined that a cancer patient was receiving eight drugs on average and 82.7% of them had polypharmacy. In the study, approximately 3.5 DDIs were detected per patient. It was found 85% of these interactions were medium and high level interactions that should be clinically take into account. It was determined that the minimum drug using group among the cancer types were breast cancer patients and there were less DDIs compared to patients with other tumor types (p=0.01). It was detected that 48% of the participants had at least one comorbidity other than cancer.
Conclusion: In the study, it was determined that comorbidities and polypharmacy are quite common in cancer patients. As a result of polypharmacy, a significant amount of DDIs have been found among cancer patients. In order to preventing the DDIs, all stakeholders have important responsibilities and multi-center studies are needed on this issue.
References
- 1. Arslan, D., Tural, D., & Akar, E. (2013). Herbal administration and interaction of cancer treatment. Journal of Palliative Medicine, 16(11), 1466-1476.
- 2. Singh, D., Gupta, R., & Saraf, S. A. (2012). Herbs-are they safe enough? an overview. Critical Reviews in Food Science
and Nutrition, 52(10), 876-898.
- 3. Murphy, C. C., Fullington, H. M., Alvarez, C. A., Betts, A. C., Lee, S., Haggstrom, D. A., et al. (2018). Polypharmacy and
patterns of prescription medication use among cancer survivors. Cancer, 124(13), 2850–2857.
- 4. Goodin, S., Griffith, N., Chen, B., Chuk, K., Daouphars, M., Doreau, C., et al. (2011). Safe handling of oral chemotherapeutic
agents in clinical practice: recommendations from an international pharmacy panel. Journal of oncology practice, 7(1),
7–12.
- 5. Chan, A., Tan, S. H., Wong, C. M., Yap, K. Y., & Ko, Y. (2009). Clinically significant drug-drug interactions between oral
anticancer agents and nonanticancer agents: a Delphi survey of oncology pharmacists. Clinical therapeutics, 31 Pt 2,
2379–2386.
- 6. Williams, G. R., Mackenzie, A., Magnuson, A., Olin, R., Chapman, A., Mohile, S., et al. (2016). Comorbidity in older adults
with cancer. Journal of geriatric oncology, 7(4), 249–257.
- 7. Li, D., Soto-Perez-de-Celis, E., & Hurria, A. (2017). Geriatric assessment and tools for predicting treatment toxicity in
older adults with cancer. Cancer journal (Sudbury, Mass.), 23(4), 206–210.
- 8. Gnjidic, D., & Johnell, K. (2013). Clinical implications from drug-drug and drug-disease interactions in older people.
Clinical and experimental pharmacology & physiology, 40(5), 320–325.
- 9. Cresswell, K. M., Fernando, B., McKinstry, B., & Sheikh, A. (2007). Adverse drug events in the elderly. British medical
bulletin, 83, 259–274.
- 10. Tulner, L. R., Kuper, I. M., Frankfort, S. V., van Campen, J. P., Koks, C. H., Brandjes, D. P., et al. (2009). Discrepancies in
reported drug use in geriatric outpatients: relevance to adverse events and drug-drug interactions. The American journal
of geriatric pharmacotherapy, 7(2), 93–104.
- 11. Riechelmann, R. P., & Del Giglio, A. (2009). Drug interactions in oncology: how common are they?. Annals of oncology :
official journal of the European Society for Medical Oncology, 20(12), 1907–1912.
- 12. Miranda, V., Fede, A., Nobuo, M., Ayres, V., Giglio, A., Miranda, M., & Riechelmann, R. P. (2011). Adverse drug reactions and
drug interactions as causes of hospital admission in oncology. Journal of pain and symptom management, 42(3), 342–
353.
- 13. Scripture, C. D., & Figg, W. D. (2006). Drug interactions in cancer therapy. Nature reviews. Cancer, 6(7), 546–558.
- 14. Carcelero, E., Anglada, H., Tuset, M., & Creus, N. (2013). Interactions between oral antineoplastic agents and
concomitant medication: a systematic review. Expert opinion on drug safety, 12(3), 403–420.
- 15. Sharifi, H., Hasanloei, M. A., & Mahmoudi, J. (2014). Polypharmacy-induced drug-drug interactions; threats to patient
safety. Drug research, 64(12), 633–637.
- 16. Shrestha, S., Shrestha, S., & Khanal, S. (2019). Polypharmacy in elderly cancer patients: Challenges and the way clinical
pharmacists can contribute in resource-limited settings. Aging medicine (Milton (N.S.W)), 2(1), 42–49.
- 17. Zheng, W. Y., Richardson, L. C., Li, L., Day, R. O., Westbrook, J. I., & Baysari, M. T. (2018). Drug-drug interactions and their
harmful effects in hospitalised patients: a systematic review and meta-analysis. European journal of clinical
pharmacology, 74(1), 15–27.
- 18. Wang, L., Cao, Y., Ren, M., Chen, A., Cui, J., Sun, D., & et al. (2017). Sex differences in hazard ratio during drug treatment
of non-small-cell lung cancer in major clinical trials: a focused data review and meta-analysis. Clinical therapeutics,
39(1), 34–54.
- 19. Nagini, S. (2017). Breast cancer: Current molecular therapeutic targets and new players. Anti-cancer agents in
medicinal chemistry, 17(2), 152–163.
- 20. Fogli, S., Del Re, M., Curigliano, G., van Schaik, R. H., Lancellotti, P., & Danesi, R. (2019). Drug-drug interactions in breast
cancer patients treated with CDK4/6 inhibitors. Cancer treatment reviews, 74, 21–28.
- 21. Renzi, C., Kaushal, A., Emery, J., Hamilton, W., Neal, R. D., Rachet, B., et al. (2019). Comorbid chronic diseases and cancer
diagnosis: disease-specific effects and underlying mechanisms. Nature reviews. Clinical oncology, 16(12), 746–761.
- 22. Morishima, T., Matsumoto, Y., Koeda, N., Shimada, H., Maruhama, T., Matsuki, D., et al. (2019). Impact of comorbidities on
survival in gastric, colorectal, and lung cancer patients. Journal of epidemiology, 29(3), 110–115.
- 23. Strawson, J. (2018). Nonsteroidal anti-inflammatory drugs and cancer pain. Current opinion in supportive and
palliative care, 12(2), 102–107.
- 24. Karakoç, M. D. (2020). Onkoloji hastalarının tamamlayıcı ve alternatif tedavi yöntemlerini kullanma durumları.
Pamukkale Tıp Dergisi, 13(1), 69-80.
- 25. Chen, N., Cui, D., Wang, Q., Wen, Z., Finkelman, R. D., & Welty, D. (2018). In vitro drug-drug interactions of budesonide:
inhibition and induction of transporters and cytochrome P450 enzymes. Xenobiotica; the fate of foreign compounds in
biological systems, 48(6), 637–646.
- 26. Gattis, W. A., & May, D. B. (1996). Possible interaction involving phenytoin, dexamethasone, and antineoplastic agents:
a case report and review. The Annals of pharmacotherapy, 30(5), 520–526.
- 27. Celio, L., Niger, M., Ricchini, F., & Agustoni, F. (2015). Palonosetron in the prevention of chemotherapy-induced nausea
and vomiting: an evidence-based review of safety, efficacy, and place in therapy. Core evidence, 10, 75–87.
- 28. Patel, P., Leeder, J. S., Piquette-Miller, M., & Dupuis, L. L. (2017). Aprepitant and fosaprepitant drug interactions: a
systematic review. British journal of clinical pharmacology, 83(10), 2148–2162.
- 29. Schnell F. M. (2003). Chemotherapy-induced nausea and vomiting: the importance of acute antiemetic control. The oncologist, 8(2), 187–198.
- 30. Ho, C. L., Su, W. C., Hsieh, R. K., Lin, Z. Z., & Chao, T. Y. (2010). A randomized, double-blind, parallel, comparative study to
evaluate the efficacy and safety of ramosetron plus dexamethasone injection for the prevention of acute chemotherapy-
induced nausea and vomiting. Japanese journal of clinical oncology, 40(4), 294–301.
- 31. Yeh, Y. C., McDonnell, A., Klinger, E., Fowler, B., Matta, L., Voit, D., et al. (2011). Comparison of healthcare resource use
between patients receiving ondansetron or palonosetron as prophylaxis for chemotherapy-induced nausea and
vomiting. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy
Practitioners, 17(3), 179–185.
- 32. Astrand B. (2009). Avoiding drug-drug interactions. Chemotherapy, 55(4), 215–220.
- 33. Riu-Viladoms, G., Carcelero San Martín, E., Martín-Conde, M. T., & Creus, N. (2019). Drug interactions with oral
antineoplastic drugs: The role of the pharmacist. European journal of cancer care, 28(1), e12944.
- 34. Kratz, T., & Diefenbacher, A. (2019). Psychopharmacological treatment in older people: avoiding drug interactions and
polypharmacy. Deutsches Arzteblatt international, 116(29-30), 508–518.