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    -  Palatty PL
    -  Adnan M
    -  George T
    -  Rao S
    -  Baliga MS

 
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ORIGINAL ARTICLE
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Audit of drug–drug interactions and adverse drug reactions due to polypharmacy in older cancer patients: First report from India


1 Department of Pharmacology, Father Muller Medical College Hospital, Kankanady, Mangalore, Karnataka, India
2 Father Muller Medical College Hospital, Kankanady, Mangalore, Karnataka, India
3 Department of Radiation Oncology, Mangalore Institute of Oncology, Pumpwell, Mangalore, Karnataka, India
4 Father Muller Research Centre, Kankanady, Mangalore, Karnataka, India

Correspondence Address:
Manjeshwar S Baliga,
Father Muller Research Centre, Kankanady, Mangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_565_18

  Abstract 


Background: In elderly people, the body's metabolic processes are not optimal and pharmacokinetics and pharmacodynamic profile of drugs are compromised or reduced. Under these conditions, the concomitant use of diverse classes of drugs can potentially increase the risk of adverse reactions and drug interactions. This will consequentially affect the already debilitated organ system. As far as the authors are aware, there are no studies addressing the drug–drug interactions and adverse drug reactions due to polypharmacy in older patients with cancer and therefore, we conducted this study.
Methods: This was an observational chart-based study and was carried out in a tertiary care cancer hospital. The data concerning prescription of all prescribed medications were noted down from the medication chart of the patient in the wards.
Results: The most common drug-to-drug interaction that could have happened was due to the combination of theophylline with budesonide (26.10%). Adverse drug reactions were noted during the course of time, the most common being nausea and vomiting (71.9%).
Conclusions: As the geriatric population is increasing, the need to address medical problems among aged patients with cancer is the need of the hour. The adverse drug reactions and drug interactions that have occurred were lesser when compared to published observations.


Keywords: Adverse drug reactions, drug audit, drug–drug interactions, geriatric oncology, polypharmacy, prescription pattern



How to cite this URL:
Paul T, Palatty PL, Adnan M, George T, Rao S, Baliga MS. Audit of drug–drug interactions and adverse drug reactions due to polypharmacy in older cancer patients: First report from India. Indian J Cancer [Epub ahead of print] [cited 2020 Oct 20]. Available from: https://www.indianjcancer.com/preprintarticle.asp?id=295102



  Introduction Top


The management of geriatric oncology patients with antineoplastic agents requires knowledge of the pharmacologic effects on the older population.[1],[2],[3],[4],[5],[6],[7] Elderly oncology patients with multiple comorbidities are at an elevated risk for adverse drug reactions associated with polypharmacy and drug drug interactions. This is due to the altered pharmacokinetic/pharmacodynamic status in these patients and also the narrow therapeutic window associated with antineoplastic drugs. Proper understanding of the effects of drugs on older patients is imperative in avoiding undesired consider changing to adverse reactions. As participation of old people is less in clinical trials, the knowledge of adverse drug reactions on geriatric community is very limited.

From a terminological perspective, “adverse drug reaction or adverse drug effect is a term referring to unwanted, uncomfortable, or dangerous effects that a drug may have,” while drug–drug interaction is defined as “a change in a drug's effect on the body when the drug is taken together with a second drug.[2-4]” Research suggests that drug–drug interaction may cause delayed, decreased or enhanced absorption of either drug. This can consequentially reduce or augment the action of either or both drugs or cause undesirable effects.

Prescribing for elderly patients requires proper knowledge of the efficacy of the medication in weak geriatric patients, assessment of risk of adverse reactions, discussion of harm: benefit ratio, a decision about dose regime, and careful monitoring of patient's response, to ensure maximum benefit for the patient.[8] Elderly cancer patients can have multiple prescriptions for comorbidities and the chance to have an adverse reaction would be more if prescription is given without proper understanding of drug interaction. Several comorbid conditions can affect the elderly and reduce the overall survival. However, most of these conditions are treatable with prescription medications and hence can improve the condition and standard of living of patient. Adequate and proper medication for the comorbid conditions with adequate monitoring should be the key words for treatment of illnesses in the elderly.

From a clinical perspective, special care should be taken to make sure that there is no underprescription or overprescription. High prevalence of polypharmacy in the geriatric community and the problems attributed with it are well known, but it is more or less a necessary evil that cannot be eliminated. The reason for an increased number of prescriptions per patient is due to the increased comorbid conditions associated with the elderly. The only way the adverse effects of polypharmacy can be reduced is by having proper communication between the treating clinicians of different disciplines with clinical pharmacologists. The aim of this study is to observe the prevalence of polypharmacy in geriatric population and how it affects the geriatric health.


  Materials and Methods Top


The study was done at department of medical oncology at Father Muller Hospital, Mangalore, India. The study population included geriatric patients (above 60) diagnosed with cancer receiving more than five pharmacological agents as part of their treatment/care. The data necessary for the study were from the medical case records. The comorbid conditions afflicting the cancer patients included in the study were noted. In addition to this the probable drug interactions were looked for and the adverse drug reactions were graded using the WHO causality scale. The study was conducted after obtaining permission from the institutional ethics committee. The relevant details from the case records form were entered and tabulated to Microsoft Excel. The data were subjected to frequency and percentage using SPSS statistical software program.


  Results Top


In the present study, a total of 152 geriatric patient details were recorded. The details of the patients, the clinical treatment conditions, and adverse effects observed are represented in [Table 1], [Table 2], [Table 3] and [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]. The male-to-female ratio was 3:2. The age distribution of the sample showed that most of them (41.4%) were in the age group of 60–65 [Table 1] and [Figure 1]. Majority of the patients were married (98%) and were living with spouse (63.8%). The geriatric population we surveyed had a larger frequency of carcinoma lung (24.46%), followed by head and neck (20.86%) and esophagus (15.11%) [Figure 2]. Comorbid conditions were seen in 51.3% of the patients and hypertension (65.4%) was the most common ailment [Figure 3]. Among the patients surveyed, 85.5% were receiving cancer chemotherapy. The most commonly used anticancer drug was cisplatin (26.58%) followed by 5-flurouracil (18.35%) and temozolide (14.55%) [Figure 4]. With regard to adjunct/supportive drugs, the steroid dexamethasone, pantoprazole, morphine, and ranitidine were prescribed [Table 2]. Antimicrobials were used when the patient was confirmed to be infected and levofloxacin (23%) was the most commonly used drug. Among the drugs used for cardio vascular complications, the most commonly used drug was amlodipine (52%), followed by tranexamic acid (16%). With respect to drugs used to treat disorders of the central nervous system (CNS), diazepam (35%), phenytoin (18%), and amitriptyline (18%) were common. Insulin was used in 67% for the management of diabetes. The details on the probable drug-to-drug interaction and the severity are enlisted in [Table 3].
Table 1: Sociodemographic and treatment details of the study group

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Table 2: List of class and individual non-oncology drugs administered

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Table 3: Details on the probable drug-to-drug interactions

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Figure 1: Graphical representation of the age and percentage of the study population

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Figure 2: Details on the sites of cancer and frequency

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Figure 3: Comorbidities and percentage

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Figure 4: Details on the chemotherapeutic drugs and percentage being administered

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Figure 5: Type of the adverse effects and percentage

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  Discussion Top


Reports indicate that the prevalence of cancer increases with senescence and that almost 50% of all cancers happen in the elderly.[9] Cancer chemotherapeutic agents in the elderly have a variation in their pharmacokinetics and pharmacodynamic profile. Multiple disease pathologies in the elderly compromise visceral functioning and alter drug actions. An enquiry into the common comorbid conditions prevailing in the elderly would help in customizing dose response. On an average, a geriatric patient is prescribed 6.2 medications.[3],[4] Simultaneous use of varied drugs would potentially increase risk of adverse reactions and drug interactions, upon a weak organ system. Thus, there is a significant challenge in treating elderly people afflicted by cancer. There are a few studies addressing these issues.[3-11] The available database of geriatric pharmacology at present is limited. Availability of such data would lead to optimal choice of drugs with minimal risk for potential adverse drug reactions and drug interactions.

In cancer care of the elderly, having comorbidities in higher proportion, polypharmacy is a widespread phenomenon. Studies by Lindley and coworkers (1992) have shown that among 103 patients studied, 27.0% who were on medication experienced 151 adverse drug reaction (ADR), of which 75 (49.7%) were due to drugs with absolute contraindications and/or were unnecessary.[10] In our study, we were able to come across myriad adverse drug reactions, nausea and vomiting (60.7%) followed by anxiety (18%) being the most common [Figure 5]. These observations are in divergence to the earlier reports where Mallik and coworkers[11] observed that amongst the side effects, hematological (40.47%) and gastrointestinal (33.33%) were common. The investigators specifically reported that grade I neutropenia was the most common ADR (28.6%) followed by emesis (21.4%).[11]

With regards to drug–drug interactions in geriatric people with cancer, the reports are very less. Seminal studies by Reichelmann and coworkers[12] have shown that the potential drug interactions were common among cancer patients and that they were predominate with medications used to treat comorbid conditions. To substantiate these, recent reports[13],[14],[15] suggest that elderly patients with cancer are exposed to severe drug interactions and potentially inappropriate medications.


  Conclusions Top


Drug–drug interactions and adverse drug reactions are a major issue in elderly people undergoing cancer treatment. In clinics, emphasis should be on avoiding drug interactions and choosing drugs with the lowest risk of complications. Efforts should also be directed towards stringent pharmacovigilance and dissemination of the information, as greater understanding of drug-related problems will enable early detection and appropriate management of drug-related problems, thereby improving patient care for elderly patients with cancer. In addition to this, it is also important that necessary training and implementation of the recommendations on correct/appropriate pharmacological treatment for comorbidities, geriatric illness, and supportive care should be planned by focusing on toxicities of the drug, the drug–drug, and drug–food interactions in the elderly.[16],[17],[18] It is suggestive that clinicians dealing with elderly cancer patients should be more cautious when prescribing/planning drugs and the use of software that assists in clinical decision and detecting drug–drug interactions should also be considered.[14] In addition to this, efforts should also be toward educating the patients on the correct method and timing of drug intake and also on adherence to the medication prescription.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
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;77:703-7.  Back to cited text no. 1
    
2.
Sokol KC, Knudsen JF, Li MM. Polypharmacy in older oncology patients and the need for an interdisciplinary approach to side-effect management. J Clin Pharm Ther 2007;32:169-75.  Back to cited text no. 2
    
3.
Sikdar KC, Dowden J, Alaghehbandan R, MacDonald D, Peter P, Gadag V. Adverse drug reactions in elderly hospitalized patients: A 12-year population-based retrospective cohort study. Ann Pharmacother 2012;46:960-71.  Back to cited text no. 3
    
4.
Park JW, Roh JL, Lee SW, Kim SB, Choi SH, Nam SY, et al. Effect of polypharmacy and potentially inappropriate medications on treatment and posttreatment courses in elderly patients with head and neck cancer. J Cancer Res Clin Oncol 2016;142:1031-40.  Back to cited text no. 4
    
5.
Sharma M, Loh KP, Nightingale G, Mohile SG, Holmes HM. Polypharmacy and potentially inappropriate medication use in geriatric oncology. J Geriatr Oncol 2016;7:346-53.  Back to cited text no. 5
    
6.
Nightingale G, Skonecki E, Boparai MK. The impact of polypharmacy on patient outcomes in older Adults with Cancer. Cancer J 2017;23:211-8.  Back to cited text no. 6
    
7.
Goh I, Lai O, Chew L. Prevalence and risk of polypharmacy among elderly cancer patients receiving chemotherapy in ambulatory oncology setting. Curr Oncol Rep 2018;20:38.  Back to cited text no. 7
    
8.
Hilmer SN, McLachlan AJ, Le Couteur DG. Clinical pharmacology in the geriatric patient. Fundam Clin Pharmacol 2007;21:217-30.  Back to cited text no. 8
    
9.
Extermann M, Meyer J, McGinnis M, Crocker TT, Corcoran MB, Yoder J, et al. A comprehensive geriatric intervention detects multiple problems in older breast cancer patients. Crit Rev Oncol Hematol 2004;49:69-75.  Back to cited text no. 9
    
10.
Lindley CM, Tully MP, Paramsothy V, Tallis RC. Inappropriate medication is a major cause of adverse drug reactions in elderly patients. Age Ageing 1992;21:294-300.  Back to cited text no. 10
    
11.
Mallik S, Palaian S, Ojha P, Mishra P. Pattern of adverse drug reactions due to cancer chemotherapy in a tertiary care teaching hospital in Nepal. Pak J Pharm Sci 2007;20:214-8.  Back to cited text no. 11
    
12.
Riechelmann RP, Tannock IF, Wang L, Saad ED, Taback NA, Krzyzanowska MK. Potential drug interactions and duplicate prescriptions among cancer patients. J Natl Cancer Inst 2007;99:592-600.  Back to cited text no. 12
    
13.
Alkan A, Yaşar A, Karcı E, Köksoy EB, Ürün M, Şenler FÇ, et al. Severe drug interactions and potentially inappropriate medication usage in elderly cancer patients. Support Care Cancer 2017;25:229-36.  Back to cited text no. 13
    
14.
Nightingale G, Pizzi LT, Barlow A, Barlow B, Jacisin T, McGuire M, et al. The prevalence of major drug-drug interactions in older adults with cancer and the role of clinical decision support software. J Geriatr Oncol 2018;9:526-33.  Back to cited text no. 14
    
15.
Balducci L, Goetz-Parten D, Steinman MA. Polypharmacy and the management of the older cancer patient. Ann Oncol 2013;24(Suppl 7):vii36-40.  Back to cited text no. 15
    
16.
Gironés Sarrió R, Antonio Rebollo M, Molina Garrido MJ, Guillén-Ponce C, Blanco R, Gonzalez Flores E, et al. Spanish Working Group on Geriatric Oncology of the Spanish Society of Medical Oncology (SEOM). General recommendations paper on the management of older patients with cancer: The SEOM geriatric oncology task force's position statement. Clin Transl Oncol 2018;20:1246-51.  Back to cited text no. 16
    
17.
Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev 2009;41:67-76.  Back to cited text no. 17
    
18.
Yeoh TT, Tay XY, Si P, Chew L. Drug-related problems in elderly patients with cancer receiving outpatient chemotherapy. J Geriatr Oncol 2015;6:280-7.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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