Abstract: Aim: The study aimed to determine the prevalence of potential drug-drug interactions (PDDIs) and potentially inappropriate medications (PIMs) among geriatrics. Methods: A prospective observational study was conducted for six months in the Department of Geriatrics, M.S. Ramaiah Teaching Hospital, Bangalore. PDDIs and PIMS were analyzed using micromedex database and Beer's criteria respectively. Results: Among 395 prescriptions, 221(56%) prescriptions showed 559 pDDIs and 41(10.4%) PIMs. Almost 281(50.3%), 260(46.5%), 16(2.7%) and 2(0.3%) pDDIs were categorised as major, moderate, minor and contraindicated respectively. Almost 321(57.5%) were synergistic and 196(35.0%) were antagonistic drug interactions. Pearson correlation value (R) is 0.9957 which showed a strong positive correlation. Conclusion: This study created awareness on drug interactions among geriatrics and help the practitioners to prescribe drugs with a low risk of pDDIs. The authors suggest PIM monitoring in geriatrics to avoid adverse effects and improve patients' quality of life.
Key Words: Adverse effects, Beer's criteria, Geriatrics, Potential Drug-Drug Interactions, Potentially Inappropriate Medications.

Introduction:

Potential drug-drug interaction is a drug related problem encountered by geriatrics. (1) Potentially inappropriate medications (PIMs) increase the risk of a drug-related problems and is probably higher than the anticipated favourable clinical outcome. (2) Drug interactions are divided into mild, moderate, and severe categories based on the intensity of reaction. (3)

Medications administered for geriatrics are susceptible to cause polypharmacy because of the higher risk of adverse pharmacodynamics and pharmacokinetics resulting in increased morbidity and mortality. (4) Polypharmacy leads to potential drug-drug interactions (pDDIs) which may increase or decrease the effectiveness or incidence of a new side effect. (5) People over 60 years are more likely to be on medication and predisposed to polypharmacy owing to comorbid diseases and decreased quality of life. Treatment of health issues in geriatrics are an area of concern and will be a major challenge in clinical practice. (6) The medications that cause unwanted effects through potential drug-drug interactions (pDDIs) are considered as inappropriate and high-risk medications. (7) The medications leading to polypharmacy should be reconciliated to minimize the pDDIs and should be chosen based on risk benefit ratio. (8) The risks associated with these medications range from slight weakness to persistent drowsiness, orthostatic hypotension, falls and fractures or even life-threatening diseases. Apart from leading to severe adverse outcomes, use of inappropriate medications in geriatrics also induces a considerable economic burden on them. (9)

Pharmacists possess in-depth knowledge on drugs and can correlate and extrapolate any unexpected symptoms or reactions experienced by the patients to potentially inappropriate medications. Pharmacist plays a major role in identification, prevention, documentation and reporting of PIMs and pDDIs. (10)

Strict PIM monitoring system should be established for all hospital departments in order to avoid harmful, unwanted effects of medications and improve patients' quality of life. All health care professionals should be motivated to identify and prevent DRPs. DDIs and PIMs are even hazardous and add to increased mortality rate. Dearth of details on PIMs related morbidity and mortality; unpredictable utilization of medications features the requirement for planning and formulation of public health policies in this field. (11) Hence, this study aimed to explore the prevalence, clinical importance of identification of pDDIs and PIMs among geriatric patients visited the hospital.

Methods:

Study design and population
It's a prospective observational study carried out for a period of 6 months from February to July 2022. The study was conducted in department of geriatrics, Ramaiah hospital, Bangalore. The study included patients of either gender aged ≥60 years visited Ramaiah hospital. Patients who were non-co-operative and unwilling to participate in the study were excluded. The study protocol was approved by Institutional Ethics Committee of Ramaiah Medical College, Bangalore.

Data collection
Prospective analysis of cases was done to identify PIMs and pDDIs in the Department of Geriatrics. The data was retrieved from case sheets, medication charts, laboratory reports and by conducting medication history interviews. The patient profile form was created which included the details of patient demographics, past medication, history of allergy, diagnosis, clinical laboratory values, medications used during admission and discharge medication.

Assessment of the prescription
The pDDI and PIMs form included the details of pDDIs with its classifications based on severity, documentation and mechanism and details of PIM respectively. pDDIs were analysed using Stockley's textbook of drug interactions, micromedex online database system and medscape drug interaction checker. The PIMs were identified using Beer's criteria.

Statistical analysis
Descriptive statistics and pearson correlation for risk factors of pDDIs (SPSS v20.0) were done to meet the objectives.

Results

The study included 395 participants, among which 226(57.2%) were males and 169(42.8%) were females. Most of them were in the age group of 60 to 75 years. Almost 198(50.1%) patients were found to be illiterate and 197(49.9%) were literates. Majority of the patients 274(69.4%) were active with no disability. Out of 395 prescriptions, 356(90.1%) prescriptions had more than 5 medications. The sociodemographic details of the patients are shown in Table 1.

Amongst the participants, 388(98.2%) had comorbidities. Most of the patients 344(87.1%) had diabetes mellitus (DM) and 340(86.1%) had hypertension (HTN). Cardiovascular disorders were observed to be prevalent 156(39.4%) followed by endocrine disorders 151(38.2%). The details are described in Table 2.

Among 395 prescriptions, 221(56.0%) prescriptions were identified with pDDIs. Out of 221 prescriptions, 123(55.7%) were males and 98(44.3%) were females. pDDIs were found to be highest 94(42.5%) among patients aged between 60-65 years followed by 58(26.2%) in patients aged between 66-70 years. Potential DDIs were categorized as 1-3, 4-6 and above 6. Among 221 prescriptions with pDDIs, 92(41.5%) prescriptions were in the range of 1-3 pDDIs followed by 110(50.0%) in the range of 4-6 and 19(8.5%) above 6 pDDIs.

Among the 559 pDDIs, linezolid with tapentadol and tramadol showed 2(0.3%) contraindications. Almost 281(50.3%) major interactions were identified. Ondansetron interacts with tramadol 36(64.4%), azithromycin 20(35.7%) and metronidazole 13(23.2%); aspirin interacts with clopidogrel 23(41.1%) and furosemide13(23.2%). Almost 260(46.5%) were of moderate severity. Iron-pantoprazole 31(55.4%); Insulin interacts with aspirin 21(37.5%) and furosemide 14(25%); atorvastatin-clopidogrel 22(39.3%); aspirin-metoprolol 12(21.4%).

Out of 559 pDDIs, 62(11.0%) were rapid, 97(17.4%) were delayed and 400(71.6%) were non-specific reactions. Among 559 pDDIs, 321(57.5%) had synergism, 196(35.0%) had antagonism and 42(7.5%) were unknown. Total of 38(6.8%) pDDIs had excellent evidence, 134(24.0%) had good and 387(69.2%) had fair documentation. The details of pDDIs are indicated in Table 3.

The mechanism, effect and frequency of pDDIs are summarized in Table 4.

Among 395 patients involved in the study, 41(10.4%) patients had PIM whereas 354(89.6%) patients had no PIM.

Pearson Correlation was done to find the relationship between risk factors (old age, comorbidities, polypharmacy, female gender and PIMs) and pDDIs. The value of R is 0.9957, this shows there is a strong positive correlation (which means that high X variable scores go with high Y variable scores and vice versa). The value of R2, the coefficient of determination is 0.9914. The P-value is 0.000338 at p <0.05. Hence, the correlation is significant.

Discussion

In our study, 395 patients were selected, in which 226(57.2%) were males and 169(42.8%) were females. Similar to our study, in a study conducted on evaluation of potential drug-drug interactions, 404 patients were included with 214(53%) males and 190(47%) females. (1) In another study conducted on potential drug-drug interactions, 100 patients were included with 61 males and 39 females. (12) In our study, mean age of patients are 77.1 ± 16.9 years, which resembles the study conducted by. (13,14) The current study had 198(50.1%) illiterate participants, which is similar to the study conducted by Bhagavathula. (12)

A total of 2557 drugs were prescribed with an average of 7.47 ± 6.5 drugs per prescription, which resembled another study which reported an average of 8.28 ± 2.77 drugs prescribed per prescription. (15) Among 395 prescriptions, 356(90.1%) prescriptions were above or equal to 5 medications and 39(9.9%) prescriptions were below 5 medications. In the study conducted by Kapadia, 19 prescriptions had less than 5 drugs, 98 prescriptions had 5-7 drugs and 140 prescriptions had ≥8 drugs. (15)

Almost 39.4% patients were diagnosed with cardiovascular disorders which was similar to another study which revealed 37% patients with cardiovascular disorders. (12)

Among 395, 43(10.8%) and 67(16.9%) patients were diagnosed with renal disorders and gastrointestinal disorders respectively which was comparable to a study conducted on DRP, which revealed 32(7.8%) renal disorders and 46(11.2%) gastrointestinal disorders. (5)

Drug interaction is recognized as the most dangerous DRPs. Polypharmacy, co-morbidities, female gender and old age are most common predisposing factors of pDDIs. Among 395 geriatric patients, 356(90.1%) had polypharmacy, 388(98.2%) had comorbidities, and 166(42.0%) were females. In a study conducted by Fatemeh, 81% patients had polypharmacy similar to our study. (16)

Our work revealed that the overall prevalence of pDDIs was 56%. In other studies, prevalence rate of pDDIs was found to be 36.9%, 67.0% and 78%. (17,18,12) Prevalence of pDDIs was found to be major among males 123(45.7%) compared with females 98(44.3%) which is identical to another study conducted where, 79(62.70%) were males and 47(37.30%) were females. (19) But, in contrast to our results, the study conducted by Jimmy showed 46(38.3%) males and 74(61.6%) females. (14)

Among 221 prescriptions with pDDIs, 110(50.0%) prescriptions had 4-6 pDDIs. It is parallel to another study, which revealed that 52% prescriptions had 4-6 pDDIs. (5)

Among the 559 pDDIs, 2(0.3%) pDDIs were contraindicated; 281(50.3%), 260(46.5%), 16(2.7%) were of major, moderate and minor severity respectively; which is comparable with another study by Ahmad where major, moderate and minor severity were found to be 44(31.65%), 75(53.95%) and 20(14.38%) respectively. (1) In contrast to our study, the study conducted by Kapadia has reported 123 serious, 949 significant, 2328 minor reactions and 5 contraindications. (15)

Our work revealed that the overall prevalence of PIM was 10.4% in our setting. In other studies, prevalence rate was found to be 39.8%, 14.1% and 26.6 % respectively. (20-22)

Conclusions

The identified predictors responsible for pDDIs were polypharmacy, age and gender. Hence, it is important to develop a systematic approach to minimize possible pDDIs. The clinicians at the study site require educational programs in regard of identification and management of pDDIs.

This study tries to put forward the common pDDIs which we came across in the study which may be a forewarning to health care team about reactions that may occur due to an interaction, as well as provide a support material for physicians to choose alternative therapy, dose adjustments and patient monitoring. Awareness on the most prevalent pDDIs can help the practitioners to prescribe drugs with low risk for pDDIs and prevent the concomitant use of dangerous medication combinations.

This study has highlighted the prevalence of PIMs. So, this study concludes that a strict PIM monitoring system should be established for all hospital departments in order to avoid harmful, unwanted effects of medications and improve patients' quality of life. This system should be a collaborative activity of clinicians, nurse, pharmacists along with other health care professionals.

Declaration of Conflicting Interests: The author declared no potential conflicts of interest concerning this article's research, authorship, and publication.

Funding: None

Acknowledgements

We sincerely thank to all nursing, physicians, and non-teaching staff of department of geriatrics, M.S. Ramaiah Hospitals, teaching staff of faculty of pharmacy, M.S. Ramaiah University of Applied Sciences for the constant support during our project work.

Disclosure statement: The authors declare no conflict of interests.

References

1. Ahmad A, Khan MU, Haque I, et al. Evaluation of potential drug-drug interactions in general medicine ward of teaching hospital in southern India. JCDR. 2015; 9(2):FC10.
2. Corsonello A, Pranno L, Garasto S, et al. Potentially inappropriate medication in elderly hospitalized patients. Drugs & Aging. 2009;26(1):31-9.
3. Nidhi S. Concept of drug interaction. Int Res J Pharm. 2012;3(7):120-2.
4. Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin. Drug saf. 2014;13(1):57-65.
5. Bajracharya N, Swaroop AM, Rajalekshmi SG, et al. Incidence of drug-drug interactions among patients admitted to the department of general medicine in a tertiary care hospital. J. Young Pharm. 2018;10(4):450.
6. Vrdoljak D, Borovac JA. Medication in the elderly-considerations and therapy prescription guidelines. Acta. Med. Acad. 2015;44(2):159.
7. Snyder BD, Polasek TM, Doogue MP. Drug interactions: principles and practice. Aust. Prescr. 2012;35:85-88.
8. Tao L, Qu X, Gao H, et al. Polypharmacy and potentially inappropriate medications among elderly patients in the geriatric department at a single-center in China: A retrospective cross-sectional study. Medicine. 2021;100(42).
9. Aguiar JP, Brito AM, Martins AP, et al. Potentially inappropriate medications with risk of cardiovascular adverse events in the elderly: a systematic review of tools addressing inappropriate prescribing. J. Clin. Pharm. Ther. 2019;44(3):349-60.
10. Marinović I, Bačić Vrca V, Samardžić I, et al. Potentially inappropriate medications involved in drug-drug interactions at hospital discharge in Croatia. Int. J. Clin. Pharm. 2021;43(3):566-76.
11. Noblat AC, Noblat LA, Toledo LA, et al. Prevalence of hospital admission due to adverse drug reaction in Salvador, Bahia. Rev. Assoc. Med. Bras. 2011;57:42-5.
12. Bhagavathula AS, Berhanie A, Tigistu H, et al. Prevalence of potential drug-drug interactions among internal medicine ward in University of Gondar Teaching Hospital, Ethiopia. Asian Pac. J. Trop. Biomed. 2014;4:204-8.
13. Sheikh-Taha M, Asmar M. Polypharmacy and severe potential drug-drug interactions among older adults with cardiovascular disease in the United States. BMC Geriatr. 2021;21(1):1-6.
14. Jimmy OD, ShobhaRani RH, Indira R, et al. Study of drug-drug interactions in the medication charts in medicine wards at a tertiary care hospital, Bangalore. IJOPP. 2012;5(4):61-64.
15. Kapadia J, Thakor D, Desai C, et al. A study of potential drug-drug interactions in indoor patients of medicine department at a tertiary care hospital. J. Appl. Pharm. Sci. 2013;3(10):089-96.
16. Fatemeh A, Fatemeh R, Kazem H, et al. Drug-drug interactions and potentially inappropriate medications among elderly outpatients. Braz. J. Pharm. Sci. 2021;57.
17. Santos TR, Silveira EA, Pereira LV, et al. Potential drug-drug interactions in older adults: A population-based study. Geriatr Gerontol Int. 2017;17(12):2336-46.
18. Castilho EC, Reis AM, Borges TL, et al. Potential drug-drug interactions and polypharmacy in institutionalized elderly patients in a public hospital in Brazil. J. Psychiatr. Ment. Health Nurs. 2018;25(1):3-13.
19. Umretiya T, Reddy PN. Assessment of potential drug-drug interactions in the department of medicine at Basaweshwara teaching and general hospital Gulbarga. Rajiv Gandhi University of Health Sciences J Pharm Sci. 2015;5:90-6.
20. Rudolf H, Thiem U, Aust K, et al. Reduction of potentially inappropriate medication in the elderly: Results of a cluster-randomized, controlled trial in German primary care practices (RIME). Dtsch. Ärztebl. Int. 2021;118(51-52):875.
21. Fu M, Wushouer H, Nie X, et al. Potentially inappropriate medications among elderly patients in community healthcare institutions in Beijing, China. Pharmacoepidemiol. Drug Saf. 2020;29(8):923-30.
22. Alkan A, Yasar A, Karci E, et al. Severe drug interactions and potentially inappropriate medication usage in elderly patients with cancer. Support. Care Cancer. 2017;25:229-236.