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  • Evaluation Of Drug-Drug Interactions in A Hospitalized Patients: A Prospective Observational Study

  • Krishna teja pharmacy college, Tirupati, Andhra Pradesh, India.

Abstract

Background: Adverse drug reactions are largely caused by drug-drug interactions (DDIs), especially in hospitalized patients taking several medications. The risk of clinically significant interactions is greatly increased by polypharmacy, advanced age, and comorbid conditions, which can result in higher morbidity, mortality, longer hospital stays, and higher healthcare costs. Objective : To evaluate the prevalence, pattern, and severity of drug–drug interactions among hospitalized patients in a tertiary care hospital.Materials and Methods: At Sri Balaji Medical Care Hospital, a prospective observational study was carried out over a ten-month period. There were 98 hospitalized patients over the age of 15 from different departments. Every day, patient case records were examined to gather medication profiles and demographic information. A drug interaction checker was used to evaluate drug-drug interactions, and mean ± standard deviation was used to analyze the drugResults: Among the 98 study subjects, females constituted 53% and males 47%. The highest prevalence of DDIs was observed in the 61–80 years age group (33%). Combination interactions were more common than single interactions, with minor–moderate combinations accounting for 58.1% of cases. Overall, minor interactions were most frequent (48%), followed by moderate (39%) and major interactions (13%). Frequently identified interacting drug classes included antibiotics, cardiovascular drugs, and central nervous system agents. Clinically significant major interactions included combinations associated with QT prolongation, hyperkalemia, thrombogenicity, and CNS depression. Conclusion: The study demonstrates a high prevalence of potential drug–drug interactions among hospitalized patients, especially in elderly individuals and patients receiving multiple medications. Although most interactions were minor to moderate, the occurrence of major interactions highlights the importance of regular medication review, early DDI screening, and active involvement of clinical pharmacists to improve patient safety and optimize therapeutic outcomes.

Keywords

Drug-drug interactions, polypharmacy, medication safety, hospitalized patients

Introduction

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A drug is a substance that is administered to the body in order to have a biological effect. By attaching to a receptor or changing an enzyme's activity, for example, it modifies one or more biochemical processes1.Drug interactions may cause serious unwanted effects or decrease the effectiveness of certain medications. This risk is greatly increased by polypharmacy, which is especially common in elderly patients2. It is surprising to examine a patient in the modern era of medicine receiving only one or two drugs at a time. Drug interactions are influenced by the coexistence of several medical disorders as well as the necessity and practice of polypharmacy. A drug interaction occurs when one or more medications, foods, or beverages are administered simultaneously, changing the nature or effect of the drugs. One well-known factor influencing drug responsiveness and a major contributor to adverse drug responses is drug-drug interaction3.       According to reports, between 4 and 5 percent of hospital inpatients are prescribed medications that may interfere. The majority of these possible drug interactions might not happen or might go unnoticed. Drug interactions were responsible for 234 (6.9%) of the 3600 (4.3%) adverse drug responses found in 83,000 drug exposures in a large surveillance effort4. Medication-related harm remains a significant issue among older adults, with nearly half experiencing adverse health outcomes linked to potential drug exposure. Of these events, approximately 35–59% are considered preventable, highlighting the need for improved prescribing practices, careful monitoring, and strategies to minimize risks associated with medication use in this population5.

Drug interaction broadly classified into two types ;1. Pharmacokinetics interaction: Absorption interaction, Distribution interaction, Metabolism interaction, Excretion interaction

2. Pharmacodynamic interaction: Direct pharmacodynamic interaction, Indirect pharmacodynamic interaction6.

Drug interactions can have negative impacts on quality of life, length of hospital stay, morbidity, death, and health care costs7. Common risk factors associated with drug–drug interactions (DDIs) include patient-related factors such as age and gender, alterations in pharmacokinetic processes, the use of multiple medications (polypharmacy), medication errors, and the presence of comorbid conditions8. Drug-related problems are a frequent cause of illness(morbidity) and, in severe cases it can contribute to death (Mortality)9. Polypharmacy can lead to a “prescribing cascade,” where an adverse drug reaction is misinterpreted, prompting the prescription of additional, potentially unnecessary medications, which in turn increases the patient’s risk of experiencing further adverse drug reactions10.As age increases, the occurrence of multiple coexisting diseases often necessitates prescribing several medications to a single patient. Consequently, a typical 65-year-old patient is likely to be taking around five medications at the same time11.Medications most often involved in significant potential interactions are those routinely used in the everyday clinical care of elderly patients with chronic conditions12.     Exposure to drug–drug interactions (DDIs), especially those that heighten the risk of bleeding, significantly raises the probability of older adults being admitted to the hospital due to adverse drug reactions. Careful monitoring and management of such interactions are essential to reduce preventable hospitalizations and improve medication safety in this population13. Drug–drug interactions (DDIs) can lead to blood pressure fluctuations, sedation, central nervous system toxicity, cardiac arrhythmias, and other complications. Due to factors like long-term therapy and polypharmacy, preventing DDIs in these patients is challenging, posing significant difficulties for physicians in managing their treatment safely and effectively14. The concomitant use of NSAIDs and warfarin should be avoided, especially in patients over 65 or those with risk factors for NSAID-induced gastropathy, such as peptic ulcer history, steroid use, heavy smoking, or high NSAID doses. One study found a 13-fold increased risk of haemorrhagic peptic ulcers in these patients15.

MATERIALS AND METHODS:

It is a prospective study and was conducted in departments of Sri Balaji medical Care hospital (SBMHC), Renigunta, Tirupathi. The study was carried out on above 15 years age group of either sex for period of 10months

 The total of 98 subjects of all departments were enrolled in the study. for the collection of the data, the case record files of all the patients admitted in the departments were thoroughly reviewed each day during the study period.

The information recorded included the demographic details of patients, details about medications being used. The drug- drug interactions were assessed by using the drug interaction checker. The data were stored in the Microsoft excel and were analyzed by using the mean ± standard deviation.

RESULTS

The demographic details and characteristics of the patients indicate a female predominance, with 52 out of 98 subjects ( 53%) being female and 46 ( 47%) males. The most common age group was 61–80 years, comprising 32 patients ( 33%), followed by the 21-40 and 41-60 age groups each had % of the patients (28 subjects). The 0-20years age group with 7 patients ( 7 %). while those above 80 years accounted for 3.1% (3 subjects). Regarding subjects noted combination of drug interactions were a majority of cases, comprising 57 subjects, showed minor to moderate interactions. Total of 17 subjects ( 17.3% ) experienced a combination of minor, moderate, and major drug interactions. Additionally, 4(4.1%  ) subjects experienced moderate and major interactions while 3( 3.1% ) subjects experienced minor and major interactions. Among the study subjects, single drug interactions were observed with minor interactions in 12( 12.2% ) subjects, moderate in 4(4.1%  ) subjects, and major in 1( 1.1% ) subject. Among 98 subjects, drug interactions were predominantly minor (73) 48%, followed by moderate (60) 39%, while major interactions (19) 13% were least common.

 

sno

Details

Characteristics

No. of subjects

Total

1.

Gender

Male

Female

46(47%)

52(53%)

98(100%)

2.

Age

0 – 20 years AGE GROUP

21 – 40 years AGE GROUP

41 – 60 years AGE GROUP

61- 80 years AGE GROUP

81 – 100 years AGE GROUP

7(7%)

28(28.5%)

28(28.5%)

32(33%)

3(3%)

 

 

98(100%)

3.

 

Subjects noted combination of drug interactions

Minor –Moderate – major

Minor –Moderate

Minor – Major

Moderate – major

17(17.3%)

57(58.1%)

3(3.1%)

4(4.1%)

 

 

 

 

98(100%)

Subjects noted single drug interaction

Minor

Major

Moderate

12(12.2%)

1(1.1%)

4(4.1%)

4.

Total no. of drug interactions

Minor

Moderate

Major

71(48%)

58(39%)

19(13%)

 

148(100%)

 

Regarding subjects noted combination of drug interactions were a majority of cases, comprising 57 subjects, showed minor to moderate interactions. Total of 17 subjects ( 17.3% ) experienced a combination of minor, moderate, and major drug interactions. Additionally, 4(4.1%) subjects experienced moderate and major interactions while 3( 3.1% ) subjects experienced minor and major interactions. Among the study subjects, single drug interactions were observed with minor interactions in 12( 12.2% ) subjects, moderate in 4( 4.1% ) subjects, and major in 1(1.1% ) subject. Among 98 subjects, drug interactions were predominantly minor (71)48%, followed by moderate (58)39%, while major interactions (19)13% were least common.

 

Sno

description

Drug interaction

severity

In total

1

One drug may decrease the excretion rate of another drug which could result in a higher serum level

Acetaminophen + levofloxacin

Cefpodoxime proxetil +Acetaminophen

Furosemide + levofloxacin

Cefpodoxime + levocetrizine

Cefpodoxime + pantoprazole

Cefperazone + pantoprazole

Acetaminophen + Sulbactum

Pantoprazole + Sulbactam

Cefperazone + acetaminophen

Pantoprazole + Acetaminophen

Acetylcysteine + fexofenadine

Sucralfate + levosalbutamol

Doxycycline + acetaminophen

Aceclofenac + doxycycline

Ceftriaxone + tramadol

Tramadol + pantoprazole

Ceftriaxone + pantoprazole

Acetaminophen + amoxicillin

Aceclofenac + amoxicillin

Cefoperazone + tramadol

Nitrofurantoin + Flavoxate

Aceclofenac + Metoclopramide

Aceclofenac + Pantoprazole

Tazobactam + Levofloxacin

Ceftriaxone + Acetaminophen

Paracetamol + Ringers lactate

Lorazepam + levofloxacin

Furosemide + pantoprazole

Acetaminophen + meropenem

Pregabalin + doxycycline

Furosemide + ceftriaxone

Ciprofloxacin + meropenem Acetaminophen + rabeprazole Aceclofenac + rabeprazole

Aceclofenac + pregabalin

Pregabalin + acetaminophen

Pregabalin + rabeprazole

Mefenamic acid + pantoprazole

Pantoprazole + dicyclomine

Acetaminophen + dicyclomine

Aceclofenac + dicyclomine

Mefenamic acid + amoxicillin

Dicyclomine + amoxicillin

Linezolid + aceclofenac

Metformin + amoxicillin

minor

45

Valproate + lorazepam

Ticagrelor + sitagliptin

Piperacillin + levofloxacin

Glimepiride + Telmisartan

Pantoprazole + piperacillin

Pantoprazole + Tazobactum

Azithromycin + deflazacort

Ceftriaxone + amikacin

Tramadol + Amikacin

Pantoprazole + amikacin

Ceftriaxone + dexamethasone

Furosemide + tazobactum

Ranolazine + metoprolol

Moderate

13

Metronidazole + amiodarone

major

1

2

One drug may increase the excretion rate of another which could result in a lower serum level and potentially a reduction in efficacy.

 

Furosemide + Acetaminophen

Spironolactone + Metformin

Spironolactone + sitagliptin

 

minor

3

Torsemide + folic acid

Moderate

1

3

One drug may increase the hypotensive activities of another drug

Labetalol + Furosemide

Torsemide + spironolactone

Chlorthalidone + Acetaminophen

Chlorthalidone + Amlodipine

Chlorthalidone + Telmisartan

Metoprolol + nitroglycerin

minor

6

4

The risk or severity of hypertension can be increased when one drug is combined with another drug

Phenylephrine + levosalbutalmol

Linezolid + mefenamic acid

Minor

2

5

The risk or severity of QTc prolongation can be increased when one drug is combined with another drug

Azithromycin + Levocetirizine

Bilastine + Azitromycin

minor

2

Pregabalin + domperidone

Metronidazole + domperidone

Moderate

2

Azithromycin + domperidone

Levofloxacin + valproate sodium

major

2

6

The risk or severity of Tachycardia can be increased when  one drug is combined with another drug

Ipratropium + formoterol fumarate

Glycopyrronium bromide + levosalbutamol

minor

2

Ipratropium bromide + glycopyrronium bromide

major

1

7

The therapeutic efficacy of one drug can be decreased when used in combination with another drug

Torsemide + Telmisartan

Torsemide + Metformin

 

minor

2

Nortriptyline + domperidone

Glimepiride + Torsemide

moderate

2

8

The therapeutic efficacy of one drug can be increased when used in combination with another drug

Pregabalin + nortriptyline

Metoprolol + vildagliptin

 

 

moderate

2

9

The metabolism of  one drug can be decreased when  combined with another drug

Amlodipine + Azithromycin

Montelukast + dextromethorphan

Metformin + cilostazol

Atorvastatin + cilastazol

Ticagrelor + valsartan

Minor

5

Montelukast + naproxen

Naproxen + domperidone

Metronidazole + tramadol

Metronidazole + ondansetron

Montelukast + domperidone

Labetalol + Ondansetron

Labetalol + Acetaminophen

Acetaminophen + Montelukast

Levofloxacin + Doxofylline

Acetaminophen + Doxofylline

Acetaminophen + Ondansetron

Domperidone + doxofylline

Acetaminophen + metronidazole

Domperidone + acetaminophen

Dexamethasone + tramadol

Ciprofloxacin + metronidazole

Ciprofloxacin + pantoprazole

Clopidogrel + rosuvastatin

Torasemide + rosuvastatin

moderate

 

19

Tamsulosin + clonidine

Ciprofloxacin + acetaminophen

Ciprofloxacin + ondansetron

Clopidogrel + torsemide

major

4

10.

The metabolism of Azithromycin can be increased when one drug combined with another drug

Acetaminophen + Azithromcin

Hydrocortisone + tramadol

Dexamethasone + metronidazole

Clindamycin + acetaminophen

moderate

4

Theophylline + hydrocortisone

Dexamethasone + pantoprazole

Nortriptyline + acetaminophen

Major

3

11.

The risk or severity of adverse effects can be increased when one drug  is combined with another drug

Ceftriaxone + Ringers lactate

Spironolactone + sacubitril

minor

2

Calcium gluconate + ceftriaxone

Mefenamic acid + aceclofenac

Moderate

2

Dexamethasone + hydrocortisone

Major

1

12.

The risk or severity of gastrointestinal bleeding can be increased when one drug is combined with another drug

Nortriptyline + aceclofenac

minor

1

13.

Pantoprazole can cause a decrease in the absorption of  doxycycline resulting in a reduced serum concentration and potentially a decrease in efficacy

Pantoprazole + doxycycline

moderate

1

14.

The risk or severity of serotonin syndrome can be increased when ondansetron is combined with tramadol

Ondansetron + tramadol

moderate

1

15.

The risk or severity of CNS depression can be increased when one drug is combined with another drug

Lorazepam + levetiracetam

Valproate sodium + levetiracetam

Phenytoin + levetiracetam

moderate

3

16.

The risk or severity of angioedema can be increased when one drug is combined with another drug

Valsartan + sitagliptin

Sitagliptin + sacubitril

moderate

2

17.

The risk or severity of hypokalemia can be increased when  one drug is combined with another drug

Hydrocortisone + Furosemide

Deflazacort + Doxofyllin

Budesonide + levosalbutamol

Deflazacort + doxofylline

 

Moderate

4

18.

The risk or severity of hyperkalemia can be increased when one drug is combined with another drug

Telmisartan + Spironolactone

Valsartan + spironolactone

major

2

19.

Progesterone may increase the thrombogenic activities of tranexamic

Progesterone + tranexamic acid

Major

1

20.

The risk or severity of tendinopathy can be increased when Deflazacort is combined with Levofloxacin.

Deflazacort + levofloxacin

Moderate

1

21.

Levosalbutamol may increase the sympathomimetic activities of Formoterol.

Levosalbutamol + formoterol fumarate

Moderate

1

22.

Tranexamic acid may increase the thrombogenic activites of calcium

Tranexamic acid + calcium

major

1

23.

The risk or severity of sedation can be increased when  drug is combined with another drug

Clonidine + nortriptyline

Clonidine + gabapentin

Major

2

24.

Nortriptyline may increase the orthostatic hypotensive, hypotensive, and antihypertensive activities of Tamsulosin

Nortriptyline + tamsulosin

major

1

 

DISCUSSION

  • In the present study, the highest proportion of DDIs occurred in patients aged 61–80 years (33%), indicating that elderly patients are the most vulnerable group. This finding is aligns with Khaiser et al., who found that the 70–79-year age group had the highest prevalence of polypharmacy-associated DDIs. Both studies confirm that advancing age is strongly associated with increased DDI risk due to multiple comorbidities, altered drug metabolism, and reduced organ function.
  • This study observed a slight female predominance (53%) in DDI occurrence, similar to Khaiser et al., where females also showed a slightly higher prevalence of polypharmacy (53.84%) than males. This similarity may reflect increased healthcare utilization and greater chronic medication exposure among women.
  • Minor interactions were most frequent in the current study, while major interactions were less common but clinically significant. This trend aligns with Georgiev et al. (2022), who also reported that most hospitalized patient DDIs are minor-to-moderate, whereas severe interactions are fewer but require urgent clinical attention.
  • In this study, combination interactions (especially minor–moderate combinations, 58.1%) were more common than single interactions, strongly suggesting that polypharmacy is the principal driver of DDI occurrence. Khaiser et al. similarly demonstrated that patients receiving ≥5 drugs had significantly higher DDI prevalence. This reinforces the established relationship between increasing medication count and exponential rise in interaction probability.
  • In this study found frequent interactions involving:

Antibiotics (azithromycin, levofloxacin, ceftriaxone),Cardiovascular drugs (telmisartan, spironolactone, metoprolol),CNS drugs (nortriptyline, clonidine, pregabalin).This is consistent with the systematic review by Oliveira et al. (2020), which identified cardiovascular agents, diuretics, antimicrobials, and CNS drugs as the most common classes implicated in hospitalized elderly DDIs. ?

CONCLUSION

The present study highlights the significant prevalence of drug–drug interactions among hospitalized patients, with a total of 98 subjects evaluated. A higher proportion of cases was observed in females, and the elderly age group (61–80 years) was most affected, emphasizing the impact of age and polypharmacy on interaction risk.

The majority of drug interactions were of minor and moderate severity, with minor interactions being the most common overall. Combination drug interactions were more frequently observed than single interactions, particularly minor to moderate combinations, indicating the influence of multiple drug use in clinical practice. Although major interactions were less frequent, their presence underscores the need for careful monitoring due to potential serious clinical outcomes.

These findings reinforce that polypharmacy and advancing age are key risk factors for drug interactions. Early identification, regular medication review, and the use of drug interaction screening tools are essential to minimize adverse effects. Clinical pharmacists and healthcare professionals play a crucial role in improving medication safety, reducing preventable adverse drug reactions, and optimizing therapeutic outcomes.

REFERENCES

  1. Sam Baron; Sara Linton; Maureen A O’Malley, On Drugs-PMC 2023.
  2. Thomsen LA; Winterstein AG; Sondergaard B; Haugbolle LS; Melander, A. Systematic review of the incidence and characteristics of preventable adverse drug events in ambulatory care 2007.
  3. Madhav Mutalik; Dhara Sanghavi, Review Of Drug Interactions: A Comprehensive Update 2014.
  4. Quinn DI; Day RO, Clinically Important Drug Interactions. In: Speight TM, Holford HG, Editors. Avery’s Drug Treatment. 4th Ed. Auckland: Adis International; 1997.
  5. Parekh N, Ali K, Page A, Roper T, Rajkumar C. Incidence of medication-related harm in older adults after hospital discharge: a systematic review 2018.
  6. Priyanka Vitthal Kshirsagar; Pratiksha Suresh Nemane; Arati Suresh Khose; Omkar Bappadaheb Nalwade, A Review On Drug Interaction 2024.
  7. B. Gutherie; B.Makubate; V. Hernandez-Santiago; Creischulte, The Rising Tide Of Polypharmacy  And Drug-Drug Interactions: Population Database Analysis 1995-2010. 2015
  8. M. Ismail; Z. Iqbal; M.B. Khattak; A. Javaid; M.I. Khan, Potential drug-drug interactions in psychiatric ward of a tertiary care hospital: prevalence, levels and association with risk factors 2012.
  9. D.A. Roy; I. Shanfar; P. Shenoy, Drug-related problems among chronic kidney disease patients: a pharmacist-led study
  10. Rochon PA; Gurwitz JH; Optimising drug treatment for elderly people: The prescribing cascade 1997.
  11. Gallagher PF; Barry PJ; Ryan C; Hartigan I; O’Mahony D, Inappropriate prescribing in an acutely ill population of elderly patients as determined by Beers’ Criteria. Age Ageing 2008.
  12. Seymour R M; Routledge P, A. Important drug-drug interactions in the elderly. Drugs and Aging 1998.
  13. Hughes JE; Moriarty F; Bennett KE; Cahir C, Drug?drug interactions and the risk of adverse drug reaction?related hospital admissions in the older population 2023.
  14. H.B. Mezgebe, K. Sied, Prevalence of potential drug-drug interactions among psychiatric patients in auder referral hospital, mekelle, Tigray, Ethiopia 2015.
  15. Shorr RI; Ray WA; Daugherty JR; Griffin MR, Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for haemorrhagic peptic ulcer disease 1993.

Reference

  1. Sam Baron; Sara Linton; Maureen A O’Malley, On Drugs-PMC 2023.
  2. Thomsen LA; Winterstein AG; Sondergaard B; Haugbolle LS; Melander, A. Systematic review of the incidence and characteristics of preventable adverse drug events in ambulatory care 2007.
  3. Madhav Mutalik; Dhara Sanghavi, Review Of Drug Interactions: A Comprehensive Update 2014.
  4. Quinn DI; Day RO, Clinically Important Drug Interactions. In: Speight TM, Holford HG, Editors. Avery’s Drug Treatment. 4th Ed. Auckland: Adis International; 1997.
  5. Parekh N, Ali K, Page A, Roper T, Rajkumar C. Incidence of medication-related harm in older adults after hospital discharge: a systematic review 2018.
  6. Priyanka Vitthal Kshirsagar; Pratiksha Suresh Nemane; Arati Suresh Khose; Omkar Bappadaheb Nalwade, A Review On Drug Interaction 2024.
  7. B. Gutherie; B.Makubate; V. Hernandez-Santiago; Creischulte, The Rising Tide Of Polypharmacy  And Drug-Drug Interactions: Population Database Analysis 1995-2010. 2015
  8. M. Ismail; Z. Iqbal; M.B. Khattak; A. Javaid; M.I. Khan, Potential drug-drug interactions in psychiatric ward of a tertiary care hospital: prevalence, levels and association with risk factors 2012.
  9. D.A. Roy; I. Shanfar; P. Shenoy, Drug-related problems among chronic kidney disease patients: a pharmacist-led study
  10. Rochon PA; Gurwitz JH; Optimising drug treatment for elderly people: The prescribing cascade 1997.
  11. Gallagher PF; Barry PJ; Ryan C; Hartigan I; O’Mahony D, Inappropriate prescribing in an acutely ill population of elderly patients as determined by Beers’ Criteria. Age Ageing 2008.
  12. Seymour R M; Routledge P, A. Important drug-drug interactions in the elderly. Drugs and Aging 1998.
  13. Hughes JE; Moriarty F; Bennett KE; Cahir C, Drug?drug interactions and the risk of adverse drug reaction?related hospital admissions in the older population 2023.
  14. H.B. Mezgebe, K. Sied, Prevalence of potential drug-drug interactions among psychiatric patients in auder referral hospital, mekelle, Tigray, Ethiopia 2015.
  15. Shorr RI; Ray WA; Daugherty JR; Griffin MR, Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for haemorrhagic peptic ulcer disease 1993.

Photo
O.kavya
Corresponding author

Krishna teja pharmacy college

Photo
O.saraswathi
Co-author

Krishna teja pharmacy college

Photo
C. Mohana
Co-author

Krishna teja pharmacy college, Tirupati, Andhra Pradesh, India

O. Kavya, O. Saraswathi, C. Mohana Evaluation of drug-drug interactions in a hospitalized patients: A prospective observational study, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 5, 7829-7837, https://doi.org/10.5281/zenodo.20443312

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