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OR I G I N A L R E S E A R C H

Survey on Polypharmacy and Drug-Drug

Interactions Among Elderly People with

Cardiovascular Diseases at Yekatit 12 Hospital,

Addis Ababa, Ethiopia This article was published in the following Dove Press journal:

Integrated Pharmacy Research and Practice

Yelbeneh Abayneh Assefa1

Ansha Kedir1

Wubayehu Kahaliw 2

1Department of Pharmacology and

Clinical Pharmacy, School of Pharmacy,

College of Health Sciences, Addis Ababa

University, Addis Ababa, Ethiopia; 2Department of Pharmacology, School of

Pharmacy, College of Medicine and

Health Sciences, University of Gondar,

Gondar, Ethiopia

Background: Elderly people are most commonly associated with cardiac disease.

Cardiovascular diseases are interlinked with co-morbidities which require multiple drug therapy

in addition to cardiovascular drugs. This results to polypharmacy which carries a high risk of

potential drug-drug interactions. Elderly patients are at a particular risk of drug related problems

because of increased level of polypharmacy and the physiological changes which accompany

aging. This study was aimed to assess polypharmacy and potential drug-drug interactions (DDIs)

among elderly people with cardiovascular diseases at Yekatit 12 hospital.

Methodology: A retrospective cross-sectional study using patients chart review was con-

ducted on all elderly people with cardiovascular diseases at Yekatit 12 hospital in the period

between March 2018 and March 2019. The types, seriousness and level of potential DDIs

were checked using Medscape online drug interaction checker.

Results: The mean number of drugs per prescription was 4.25 ± 1.754 and the prevalence of

polypharmacy (concurrent use of 5 and more drugs) was 42.7%. Polypharmacy and potential

DDIs were significantly associated with polymorbidity (P = 0.000), being hospitalized (P =

0.047) and congestive heart failure (P = 0.016). A total of 850-potential DDIs were

identified, the mean number of potential DDIs was 3.37 per prescription. The potential

DDIs were mainly significant (73.29%) in nature and pharmacodynamics (73.06%) in

mechanism. The prevalence of total and serious potential DDIs were 84.3% and 17.3%,

respectively. Most commonly interacting drug combination was aspirin + enalapril (30.2%).

Conclusion: A higher incidence of polypharmacy and increased risk of potential DDIs in

elderly people with cardiovascular disease are major therapeutic issues at Yekatit 12

hospital.

Keywords: polypharmacy, drug-drug interaction, cardiovascular diseases, elderly

Background In many countries of the world, elderly people are significant in number and 60% of

them are found in developing countries.1 Elderly people in Ethiopia account 9.5%

from the total population.2 One-cardiovascular disease can occur as co-morbidity

with another one. Non-cardiovascular diseases are also highly associated with

cardiovascular diseases which impart complications to the heart. These complica-

tions cause several dysfunctions resulting in the use of many drugs

(polypharmacy).3

Correspondence: Wubayehu Kahaliw Department of Pharmacology, College of Medicine and Health Sciences, University of Gondar, P.O, Box 196, Gondar, Ethiopia Tel +251910532412 Email [email protected]

Integrated Pharmacy Research and Practice Dovepress open access to scientific and medical research

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Polypharmacy is defined as the concurrent use of

five or more drugs.4–8 It is associated with suboptimal

prescribing, increase in risk of falls and has a significant

effect on increasing health expenditures. Therefore, it is

a matter of interest for prescribers since it may be

regarded as irrational prescribing and it is a significant

problem among older adults.9,10 The practice of poly-

pharmacy leads to drug interactions and this in turn

causes adverse drug reactions and deterioration of func-

tional status.11–14

Drug-drug interaction (DDI) is defined as the change

in the drugs effect when a second drug is taken concur-

rently. As a result of drug-drug interaction synergistic or

additive, antagonistic or subtractive and idiosyncratic

effects may occur.15 Drug-drug interactions can be clas-

sified as pharmacokinetic, pharmacodynamics and phar-

maceutical interactions. Pharmacokinetic interactions are

the result of altered drug delivery to the site of action and

can occur at the level of absorption, distribution, meta-

bolism or clearance of the affected agent whereas

Pharmacodynamic interactions are the result of altered

drug effect at the site of action. Pharmaceutical interac-

tion is the interaction of incompatible drugs which occur

outside of the body during mixing.16

Studies indicated that there is an increased level of

multiple medications and hence drug-drug interaction

among the elderly part of the population.3 The drug-drug

interaction rate is higher in cardiovascular diseases com-

pared to other disease. The possible reason behind higher

DDI rate in cardiovascular disease may include elder age,

polypharmacy and pharmacokinetic or pharmacodynamics

nature of drugs used in cardiology.17 People in old age are

highly vulnerable to drug adverse effects because of multi-

ple drugs and aging.19,20 Physiological alterations asso-

ciated with aging make the elderly susceptible to

drug-interactions. The physiological alterations which

accompany aging are renal insufficiency and liver meta-

bolism abnormality, gut function alterations and poor

nutritional status.11

In addition, elderly patients suffering from chronic

diseases and taking sedatives/hypnotics without indication

and those with hypertension or atrial fibrillation are at high

risk of exposure to multiple drugs and potential drug-drug

interaction.3 In elderly patients, drug-drug interactions

play a significant role in the deterioration of the general

health condition, leading to affliction, poor quality of life,

prolonged hospital stays, a greater need for ambulatory

services and increased health-care costs.13

Although polypharmacy and drug interactions

reported to be common, there is sparse data on the

prevalence of polypharmacy and drug-drug interactions

in Yekatit12 hospital, Addis Ababa, Ethiopia. Hence this

study was aimed to evaluate prevalence of polyphar-

macy and types and severity of possible drug-drug inter-

actions in ambulatory and hospitalized elderly

cardiovascular patients.

Methods Description of Study Setting Yekatit 12 hospital is a referral hospital owned by Addis

Ababa Health Council. The hospital is a teaching hospital

associated with Addis Ababa University Black Lion

Hospital. It is one of the public hospitals in Ethiopia.

The hospital provides services for a population of approxi-

mately 4 million. It consists of nine departments and six

units and has 265 beds. Yekatit 12 hospital has excellent

laboratory facilities that perform most categories of rou-

tine diagnostics.

Study Design, Sample Size and Data

Collection A retrospective cross-sectional study was carried out

from March 2018 to March 2019 in Yekatit 12

Hospital. All elderly (age 50 years and above) patients’

charts of cardiovascular disease and with adequate doc-

umentation were included in the study. All cardiovascu-

lar patients’ charts age 49 years and below as well as

charts recording non-cardiovascular disease were

excluded from the study. Data were collected from 255

patients’ charts using structured data collection format

(Patient data abstraction format). The format was pre-

pared with different sections important to fill basic

demographic information like age and sex, drugs admi-

nistered, and co-morbidities or diseases identified. The

interactions between the drugs were assessed using

Medscape online drug interaction checker.18

Ethical Considerations Approval of the research ethics was obtained from School

of Pharmacy, Addis Ababa University Ethics Review com-

mittee. Prior information was sent to the administrative

authorities of the Yekatit 12 hospital about the nature and

purpose of the study through a letter from school of

Pharmacy, Department of pharmacology and clinical phar-

macy, Addis Ababa University. The data were accessed

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only by the researchers and data collector and every pre-

caution was considered for keeping confidentiality of

patient data.

Patient written informed consent form to review

their medical records was waived due to the following

justifications: personal identifiers of prescriptions were

not used in the data collection process and the institu-

tional review board of school of pharmacy, Addis

Ababa University believed that this study will not

adversely affect the rights and welfare of the subjects.

In addition, the research involves no more than mini-

mal risk.

Statistical Analysis Data were entered using Epi Info version 3.5.1 and ana-

lyzed using the Statistical Package for Social Sciences

(SPSS) version 20.0 for Windows. Results were expressed

as means ± standard deviation (SD), frequencies, and

percentages. Chi-square test was used to compare the

means of different groups among the study population

while the Mann–Whitney U-test was used to compare

continuous variables in two groups. Values of P < 0.05

were considered as significant.

Results Socio-Demographic and Related Profiles In the current study, medical charts of 255 patients with

cardiovascular disease were collected and analyzed. The

mean age was 63.54 ± 9.248 years. From the medical

charts reviewed, majority of patients were above 60

years of age. More than half (57.3%) of prescriptions

were orders for males and almost 80% of the patients

were ambulatory (Table 1).

Diagnosis, Commonly Prescribed Drugs

and Drug-Drug Interactions The most common cardiovascular diseases identified were

hypertension (46.6%), congestive heart failure (14.5%) and

stroke (13.3%). Most frequent co-morbid conditions were

endocrine disorders (24.7%), followed by respiratory pro-

blems (10.6%) and chronic kidney diseases (9%). The data

revealed that at least one co-morbid condition occurred in a

majority of patients (68.8%) (Table 2). As indicated in

Figure 1, the prevalence of polymorbidity was 71.8% with

1–3 co-morbidity (68.6%) and ≥4 co-morbidities (3.2%).

Table 1 Socio-Demographic and Related Profiles

Variable No. of Patients (%)

Gender Male 146 (57.3)

Female 109 (42.7)

Age 50–59 years 87 (34.1)

60–69 years 87 (34.1)

70 years and above 81 (31.8)

Mean age±SD 63.54 ± 9.248

Patient category Ambulatory (Outpatient) 201 (78.8)

Inpatient (Hospitalized) 54 (21.2)

Table 2 Diagnosis, Number of Prescribed Drugs and Potential

Drug-Drug Interactions

Variable No. of

Patients (%)

Number of drugs

prescribed

1 14 (5.5)

2–4 132 (51.8)

5 and more 109 (42.7)

Mean±SD 4.25 ± 1.754

Number of pDDIs No pDDI 40 (15.7)

1–3 120 (47.1)

4–6 49 (19.2)

7 and more 46 (18)

Mean ± SD 3.33 ± 3.05

Main cardiovascular diseases

diagnosed

Hypertension 124 (48.6)

Congestive Heart

Failure

37 (14.5)

Stroke 34 (13.3)

Ischemic Heart

Disease

22 (8.6)

Deep vein

thrombosis

16 (6.3)

Valvular heart

disease

9 (3.5)

Acute Coronary

Syndrome

6 (2.4)

Arrhythmia 6 (2.4)

Dyslipidemia 1 (0.4)

Other co-morbidities Endocrine

Abnormalities

63 (24.7%)

Respiratory

problems

27 (10.6 %)

CNS related 6 (2.4 %)

Chronic disease 11 (4.3%)

CKD, UTI and

Anemia

23 (9%)

Miscellaneous 8 (3.1%)

Abbreviations: pDDIs, potential drug-drug interactions; CKD, chronic kidney

disease; UTI, urinary tract infection; CNS, central nervous system.

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The occurrence of polymorbidity was more frequent in

males (76%) than in females (70.4%).

Most frequently prescribed drugs were aspirin 127

(49.8%), enalapril 122 (47.8%) furosemide 91 (35.7%),

nifedipine 90 (35.3%) and spironolactone 82 (32.2%) fol-

lowed by atenolol 79 (31%) (Figure 2). As shown in

Table 2, the average drugs prescribed per prescription was

4.25 ± 1.754 which indicated the practice of polypharmacy

in the hospital. Mean number of potential drug-drug

interactions was 3.33 ± 3.05 and almost half (47.1%) of

the study subjects encountered 1–3 interactions.

Prevalence of Polypharmacy From 255-medical chart records assessed, 5 or more

drugs were prescribed in each of the 109 (42.7%) patient

charts which indicated the occurrence of polypharmacy in

Yekatit 12 hospital. Among 109 patients who took ≥5 drugs concurrently, 65 (44.5%) were males and 44

(40.4%) were females. The prevalence of polypharmacy

was high at advanced age; however, the association

between polypharmacy and age was statistically insignif-

icant (chi-square; χ2 = 1.291, p = 0.524, phi = 0.071)

(Table 3). According to chi-square test for independence,

statistically significant association between sex and poly-

pharmacy was not observed (χ2 = 0.287, p = 0.592, phi =

−0.042) (Figure 3).

The assessment of medical records of hospitalized

patients revealed that 55.6% of the patients received ≥5 drugs concurrently whereas 39.3% of ambulatory patients

received equal number of medications. Polypharmacy was

significantly associated with hospitalized patients (chi-

square test; χ2 = 3.954, p = 0.047, phi = 0.134) (Figure 3).

The number of medications prescribed per prescription

(≥5 drugs per prescription) was higher with polymorbidity

(≥4 co-morbidities). According to Mann–Whitney U-test the

number of cases of polypharmacy was significantly higher in

the presence of polymorbidity (p < 0.001). Forty-five

(36.3%) medical charts of hypertensive patients were

No co- morb

idity

1-3 Co-m

orb idity

4 com orb

idity 0

20

40

60

80

24% 33.9%

28.2%

71.9%

64.3%

68.6%

4.1% 1.8%

3.2%

Level of co-morbidity

Pe rc

en t

Figure 1 Prevalence of Co-morbidity in gender. = Male, = Female,

= Total.

0 5 10 15 20 25 30 35 40 45 50 55 60 Diclofenac

Amlodipine

Clarithromycin

Metformin

Prednisolone

Vitamin B1

Simvastatin

Lovastatin

Ceftriaxone

Warfarin

Omeprazole

NPH insulin

Glibenclamide

Hydrochlorothiazide

Digoxin

Atenolol

Spironolactone

Nifedipine

Furosemide

Enalapril

Aspirin 49.8%

47.8%

35.7%

35.3%

32.2%

31%

18%

15.3%

11%

10.6

8.2%

7.8%

7.1%

6.3%

5.9%

5.9%

5.5%

5.1% 4.3%

3.5%

3.5%

Frequency distrribution of a single drug prescribed in medical charts of patients

D ru

g s

Figure 2 Specific drugs prescribed for the management of cardiovascular diseases.

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identified with polypharmacy. However, hypertension was

not significantly associated with polypharmacy (χ2 = 3.612,

p=0.057, phi= −0.127). On the other hand, 23 (62.2%) con-

gestive heart failure patients’ medical charts were identified

with polypharmacy and a chi-square test for independence

showed a significant association between congestive heart

failure and polypharmacy (χ2 = 5.772, p = 0.016, phi = 0.162)

(Figure 3).

Nature and Mechanism of Drug-Drug

Interactions The nature and mechanisms of DDIs are summarized in

Tables 3 and 4. Among 850-potential DDIs, pharmacody-

namic interactions were the most common constituting

73.06%, followed by pharmacokinetic (21.29%) and

mixed (5.65%) interactions. Significant DDIs were most

common constituting 73.29%, followed by minor

(19.41%) and serious (7.3%) interactions.

Demographic variables and nature of potential DDIs

are illustrated in Table 4. In 125 (85.6%) male and 90

(82.6%) female patients’ prescriptions potential DDIs

were present. The number of potential DDIs in 60–69

years old age group, ambulatory and hospitalized patients’

medical charts were 77 (88.5%), 171 (85.1%) and 44

(81.5%), respectively. However, the association between

DDIs and demographic variables (gender, age and ambu-

latory or hospitalized patients) was not statistically signif-

icant using chi-square test. On the other hand, potential

DDIs in patients with congestive heart failure and four-co-

morbid conditions and polypharmacy were 100% and

98.2%, respectively. The association between DDIs and

congestive heart failure, four-co-morbid conditions

and polypharmacy were statistically extremely significant

(P = 0.001) using Mann–Whitney U-test (Table 4).

Common Drug Groups The most frequent potential drug-drug interactions with

their respective importance and possible risks are

Table 3 Nature and Mechanisms of Potential Drug-Drug

Interactions

Nature of

Interactions

Frequency (%

per Total

Patient)

Frequency (%

per Total

pDDIs)

Mechanism of interaction

Pharmacodynamic

interaction

193 (75.7) 621 (73.06)

Pharmacokinetic

interaction

103 (40.6) 181 (21.29)

Unknown or mixed

mechanism of

interaction

45 (17.6) 48 (5.65)

Clinical types of potential

DDIs

Serious drug

interaction

44 (17.3) 62 (7.3)

Significant drug

interaction

195 (76.5) 623 (73.29)

Minor drug interaction 115 (45.1) 165 (19.41)

Abbreviations: DDIs, drug-drug interactions; pDDIs, potential drug-drug

interactions.

Age 50

-59 ye

ars

Age 60

-69 ye

ars

Age >70

ye ars Male

Fem ale

Ambulat ory

pati en

ts

Hosp ita

liz ed

pati en

ts

No c o-m

orb idity

1-3 co

-m orb

idity

4 c o-m

orb idity

Hyp ert

en sio

n

Con ges

tiv e h

ear t fa

ilu re

0

50

100

150

62.1%

37.9%

54%

46%

55.6%

44.4%

55.5%

44.5%

59.6%

40.4%

60.7%

39.3%

44.4% 55.6%

1

90.3%

9.7%

46.3% 53.7%

100% 3

63.7%

36.3% 37.8%

32.2% 1

Different variables

Pe rc

en t

Figure 3 Polypharmacy status among different variables. = No polypharmacy, = polypharmacy. 1p = 0.05, 3p = 0.001.

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presented in Table 5. The most common drug groups

identified were angiotensin-converting enzyme (ACE)

inhibitors (enalapril), NSAIDs (low dose aspirin), diuretics

(furosemide, hydrochlorothiazide and Spironolactone), ß-

blockers (Atenolol), digoxin and calcium channel blocker

(Nifedipine), lipid lowering agents (Simvastatin and

Lovastatin), proton pump inhibitors (Omeprazole) and

prednisolone.

Themost commonly identified combination of drugs with

potential dug-drug interactions were Aspirin + Enalapril

(30.2%), Enalapril + furosemide (21.6%), Aspirin +

Furosemide (19.6%), Enalapril + Spironolactone (18.4%),

Aspirin + Atenolol (18%), Aspirin + Spironolactone

(16.1%), Digoxin + Spironolactone (16.1%) and Digoxin +

Furosemide (15.7%).

Discussion In this study, medical charts of elderly (aged 50 year and

above) people with cardiovascular diseases were examined

and analyzed for the prevalence of polypharmacy and

potential drug-drug interactions. In addition, the nature

and mechanisms of drug-drug interactions, most com-

monly involved combination of drugs and the most fre-

quently occurred potential drug-drug interactions were

assessed. The majority of patients with cardiovascular

diseases were males (57.3%), which is in line with the

fact that men are more prone to heart disease compared to

women of a similar age.3 The most common diagnosis

identified was hypertension (48.6%) followed by conges-

tive heart failure and stroke. Similarly, hypertension

(57.8%) was the most frequent diagnosis found on the

study done in Italy on general elderly patients.21 The

prevalence (71.8%) of co-morbidity in our study is in

line with the prevalence of co-morbidity (35–80%) in

other studies on elderly populations.5 The most commonly

identified co-morbidities were cardiovascular disease,

endocrine abnormalities (diabetes mellitus II) and respira-

tory problems (pneumonia and chronic obstructive pul-

monary disease), which is in line with the previous study

in Bosnia and Herzegovina.22 In this study, the mean

number of co-morbidity in hospitalized patients was 4.8.

The finding of this study is lower than hospitalized

patients in Japan which depicted 7.7 mean number of co-

morbidity.8

The mean number of drugs per prescription was 4.25

with standard deviation of 1.754 which is comparable to

the data reported from previous studies in southern Brazil

(4.4 drugs per prescription) and Nigeria (3.8 drugs per

prescription).23 The mean number of prescribed drugs in

this study is lower than the study in South Africa (7.7) and

Bangladesh (7.34).1,24 The maximum number of drugs

recorded per patient were 10 which is comparable to the

finding of similar studies done in Nigeria and southern

Brazil which show a maximum of 8 and 11 drugs pre-

scribed per patient, respectively.1,23

In the current study, prevalence of polypharmacy

(42.7%) is comparable with the polypharmacy prevalence

reported from previous studies in Indian teaching hospitals

(45%), Japan (49%) and southern Brazil (43.1%).7,8,23 The

data revealed that prevalence of polypharmacy was not

significantly associated with age (P = 0.524) and gender

(P = 0.592). However, it was significantly associated with

inpatients (P = 0.047) which indicated that hospitalized

patients are at a higher risk of polypharmacy compared to

ambulatory patients.

Coming to DDIs, both ambulatory and hospitalized

patients are at higher risk of potential drug-drug interac-

tions. Majority of potential DDIs were significant

(73.29%) in nature and pharmacodynamic (73.06%) in

Table 4 Different Variables and Potential Drug-Drug Interactions

Variables Patients Without

DDIs on Their

Prescription

Patients with

DDIs on Their

Prescription

Age

50–59 years 17 (19.5%) 70 (80.5%)

60–69 years 10 (11.5%) 77 (88.5%)

≥70 years 13 (16%) 68 (84%)

Gender

Male 21 (14.4%) 125 (85.6%)

Female 19 (17.4%) 90 (82.6%)

Patient category

Ambulatory 30 (14.9%) 171 (85.1%)

Inpatient 10 (18.5%) 44 (81.5%)

Number of Drugs

Prescribed

<5 38 (26%) 108 (74%)

≥5 2 (1.8%) 107 (98.2%)

Co-Morbid

Condition

No co-morbidity 22 (30.6%) 50 (69.4%)

1–3 co-morbidity 18 (10.3%) 157 (89.7%)

4 co-morbidity 0 (0%) 8 (100%)

Hypertension 20 (16.1%) 104 (83.9%)

Congestive heart

failure

0 (0 %) 37 (100%)

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Table 5 Potential Drug-Drug Interactions Identified from Medical Records in Yekatit 12 Hospital

Drug Combinations pDDIs

(%)

Clinical Types of

pDDIs

Mechanism of

pDDIs

Potential Risk

Aspirin + Enalapril 77 (30.2) Significant PD, antagonism Aspirin may attenuate the vasodilator and hypotensive

effects of Enalapril.

Enalapril + Furosemide 55 (21.6) Significant PD, synergism Risk of acute hypotension, renal insufficiency.

Aspirin+ Furosemide 50 (19.6) Minor PD, antagonism Blunting of the diuretic effect of furosemide

Enalapril + Spironolactone 47 (18.4) Significant PD, synergism Risk of hyperkalemia

Aspirin + Atenolol 46 (18) Significant PD, antagonism Blunting of the antihypertensive effect of Atenolol and

risk of hyperkalemia

Aspirin + Spironolactone 41 (16.1) Significant PD Risk of hyperkalemia

Digoxin + Spironolactone 41 (16.1) Significant PK and PD Digoxin toxicity and increase serum potassium

Digoxin + Furosemide 40 (15.7) Significant PD, synergism Digoxin toxicity

Atenolol + Nifedipine 27 (10.6) Significant PD Both increase anti-hypertensive channel blocking

Atenolol + Spironolactone 27 (10.6) Significant PD Risk of hyperkalemia

Aspirin + Digoxin 25 (9.8) Significant PD Risk of hyperkalemia

Aspirin + Glibenclamide 17 (6.7) Minor PK Risk of hypoglycemia

Aspirin + NPH insulin 16 (6.3) Minor PD, synergism Risk of hypoglycemia

Enalapril + Glibenclamide 16 (6.3) Significant PD, synergism Risk of hypoglycemia

Aspirin + Hydrochlorothiazide 13 (5.1) Minor PK Risk of bleeding

Enalapril + NPH insulin 11 (4.3) Significant PD, synergism Risk of hypoglycemia

Atenolol + Digoxin 9 (3.5) Significant PD, synergism Enhanced bradycardia and increase in serum potassium

Spironolactone + Prednisolone 9 (3.5) Significant PK Increase in the level or effect of Prednisolone.

Furosemide + Prednisolone 8 (3.1) Minor PD, synergism Risk of hypokalemia

Furosemide + Ceftriaxone 8 (3.1) Minor PD, synergism Increased risk of nephrotoxicity

Aspirin + Ceftriaxone 8 (3.1) Minor PK Risk of bleeding

Aspirin + Prednisolone 6 (2.4) Significant PK and PD Increased risk of GI ulceration

Nifedipine + Digoxin 6 (2.4) Significant PK Digoxin toxicity

Enalapril + Carbamazepine 5 (2) Significant PK Increases levels of carbamazepine

Spironolactone + Lovastatin 5 (2) Significant PK Increases level of Lovastatin

Nifedipine + Simvastatin 8 (3.1) Serious PK Musculoskeletal toxicity

Digoxin + Omeprazole 7 (2.7) Serious PK Digoxin toxicity

Digoxin + Clarithromycin 4 (1.6) Serious PK Digoxin toxicity

Nifedipine + Lovastatin 4 (1.6) Serious PK Musculoskeletal toxicity

Rifampin + Warfarin 3 (1.2) Serious PK Decreased anticoagulation effect of warfarin

Heparin + Warfarin 3 (1.2) Serious PD Risk of bleeding

Abbreviations: PD, pharmacodynamic; PK, pharmacokinetic; pDDIs, potential drug-drug interactions.

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mechanism. According to the present study, prevalence of

potential DDIs were not associated with age (P = 0.343)

and gender (P = 0.626) which is in agreement with other

studies at different settings.23 This study showed that a

significant association was observed between congestive

heart failure and potential DDIs (P = 0.01). This indicated

that patients diagnosed and treated for congestive heart

failure are at higher risk of suffering from the adverse

effects of DDIs. The prevalence of potential DDIs were

also significantly associated with polypharmacy (P =

0.000) and four co-morbidities (P = 0.000) which showed

multiple medications and polymorbidity (≥4 co-morbid-

ities) are significant predictors of potential DDIs.23

With respect to specific drugs prescribed, aspirin, ena-

lapril, furosemide, nifedipine and spironolactone were the

most frequent which is in line with previous study in

Italy.23 The most commonly identified potential DDIs

were mainly due to aspirin, enalapril, furosemide, spiro-

nolactone, atenolol, digoxin and nifedipine in combination

with each another or with other drugs.

The majorities of identified interactions were of sig-

nificant in nature, pharmacodynamic in mechanism and

mainly related to drugs acting on cardiovascular system

which is in agreement with findings elsewhere.23 In fact,

there are DDI reports in the literature, but there is little

agreement among them with respect to the type, nature and

clinical importance of interactions. From potential interac-

tion with minor intensity, aspirin and furosemide combina-

tion was the most frequently identified one in which the

diuretic effect of furosemide could be blunted by the

pharmacodynamic antagonism caused by aspirin. An inter-

action between aspirin with antidiabetic agents

(Glibenclamide and NPH insulin) was also common and

lead to possible risk of hypoglycemia. In addition, minor

interaction was identified between aspirin and hydrochlor-

othiazide which is pharmacokinetic in mechanism and

might lead to bleeding.

The data revealed that significant DDIs were pharma-

codynamic in mechanism. Among medication combina-

tions, Aspirin + enalapril, enalapril + furosemide, aspirin

+ atenolol, aspirin + spironolactone and digoxin + furose-

mide were the most commonly encountered combination

with significant interactions. Such types of interaction

require close monitoring of the clinical outcome or possi-

ble risks. Aspirin might attenuate vasodilator and hypoten-

sive effects of enalapril while an interaction between

enalapril and furosemide might have a combined risk of

acute hypotension and renal insufficiency.

Even though diuretics are widely used to optimize

therapeutic effects and diminish adverse events, loop and

thiazide diuretics largely contribute to moderate intensity

interactions. The interaction between loop and thiazide

diuretics is pharmacodynamic interaction and leads to

loss of drug efficacy.

Nifedipine + simvastatin, digoxin + omeprazole and

digoxin + clarithromycin combinations were the most

common serious intensity pharmacokinetic interactions.

A combination of nifedipine and simvastatin affects the

metabolism and increases the level of simvastatin which

lead to musculoskeletal toxicity while those interactions

between digoxin and omeprazole or clarithromycin

increase level of digoxin and lead to digoxin toxicity.

Another serious pharmacodynamic interaction identified

was between heparin and warfarin which ultimately lead

to increased anticoagulation (higher incidence of bleed-

ing). Co-administration of drugs which are potentially

interacting might increase the number of adverse events

which can be confused with the severity of co-morbidities.

The consequences of such interactions include a longer

duration of treatment period with administration of more

drugs to patients, resulting in a higher probability of drug-

drug interactions.

Conclusion The prevalence of polypharmacy was found associated

with increased number of co-morbidity and inpatient pre-

scriptions. The prevalence of total and serious potential

drug-drug interactions were 84.3% and 17.3%, respec-

tively. The majority of interactions were pharmacody-

namic in mechanism (73.06%) and significant in nature

(73.29%). The prevalence of potential drug-drug interac-

tions were significantly associated with polypharmacy and

polymorbidity (≥4 co-morbidities). Based on the finding in

the current study, drugs acting on cardiovascular system

including low dose aspirin, diuretics, angiotensin-convert-

ing enzyme inhibitors, calcium channel blockers, beta-

blockers and digoxin were most commonly and frequently

implicated in potential drug-drug interactions. A higher

incidence of polypharmacy and increased risk of potential

drug-drug interactions in elderly people with cardiovascu-

lar disease are major therapeutic issues at Yekatit 12

hospital.

Disclosure The authors have no conflict of interest to disclose.

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