Short Communication International Journal of
Pharmacy Practice International Journal of Pharmacy Practice 2014, ••, pp. ••–••
Frequency, types and factors associated with potentially harmful drug interactions in ambulatory elderly patients in Nigeria Kazeem B. Yusuffa,b and Chinyere Nma Okoha a Department of Clinical Pharmacy & Pharmacy Administration, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria and bDepartment of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Hofuf Al-Ahsa, Kingdom of Saudi Arabia
Keywords ambulatory elderly patients; drug interactions; Nigeria Correspondence Dr Kazeem B. Yusuff, Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, P.O Box 400, Hofuf Al-Ahsa 31982, Kingdom of Saudi Arabia. E-mail: [email protected]
; [email protected]
Received January 21, 2014 Accepted November 8, 2014 doi: 10.1111/ijpp.12167 Name of Ethics Committee: Ethics Committee of the Oyo State Hospital Management Board Date of approval: 5 February 2010 Approval number: 05/02/2010/45 OYHMB
Abstract Objective To determine the frequency, types and factors associated with potentially harmful drug interactions among ambulatory elderly (≥65 years) patients in Ibadan, Nigeria. Methods A 4-week cross-sectional study was conducted among 229 elderly patients who consented and were prescribed two or more medicines within a 4-week study period at a major 256-bed secondary care facility in Ibadan, Nigeria. Chi-square and risk ratio were used to identify the factors associated with the potentially harmful drug–drug interactions. Key findings Potentially harmful drug–drug interactions were identified in about two-thirds (65%, 149/229) of the patients. The risk of occurrence drug interactions was significantly higher among patients who had at least six prescribed medicines (relative risk: 7.8 (95% confidence interval, 6.9 to 9.5) (P < 0.001)), and a significant majority were also females (73.8%) (110) (P < 0.001). The most frequent interacting drug combination was angiotensin-converting enzyme inhibitors and amiloride + hydrochlorothiazide (34.7%). Conclusion Potentially harmful drug interactions that are significantly associated with high multiple prescribing are considerable among elderly patients in Nigeria.
Introduction Appropriate prescribing which takes into careful consideration patient-specific factors is critical to the achievement of positive outcome of medication use. This is particularly important for the elderly population (65 years and above) due to altered pharmacokinetic and pharmacodynamics and the increased risk of adverse events especially from drug interactions. Ageing is also associated with higher prevalence of multiple co-morbidities which often attract multiple drug therapy.[2,3] Multiple prescribing, prescribing cascade and poly-pharmacy are known strong predictors of potentially harmful drug interactions among the elderly.[4,5] The incidence of multiple prescribing and the associated potentially harmful drug interactions episodes among the elderly are well reported in developed settings. However, there is paucity of published data about this phenomenon in © 2014 Royal Pharmaceutical Society
Sub-Saharan Africa. This is despite an increasing life expectancy and the associated increase in the elderly population worldwide. A number of previous studies in Nigeria have reported the occurrence of drug interactions among adult medical outpatients.[7,8] However, there is paucity of studies focused on a highly vulnerable group like the elderly population. Yet multiple and inappropriate drug prescribing, inadequate medication history and unauthorized self-medication practices are pervasive in Nigeria and ab initio predisposed the elderly to the risk of potentially harmful drug interactions. Hence, an exploratory study which provides an insight into perspective from such a setting will significantly add to the global knowledge in the study area. The objective of the study was to determine the frequency, types and factors associated International Journal of Pharmacy Practice 2014, ••, pp. ••–••
with potentially harmful drug interactions among ambulatory elderly patients in a developing setting like Nigeria.
Methods A 4-week cross-sectional exploratory study was conducted between 31 May and 24 June 2010 at the General Medical Outpatients Clinics of Adeoyo General Hospital, Ring Road, Ibadan. This is a major 256-bed secondary care facility located in Ibadan, a cosmopolitan city of 2.5 million residents of diverse background and ethnicity. Ethical clearance was obtained on 2 April 2010 from the Ethics Committee of Oyo State Hospital Management Board and office of the Chief Consultant in charge of the study site. All elderly patients aged 65 years and above who consented and were prescribed two or more medicines within the study period were included. Six patients declined participation and were excluded. Data extraction was completed using a specific form previously piloted on 20 patients at the study site. Data collected during pilot testing was excluded from the final results. The data extracted include age, gender, age, diagnosis, names and number of medicines prescribed including dose, frequency and duration, and potentially harmful drug interactions. The diagnoses were coded with the International Statistical Classification of Diseases and related Health problems, 10th revision (ICD-10) version for 2014. The appropriateness of drug regimen (dose and frequency) and presence of potentially harmful drug interactions were assessed against the British National Formulary (BNF) and as categorized by the BNF (hazardous and must be avoided) and Stockley’s drug interactions (clinically important), respectively. Data analysis was done with spss version 15.0 for Windows (SPSS Inc, Chicago, IL, USA). Results were presented as means (standard deviations (SDs)), percentages and risk ratios (RRs): (95% confidence interval (CI)). Chi-squared test was used to test for significant difference between dichotomous groups. An a-priori level of statistical significance of P < 0.05 was used for all comparisons.
Results The demographics of the cohort is as shown in Table 1. The most frequent diagnoses were hypertension (51.3%, 160/312) and type 2 diabetes (18.6%, 58/312). The mean number of medicines prescribed was 5.4 (SD 2.6) (min–max, 2–9), and about two-third of the patients (59.4%, 136/229) were prescribed at least six medicines. The most frequently prescribed pharmacological class was anti-hypertensive medicines (47.6%, 589/1237; Table 2). Potentially harmful drug interactions were identified in 65% (149/229) of patients, and the proportion of interactions was significantly higher among females (73.8%; 110) (P < 0.001). Of the patients prescribed © 2014 Royal Pharmaceutical Society
Drug–drug interactions in elderly patients
Demographic characteristic of the cohorts studied Age ± SD years
Gender Male Female
70 ± 6.3 68 ± 6.7
n = 229 (%)
71 (31) 158 (69)
Diagnoses (n = 312)
n (%) ICD-10-CM
Hypertension Type 2 diabetes Osteoarthritis Congestive cardiac failure Peptic ulcer disease Asthma Right hemispheric cerebrovascular disorder Spondylitis Benign prostatic hypertrophy Psychomotor disorder Colitis Bowel obstructive disorder Gouty arthritis Thyrotoxicosis
160 (51.3) 110 58 (18.6) E11 54 (17.3) M17.0 9 (2.9) 150 6 (1.9) K25 6 (1.9) J45 2 (0.9) 161.1 4 (0.6) M45 2 (0.3) N40.0 1 (0.3) 308.2 1 (0.3) 52.9 1 (0.3) 56.69 1 (0.3) M10.0 1 (0.3) E05
Number of medicines prescribed (n = 1237); (mean ± SD = 5.4 ± 2.6)
Number of cohorts = 229 (%)
2 3 4 5 6 7 8 9
36 (15.7) 30 (13.1) 19 (8.2) 8 (3.5) 40 (17.5) 52 (22.7) 26 (11.4) 18 (7.9)
Cohorts with potentially harmful DIs
n = 149 (%)
39 (26.2) 110 (73.8)
Number of medicines prescribed for cohorts with DIs
n = 149 (%)
2 3 4 5 6 7 8 9
17 (11.4) 12 (8.1) 4 (2.7) 3 (2.0) 17 (11.4) 52 (34.9) 26 (17.5) 18 (12.0)
Potentially harmful drug combinations ACEIs + amiloride + hydrochlorothiazide ACEIs + NSAIDs ACEIs + spironolactone OHAs + aspirin NSAIDs + amiloride + hydrochlorothiazide ARBs + spironolactone ARBs + NSAIDs ARBs + amiloride + hydrochlorthiazide NSAIDs + furosemide
n = 222 (%) 77 (34.7) 52 (23.4) 33 (14.9) 33 (14.9) 12 (5.4) 6 (2.7) 5 (2.3) 2 (0.9) 2 (0.9)
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; DI, drug interaction; ICD-10-CM, International Statistical Classification of Diseases and related Health problems-Clinical Modification, 10th revision; NSAID, non-steroidal anti-inflammatory drug; OHA, oral hypoglycaemic agents; SD, standard deviation.
International Journal of Pharmacy Practice 2014, ••, pp. ••–••
Kazeem B. Yusuff and Chinyere Nma Okoh
Pattern of drug prescribing among the cohorts
Medicines prescribed Anti-hypertensive ACEIs Ramipril Lisinopril Enalapril CCBs Amlodipine Nifedipine Diuretics HCT + Amiloride HCT Spironolactone Furosemide Beta-blockers Atenolol Propanolol ARBs Losartan Alpha-blockers Prazocin Analgesic/NSAIDs Paracetamol Tramadol Chymoral Co-proxamol Diclofenac Naproxen Meloxicam Piroxicam Ibuprofen Oral hypoglycaemics Metformin Glimepride Glibenclamide Pioglitazone Rosiglitazone Meglitinide Aspirin (low dose) Sedatives/hypnotics Diazepam Antispasmodics Orphenadrine Methocarbamol Tizanidine Anti-ulcers Cimetidine Antacids Omeprazole Antibiotics Metronidazole Clarithromycin Amoxicillin Anti-asthmatics Salbutamol Aminophyllin Hydrocortisone Anti-thyroid Lugol solution
n = 1237
n (%) 589 (47.6)
228 139 67 22 157 124 33 149 87 20 25 17 25 24 1 20 20 10 10
Discussion Summary of the main findings 216 (17.7)
59 39 20 10 65 11 5 4 3 159 (12.9) 67 48 19 21 3 1 97
97 (7.8) 71 (5.7)
71 49 (3.9) 27 13 9 36 (2.9) 14 13 9
Potentially harmful drug interactions were identified in about two-thirds of the patients (65%), and the risk of occurrence of drug interactions was significantly higher among patients who had at least six prescribed medicines. The proportion of drug interactions was also significantly higher among females (74%). The most frequent interacting drug combinations were ACEIs and amiloride + hydrochlorothiazide (35%), and ACEIs + NSAIDs (24%).
Strength and limitations Patient selection appeared skewed towards the female gender, but the mid-year sampling strategy, a valid procedure commonly used in epidemiological study, may mitigate probable selection bias and reflect the distribution pattern among elderly outpatients at the study site. In addition, this pattern may also suggest that elderly females were probably more adherent with clinic attendance or seek medical help at the study site in relatively greater proportion. The study provides, to the best of our knowledge, the first snapshot of the incidence of potentially harmful drug interaction episodes among a vulnerable group like the elderly in a Sub-Saharan African setting.
12 (0.9) 8 2 2
Discussion of findings 7 (0.6)
4 1 2 1 (0.08) 1
ACEI, angiotensin-converting enzyme inhibitor; ARBs, Angiotensin Receptor Blockers; CCBs, Calcium Channel Blockers; HCT, hydrochlorothiazide; NSAID, non-steroidal anti-inflammatory drug.
© 2014 Royal Pharmaceutical Society
one to five medicines (40.6%, 93/229), 38.7% (36/93) were exposed to drug interactions, while 83% (113/136) of patients who were prescribed six to nine medicines (59.4%. 136/229) were exposed to drug interactions. The relative risk of drug interactions was significantly higher in patients prescribed at least 6 medicines (RR: 7.8 (95% CI, 6.9 to 9.5) (P < 0.001). The most frequent drug combinations were angiotensin-converting enzyme inhibitors (ACEIs) and amiloride + hydrochlorothiazide (34.7%, 77/222) and ACEIs + non-steroidal anti-inflammatory drugs (NSAIDs) (23.4%, 52/222) (Table 1). The dose and regimen of all prescribed medicines were within the range stated in the reference used for assessment.
The identification of potentially harmful drug interactions in about two-thirds of the patients who were prescribed at least six medicines is consistent with similar findings reported among the elderly population from other countries.[2,3,5,12,13] Multiple co-morbidities such as hypertension, type 2 diabetes and osteoarthritis, which were the most frequent diagnoses, often attract multiple prescribing and ab initio increase the patients’ risk of exposure to potentially harmful drug interaction. A continuous quality improvement programme which International Journal of Pharmacy Practice 2014, ••, pp. ••–••
Drug–drug interactions in elderly patients
promotes safe prescribing and regularly monitors multiple prescribing is clearly warranted. The risk of exposure to potentially harmful drug interactions was significantly associated with the female gender. Perhaps, the females tend to live longer and hence appeared to constitute the larger proportion of the elderly population. Hence, the risks of multiple chronic medical conditions and multiple prescribing may be underlining the higher risks of adverse drug interactions associated with the female gender. The identification of antihypertensive medicine combinations as accounting for majority of the drug interaction episodes is similar to the findings of Bacic-Vrca et al. who reported that anti-hypertensive medicines were involved in 51% of potential drug interactions in elderly Croatians. Concurrent use of NSAIDs with ACEIs, amiloride + hydrochlorothazide and the co-administration of ACEIs/ ARBs and spironolactone or amiloride + hydrochlorothiazide is potentially harmful.[15,16] Such unsafe prescribing practice could yet be a significant contributor to the welldocumented poor blood pressure control and mortality due to malignant hypertension in Nigeria.
Conclusion The incidence of potentially harmful drug interactions that is significantly associated with multiple prescribing of antihypertensives, NSAIDs and OHAs is considerable among elderly patients in Nigeria.
References 1. ElDesoky ES. Pharmacokineticpharmacodynamic crisis in the elderly. Am J Ther 2007; 14: 488–498. 2. Chrischilles EA et al. Use of medications by persons 65 and over: data from the established populations for epidemiologic studies of the elderly. J Gerontol 1992; 47: 137–144. 3. Kaufman DW et al. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA 2002; 287: 337– 344. 4. Gill SS et al. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Arch Intern Med 2005; 165: 808–813. 5. Bjorkman IK et al. Drug-drug interactions in the elderly. Ann Pharmacother 2002; 36: 1675–1681. 6. United Nations Population Division. World Population Prospects: The 2010 © 2014 Royal Pharmaceutical Society
Declarations Conflict of interest The Author(s) declare(s) that they have no conflicts of interest to disclose.
Funding The research received no specific grant from any funding agency.
Acknowledgement We acknowledge the guidance and support of Professor Fola Tayo (Retired Professor of Clinical Pharmacy), Health Systems Management Consultants Limited, No 1, Jubilee road, Magodo G.R.A. Phase II, Lagos, Nigeria.
Authors’ contributions Kazeem B. Yusuff contributed significantly to study conception and design, data analysis and interpretation, and development and review of the manuscript. He had complete access to the study data. Chinyere Nma Okoh contributed significantly to data collection, analysis and interpretation. She also participated in reviewing the manuscript for intellectual content and had complete access to the study data. All Authors state that they had complete access to the study data that support the publication.
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