Drugs - Real World Outcomes (2020) 7:109–117 https://doi.org/10.1007/s40801-020-00180-0 ORIGINAL RESEARCH ARTICLE Adverse Drug Reactions in Selected Wards of the Yangon General Hospital and Yangon Specialty Hospital During the First Quarter of 2019: An Active Pharmacovigilance Study in Myanmar Lwin Moe May1 · Albert Figueras2 · Ye Htut Linn1 · Maw Than Htike1 · Mi Kun Kaw San1 · Nyein Chan Pyae1 · Khin Hnin Aye1 · Ei Ei Aung1 · Nilar Win1 · Wine Thawda1 · Zin Wah Linn1 · Yin Min Kyaw1 · Ya Min1 · Zaw Win Than1 · Moe Pan Khaing1 · Thurein Win1 · Pyi Phyo Htet1 · Nu Nu Aye1 Published online: 10 February 2020 © The Author(s) 2020 Abstract Background Previous studies in Europe and the USA have reported a high prevalence of adverse drug reactions (ADRs), but data on local ADRs in Myanmar are sparse. Objective Our objective was to study ADRs in patients admitted to selected wards of Yangon General Hospital (YGH) and Yangon Specialty Hospital (YSH), Myanmar. Methods This was a prospective observational study in three hospital wards during the first quarter of 2019. Suspected ADRs were carefully investigated in a face-to-face interview with each patient and via review of clinical records. Patients transferred to other wards or discharged were followed-up by the researchers until day 28 after admission. ADRs were divided into those that (1) led to the admission and (2) occurred during the hospital stay or after discharge (up to day 28 after admission). Results A total of 65 ADRs were identified, with 47 (29.4%) of 160 patients experiencing at least one ADR. Among these, 16 (24.6%) had led to hospital admission and 49 (75.4%) occurred in 31 patients during their hospital stay. Of 160 patients, 21 had taken at least one herbal remedy and six of these developed an ADR. Five ADR–drug associations (hypokalaemia with methylprednisolone, increased transaminase levels with standard antituberculosis drugs, upper gastrointestinal bleed- ing with nonsteroidal anti-inflammatory drugs, constipation with tramadol, and increased transaminase levels with herbal remedies) represented 18 (27.7%) of the 65 ADRs in this study. According to the Schumock and Thornton preventability scale, more than half of these ADRs (35 [53.9%]) were preventable. Conclusion The present study highlights the existence of ADRs among patients attending these hospitals. The implementa- tion of active pharmacovigilance in hospitals could be a helpful first step to improving the awareness of unwanted effects of medicines and patient safety, as well as a way to strengthen the national pharmacovigilance system in countries such as Myanmar. 1 Introduction Multiple studies have emphasised the high prevalence and potential seriousness of adverse drug reactions (ADRs), Electronic supplementary material The online version of this especially among aged patients and those receiving poly- article (https​://doi.org/10.1007/s4080​1-020-00180​-0) contains pharmacy. ADRs are especially relevant in hospitalised supplementary material, which is available to authorized users. patients, with one meta-analysis reporting an estimated * Lwin Moe May 6.7% of hospitalised patients in the USA developing a seri- lwinmoemay@gmail.com ous unwanted effect and a fatality rate of 0.32% [1]. In the USA, an estimated 2,216,000 serious ADRs occurred in 1 Department of Pharmacology, University of Medicine hospitalised patients and caused over 106,000 deaths in 1, Yangon, No. 245, Myoma‑Kyaung Street, Lanmadaw Township, Yangon 11131, Myanmar 1994 [1]. According to a European Commission report, 2 3–10% of hospital admissions between 2012 and 2014 were Fundació Institut Català de Farmacologia, Department of Pharmacology, Therapeutics and Toxicology, Universitat caused by ADRs, totalling about 2.5–8.4 million annually, Autònoma de Barcelona, Barcelona, Spain Vol.:(0123456789) 110 L. M. May et al. found that 115 of 128 patients (88.3%) experienced ADRs, Key Points and a total of 349 adverse effects were reported in 6 months [8]. This initial study to determine the prevalence of adverse To initiate a drug safety strategy for Myanmar, the first drug reactions (ADRs) in two hospitals in Myanmar step is to provide evidence that ADRs are frequent in the found that almost one-third of the participating hospital- country and to raise awareness among health profession- ised patients presented with an unwanted effect. als and drug authorities about the frequent complications One-quarter of the observed ADRs were associated with of medical treatment. Therefore, the present study aimed to only three ADR–medicine combinations. Addition- describe ADRs leading to hospital admission or occurring ally, more than one-half of the identified ADRs in the in patients admitted to selected wards of Yangon General study sample were considered preventable effects. Thus, Hospital (YGH) and Yangon Specialty Hospital (YSH). increased awareness of pharmacovigilance could avoid many such cases and increase patient safety. 2 Methods Six patients presented an ADR attributed to herbal rem- edies. Pharmacovigilance in settings with a high use of A prospective observational study was designed and con- such traditional remedies should include clear guidance ducted in one medical and one surgical ward in YGH and on their potential toxicity. one rheumatology ward in YSH between 1st January and 31st March 2019. YGH is a 1500-bed hospital and one of the biggest teaching hospitals in Myanmar, and YSH and 2.1–6.5% of hospitalised patients experienced an ADR, is a 500-bed hospital; both hospitals admit adult patients corresponding to 1.8–5.5 million annually [2]. (aged > 12 years according to the country’s clinical clas- On the other hand, most emergency hospitalisations for sification). All patients admitted to the wards under study recognised ADRs in older adults resulted from a few com- in YGH and YSH during the study period were identified monly used medications [3], suggesting that understanding during the first 24 h after admission to be followed-up until of pharmacovigilance, awareness of potential ADRs, and hospital discharge or day 28 after admission. identification of patients at risk could help prevent many Exclusion criteria were any patients who took an over- of these situations, which prompt emergency admissions dose (deliberately or not), were critically ill (unstable vital or complicate the clinical course of already hospitalised signs, tracheotomy, or mechanical ventilation), were unable patients. to understand and answer questions (i.e., could not speak In 1968, the World Health Organization (WHO) estab- Myanmar), or refused to participate or withdrew from the lished its Programme for International Drug Monitoring in study. response to the thalidomide disaster [4]; 136 countries are Researchers were trained in how to identify ADRs, now full members and 29 are associate members of this pro- complete the reporting form (see the online Appendix), gramme. In 2018, Myanmar became an associate member and review patients’ treatment charts and laboratory test [5]. Thus, the pharmacovigilance programme in Myanmar results, and were given resources describing common ADRs. is at a very preliminary stage, although Myanmar’s ADR Researchers were also trained in how to use the assessment reporting system was established in 2002 and the Myanmar tools adopted for the present study. A workshop was con- Food and Drug Administration (FDA) has distributed an ducted to ensure researchers used diagnostic criteria and ADR reporting form to central, state, and regional hospi- applied the algorithms consistently. tals; health offices; and drug advisory committee members. Potential study participants were given a full explanation An implementation research report by postgraduate stu- of objectives, procedures, benefits, and possible risks of the dents and specialist clinicians from eight teaching hospitals study. Patients who were willing to participate in the study under University of Medicine 1, Yangon, found that 44.9% provided written informed consent; one patient refused to of respondents had poor awareness of the ADR reporting participate (Fig. 1). system and that several barriers to ADR reporting existed All included patients attended a face-to-face interview [6]. Another study conducted in eight teaching hospitals in during which they were asked about suspected ADRs, and Yangon showed that most assistant surgeons were not aware researchers reviewed patients’ clinical charts and laboratory of the ADR reporting system (79.3%), the ADR reporting test results. Researchers (14 clinical pharmacologists from form (89.7%), or the department to which ADRs should be the University of Medicine 1, Yangon) visited the study reported (83.3%) [7]. ward daily to identify any suspected ADRs in the recruited A prospective observational study conducted for antimy- patients during a 4-week period (28 days). All clinical cobacterial drugs in a tuberculosis campaign in Myanmar staff were officially informed that a study on ADRs was Hospital Pharmacovigilance in Myanmar: A Pilot Study 111 taking place. If patients were transferred to another ward, the medical ward, 59 (36.9%) to the surgical ward, and 24 the researchers followed them and continued observations (15.0%) to the rheumatology ward. for ADRs. If the patient was discharged from hospital, the A total of 65 ADRs were identified in 47 patients; 29.4% researcher phoned them daily until the end of the follow-up of patients admitted to these selected wards presented at least period (day 28 after admission) to check for the occurrence one suspected ADR. In 16 of these patients (one ADR each), of any ADR. the adverse effect was what led to admission; the remaining An ADR was defined according to the classical WHO 49 ADRs appeared in 31 patients during their hospital stay definition (“Any response to a drug which is noxious, unin- (48 ADRs) or after discharge and before day 28 (one ADR). tended and which occurs at doses normally used in man Table 1 shows the characteristics of all the recruited patients for prophylaxis, diagnosis, or therapy of disease, or for the and the subsample of patients presenting one or more ADRs. modification of physiological function”) [4]. All identified The mean age of recruited patients was 46.7 ± 17.2 years; suspected ADRs were discussed by the study team of cli- patients who presented an ADR were younger than those nicians and pharmacologists weekly. The British National who did not. The initial sample of patients included 93 Formulary and specific bibliographic websites were used women (58.1%) and 67 men (41.9%), and a significantly to assess previous knowledge about the identified ADRs. higher proportion of women presented an ADR. Patients Each suspected ADR was classified according to the WHO- presenting an ADR took significantly more medications Adverse Reactions Terminology (ART) dictionary. Causality (12.15 ± 6.12) than those without ADRs (7.99 ± 4.15). No was assessed using the Naranjo algorithm [9]. The severity differences were seen in incidence of comorbidities and of the ADR was also categorised according to the Hartwig liver disease between patients with and without ADRs, but severity scale [10], and preventability was assessed using a higher proportion of those presenting a suspected ADR the Schumock and Thornton preventability scale [11]. Poly- had renal disease. pharmacy was defined as more than five drugs being taken The distribution of patients with ADRs in the differ- concomitantly by a single patient, and ‘increased transami- ent wards was as follows: 19 in the medical unit (24.7% of nase’ was used when the transaminase level was at least 1.5 patients admitted to that ward), 17 in the rheumatology unit times higher than the upper normal reference value given by (70.8% of the patients admitted to that ward), and 11 in the the hospital laboratory. surgical unit (18.6% of those admitted in that ward). The multivariate analysis showed statistically significant differ- 2.1 Data Analysis ences in the proportion of ADRs identified in the different wards, with the highest proportion in rheumatology (OR Continuous variables were presented as means ± standard 0.214 [95% CI 0.072–0.632]; p < 0.0001) (see Table 2). deviations, and categorical variables were presented as num- Up to 61 ADRs could be attributed to 28 different medi- ber and percentage. The variables were compared between cines and six herbal remedies, whereas the causal medicine patients with ADRs and those without ADRs using descrip- could not be clearly identified in four ADRs because of tive statistical tests, the independent samples t test for con- the concomitant use of different medicines (Table 3). The tinuous variables, and the Chi-squared test for categorical therapeutic groups most associated with these ADRs were variables. Binary logistic regression (univariate and multi- corticosteroids (16 [29.1%]), nonsteroidal anti-inflammatory variate analysis using a forward conditional method) was drugs (NSAIDs; 8 [14.4%]); opioids (7 [12.7%]); and anti- performed to examine possible associations between ADR bacterials (6 [10.8%]). Table 3 summarizes the six herbal occurrence and different variables. Possible confounders remedies suspected to have caused six of the ADRs. were adjusted for (age, sex, type of wards, comorbidities, More than one-third of the suspected ADRs (23 [35.4%]) liver and renal diseases), and the results were presented as involved the gastrointestinal system, 14 (21.5%) were blood odds ratios (ORs) with 95% confidence intervals (CIs). The and electrolyte disturbances, ten (15.4%) were liver disor- reported p values are two-tailed, and an α level of 0.05 was ders, and eight (12.3%) were classified as ‘general ADRs’ used to assess statistical significance. SPSS version 20 was according to the WHO-ART dictionary. The most frequent used for data entry and analysis. individual ADRs identified were increased transaminase lev- els in ten patients (four taking standard antimycobacterial drugs, three taking herbal remedies, two taking a combi- 3 Results nation of drugs, and one taking ranitidine). Nine patients presented nausea/vomiting (13.8%) associated with diverse During the study period, 160 patients admitted to the medicines, seven patients presented hypokalaemia (five of selected wards of YGH and YSH gave informed consent to which were after receiving methylprednisolone), five were be monitored for potential adverse effects up to 28 days after diagnosed with upper gastrointestinal bleeding, and two had admission. Almost one-half (77 [48.1%]) were admitted to perforated peptic ulcers (Table 4). 112 L. M. May et al. Fig. 1  Flowchart describing the patient selection and follow-up process (see Methods). ADR adverse drug reaction, YGH Yangon General Hospi- tal, YSH Yangon Specialty Hospital The most frequent ADRs-suspected drug combina- increased liver enzymes levels receiving antimycobacte- tions in the present study were low potassium levels in five rial drugs, three patients with upper gastrointestinal bleed- patients receiving methylprednisolone, four patients with ing receiving an NSAID or low-dose aspirin, three patients Hospital Pharmacovigilance in Myanmar: A Pilot Study 113 Table 1  Characteristics of patients admitted to the medical, surgical, and rheumatology units of the included hospitals presenting at least one ADR (n = 47) and those not presenting ADRs (n = 113) Variable ADRs t test p value (inde- pendent sample Present Absent Total t test) Age (years) 40.8 ± 17.6 49.2 ± 16.5 46.7 ± 17.2 − 2.862 0.005* No. of medications 12.15 ± 6.12 7.99 ± 4.15 9.21 ± 5.16 4.982 < 0.001* Variable ADRs OR (95% CI) p (Chi-squared) Present Absent Total Age (years) < 60 37 (32.5) 77 (67.5) 114 (100.0) 1.730 (0.775–3.861) 0.178 ≥ 60 10 (21.7) 36 (78.3) 46 (100.0) Sex Male 10 (14.9) 57 (85.1) 67 (100.0) 0.266 (0.121–0.585) < 0.001** Female 37 (39.8) 56 (60.2) 93 (100.0) Ward Rheumatology 17 (70.8) 7 (29.2) 24 (100.0) 0.135 (0.049–0.375) < 0.001** Surgical 11 (18.6) 48 (81.4) 59 (100.0) 1.429 (0.620–3.296) 0.402 Medical 19 (24.7) 58 (73.5) 77 (100.0) Comorbidity Present 20 (27.8) 52 (72.2) 72 (100.0) 0.869 (0.437–1.726) 0.688 Absent 27 (30.7) 61 (69.3) 88 (100.0) Liver disease Present 2 (14.3) 12 (85.7) 14 (100.0) 0.374 (0.080–1.741) 0.194 Absent 45 (30.8) 101 (69.2) 146 (100.0) Renal disease Present 9 (56.3) 7 (43.8) 16 (100.0) 3.586 (1.249–10.300) 0.013** Absent 38 (26.4) 106 (73.6) 144 (100.0) Data are presented as mean ± standard deviation or N (%) unless otherwise indicated ADR adverse drug reaction, CI confidence interval, OR odds ratio, SD standard deviation *Independent sample t test, p < 0.001 **Binary logistic regression, p < 0.05 Table 2  Adjusted odds ratio for Variable ADR Adjusted OR (95% CI) p value a multiple logistic regression model taking into account the Present Absent presence or absence of adverse drug reactions, the wards where Wards patients had been admitted, and Rheumatology 17 (70.8) 7 (29.2) 0.214 (0.072–0.632) 0.005 the total number of medications Surgical 11 (18.6) 48 (81.4) 1.111 (0.463–2.664) 0.814 received Medical 19 (24.7) 58 (73.5) Medications (n) 12.15 ± 6.12 7.99 ± 4.15 0.888 (0.817–0.965) 0.005 The model correctly classifies 76.9% of cases. The Chi-squared value associated with the Hosmer–Leme- show (Chi-squared = 7.386, df = 8, p = 0.496) indicates a good overall model fit. Data are presented as mean ± standard deviation or N (%) unless otherwise indicated ADR adverse drug reaction, CI confidence interval, OR odds ratio with constipation receiving tramadol, and three patients with Causality assessment of the 65 identified ADRs according increased transaminase levels receiving herbal remedies. to the Naranjo algorithm showed five ‘definite’ (7.7%), 27 These five pairs of ADR–suspected drugs represented more ‘probable’ (41.5%), and 33 (50.8%) ‘possible’ associations. than one-quarter of the 65 ADRs identified in this study. According to the Hartwig severity scale, 45 ADRs required 114 L. M. May et al. Table 3  Classification of the Medicines, therapeutic group Active ingredient (n) ADRs suspected medicines involved in the 65 ADRs identified in the Corticosteroids Methylprednisolone (12) 16 (29.1) different wards of the included Prednisolone (4) hospitals NSAIDs Aspirin (80 mg) (2) 8 (14.4) Diclofenac (2) Other NSAIDs (4) Opioids Tramadol (4) 7 (12.7) Codeine (1) Nalbuphine (2) Antibacterial agents Levofloxacin (3) 6 (10.8) Other (3) Antimycobacterial drugs HRZE (4) 4 (7.3) Drugs used in rheumatology Cyclophosphamide (3) 4 (7.3) Hydroxychloroquine (1) Cardiovascular drugs ACEIs and CCBs (2) 3 (5.5) Isosorbide mononitrate (1) Blood disorders Warfarin (2) 3 (5.5) Tranexamic acid (1) Othera 4 (7.3) Total patients with ADRs caused by drugs 55 (100) ADRs in patients receiving more than one d­ rugb 4 ADRs in patients taking herbal remedies Pan Wut Hmone (increased transaminase) 1 Myat Thu Kha (increased transaminase) 1 Tha Hmar Ni (increased transaminase) 1 Chan Saint (haematemesis and melena) 1 Kyar Pyan (haematemesis and melena) 1 Unknown (congestive heart failure) 1 Total ADRs in patients taking herbal remedies 6 ADRs are presented as n (%). 55 ADRs were attributed to single drugs, four ADRs were diagnosed in patients receiving more than one medicine and the causal medicine could not be clearly identified; six ADRs were attributed to herbal remedies ACEIs angiotensin-converting enzyme inhibitors, ADR adverse drug reaction, CCBs calcium channel blockers, HRZE isoniazid + rifampicin + pyrazinamide + ethambutol, NSAID nonsteroidal anti-inflamma- tory drug a One patient each: insulin, mesna, ranitidine, potassium chloride b The four ADRs diagnosed in patients treated with more than one medicine, and the causal one could not be identified: (1) a combination of frusemide and methylprednisolone was associated with hypokalae- mia; (2) levofloxacin, perindopril, and statin associated with increased transaminase levels; (3) sulbactam, cefoperazone, metronidazole, and azithromycin associated with gastrointestinal disturbance; and (4) val- proate and leflunomide associated with increased transaminase levels some action (69.2%) and 20 required no change in treatment A few of these preventable ADRs were potentially severe: at (30.8%). Among the 45 ADRs requiring some action, 20 least five cases of hypokalaemia associated with methylpred- received another treatment (44.4%); 16 (35.5%) led to hos- nisolone, three cases of gastrointestinal bleeding associated pital admission; six (13.3%) required treatment with the sus- with NSAIDs, three cases of increased transaminase levels, pected drug to be held, discontinued, or otherwise changed; and two of gastrointestinal bleeding after taking a traditional and three (6.7%) prolonged the hospital stay. medicine. Analysis with the Schumock preventability scale identi- As noted, admission of 16 of these 160 patients was fied the ADRs that could have been avoided. More than one- prompted by an ADR (10% of the study sample): six cases half of the ADRs either definitely or probably could have of increased liver enzymes (four caused by HRZE [iso- been prevented (25 [38.5%] and 10 [15.4%], respectively). niazid + rifampicin + pyrazinamide + ethambutol] and two Hospital Pharmacovigilance in Myanmar: A Pilot Study 115 Table 4  Association between Organ/system N (%) Suspected ADRs n Associated drugs (n) ADR and suspected medicine in the 65 ADRs observed in this Digestive 23 (35.4) Nausea/vomiting 9 Levofloxacin (2) study Cyclophosphamide (2) Codeine (1) Ketorolac (1) Nalbuphine (1) Tramadol (1) Combined ­medicinesa (1) Constipation 4 Tramadol (3) Diclofenac (1) Upper gastrointestinal bleeding 5 NSAID (2) Herbal remedy (2) ASA (80 mg) (1) Peptic ulcer perforation 2 NSAIDs (2) Gastritis 1 Prednisolone (1) Loss of appetite 1 Cyclophosphamide (1) Loose stools 1 Piperacillin (1) Blood 14 (21.5) Hypokalaemia 7 Methylprednisolone (5) Insulin (1) Combined ­medicinesa (1) Increased INR 2 Warfarin (2) Bruise 2 Aspirin (1) Methylprednisolone (1) Hyperglycaemia 1 Methylprednisolone (1) Hyperkalaemia 1 Potassium chloride (1) Leucocytosis 1 Prednisolone (1) Liver 10 (15.4) Increased transaminase level 10 HRZE (4) Herbal remedy (3) Combined ­medicinesa (2) Ranitidine (1) General 8 (12.3) Chill 1 Mesna (1) Dizziness 3 Nalbuphine (1) Cilnidipine (1) Metronidazole (1) Headache 2 Cefepime (1) Isosorbide mononitrate (1) Proximal myopathy 1 Prednisolone (1) Sore throat 1 Methylprednisolone (1) Respiratory 4 (6.2) Dry cough 1 Enalapril (1) Chest infection 3 Prednisolone (1) Methylprednisolone (2) Skin 3 (4.6) Itchiness (2) 2 Levofloxacin (1) Tranexamic acid (1) Poor wound healing (1) 1 Methylprednisolone (1) Eyes 2 (3.1) Blurred vision 1 Hydroxychloroquine (1) Glaucoma 1 Steroid (1) Cardiovascular 1 (1.5) Congestive heart failure 1 Herbal remedy (1) Each patient can present more than one ADR; one medicine can produce more than one ADR ADR adverse drug reaction, ASA acetylsalicylic acid, HRZE isoniazid, rifampicin, pyrazinamide, ethambu- tol, INR international normalised ratio, NSAIDs nonsteroidal anti-inflammatory drugs a Combined medicines: (1) a combination of frusemide and methylprednisolone was associated with hypokalaemia; (2) levofloxacin, perindopril, and statin was associated with increased transaminase levels; (3) sulbactam, cefoperazone, metronidazole, and azithromycin were associated with gastrointestinal distur- bances, and (4) valproate and leflunomide were associated with increased transaminase levels 116 L. M. May et al. attributed to herbal remedies), five gastrointestinal bleeding added to explore the prevalence of suspected ADRs in such (two attributed to NSAIDs, two to herbal remedies, and one a ward. to low-dose aspirin), two gastric ulcer perforations associ- Our findings indicated that 29.4% of patients were either ated with NSAIDs, one heart failure attributed to a tradi- admitted because of an ADR or developed an ADR dur- tional medicine, one hyperglycaemia due to methylpredni- ing hospitalisation. The prevalence of ADRs in the present solone, and one prednisolone-induced chest infection. study was high, but it should be remembered that researchers performed an active search for ADRs and that the reporting system is not well practised in Myanmar. Therefore, data on 4 Discussion the incidence of ADRs are also scant. A study conducted in eight tertiary care teaching hospitals in Yangon showed The present active pharmacovigilance study conducted in that 48.1% of the postgraduate students (who were training two hospitals in Yangon, Myanmar, showed that, in the to become specialist clinicians) had never heard of ADRs, selected wards, 29.4% of the admitted patients were diag- 91.4% had not seen the Myanmar ADR reporting form, and nosed as having at least one ADR, either prompting the 82.8% did not know which department an ADR should be admission (16 patients [10%]) or complicating their hos- reported to [6]. Therefore, the main barriers to ADR report- pitalisation (31 patients [19%]). A systematic review and ing seem to be related to the awareness of ADRs, as has been meta-analysis published in 2017 showed a wide range of described in other countries [15]. ADR prevalence in inpatients in Western countries, ranging Three ADR-suspect drug pairs accounted for almost one- from 3.9 to 57.9% in 12 studies [12]. A 3-month study con- quarter of the identified ADRs, found in one-third of the ducted in Singapore General Hospital, a 1600-bed tertiary patients included in the study sample. These cases and a teaching hospital, reported the prevalence of all ADRs at few other identified ADRs were well-known and, accord- admission to be 12.4% (95% CI 10.5–14.6) and of ADRs ing to the Schumock and Thornton scale [11], potentially causing admission to be 8.1% (95% CI 6.5–10.0); the most avoidable. These findings agree with those of other larger common ADRs were related to the gastrointestinal system, studies conducted in other countries, which also described and cardiovascular drugs were the most frequently involved a concentration of ADRs in a few well-known unwanted drugs [13]. effects produced by some common medicines [3]. Prevention Two-thirds of the ADRs in the current study required in pharmacovigilance is very important to increase patient some action from health professionals to be stopped or safety and the quality of healthcare. cured, thus suggesting that awareness of the adverse effects of drugs and potentiating of pharmacovigilance in hospitals is important to improve not only quality of care but also 5 Conclusions patient safety. Last, but not least, according to the Schumock preventability scale, more than one-half of these ADRs The present study was conducted in two tertiary care uni- could have been avoided, another reason to consider these versity hospitals of Yangon during the first quarter of 2019. results as a starting point to raise awareness of the important Therefore, the figures obtained cannot be extrapolated to role of hospital pharmacovigilance, one of the cornerstones other hospitals or even to the rest of the country. Notwith- of a national pharmacovigilance programme. standing this limitation, the suspected ADRs actually hap- ADRs can be undiagnosed unless a health professional pened. Therefore, the study achieved the main objective of specifically asks about them. If not identified as an ADR, providing evidence to participating hospitals that ADRs do these symptoms easily become candidates for cascade treat- occur, a first step to increasing awareness of drug safety and ments, which lead to polypharmacy, potential drug–drug strengthening pharmacovigilance in Myanmar. interactions, and additional ADRs [14]. Since ADRs some- times hide behind common presenting symptoms and occa- Acknowledgements The authors thank Professor Dr. Zaw Than Htun, Professor Dr. Zaw Wai Soe, Dr. Theingyi Zin, Dr. Valerio Reggi, and sionally present bizarrely, a good anamnesis will help iden- Dr. Susann Roth. We also thank Dr. Lei Htay and our colleagues at tify these hidden ADRs. In both situations, knowledge of the Department of Pharmacology, University of Medicine 1, Yangon, pharmacovigilance, the pharmacovigilance system, and how Department of Rheumatology, 500-bed Yangon Specialty Hospital, to report suspected ADRs is important [15]. Department of Medicine and Department of Surgery, Yangon General Hospital, for their kind help, advice, and support. The present study showed that one surgical ward, one medical ward, and one speciality ward are suitable places to study the prevalence of ADRs because almost all hospitals Compliance with Ethical Standards in our country contain surgical and medical wards, so both Conflict of interest Lwin Moe May, Albert Figueras, Ye Htut Linn, wards can represent most hospitals. One speciality ward was Maw Than Htike, Mi Kun Kaw San, Nyein Chan Pyae, Khin Hnin Aye, Ei Ei Aung, Nilar Win, Wine Thawda, Zin Wah Linn, Yin Min Kyaw, Hospital Pharmacovigilance in Myanmar: A Pilot Study 117 Ya Min, Zaw Win Than, Moe Pan Khaing, Thurein Win, Pyi Phyo 4. WHO. The Importance of Pharmacovigilance. http://apps.who. Htet, Nu Nu Aye have no conflicts of interest that are directly relevant int/medic​inedo​cs/pdf/s4893​e/s4893​e.pdf?ua=1. Accessed 23 Oct to the content of this article. 2019. 5. Uppsala Monitoring Center. Members of WHO Programme for Funding This research was funded by the Department of Medical International Drug Monitoring. Uppsala Reports 2019;80:4–5. Research External Grant 2019 (ID: 12/2019) of the Ministry of Health https​://view.publi​t as.com/uppsa​la-monit​oring​-centr​e/uppsa​la- and Sports, Republic of the Union of Myanmar. Training and consul- repor​ts-80/page/1. Accessed 23 Oct 2019. tancy activities by Albert Figueras were partly supported by the Asian 6. Aye-Pwint-Phyu, Waing-Thawdar, Ye-Htut-Linn Kay-Khine-Thu, Development Bank (TA-8763 REG: Drug Safety Expert)—(replace- Thida-Tun, Lwin-Moe-May. Myat Myat Soe and Nu-Nu-Aye ment of regulatory specialist/contract no. 120958-S85781). (2018). Barriers to Implementing Adverse Drug Reaction Report- ing System. Technical Report of Department of Pharmacology, Ethical Approval The Ethics Review Committee, Department of University of Medicine 1, Yangon (Thesis), 2018. Medical Research, Ministry of Health and Sports, Republic of the 7. Thura-Kyaw. Knowledge, attitude and practice of adverse drug Union of Myanmar, approved this study (approval number: Eth- reaction reporting system among the assistant surgeons in teaching ics/DMR/2018/131). All procedures performed in this study were hospitals. M.Med.Sc (Pharmacology), University of Medicine 2, in accordance with the ethical standards of the institutional and/or Yangon (Thesis), 2017. national research committee and with the 1964 Helsinki declaration and 8. Nang-Khan-Li. Active monitoring of adverse drug reactions on its later amendments or comparable ethical standards. Written informed fixed dose combinations of anti-tuberculous drugs. M.Med.Sc consent was obtained from all individual participants included in the (Pharmacology), University of Medicine 2, Yangon (Thesis), study. 2017. 9. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ. A method for estimating Open Access This article is licensed under a Creative Commons Attri- the probability of adverse drug reactions. Clin Pharmacol Ther. bution-NonCommercial 4.0 International License, which permits any 1981;30:239–45. non-commercial use, sharing, adaptation, distribution and reproduction 10. 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