INTRODUCTION:

There have been major concerns over the safety of medicines and healthcare delivery system globally, including Bangladesh. ^[1-5] Injury caused by medicine can reach up to an extent that is comparable to four jumbo jet crashes every alternate day only in the United States. ^[6-8] Occurrence of adverse drug reactions (ADRs) remain between 4th and 6th leading cause of death in the US with an overall incidence rate of 6.7% of which 0.32% were fatal (hospitalized cases). ^[9-10] Hospitalization due to ADR and ADR- following hospitalization remain major issues in UK and USA. ^[11-13] Similar or even higher ADR rates have also been reported from India, Bangladesh, and other developing countries. ^[14-17] Definition of ADR was much debated and as such various definitions were adopted by some experts and the World Health Organization (WHO). Some reports emphasized on the noxious and unintended serious outcomes of the drug used while others reported on the harm caused by medications and leading to a subsequent negative effect on patient safety. ^[18]

PV the pharmacological science related to detection, assessment, understanding and prevention of ADRs, remains very significant in ensuring drug safety. ^[19-22] Effective post-marketing surveillance systems for ADR have been developed in UK and US since long. ^[23-24] ‘Yellow Card’ reporting system exists for reporting ADR in The UK, used by the doctors in The UK for reporting ADRs though it is not mandatory. ^[25-26]A number of the developed and developing countries have their own reporting system and PV center too. ^[21,27] Bangladesh being developing nation but has very rapidly growing pharmaceutical sector over the past few decades. Bangladesh currently exports drugs to 55 countries since the 80's. But PV system has not been developed here still and lack many essential components, especially on the awareness ADR reporting. ^{[1,20-21,28-29]} Bangladesh like other developing countries under-reporting of adverse drug reactions remains one of the major factors that contribute to PV program letdown.^[29-32]Therefore it is imperative, that the PV system and the ADR monitoring system be strengthened more in Bangladesh since major electronic databases that we searched failed to produce such evidence. No ongoing researches were found on ADR or PV systems in Bangladesh.

MATRIALS AND METHODS:

This updated review was designed based on synthesis of published materials extract relevant information and analyze related data) on ADR and PV in Bangladesh. Topic/ subject searches: definition of ADR and PV, incidences and factors involving ADRs globally and in Bangladesh, ADR monitoring and PV systems in Bangladesh and other countries. A computerized literature search was performed utilizing major search engines like: Google, Google Scholar, PubMed and Research Gate using 4 keywords: adverse drug reactions, side effects, drug reactions and pharmacovigilance in Bangladesh. The search was carried out for the period of 1971 through 2014 (since inception of Bangladesh). All published relevant original papers or review articles, case reports, letter to the editor and reports on ADR and PV in any journals and newspaper were included in the search.

RESULTS, DISCUSSION AND CONCLUSION:

Google, Google Scholar, and Pub Med were used to search the relevant documents and revealed only 19 publications relating ADRs and PV in Bangladesh (from 1971 through 2014) in various sources and journals. Among these 19, one was reported in the daily newspaper and other two reports one from (USAID) and Systems for Improvised Access to Pharmaceuticals and Services Program (SIAPS) project and the other on Uppsala Monitoring Centre update report, of the remaining, 7 were original research papers (37%), 6 were review articles (32%), and the rest (31%) comprised case reports, letter to the editor and others. Methodologically 5 were prospectively designed cross-sectional studies, 4 were descriptive and 1was observational study and remaining were of other categories. Most of the papers/reports that were published was after 2010, showed due concerns about ADR and PV in Bangladesh.

Of the total 19 publications only 2 were case reports on SJS, first one in 2005 following Levofloxacin intake by a 15-year-old male with a fatal outcome, and the other fatal case in 2008 was a 40 years old female taking azithromycin.^[33-34]Of 7 original studies conducted over the period of 2004-2014, revealed skin was the most affected system with ADR.^[16-17,
35] Highest number ADRs were reported due to antibiotics (AB) intake (43%-53%) followed by NSAIDs (27%-33%). ^[16-17] Though fatality rate was quite low as most of the studies reported except one having very high fatality rates (25%) most of which were SJS and TEN, SJS being in 55% alone. ^[35] Two studies were only had cutaneous manifestations of ADRs pertaining to use of different drugs. ^[36-37] It was reported that 24% SJS cases due to use of some offending drugs: sulphonamides (42%), indigenous drugs (25%), anticonvulsants (25%) and quinolones (8%). ^[36]More recently, another study described 45% cutaneous ADRs were the fixed drug eruptions type, 20% urticarial and 15% SJS. ^[37]Highest number of cases was due to sulfur-containing drugs (40%) followed by NSAIDs (30%), quinolones (30%) and Metronidazole (15%). ^[37]

Males were found to be affected more often than females in two of the studies. ^{[35, 37]} But another study reported ^[38]females to be more affected by ADRs due to anti-tubercular therapy (DOTS). Considering the review articles, it clearly demonstrates a marked deficiency in ADR monitoring systems in Bangladesh including a gross lack of the awareness in reporting ADRs.^{[20-21, 39]} However most authors describe the current situation of PV in Bangladesh agreeing to accept the inadequacy of scientific and administrative initiatives both by Government and non-government organizations towards bringing a positive change in PV situation in the country.^[20-21] In a newspaper report mentioned ^[29]that only 50 ADRs reported in 20 years (1994-2013) as reported to the Directorate General of Drug Administration, Government of Bangladesh and among those reports only 20% of those were complete. The Same article concluded that despite having quality pharmaceutical industries in Bangladesh, but the country is still facing barriers in drug export to developed countries only because not attaching the proper ADR/PV reports. ^[29] Another study report also mentioned similar issues. ^[22]This study also revealed many gaps in PV system and ADR monitoring in Bangladesh. ^[21] Despite having Government agencies and other stakeholders working on PV very little development was noted.^[40]The good news was found in UPPSALA monitoring center (The WHO) website where they declared the joining of Bangladesh in the WHO program by submitting first reports of ADRs to VigiBase® through VigiFlow® in December 2014. Bangladesh applied for this membership in 2013. ^[41]

Though we have employed a literature review search to yield all relevant data on ADRs in Bangladesh, however, some of the ADRs cases might be dropped out due to i) some cross references reporting only descriptive findings rather than numbers of ADRs, ii) our search might have certain limitations of not being able to find out every related article as usually done by a systematic review, and, iii) some of the ADRs which might have really occurred in the country but not reported anywhere or not been data based/incorporated in the web, as of today. However, it is noteworthy that not a single case of ADRs was found to be recorded in the website of DGDA, Bangladesh though a literature review in Bangladesh revealed 19 publications with varying numbers of ADR cases. But the Adverse Drug Reaction Advisory Committee (ADRAC) reported that only 13 ADR cases were reported to them officially until late 2010. ^[39]

Another 1990’s tragic issue essentially demands to be noted here pertaining to child fatality due to adulteration of paracetamol suspensions using diethylene glycol a potentially lethal solvent claiming 339 children’s life in Bangladesh. Further similar tragic child deaths were recorded owing to same reason tolling 28 immature lives earlier in this decade. ^[20] These facts evidence that much other similar on/fatal ADRs might take place unnoticed. Since this review evidences certain gaps and lacks in reporting ADRs or not recording with the ADRAC thus remain unpublished. This might reflect as one reason why we found only 19 relevant papers on ADRs. However, this updated review has been capable of unveiling the fact that ADRs remain a major public health hazard focusing important clinical-epidemiological and socio-legal consequences. To combat such atrocities of the pharmaceutical product in Bangladesh and also many other developing countries healthcare professionals including medical doctors’ professional skill, attitude, and commitment need to improve comprehensively. ^[42-45] As it is believed, once the bad habit is developed it very difficult to modify. There has been the urgent need of careful designing all health professional curriculums to rectify the issue from early student life of all related health professional course. ^[42-45]

· It is imperative that Bangladesh possess a strong pharmacovigilance system mandatorily through periodic PV inspections in collaboration with pharmacoepidemiologists and related IT sector.

· The country essentially requires a clinical trial and post-marketing surveillance database to record serious adverse effects (SAEs) and ADRs officially towards conforming signal detection.

· It is crucial that medical education should properly focus on adequate training for the medical students/interns/nurses and the pharmacists/medical assistants on PV covering both the vast majority rural health care centers and urban hospitals/ medical colleges.

· Finally, both the Govt. and NGO level healthcare service delivery organizations must have proper access to required database facilities so as to report, record and disseminate all relevant data pertaining to ADRs.

ACKNOWLEDGEMENT:

Authors possess no conflict of interest. This work obtained no funding

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Received on 29.06.2015 Modified on 20.07.2015

Research J. Pharm. and Tech. 8(11): Nov., 2015; Page 1598-1602

DOI: 10.5958/0974-360X.2015.00287.5