Discussion
The incidence of ADRs reported in this longitudinal study is high and the majority were the causes of admission in Internal Medicine wards. This finding is similar to that of Pirmohamed et al in the UK in which prevalence of 6.5% of ADRs was reported, and more than two-thirds of ADRs led to hospital admission [21] but contracts, findings of Bouvy et al. 10.1 %, in a systematic review in Europe [22]. The differences in our findings possibly reflect different settings. There are no similar prospective studies from Nigeria with which to compare our findings. A retrospective study in Lagos reported ADRs incidence slightly higher than that of this study. However, the finding was similar to those reported from other developing countries [2]. Most of the ADRs are avoidable and preventable. This is similar to most studies in developed and developing countries [2,22,23]. ADRs at admission represents almost two-thirds of the reported ADRs, and mostly due to self-medication, drug abuse and /or misuse. This emphasized a need for the inclusion of community education/actions on any planned intervention to reduce the incidence of ADRs.
The system/organ mostly affected were GIT and CNS. Studies have reported the commonest system affected as CNS, GIT, and metabolic [20,24-27]. System/organ affected and the drugs implicated usually reflect the pattern of diseases in the hospital and the drugs used. Our findings are not unconnected with the drugs most abused by the populace. In Nigeria analgesics especially NSAIDs, in addition to antimicrobial agents are the most abused/misused drugs [28]. NSAIDs use have been associated with upper GI bleeding possibly on background peptic ulcer disease in Nigeria [29]. Oral Hypoglycaemic agents (OHAs)-induced hypoglycaemia resulted from self-medication, drug misuse and transcription error for prescribed OHAs and insulin. OHAs-induced hypoglycaemia as reported in this study was common as the cause of hospital admission. The consequence is grave and may worsen among alcoholics and those with background liver diseases, as well as elderly with impaired cognitive function which was the case in one of the patients. Our study is similar to studies by Mouton et al. in South Africa [30]. Contrarily, in a study in South Africa, Mehta et al reported the most common drugs for the observed ADRs to be ARTs and drugs for the management of opportunistic infections [8]. This is because of the high prevalence of HIV in the setting and the majority of the reported ADRs were among HIV/AIDs patients. Similarly, spontaneous ADRs reporting to the National Pharmacovigilance Centre in Nigeria reported antiretroviral drugs as the commonest suspected drugs and general disorders as the most common system/organ affected [31].
Most of the life-threatening ADRs reported were SJS/TEN. These ADRs are rare but fatal and responsible for the majority of the deaths recorded in this study. The drugs implicated were cotrimoxazole and herbal concoction ingested through self-medication. Cotrimoxazole in Nigeria and most LMICs are obtained as an over-the-counter drug, and this easy accessibility and affordability increase the predisposition to this life-threatening ADRs. Studies have reported SJS/TEN as common fatal ADRs reported in developing countries [32,33]. Some drugs reported as having high risks of causing SJS/TEN are anti-infective sulfonamide, antiepileptic drugs, nevirapine and herbal medications [33], similar to our findings. Although while the genetic predisposition is still evolving, there has been an association between SJS/TEN and the use of drugs like phenytoin, carbamazepine and cotrimoxazole [34]. However, similar to our findings, a multicenter study in sub-Saharan Africa involving four countries reported cotrimoxazole as the most implicated suspected drug for the development of SJS/TEN [35]. In this study, although mostly obtained by self-medication and as a cause of admission, one of our patients on nevirapine-based ART taking cotrimoxazole as prophylaxis had SJS, while another patient on prescribed carbamazepine as branded, Tegretol and concomitantly took generic had SJS/TEN which she survived. There is, therefore, a need for sensitization of the public and possible individualization of therapy (pharmacogenomics) for those who might benefit from its usage for treatment or prophylaxis. For examples, studies have shown that individuals with HLA-B*15:02, HLA-C*06:02, and HLA-C*08:01 have several folds increase risk of developing co-trimoxazole-induced SJS/TEN [36], and HLA-C*04:01 was associated with nevirapine-induced SJS/TEN [37].
Furthermore, the use of herbal concoction and supplements and ADRs were important findings in this study. This corroborates the need for ADRs reporting following the use of herbal medications and supplements. Although in Nigeria, NAFDAC has taken a bold step at including the spontaneous reporting of herbal medications in her national pharmacovigilance, there is a need to increase the awareness among people to report any observed ADRs to not only herbal medications registered by NAFDAC to prevent this menace. In addition, healthcare professionals must include a history of herbal medication intake and/or ADRs during clinical clerkship. Studies have shown that herbal medications and supplements constitute an important cause of ADRs [38-40].
Alcohol intake and duration of hospital stay are the factors that significantly associated with the development of ADRs in this study. Reasons include the fact that alcohol affect the metabolism of many drugs; alcohol-drug interactions; chronic alcohol intake and enzyme induction; chronic alcohol intake and liver diseases [41]. Alcohol has been reported as an important predictor of ADRs, especially among the elderly [42,43]. During hospitalisation, patients with prolonged hospital stay have the tendency of taking more medications and similar to alcohol, possibilities of drug interactions and ADRs. Development of ADRs by patients may result in prolongation of hospital stay and is a measure of severity of ADRs, however, other reasons such as the disease condition, age, multiple medications, multiple organ failure may be the reason for the prolonged hospital stay. Similar to our findings, studies have reported prolongation of hospital stay as an independent risk factor for the development of ADRs [26,27,44].