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].