Patterns of adverse drug reaction signals in NAFDAC Pharmacovigilance activities from September to November,2014

1 Introduction

Pharmacovigilance and adverse drug reaction signals detection program is coordinated by the Uppsala Monitoring Centre (UMC) [1] and has 106 full member countries and 34 associate members as at August, 2011. Nigeria was granted full membership as the 74th member country in September 2004. In Nigeria, the National Pharmacovigilance Centre (NPC) is domicile in National Agency for Food and Drugs Administration and Control (NAFDAC) and has the data bank of all reported adverse drug reactions in Nigeria.

It is the obligation of the medical community, pharmaceutical industry, and health authorities to ensure that marketed drugs have acceptable risk-benefit ratio [2]. Adverse drug reaction signals are reported information on possible causal relationships between an adverse event and a drug. The study of Pacurariu et al. [3] clearly showed the importance of spontaneous reporting in signal detection and monitoring of safety issues throughout the entire life cycle of a medicinal product. Spontaneous adverse drug events (ADE) reporting is the main source of data for assessing the risk/benefit of drugs available in the pharmaceutical market. However, its major limitation is underreporting, which hinders and delays the signal detection by Pharmacovigilance activities [4]. Thus, the new pharmacovigilance legislation underlines the relevance of other sources of information (such as scientific literature) for the evaluation of the benefit-risk balance of certain medicinal products [5].

A report on data mining approach for signal detection and analysis [6] elucidated the relevance of the use of Bayesian Confidence Propagation Neural Network (BCPNN) for the analyses of over 2.5 million data for signal detections. The aforementioned study revealed the inevitable use of statistical instruments in unbiased and scientifically sound affirmation of signals.

In this present study, data mining of ADR reports from September to November, 2014 were carried out with the intention to describe the pattern of ADRs and generate possible signals.

2 Methodology

Pharmacovigilance activities in Nigeria are coordinated by Pharmacovigilance and Post-Marketing Surveillance Directorate which is one of the 13 directorates in National Agency for Food and Drugs Administration and Control (NAFDAC). Spontaneous adverse drug reporting system is usually practice in Nigeria using a standard structured yellow form for reporting suspected adverse drug reactions (Fig. 1). The five (5) general components of the form are patient’s details, adverse drug reaction details, suspected drug details, concomitant medicines details and sources of report. All completed adverse drug reaction forms are submitted to NPC for documentation and possible signal detections. A filled yellow/adverse reaction form is known as the individual case study report (ICSR).

As at November, 2014, NPC has over 3,000 reported adverse drug reaction cases which have been properly entered into the ADR data bank. Data mining of ADR reports from September to November, 2014 were carried out in this present study with the intention to describe the pattern of ADRs and generate possible signals. The data were analyzed using SPSS version 17.

3 Results and discussion

A total of about 100 reported cases with arrays of adverse drug reactions were reported between September and November, 2014.

The findings obtained revealed age range of 31–40 years (34.3%) as the most prevalent reported age of patients. This observation corroborates the previous local studies of Agu et al. [7] and Agu and Oparah [8] which reported 35.5 years as the mean age of patients reported to have adverse reactions to anti-retroviral agents. Most of the reports emanated from South -West region (47.4%), followed by North-Central region (21.7%). The aforementioned may be due to the level of education, awareness and commitment of the reporters in those regions. It is quite known that nurses constituted the highest number of heath care professionals in both public and private institutions, but the observation in this report showed nurses (7%) as the least professionals reporting ADRs (Table 1). This may underscore an indication for more training tailored towards the nurses for effective and committedreporting

Quantitative methods are increasingly used to analyze spontaneous reports for signal detection [9]. Signal is a new safety finding within safety data that may require further investigation and causal relationship between drugs and adverse reactions. Report of Pontes et al. [5] explained the relevance of scientific literatures in evaluating benefit-risk ratio. Reported cases between September and November, 2014 showed Efavirenz/Tenofovir/Lamivudine combination to be reported in 22 times (24.2%) (Table 2) and was found to have highest episodes of ADRs, while efavirenz alone which was reported in 8 times (8.8%) has spinning sensation in the head reported twice and HIV (63.3%) was the highest reported indication of drug use (Table 3). Table 4 showed detailed list of reported ADRs and the suspect drugs. Studies of Weib et al. [10] and Burger et al. [11] have shown Efavirenz to cause oxidative stress, endoplasmic reticulum stress, central nervous system toxicity and suicidal tendency effects. Thus, there may be positive correlation between the documented literatures and central nervous system adverse reactions of Efavirenz as observed in this present ADRs analyses. However, there is need for further vigilance to ascertain the causal relationship between these drugs and the reported ADRs. Zidovudine/Lamivudine/Nevirapine combination in concomitant use with Cotrimoxazole were reported 8 times with generalized maculopapular rashes on the trunk with some area of hyper pigmentation with intense itching documented twice and big/swollen rashes all over the faces. The study of Oreagba et al. [12] also documented skin reactions and rashes to be common ADRs with antiretroviral combination containing Zidovudine.

In addition, Zidovudine was reported four times to cause severe anaemia. These observations agreed with Parkes-Ratanshi et al. [13] that showed Zidovudine containing therapy to produce severe anaemia among Ugandan patients. The use of Cotrimoxazole concomitantly with Zidovudine/Lamivudine/Nevirapine as well as artemeter-lumefantrine combinations was reported to cause generalized body rash with eruption of the skin twice. These observations are consolidating the known body rash with eruption of the skin reaction caused by cotrimoxazole and nevirapine as documented in literature. These findings underscore the need for caution with the concurrent use of these agents with the intention to always weigh the risk-benefit profile. Metformin was reported 7 times (7.7%) and elevated high blood pressure was predominant in occurrence in the reported metformin ADRs. The aforementioned report is not consistent with the reported observation where metformin decreased the diastolic blood pressure of non-diabetic rats [14]. However, more surveillance in this regard is advocated and quality of reports should also be ensured (Table 4).

Drugs manufactured from India are the most reported (78.6%) country of drug manufacture. This may further probe into the standard and wholesomeness of products from this source.

In conclusion, continuous spontaneous reporting of ADRs is advocated so as to further establish the causal event relationships of drugs and subsequent regulatory decision on dangerous drugs.

Conflict of interest

There is no conflict of interest in this research.