A Retrospective Review of Serious Adverse Drug Reaction Reports in the Nigerian VigiFlow Database from September 2004 to December 2016
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Adverse drug reactions (ADRs) are a source of concern in healthcare as they negatively affect patients. Serious adverse drug reactions (SADRs) have an even greater impact on patients and the system in terms of morbidity and financial burden. The establishment of National Pharmacovigilance Centers (NPCs) has enhanced ADR reporting in Africa. The Nigerian Pharmacovigilance Centre has been collecting ADR reports using VigiFlow since 2004.
The aim of this study was to identify and analyze SADR reports in the Nigerian VigiFlow database in order to profile the patients with SADRs, the medicines most implicated, system organ classes (SOCs) affected, outcome of such reactions, including fatalities, and ADR reporting trends over the years. We also looked at the data elements provided in the reports as a proxy measure of report quality.
We retrospectively assessed all individual case safety reports (ICSRs) received by the NPC in Nigeria and entered into VigiFlow as SADR reports between September 2004 and December 2016. We defined SADR as any untoward reaction to any medicine dose that resulted in death, required in-patient hospitalization or prolongation of existing hospitalization, resulted in congenital anomaly, persistent or significant disability/incapacity or was life-threatening. The suspected SADRs were analyzed at the Medical Dictionary for Regulatory Activities SOC and Preferred Term levels.
A total of 11,222 ICSRs were entered into VigiFlow during the study period, of which 298 (3%) were classified as SADR reports. Adults were the most affected (244/282; 87%). The median number of medicines per report was 3 (interquartile range = 2–4.75). Nevirapine (36/336; 11%), as a single entity, was the most reported medicine. Human immunodeficiency virus (HIV) infection affected 128/232 (55%) of those with SADRs. There was no statistically significant association between the number of reactions per report and sex of the patients (p = 0.280), their age groups (p = 0.670), or the number of medicines per report (p = 0.640). Hospitalization was the most frequently cited reason for classifying a report as serious (151/276; 53%) and death was reported in 48 cases (48/283; 17%). Based on the SOC, skin and subcutaneous tissue disorders (139/550; 25%) was the most affected, while anemia (55/550; 10%) was the most reported specific reaction. A substantial number of patients (107/256; 42%) either recovered fully or were recovering from the SADRs. The number of SADR reports received varied by year with no consistent trend.
There is under-reporting of ADRs in the Nigerian VigiFlow® database, particularly SADRs and those involving pediatric and geriatric age groups. Given that over half of the SADR reports involved antiretroviral drugs, it is imperative to increase the surveillance of ADRs related to this class of drugs through regular clinical assessment of reports and provision of feedback on the findings to healthcare providers. Direct consumer reporting should also be encouraged as a means of increasing ADR reporting.
CKO conceived the study. CKO and AA developed the proposal for the study. KAO and IO reviewed the proposal. ECA extracted data from VigiFlow for analysis. CKO and DY analyzed the extracted data. CKO drafted the manuscript. AI, IO, KAO, AA, ECA, DY reviewed and approved the manuscript.
Compliance with Ethical Standards
The authors received no funding for this study.
Conflict of interest
C.K. Ogar declares no conflict of interest relating to this article. A. Abiola declares no conflict of interest relating to this article. D. Yuah declares no conflict of interest relating to this article. A. Ibrahim declares no conflict of interest relating to this article. I.A. Oreagba declares no conflict of interest relating to this article. E.C. Amadi declares no conflict of interest relating to this article. M.C. Adeyeye declares no conflict of interest relating to this article. K.A. Oshikoya declares no conflict of interest relating to this article.
Ethics approval was not required for this study.
- 1.World Health Organization. The importance of pharmacovigilance. Safety monitoring of medicinal products. Geneva: World Health Organization; 2002.Google Scholar
- 3.International Conference on Harmonization of technical requirements for registration of pharmaceuticals for human use. ICH harmonized tripartite guideline post-approval safety data management: definitions and standards for expedited reporting E2D. Current Step 4 version dated 12 November 2003. https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E2D/Step4/E2D_Guideline.pdf. Accessed 10 Dec 2018.
- 7.la Santos A. Direct Patient reporting in the European Union: a snapshot of reporting systems in seven member states. Amsterdam: Health Action International; 2015. http://apps.who.int/medicinedocs/documents/s22088en/s22088en.pdf. Accessed 8 Dec 2018.
- 9.National Bureau of Statistics. Demographic Statistics Bulletin; 2017. https://nigerianstat.gov.ng/download/775. Accessed 6 Dec 2018.
- 10.Scott-Emuakpor A. The evolution of health care systems in Nigeria: which way forward in the twenty-first century. Niger Med J. 2010;51:53–65.Google Scholar
- 11.Federal Ministry of Health, Nigeria. National Drug Policy, 2005. ISBN 978-067-237-0.Google Scholar
- 12.National Agency for Food and Drug Administration and Control NAFDAC Act 2004. http://www.nafdac.gov.ng/index.php/about-nafdac/nafdac-act. Accessed 3 Aug 2016.
- 13.Ogar CK, Ibrahim A, Osakwe AI, Jajere F, Kigbu-Adekunle AA, Alonge K, et al. Pharmacovigilance Rapid Alert System for Consumer Reporting (PRASCOR): a look at its quantitative contribution to spontaneous reporting in Nigeria from August 2012 to February 2017. Pharm Med. 2018;32:131. https://doi.org/10.1007/s40290-018-0228-8.CrossRefGoogle Scholar
- 15.Oshikoya KA. Treating children for malaria fever in the face of counterfeit and fake medicines. Int J Med Med Sci. 2010;2:1–2.Google Scholar
- 16.Fehintola FA. Dipyrone: the ban, the justification. Afr J Med Med Sci. 2005;34:403–4.Google Scholar
- 18.The use of the WHO-UMC system for standardized case causality assessment. https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdf. Accessed 14 Feb 2019.
- 19.Uppsala Monitoring Centre. Safety monitoring of medicinal products: guidelines for setting up and running a pharmacovigilance centre. UMC, WHO Collaborating Centre for International Drug Monitoring, Sweden; 2000.Google Scholar
- 20.Kiguba R, Ndagije HB, Nambasa V, Bird SM. Adverse Drug Reaction Onsets in Uganda’s VigiBase®: delayed international visibility, data quality and illustrative signal detection analyses. Pharmaceut Med. 2018;32(6):413–27.Google Scholar
- 24.Kamalraj R, Revathy J, Vijey Aanandhi M, Murugan M, Ramamakumar KPV. Incidence, severity and financial burden associated with suspected unexpected serious adverse reactions (SUSARS) that arise in clinical trials. Asian J Phar Clin Res. 2012;5(Suppl 3):98–101.Google Scholar
- 26.Agu KA, Isah MA, Oqua D, Habeeb MA, Agada PO, Ohiaeri SI, Ali PN, Iyaji PG, King RC, Aiyenigba B, Torpey K, Chabikuli ON, Wutoh AK. Incidence of adverse drug reactions in patients on antiretroviral therapy: a study of pharmaceutical care in HIV interventions in Nigeria. West Afr J Pharm. 2014;24(1):30–42.Google Scholar
- 31.Federal Ministry of Health, Department of Public Health, 2015. 2014 National HIV sero-prevalence sentinel survey among pregnant women attending antenatal clinics in Nigeria. National AIDS/STI Control Programme.Google Scholar
- 32.Parkes-Ratanshi R, Katende D, Levin J, Wakeham K, Heiner G, Kamali A, Lalloo DG. Development of severe anemia and changes in hemoglobin in a cohort of HIV-infected Ugandan adults receiving zidovudine, stavudine, and tenofovir containing antiretroviral regimens. J Int Assoc Provid AIDS Care. 2015;14:455–62.CrossRefGoogle Scholar
- 35.U.S. Department of Health and Human Services. Drugs. Zidovudine. AIDSinfo. https://aidsinfo.nih.gov/drugs/4/zidovudine/0/patient. Accessed 15 Jan 2019.
- 36.Summary of Product Characteristics. Zidovudine 100 mg capsule. Aurobindo Pharma—Milpharm Ltd. https://www.medicines.org.uk/emc/product/4490/smpc. Accessed 15 Jan 2019.
- 37.Lamivudine/zidovudine Mylan 150 mg/300 mg Fil-coated Tablets. Patient Information leaflet. Generics UK T/A Mylan. https://www.medicines.org.uk/emc/product/9440/pil. Accessed 15 Jan 2019.
- 40.Moodley A, Rae W, Bhigjee A. Visual loss in HIV-associated cryptococcal meningitis: a case series and review of the mechanisms involved. S Afr J HIV Med. 2015;16(1), Art. #305. https://sajhivmed.org.za/index.php/hivmed/article/view/305/585. Accessed 15 Jan 2019.
- 41.Kestelyn PG, Cunningham ET. HIV/AIDS and blindness. Bull World Health Organ. 2001;79:208–13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2566369/pdf/11285664.pdf. Accessed 15 Jan 2019.
- 42.Committee on Quality of Health Care in America: Institute of Medicine. To err is human: building a safer health system. National Academy Press, Washington, DC; 2000.Google Scholar