Advertisement

Pharmaceutical Medicine

, Volume 33, Issue 2, pp 145–157 | Cite as

A Retrospective Review of Serious Adverse Drug Reaction Reports in the Nigerian VigiFlow Database from September 2004 to December 2016

  • Comfort Kunak OgarEmail author
  • Abiodun Abiola
  • Daniel Yuah
  • Ali Ibrahim
  • Ibrahim Adekunle Oreagba
  • Emmanuel C. Amadi
  • Mojisola Christianah Adeyeye
  • Kazeem Adeola Oshikoya
Original Research Article
  • 7 Downloads

Abstract

Background

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.

Objective

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.

Method

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.

Results

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.

Conclusion

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.

Notes

Author Contributions

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

Funding

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.

Ethical approval

Ethics approval was not required for this study.

References

  1. 1.
    World Health Organization. The importance of pharmacovigilance. Safety monitoring of medicinal products. Geneva: World Health Organization; 2002.Google Scholar
  2. 2.
    Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet. 2000;356(9237):1255–9.CrossRefGoogle Scholar
  3. 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.
  4. 4.
    Hazell L, Shakir SA. Under-reporting of adverse drug reactions: a systematic review. Drug Saf. 2006;29(5):385–96.CrossRefGoogle Scholar
  5. 5.
    Kharkar M, Bowalekar S. Extent of under reporting of adverse drug reactions (ADRs) in India: evaluation using logistic regression analysis (LRA) model. J Clin Trials. 2014;4:1.  https://doi.org/10.4172/2167-0870.1000155.Google Scholar
  6. 6.
    Tandon VR, Mahajan V, Khajuria V, Gillani Z. Under-reporting of adverse drug reactions: a challenge for pharmacovigilance in India. Indian J Pharmacol. 2015;47(1):65–71.CrossRefGoogle Scholar
  7. 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.
  8. 8.
    Oshikoya KA, Awobusuyi JO. Perceptions of doctors to adverse drug reaction reporting in a teaching hospital in Lagos Nigeria. BMC Clin Pharmacol. 2009;9:14.CrossRefGoogle Scholar
  9. 9.
    National Bureau of Statistics. Demographic Statistics Bulletin; 2017. https://nigerianstat.gov.ng/download/775. Accessed 6 Dec 2018.
  10. 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. 11.
    Federal Ministry of Health, Nigeria. National Drug Policy, 2005. ISBN 978-067-237-0.Google Scholar
  12. 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. 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
  14. 14.
    Oreagba IA, Oshikoya KA, Ogar C, Adefurin AO, Ibrahim A, Awodele O, Oni Y. Adverse reactions to fluoroquinolones in the Nigerian population: an audit of reports submitted to the National Pharmacovigilance Centre from 2004 to 2016. Pharmacol Res Perspect. 2017;5(2):e00297.CrossRefGoogle Scholar
  15. 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. 16.
    Fehintola FA. Dipyrone: the ban, the justification. Afr J Med Med Sci. 2005;34:403–4.Google Scholar
  17. 17.
    Awodele O, Ibrahim A, Orhii P. Patterns of adverse drug reaction signals in NAFDAC Pharmacovigilance activities from September to November 2014. Int J Risk Saf Med. 2016;28:13–23.  https://doi.org/10.3233/JRS-160669.CrossRefGoogle Scholar
  18. 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. 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. 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
  21. 21.
    Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients. A meta-analysis of prospective studies. JAMA. 1998;279:1200–5.CrossRefGoogle Scholar
  22. 22.
    Aagaard L, Strandell J, Melskens L, Petersen PS, Holme Hansen E. Global patterns of adverse drug reactions over a decade: analyses of spontaneous reports to VigiBase. Drug Saf. 2012;35(12):1171–82.CrossRefGoogle Scholar
  23. 23.
    Arulmani R, Rajendran SD, Suresh B. Adverse drug reaction monitoring in a secondary care hospital in south India. Br J Clin Pharmacol. 2008;65(2):210–6.CrossRefGoogle Scholar
  24. 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
  25. 25.
    Jose J, Rao PG. Pattern of adverse drug reactions notified by spontaneous reporting in an Indian tertiary care teaching hospital. Pharmacol Res. 2006;54(3):226–33.CrossRefGoogle Scholar
  26. 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
  27. 27.
    Agu KA, Oparah AC. Adverse drug reactions to antiretroviral therapy: Results from spontaneous reporting system in Nigeria. Perspect Clin Res. 2013;4(2):117–24.CrossRefGoogle Scholar
  28. 28.
    Obebi Cliff-Eribo K, Sammons H, Star K, Ralph Edwards I, Osakwe A, Choonara I. Adverse drug reactions in Nigerian children: a retrospective review of reports submitted to the Nigerian Pharmacovigilance Centre from 2005 to 2012. Paediatr Int Child Health. 2016;29:1–5.CrossRefGoogle Scholar
  29. 29.
    Nguyen JK, Fouts MM, Kotabe SE, Lo E. Polypharmacy as a risk factor for adverse drug reactions in geriatric nursing home residents. Am J Geriatr Pharmacother. 2006;4(1):36–41.CrossRefGoogle Scholar
  30. 30.
    Davies EC, Green CF, Taylor S, Williamson PR, Mottram DR, et al. Adverse drug reactions in hospital in-patients: a prospective analysis of 3695 patient-episodes. PLoS One. 2009;4(2):e4439.  https://doi.org/10.1371/journal.pone.0004439.CrossRefGoogle Scholar
  31. 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. 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
  33. 33.
    Oreagba IA, Usman S, Olayemi S, Oshikoya K, Opanuga O, Adeyemo T, Lesi O, Dodoo AN, Akanmu A. Pharmacoepidemiology of antiretroviral drugs in a teaching hospital in Lagos, Nigeria. Ghana Med J. 2014;48(4):194–203.CrossRefGoogle Scholar
  34. 34.
    Prajapati K, Desai M, Shah S, Panchal J, Kapadia J, Dikshit R. An analysis of serious adverse drug reactions at a tertiary care teaching hospital. Perspect Clin Res. 2016;7(4):181–6.CrossRefGoogle Scholar
  35. 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. 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. 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.
  38. 38.
    Geier SA, Held M, Bogner JR, Kronawitter U, Berninger T, Klauss V, Goebel FD. Impairment of tritan colour vision after initiation of treatment with zidovudine in patients with HIV disease or AIDS. Br J Ophthalmol. 1993;77:315–6.CrossRefGoogle Scholar
  39. 39.
    Lalonde RG, Deschenes JG, Seamone C. Zidovudine-induced macular edema. Ann Intern Med. 1991;114:297–8.CrossRefGoogle Scholar
  40. 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. 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. 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
  43. 43.
    Lopez-Gonzalez E, Herdeiro MT, Figueiras A. Determinants of under-reporting of adverse drug reactions: a systematic review. Drug Saf. 2009;32(1):19–31.CrossRefGoogle Scholar
  44. 44.
    Gupta Rohini, Malhotra Apoorva, Malhotra Pavan. A study on determinants of underreporting of adverse drug reactions among resident doctors. Int J Res Med Sci. 2018;6(2):623–7.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Comfort Kunak Ogar
    • 1
    Email author
  • Abiodun Abiola
    • 1
  • Daniel Yuah
    • 1
  • Ali Ibrahim
    • 1
  • Ibrahim Adekunle Oreagba
    • 2
  • Emmanuel C. Amadi
    • 1
  • Mojisola Christianah Adeyeye
    • 1
  • Kazeem Adeola Oshikoya
    • 3
  1. 1.National Agency for Food and Drug Administration and Control (NAFDAC)AbujaNigeria
  2. 2.University of LagosLagosNigeria
  3. 3.Pharmacology, Therapeutic and Toxicology DepartmentLagos State University College of MedicineLagosNigeria

Personalised recommendations