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Safety of Artemisinin-Based Combination Therapies in Nigeria: A Cohort Event Monitoring Study

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Abstract

Background

A pilot programme of Cohort Event Monitoring (CEM) was conducted across the six geopolitical zones of Nigeria on patients treated for uncomplicated malaria with artemisinin-based combination therapy (ACT). The emergence and spread of malaria parasites resistant to commonly available antimalarial drugs necessitated a shift in policy for malaria treatment by the Federal Government from the use of chloroquine and sulphadoxine-pyrimethamine (SP) as first-line treatments to ACTs. Initial reports following deployment of ACTs in clinical settings raised safety concerns regarding their use. Although artemisinin and its derivatives are generally thought to be safe, there are currently few or no data on their safety among populations in Nigeria.

Objectives

The main objectives of the CEM programme were to proactively determine the adverse event (AE) profile of artesunate/amodiaquine (AA) and artemether/lumefantrine (AL) in real-life settings and to find out the factors predisposing to AEs.

Methods

The CEM study was observational, longitudinal, prospective, and inceptional. Patients were observed in real-life situations. It was conducted in six public health facilities in Nigeria on patients with a clinical diagnosis of uncomplicated malaria treated with ACTs. Patients were prescribed one of the ACTs on an alternate basis as they enrolled into the programme. Follow-up reviews were undertaken on days 3 and 7 following commencement of ACT treatment. At follow-up, patients were evaluated for any clinical event that they might have experienced following the use of the ACTs. We report the result of this initial pilot in which 3,010 patients treated for uncomplicated malaria with AA or AL were enrolled.

Results

The seven most common AEs seen were general body weakness 25.0/36.6 % (AL/AA); dizziness 11.9/17.2 % (AL/AA); vomiting 8.0/10.2 % (AL/AA); abdominal pain 8.5/7.2 % (AL/AA); insomnia 6.3/5.9 % (AL/AA); body pains 3.4/5.2 (AL/AA) %; anorexia 8.5/4.6 % (AL/AA). Most adverse events occurred from day 1 and peaked by day 2 and 3 of medication with the mean duration of events being 3 days. By the end of the follow-up visit on day 7, the AEs had resolved in the majority of patients. Adverse events were more common in the AA group than AL revealing a better safety profile for AL (p < 0.001). Both ACTs demonstrated good ability to resolve the clinical symptoms of uncomplicated malaria.

Conclusion

In conclusion, this pilot CEM programme suggests that adverse events with ACTs were common. However, serious life-threatening events were not common. It appears that ACTs have a tolerable safety profile among Nigerians.

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Acknowledgments

The Cohort event monitoring (CEM) team would like to express its appreciation to all doctors, pharmacists, nurses, and health workers in the six health facilities across Nigeria for their support and/or involvement in this work.

Special acknowledgement goes to the authorities of the six institutions for allowing the use of their Institutions for this pilot programme.

Special appreciation also goes to the Director General of the National Agency for Food and Drug Administration and Control (NAFDAC), Nigeria, the host agency for the programme, for the financial supplement that facilitated completion of monitoring of the programme, including the provision of secretarial services.

The CEM programme was made possible by a grant and training from the WHO Department of Essential Medicines and Health Products, WHO, Geneva, Switzerland. The National Malaria Control Programme, Federal Ministry of Health (FMoH), Abuja and Society for Family Health Abuja-Nigeria, and Yakubu Gowon Centre Nigeria provided the programme drugs and long-lasting insecticide-treated mosquito nets for use as incentives plus travel subsidies for participants in the programme.

We acknowledge Dr. (Mrs.) Ogori Taylor, WHO Nigeria, Dr. BM Afolabi, Dr. Ntadam, the National Malaria Control Programme, Nigeria, and a host of others for their assistance in the training, sponsorship, and contributions to the project.

Dr. Pal is an employee of WHO, which partially funded the CEM programme.

Dr. Suku has received funds from the WHO to attend meetings to present the CEM work. Dr. Nyong received site coordinator honorarium from NAFDAC Nigeria for travel for review meetings in Abuja during the preparation for the study. Provisions of the ACTs were undertaken by the WHO, NAFDAC, and Federal Ministry of Health.

None of the other authors declared any conflict of interest.

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Authors and Affiliations

  1. Department of Clinical Pharmacology and Therapeutics, College of Medical Sciences, PMB1069, University of Maiduguri, Maiduguri, Borno State, Nigeria

    Peter Usman Bassi

  2. National Pharmacovigilance Centre NAFDAC Abuja, FCT, Abuja, Nigeria

    Adeline I. Osakwe, Comfort Suku & Musa Kalat

  3. Clinical Pharmacology Unit, University of Benin Teaching Hospital, Benin, Edo State, Nigeria

    Ambrose Isah

  4. Department of Paediatrics, Federal Medical Centre, Gombe, Gombe State, Nigeria

    Iliya Jalo

  5. Department of Paediatrics, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State, Nigeria

    Robinson Daniel Wammanda

  6. Department of Paediatrics, Nnamdi Azikwe University Teaching Hospital, Enugu, Enugu State, Nigeria

    Chika Ugochukwu

  7. Department of Obstetrics and Gynaecology, University College Hospital, Ibadan, Oyo State, Nigeria

    Olubukula Adesina

  8. Department of Paediatrics, University of Uyo Teaching Hospital, Uyo, Akwa-Ibom State, Nigeria

    Eno Etim Nyong

  9. MOPD Clinic, Nigerian Institutes for Pharmaceutical Research and Development, Idishin Abuja–FCT, Abuja, Nigeria

    Frank Osungwu

  10. WHO Department of Essential Medicine and Health Products, WHO, Geneva, Switzerland

    Shanti Pal

  11. Department of Mathematics and Statistics, University of Maiduguri, Maiduguri, Borno State, Nigeria

    Sylvester Chigozie Nwoasu

  12. Uppsala Monitoring Centre, WHO Collaborating Centre for International Drug Monitoring, Uppsala, Sweden

    Magnus Wallberg

  13. Private Consultant in Pharmacovigilance and Pharmacoepidemiology, Dunedin, New Zealand

    David Coulter

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  1. Peter Usman Bassi
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Correspondence to Peter Usman Bassi.

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Bassi, P.U., Osakwe, A.I., Isah, A. et al. Safety of Artemisinin-Based Combination Therapies in Nigeria: A Cohort Event Monitoring Study. Drug Saf 36, 747–756 (2013). https://doi.org/10.1007/s40264-013-0044-8

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