title: Safety of Artemisinin-Based Combination Therapies in Nigeria: A Cohort Event Monitoring Study.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medical Sciences, PMB1069, University of Maiduguri, Maiduguri, Borno State, Nigeria. pubassi@gmail.com
authors.forename: Peter Usman
authors.initials: PU
authors.lastname: Bassi
authors.affiliation: National Pharmacovigilance Centre NAFDAC Abuja, FCT, Abuja, Nigeria.
authors.forename: Adeline I
authors.initials: AI
authors.lastname: Osakwe
authors.affiliation: Clinical Pharmacology Unit, University of Benin Teaching Hospital, Benin, Edo State, Nigeria.
authors.forename: Ambrose
authors.initials: A
authors.lastname: Isah
authors.affiliation: National Pharmacovigilance Centre NAFDAC Abuja, FCT, Abuja, Nigeria.
authors.forename: Comfort
authors.initials: C
authors.lastname: Suku
authors.affiliation: National Pharmacovigilance Centre NAFDAC Abuja, FCT, Abuja, Nigeria.
authors.forename: Musa
authors.initials: M
authors.lastname: Kalat
authors.affiliation: Department of Paediatrics, Federal Medical Centre, Gombe, Gombe State, Nigeria.
authors.forename: Iliya
authors.initials: I
authors.lastname: Jalo
authors.affiliation: Department of Paediatrics, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State, Nigeria.
authors.forename: Robinson Daniel
authors.initials: RD
authors.lastname: Wammanda
authors.affiliation: Department of Paediatrics, Nnamdi Azikwe University Teaching Hospital, Enugu, Enugu State, Nigeria.
authors.forename: Chika
authors.initials: C
authors.lastname: Ugochukwu
authors.affiliation: Department of Obstetrics and Gynaecology, University College Hospital, Ibadan, Oyo State, Nigeria.
authors.forename: Olubukula
authors.initials: O
authors.lastname: Adesina
authors.affiliation: Department of Paediatrics, University of Uyo Teaching Hospital, Uyo, Akwa-Ibom State, Nigeria.
authors.forename: Eno Etim
authors.initials: EE
authors.lastname: Nyong
authors.affiliation: MOPD Clinic, Nigerian Institutes for Pharmaceutical Research and Development, Idishin Abuja-FCT, Abuja, Nigeria.
authors.forename: Frank
authors.initials: F
authors.lastname: Osungwu
authors.affiliation: WHO Department of Essential Medicine and Health Products, WHO, Geneva, Switzerland.
authors.forename: Shanti
authors.initials: S
authors.lastname: Pal
authors.affiliation: Department of Mathematics and Statistics, University of Maiduguri, Maiduguri, Borno State, Nigeria.
authors.forename: Sylvester Chigozie
authors.initials: SC
authors.lastname: Nwoasu
authors.affiliation: Uppsala Monitoring Centre, WHO Collaborating Centre for International Drug Monitoring, Uppsala, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Wallberg
authors.affiliation: Private Consultant in Pharmacovigilance and Pharmacoepidemiology, Dunedin, New Zealand.
authors.forename: David
authors.initials: D
authors.lastname: Coulter
mesh_terms: D000293:Adolescent; D000328:Adult; D000655:Amodiaquine / Q000008:administration & dosage / Q000009:adverse effects; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects*; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000078102:Lumefantrine; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D009549:Nigeria; D011247:Pregnancy; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D000655:Amodiaquine; C031327:artemisinin; D000078102:Lumefantrine