title: Safety Profile of Artemether-Lumefantrine: A Cohort Event Monitoring Study in Public Health Facilities in Tanzania.
abstract: OBJECTIVE
  Artemisinin combination therapies such as artemether-lumefantrine (AL) are effective for first-line treatment of uncomplicated acute Plasmodium falciparum malaria. However, the safety profile of AL in large populations has not been fully assessed. The objective of this study was to establish the safety of AL in public health facilities in Tanzania using the Cohort Event Monitoring (CEM) method.
  
  
  METHODS
  Patients who presented to public health facilities in four regions of Tanzania who were prescribed AL were enrolled in a CEM study, a prospective, observational cohort study to establish a profile of adverse events (AEs) for the medicine when used in routine clinical practice. Pre- and post-treatment forms were used to record baseline information and new health events before and 7 days after treatment.
  
  
  RESULTS
  A total of 8040 patients were enrolled in the study, of whom 6147 were included in the analysis. Following treatment initiation, a total of 530 AEs were reported in 6% (383) of the patients. The most frequent post-treatment AEs were in alimentary system (42%), including vomiting, nausea, diarrhoea, abdominal pain and anorexia, followed by AEs in the neurological system (25%). Causality assessment of the events showed that 51.9% (275/530) were possibly related to AL. There was a significant difference in the frequency of AEs by age-group with an increase in the number of AEs as age increased (P < 0.001). There was no statistically significant difference in the frequency of the events between males and females (P = 0.504). The AE profile was consistent with the AEs reported in the product information and in other studies; no new adverse drug reactions were identified. The majority of the reported AEs were the same as the symptoms of malaria and therefore indistinguishable from the underlying disease.
  
  
  CONCLUSIONS
  The safety profile of AL for treatment of malaria continues to be favourable. CEM as a pharmacovigilance tool has proven to provide reliable safety data in a short period.
authors.affiliation: Department of Clinical Trials Control and Pharmacovigilance, Tanzania Food and Drugs Authority, P.O. Box 77150, Dar Es Salaam, Tanzania. alambopharm@yahoo.com.
authors.forename: Alambo K
authors.initials: AK
authors.lastname: Mssusa
authors.affiliation: Directorate of Medicines and Complementary Products, Tanzania Food and Drugs Authority, P.O. Box 77150, Dar Es Salaam, Tanzania.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Fimbo
authors.affiliation: Department of Clinical Trials Control and Pharmacovigilance, Tanzania Food and Drugs Authority, P.O. Box 77150, Dar Es Salaam, Tanzania.
authors.forename: Alex F
authors.initials: AF
authors.lastname: Nkayamba
authors.affiliation: Pharmaceutical Services Unit, Ministry of Health and Social Welfare, P.O. Box 9083, Dar Es Salaam, Tanzania.
authors.forename: Henry F
authors.initials: HF
authors.lastname: Irunde
authors.affiliation: Directorate of Medicines and Complementary Products, Tanzania Food and Drugs Authority, P.O. Box 77150, Dar Es Salaam, Tanzania.
authors.forename: Hiiti B
authors.initials: HB
authors.lastname: Sillo
authors.affiliation: Directorate of Laboratory Services, Tanzania Food and Drugs Authority, P.O. Box 77150, Dar Es Salaam, Tanzania.
authors.forename: Danstan H
authors.initials: DH
authors.lastname: Shewiyo
authors.affiliation: Uppsala Monitoring Centre, WHO Collaborating Centre for International Drug Monitoring, Box 1051, 75140, Uppsala, Sweden.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Hill
authors.affiliation: Unit of Pharmacology and Therapeutics, School of Pharmacy, Muhimbili University of Health and Allied Sciences, P.O. Box 65013, Dar Es Salaam, Tanzania.
authors.forename: Omary M
authors.initials: OM
authors.lastname: Minzi
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004338:Drug Combinations; D016903:Drug Monitoring / Q000379:methods* / Q000639:trends; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000009:adverse effects*; D006268:Health Facilities / Q000639:trends; D006801:Humans; D007223:Infant; D008288:Malaria / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011446:Prospective Studies; D013636:Tanzania / Q000453:epidemiology; D014839:Vomiting / Q000139:chemically induced; D055815:Young Adult
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes