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Antimalarial Drug Combination Therapy ANTIMALARIAL DRUG COMBINATION THERAPY ANTIMALARIAL DRUG COMBINATION THERAPY Report of a WHO Technical Consultation World Health Organization, Geneva WHO, 2001 2 Text editor: M. Geyer Layout and production: Graficim The authors wish to recognise the contributions made to the writing of this report at country level by Ministries of Health and other partners, Regional Offices of WHO, and at a global level by mission reports, partners and the RBM team. Roll Back Malaria World Health Organization 20 Avenue Appia, CH-1211 Geneva 27, Switzerland Tel: +41 (22) 791 3606, Fax: +41 (22) 791 4824, E-mail: [email protected] Web site: http://www.rbm.who.int/ WHO/CDS/RBM/2001.35 © Copyright 2001 by Roll Back Malaria/World Health Organization This document is not a formal publication of the World Health Organization and all rights are reserved by the Organization. The document may, however, be freely reviewed, abstracted, reproduced or translated, in part or in whole, but not for sale nor for use in conjunction with commercial purposes. The designations employed and the presentation of the material in this document, including maps and tables do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omission excepted, the names of proprietary products are distinguished by initial capital letters. Report of a Technical Consultation, WHO, Geneva, 4-5 April 2001 CONTENTS Introduction .............................................................................................................................................................................................................................................................................................................5 1. Combination therapy in the context of treatment policy .....................................................................................................................................................6 1.1 Purpose of drug policy...................................................................................................................................................................................................................................................6 1.2 Combination therapy with antimalarial drugs .........................................................................................................................................................................7 Rationale for the use of combination therapy in Africa .............................................................................................................................................7 2. Antimalarial therapy combination drugs...........................................................................................................................................................................................................9 2.1 Non-artemisinin based combinations ................................................................................................................................................................................................9 Chloroquine plus sulfadoxine-pyrimethamine.........................................................................................................................................................................9 Amodiaquine plus sulfadoxine-pyrimethamine ................................................................................................................................................................10 TM Atovaquone-proguanil (Malarone )...................................................................................................................................................................................................11 TM Mefloquine-sulfadoxine-pyrimethamine (Fansimef ).............................................................................................................................................11 Quinine plus tetracycline or doxycycline......................................................................................................................................................................................12 2.2 Artemisinin-based combinations...............................................................................................................................................................................................................12 Artesunate plus chloroquine.............................................................................................................................................................................................................................13 Artesunate plus amodiaquine..........................................................................................................................................................................................................................14 Artesunate plus sulfadoxine-pyrimethamine .........................................................................................................................................................................14 Artesunate plus mefloquine...............................................................................................................................................................................................................................14 TM TM Artemether-lumefantrine (Coartem , Riamet ).........................................................................................................................................................15 2.3 Combinations in the pipeline ........................................................................................................................................................................................................................16 Piperaquine-dihydroartemisinin-trimethoprim (ArtecomTM ) and ArtecomTM plus 3 TM primaquine (CV8 ) ....................................................................................................................................................................................................................................................16 Pyronaridine plus artesunate............................................................................................................................................................................................................................17 Naphthoquine plus dihydroartemisinin .........................................................................................................................................................................................17 TM TM Chlorproguanil-dapsone plus artesunate (CDA or Lapdap plus ) ..............................................................................................18 3. Implementation issues ....................................................................................................................................................................................................................................................................18 3.1 Criteria for selection of combinations of antimalarial drugs...........................................................................................................................18 Therapeutic efficacy.......................................................................................................................................................................................................................................................19 Safety ....................................................................................................................................................................................................................................................................................................19 Consumer acceptability ...........................................................................................................................................................................................................................................19 Consumer compliance...............................................................................................................................................................................................................................................20 Costs and cost effectiveness .............................................................................................................................................................................................................................20 Potential to delay or prevent development of resistance ........................................................................................................................................20 3.2 Technical requirements and process for introducing combination therapy.............................................................................21 Drug registration................................................................................................................................................................................................................................................................21
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