# This topic needs a title **URL:** \ **Category:** e-drug\ **Created:** [March 23, 2004, 4:00pm UTC](https://talk.edrugplus.org/t/this-topic-needs-a-title/19162 "2004-03-23T16:00:01Z")\ **Posts on this page:** 1\ **Page:** 1
**Author:** ![owner-e-drug](https://avatars.discourse-cdn.com/v4/letter/o/bbce88/32.png) [@owner-e-drug](https://talk.edrugplus.org/u/owner-e-drug)\ **Post date:** [March 23, 2004, 4:00pm UTC](https://talk.edrugplus.org/t/this-topic-needs-a-title/19162/1 "2004-03-23T16:00:01Z")
X-no-archive: yes E-DRUG: WHO prequalifies artesunate for malaria -------------------------------------------- On 18 March WHO prequalified a second product for malaria: artusenate 50mg tablets from Sanofi (France), made by Guilin Pharmaceutical Co. Ltd, Guangx, China. See [http://mednet3.who.int/prequal/mal/mal\_suppliers\_(second-edition).pdf](http://mednet3.who.int/prequal/mal/mal_suppliers_(second-edition).pdf) Artesunate was already being sold for \>10 years, but as there was no "originator" (the product is known in China for more than 2000 years; as there was no possibility to patent it, few drug companies were interested to do all the preclinical safety and tox studies), it was difficult for WHO to apply its stringent prequalification criteria (see [http://mednet3.who.int/prequal/default.shtml](http://mednet3.who.int/prequal/default.shtml)). The prequalification of artesunate tablets now opens Global Fund receivers to order an alternative product from the previously registered Co-artem (artemether + lumefantrine, made by Novartis). Artesunate should however be used in COMBINATION with another anti-malarial. See WHO/Roll Back Malaria guidelines: ------- Position of WHO's Roll Back Malaria Department on malaria treatment policy Background Global malaria control is being threatened on an unprecedented scale by rapidly growing resistance of Plasmodium falciparum to conventional monotherapies such as chloroquine, sulfadoxine-pyrimethamine (SP) and amodiaquine. Multi-drug resistant falciparum malaria is widely prevalent in South-East Asia and South America. Now Africa, the continent with highest burden of malaria is also being seriously affected by drug resistance. WHO recommendations As a response to the antimalarial drug resistance situation, WHO recommends that treatment policies for falciparum malaria in all countries experiencing resistance to monotherapies should be combination therapies, preferably those containing an artemisinin derivative (ACT - artemisinin-based combination therapy). Following are the therapeutic options currently recommended by WHO: artemether/lumefantrine artesunate plus amodiaquine artesunate plus sulfadoxine/pyrimethamine (in areas where SP efficacy remains high) amodiaquine plus sulfadoxine/pyrimethamine, in areas where efficacy of both amodiaquine and sulfadoxine/pyrimethamine remains high (mainly limited to West Africa). artesunate plus mefloquine, an additional recommended combination treatment which is reserved for areas of low transmission. The current WHO policy on antimalarial treatment is based on the recommendations and conclusions of two consultations of international experts on malaria chemotherapy, held in November 2000 and April 2001 (see ANNEX I). WHO strategic position on expanding access to ACT Over the last three years around 20 countries (7 in Africa) have updated their treatment policies to include ACTs as 1st-line or 2nd-line treatment of malaria. This was based on WHO advice, and was made possible with the participation of RBM partners and increased mobilization of international funding. In 2002 the Global Fund to fight AIDS, Tuberculosis and Malaria (GFATM) was established, and it has become one of the main international funding mechanism to support the implementation of highly effective interventions for the control of these three diseases in endemic developing countries. The GFATM has become the largest financial supporter of ACTs in countries. A total of US$30 million has been committed over the full 5-year life of GFATM Board-approved proposals from African countries for the purchase of ACTs in three proposal rounds. Moreover, as a result of flexibility in the use of funds committed to these programmes, even more funds may be allocated to purchase ACTs as countries continuously evaluate their drug policies and how to best utilize grants from the GFATM. Indeed a number of recipient countries in Africa, which originally requested funding for chloroquine, are already in the process of re-evaluating their drug policies towards the use of ACTs, examples being Senegal, Ghana, Benin, Mali, Chad, and The Gambia. In addition to the GFATM, national Governments and RBM partners, such as UN Organizations, Bilateral Agencies and NGOs (MSF in particular) have contributed to the sourcing and financing of ACTs. The single non artemisinin-based combination therapy (amodiaquine plus SP), listed among WHO recommended options is reserved for countries which, for whatever reason, are unable to move into ACTs. However, the following limitations of this option should be noted: The number of countries where efficacy is high of both amodiaquine and SP is limited and mainly restricted to West Africa. As both amodiaquine and SP are currently in wide usage as monotherapies it is unlikely that the adoption of this combination therapy will significantly delay the spread of resistance to either drug. Therefore, the adoption of CT with amodiaquine plus SP is likely to be a short-term solution. Even in areas where the efficacy of both amodiaquine and SP remain high, their combined use will compromise the useful therapeutic life of both, and thus endanger their potential use as partner drugs for artesunatein ACTs. There is currently no replacement for SP as a drug for Intermittent Preventive Treatment (IPT) in pregnancy. Rather than compromise its therapeutic life by using it as a component of a CT, SP should be reserved for IPT. As the process of drug policy change and implementation is resource- and time-intensive (experience shows it to take from one to three years), all efforts for improving access to treatment should be directed towards implementing the most effective and durable treatment policy. One of the principal reasons for countries wishing to adopt non artemisinin based combinations (CTs) is their lower price. However, multiple financial mechanisms are now available in countries, and international support is being mobilised to help countries adopt ACTs, and an increasing number of countries are now replacing ineffective monotherapies with ACTs. To facilitate access to ACTs, WHO has, in collaboration with UNICEF, established a system for pre-qualification of manufacturers of artemisinin derivatives, negotiated price agreements with manufacturers, engaged in international procurement, and set up systems of pharmacovigilance. A service for malaria medicines and supplies is now being established by WHO and RBM partners to facilitate access to ACTs. This will be a component of a larger facility for improving access to medicines and supplies for HIV-AIDS, TB and Malaria. Conclusions Consistent with WHO recommendations, malaria endemic countries which are experiencing resistance to currently used antimalarial drug monotherapies (chloroquine, sulphadoxine/pyrimethamine or amodiaquine) should change treatment policies to the highly effective artemisinin-based combination treatments (ACTs). We call on all RBM partners to unite in a global coalition to mobilise expertise and resources to support countries to access ACTs and to make these drugs affordable to the people in need. \* \* \* ANNEX I WHO Informal Consultation on the Use of Antimalarial Drugs (13-17 November 2000) The meeting reviewed and updated recommendations on the use of antimalarial drugs for malaria prevention and treatment of uncomplicated malaria, and to assess the implications of latest drug developments for national treatment policies. The experts elaborated a specific definition of antimalarial combination therapy, and highlighted the strategic value of drug combinations for national malaria control programmes and those involved in implementing antimalarial treatment policies. In particular, the experts recognized and widely accepted: "the potential value of drug combinations, notably those containing an artemisinin derivative, to improve efficacy, delay development and selection of drug-resistant parasites and thus prolong the therapeutic life of existing antimalarial drugs. Combinations that do not contain an artemisinin derivative could be a preferred option for reasons of cost and accessibility in some countries." WHO Technical Consultation on Antimalarial Combination Therapy (4-5 April 2001) In view of the recognition of the role of combination therapy, WHO convened a technical consultation to review existing evidence on combination therapy for malaria and to make specific choices on appropriate combinations for use. The Technical Consultation strongly endorsed the potential of combination therapy for use in Africa. It recommended the following four combination therapies with potential for deployment, on the basis of the available safety and efficacy data, which are listed below in prioritized order, if costs were not an issue: artemether/lumefantrine; artesunate (3 days) plus amodiaquine; artesunate (3 days) plus sulfadoxine/pyrimethamine (SP), in areas where SP efficacy is high; amodiaquine plus SP, in areas where efficacy of both drugs remains high - mainly limited to countries in West Africa. The consultation recognized that increased funding would be required to facilitate the appropriate exploration of use and purchase of optimal antimalarial drugs. Failure to assure funding for antimalarial drugs will provide a major obstacle for many countries in Africa in moving to combination therapy. Options that were not recommended for policy included: chloroquine-based combinations (CQ + SP and CQ + artesunate) one-day treatment of artesunate + SP mefloquine-based combinations (e.g. mefloquine plus artesunate) in areas of high malaria transmission one-day treatment of artesunate plus mefloquine in the acute phase of a complex emergency or malaria epidemics The committee also recommended the accelerated development of other artemisinin-based combination therapies which are in the pipeline, in particular of: piperaquine/dihydroartemisinin, chlorproguanil/dapsone/artesunate and pyronaridine/artesunate. ------ MSF MSF also recommends combination products or co-blisters, NOT to use artesunate in isolation. See [http://www.accessmed-msf.org/prod/publications.asp?scntid=2442003111212&cont](http://www.accessmed-msf.org/prod/publications.asp?scntid=2442003111212&cont) enttype=PARA& Or full report (3.5MByte!) [http://www.accessmed-msf.org/documents/malariaACTNOWlow.pdf](http://www.accessmed-msf.org/documents/malariaACTNOWlow.pdf) ----- [MEDLINE on artusenate & SANOFI] Med Trop (Mars). 1998;58(3 Suppl):70-2. Positioning, labelling and control of medical information: artesunate strategy and Arsumax development story. Moneton P, Ducret JP. Sanofi Winthrop AMO, Gentilly, France. philippe.moneton@sanofi.com Sanofi decided, some years ago, to help developing a molecule of a new type called artesunate, a semisynthetic derivative from Qinghaosu, or artemisinine, a sesquiterpenic lactone extracted from the leaves of a world wide spread plant: Artemisia annua. After having signed a secrecy agreement with a local pharmaceutical company in China manufacturing artesunate, Sanofi started, in 1993, the assessment of all the data transmitted as well as the plant involved in the artesunate tablet manufacturing. As conclusions of the whole audit performed on this project were judged satisfactory, Sanofi signed a cooperation agreement with this Chinese pharmaceutical firm in order to be allowed to start further development work required to guarantee quality and safety of artesunate 50 mg tablets called Arsumax, and to complete a registration dossier acceptable for Health Authorities in French-speaking Africa. Pharmaceutical, pharmacotoxicological and clinical documentation were widely completed, and entirely reformated according to European guidelines. The registration dossier was submitted in all French speaking African countries. The approval has been obtained in 13 countries. Due to its fast efficacy, its absence of undesirable effects, its presentation in tablets, its quite simple dosage (one box for a treatment), Arsumax positioned itself as an accurate second line antimalaric treatment. PMID: 10212905 [PubMed - indexed for MEDLINE] -- To send a message to E-Drug, write to: e-drug@healthnet.org To subscribe or unsubscribe, write to: majordomo@healthnet.org in the body of the message type: subscribe e-drug OR unsubscribe e-drug To contact a person, send a message to: e-drug-help@healthnet.org Information and archives: [http://www.essentialdrugs.org/edrug](http://www.essentialdrugs.org/edrug)