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Effectiveness and risk with LapDap. A classic dilemma Personal views: I Ralph Edwards. What is LapDap. Two very old drugs, combined for a new indication: Malaria Chlorproguanil An little used anti-malarial Dapsone An anti-leprotic and immunomodulator. Mystic Herbal balm ?.
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Effectiveness and risk with LapDap A classic dilemma Personal views: I Ralph Edwards
What is LapDap • Two very old drugs, combined for a new indication: Malaria • Chlorproguanil • An little used anti-malarial • Dapsone • An anti-leprotic and immunomodulator
Mystic Herbal balm ? Mystic Herbal balm ?
Is the combination effective in malaria? • Yes, in studies of nearly 3000 African subjects (nearly all children) published in the Lancet and submitted to the UK MHRA, it is very effective • Also in sulfadoxine-pyrimethamine resistance • In Asia there is considerable resistance developed • The time window for effective use in Africa may be limited It is also cheap: around the same price as chloroquine
Is it safe? • Considerable inter-individual variability in plasma levels of both drugs • ? Genetic polymorphisms • No PK studies in elderly or diseased • Limited previous experience in children • Dapsone dose about 2x its use in leprosy, and close to toxic dose • Limited experience with chlorproguanil, but no major problems
But….. • Dapsone causes: • Variably severe haemolysis in people with G6PD deficiency • >20% of Africans have the deficiency to some extent • They will not know they have it unless tested • Methaemaglobinaemia, with reduced oxygen carryng capacity Malaria also causes haemolysis!!
Registration of LapDap • First registered in UK, now in <20 African countries • UK conditions are: • Prescription only • Contraindicated in G6PD There is no serious restriction on availability imposed in Africa About 50% of patients who treat themselves for malaria do not have the disease How will patients know they are G6PD deficient anyway
Review of Safety of Chlorproguanil/DapsoneWHO Technical ConsultationGeneva, 1-2July, 2004Publ. March 2005 The executive summary only
Chlorproguanil/Dapsone • Should be used only if the diagnosis of malaria is confirmed. • Should only be used after anaemia have been excluded by a reliable clinical or laboratory test and G6PD deficiency by a reliable laboratory test. • The diagnosis of methaemoglobinemia is less important
Chlorproguanil/Dapsone • In areas where G6PD deficiency is prevalent, it is important before using CPG-DDS to know the level of anaemia and the G6PD status of the patient. If appropriate tests are not possible, an alternative antimalarial medicine should be used. • If there is no suitable alternative, CPG-DDS should be used taking into account all the risks associated with this medicine.
Chlorproguanil/Dapsone • These recommendations are to be reconsidered when more data becomes available from pharmacovigilance and active post-marketing surveillance. • Safety studies have yet to be done!
Implications • What is its safety on repeated use? • Is this a good combination with artemesinin derivatives? • For: Cheap and effective • Against: Safety, as we assess it now