Effectiveness and risk with LapDap

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Effectiveness and risk with LapDap

• A classic dilemma
• Personal views
• I Ralph Edwards

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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

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Mystic Herbal balm ?
Mystic Herbal balm ?
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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
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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

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But..

• Dapsone causes
• Variably severe haemolysis in people with G6PD
  deficiency
• gt20 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!!
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Registration of LapDap

• First registered in UK, now in lt20 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
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Pull out, Bettyl Pull out...Youve hit on artery
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Review of Safety of Chlorproguanil/DapsoneWHO
Technical ConsultationGeneva, 1-2July,
2004Publ. March 2005
The executive summary only
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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

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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.

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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!

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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

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