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Occupational Medicine 2015;65:417
© The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine.
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LETTER TO THE EDITOR
Unexpected pharmacological and
toxicological effects of tafenoquine
I read with interest the recent case report by Cannon
etal. , describing a case of occupational asthma result-
ing from exposure to the 8-aminoquinoline tafenoquine,
a transmission-blocking antimalarial currently in late
stage development [2,3].
Their report, the rst describing the asthmagenicity of
the drug, is particularly unexpected given historical lit-
erature from the 1950s and 1960s describing seemingly
successful investigations into the use of quinolines as bron-
chodilators in the treatment of bronchial asthma [4,5].
More recent reports have also suggested that the quino-
lines may be effective anti-inammatory agents [6,7].
Broader use of the 8-aminoquinolines has historically
been limited owing to ndings of idiosyncratic neurotoxic-
ity [8,9], with a fatal human case marked by widespread
neuronal degeneration within the brainstem . The new
nding of unexpected and idiosyncratic asthmagenicity
suggests a need to more thoroughly dene the potentially
complex pharmacology and toxicology of tafenoquine prior
to the drug’s more widespread use, particularly among
asymptomatic populations in planned antimalarial mass
drug administration. Pharmacogenetic investigations, par-
ticularly of common polymorphisms in drug metabolizing
and transport enzyme genes , may provide insight into
the drug’s unexpected effects and should be considered
both in future pre-licensing studies and in occupational
medicine investigations of idiosyncratic toxicity.
Conicts of interest
The author has been retained as consultant and expert
witness in criminal and civil cases involving claims of
antimalarial toxicity. The author has no other nancial or
other conicts of interest to report.
Department of MentalHealth,
Johns Hopkins Bloomberg School of PublicHealth,
624 N.Broadway, Room782, Baltimore, MD 21205,USA
e-mail: r firstname.lastname@example.org
1. Cannon J, Fitzgerald B, Seed M, Agius R, Jiwany A,
Cullinan P. Occupational asthma from tafenoquine in the
pharmaceutical industry: implications for QSAR. Occup
Med (Lond) 2015;65:256–258.
2. Renslo AR. Antimalarial drug discovery: From qui-
nine to the dream of eradication. ACS Med Chem Lett
3. Marcsisin SR, Sousa JC, Reichard GA et al. Tafenoquine
and NPC-1161B require CYP 2D metabolism for anti-
malarial activity: implications for the 8-aminoquinoline
class of anti-malarial compounds. Malar J 2014;13:2.
4. Geschickter CF. Quinoline therapy in asthma: a report of
500 cases. South Med J 1955;48:497–509.
5. Young RC Jr, Murray AJ, Carr C, Harden KA.
Phthalamaquin: its effect in the treatment of bronchial
asthma as determined by studies of ventilatory function. J
Natl Med Assoc 1965;57:189–193.
6. Mukherjee S, Pal M. Quinolines: a new hope against
inammation. Drug Discov Today 2013;18:389–398.
7. Mukherjee S, Pal M. Medicinal chemistr y of quinolines as
emerging anti-inammatory agents: an overview. Cur r Med
8. Schmidt IG, Schmidt LH. Neurotoxicity of the 8-amino-
quinolines. III. The effects of pentaquine, isopentaquine,
primaquine, and pamaquine on the central nervous sys-
tem of the rhesus monkey. J Neuropathol Exp Neurol
9. Sipe JC, Vick NA, Schulman S, Fernandez C. Plasmocid
encephalopathy in the rhesus monkey: a study of
selective vulnerability. J Neuropathol Exp Neurol
10. Loken AC, Haymaker W. Pamaquine poisoning in man,
with a clinicopathologic study of one case. Am J Trop Med