Miltefosine

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Miltefosine (hexadecylphosphocholine; Milteforan®) is a phospholipid drug used as both a chemotherapy drug and treatment for canine leishmaniasis[1].

This drug is an orally bio-available chemical that was originally studied as an antitumor agent. Subsequent to the serendipitous laboratory finding that miltefosine was active against Leishmania in vitro, it was tested in dogs in vivo and found to be an effective agent at eliminating parasitemia[2]. The advantage of this drug is that its direct anti-parasitic activity is not dependent on a functional immune system[3].

Recently registered for the oral treatment of canine leishmaniasis in several European countries, miltefosine has been used in combination with marbofloxacin and/or allopurinol, with good efficacy even when used as a stand-alone therapy[4]. However, clearance of the parasite, as evidence by PCR testing of L. infantum antigens is rarely complete when used alone[5].

Unlike the anitmonials such as meglumine antimonite, there are no reported nephrotoxic effects with this drug[6] and only mild vomiting as a noteworthy side-effect in some dogs[7].

However, teratogenicity[8], prolonged treatment, high cost and the rapid development of drug resistance (due to its long half-life) have limited its use in some cases[9].

Recommended dose rate in dogs is 2 mg/kg orally once daily for 28 days in conjunction with allopurinol at 10 mg/kg orally twice daily for 7 months[10] to potentiate the efficacy of both drugs and limit drug resistance.

References

  1. Faucher B & Piarroux R (2011) Visceral leishmaniasis: an update. Rev Med Interne 32(9):544-551
  2. Foglia Manzillo V et al (2009) Resolution of tongue lesions caused by Leishmania infantum in a dog treated with the association miltefosine-allopurinol. Parasit Vectors 2(1):S6
  3. Kuhlencord A et al (1992) Hexadecylphosphocholine: oral treatment of visceral leishmaniasis in mice. Antimicrob Agents Chemother 36:1630–1634
  4. Farca AM et al (2012) Canine leishmaniosis: in vitro efficacy of miltefosine and marbofloxacin alone or in combination with allopurinol against clinical strains of Leishmania infantum. Parasitol Res 110(6):2509-2513
  5. Andrade HM et al (2011) Evaluation of miltefosine for the treatment of dogs naturally infected with L. infantum (=L. chagasi) in Brazil. Vet Parasitol 181(2-4):83-90
  6. Bianciardi P et al (2009) Administration of miltefosine and meglumine antimoniate in healthy dogs: clinicopathological evaluation of the impact on the kidneys. Toxicol Pathol 37(6):770-775
  7. Woerly V et al (2009) Clinical efficacy and tolerance of miltefosine in the treatment of canine leishmaniosis. Parasitol Res 105(2):463-469
  8. Shukla AK et al (2010) Rational approaches for drug designing against leishmaniasis. Appl Biochem Biotechnol 160(8):2208-2218
  9. Croft SL et al (2006) Drug Resistance in Leishmaniasis. Clin Microbiol Rev 19:111–126
  10. Miró G et al (2009) Multicentric, controlled clinical study to evaluate effectiveness and safety of miltefosine and allopurinol for canine leishmaniosis. Vet Dermatol 20(5-6):397-404