Efficacy, Safety, and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis

Clin Infect Dis. 2016 Feb 1;62(3):334-341. doi: 10.1093/cid/civ882. Epub 2015 Oct 20.

Abstract

Background: Available treatments for lymphatic filariasis (LF) are limited in their longterm clearance of microfilaria from the blood. The safety and efficacy of a single-dose triple-drug therapy of the antifilarial drugs diethylcarbamazine (DEC), ivermectin (IVM), and albendazole (ALB) for LF are unknown.

Methods: We performed a pilot study to test the efficacy, safety, and pharmacokinetics of single-dose DEC, IVM, and ALB in Wuchereria bancrofti-infected Papua New Guineans. Adults were randomized into 2 treatment arms, DEC 6 mg/kg + ALB 400 mg (N = 12) or DEC 6 mg/kg + ALB 400 mg + IVM 200 μg/kg (N = 12), and monitored for microfilaria, parasite antigenemia, adverse events (AEs), and serum drug levels.

Results: Triple-drug therapy induced >2-log reductions in microfilaria levels at 36 and 168 hours after treatment compared with approximately 1-log reduction with 2 drugs. All 12 individuals who received 3 drugs were microfilaria negative 1 year after treatment, whereas 11 of 12 individuals in the 2-drug regimen were microfilaria positive. In 6 participants followed 2 years after treatment, those who received 3 drugs remained microfilaria negative. AEs, particularly fever, myalgias, pruritus, and proteinuria/hematuria, occurred in 83% vs 50% of those receiving triple-drug compared to 2-drug treatment respectively (P = .021); all resolved within 7 days after treatment. No serious AEs were observed in either group. There was no significant effect of IVM on DEC or ALB drug levels.

Conclusions: Triple-drug therapy is safe and more effective than DEC + ALB for Bancroftian filariasis and has the potential to accelerate elimination of lymphatic filariasis.

Clinical trials registration: NCT01975441.

Keywords: albendazole; chemotherapy; diethylcarbamazine; ivermectin; lymphatic filariasis.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albendazole / administration & dosage*
  • Albendazole / adverse effects
  • Albendazole / pharmacokinetics
  • Animals
  • Diethylcarbamazine / administration & dosage*
  • Diethylcarbamazine / adverse effects
  • Diethylcarbamazine / pharmacokinetics
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Elephantiasis, Filarial / drug therapy*
  • Female
  • Filaricides / administration & dosage*
  • Filaricides / adverse effects
  • Filaricides / pharmacokinetics
  • Humans
  • Ivermectin / administration & dosage*
  • Ivermectin / adverse effects
  • Ivermectin / pharmacokinetics
  • Male
  • Middle Aged
  • Papua New Guinea
  • Parasitemia / drug therapy
  • Pilot Projects
  • Serum / chemistry
  • Single-Blind Method
  • Treatment Outcome
  • Wuchereria bancrofti / isolation & purification
  • Young Adult

Substances

  • Filaricides
  • Ivermectin
  • Albendazole
  • Diethylcarbamazine

Associated data

  • ClinicalTrials.gov/NCT01975441