Echinococcosis Medication

Updated: Apr 06, 2015
  • Author: Dominique A Vuitton, MD, PhD; Chief Editor: Burke A Cunha, MD  more...
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Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity, to prevent complications, and to eradicate infection.

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Benzimidazole anthelmintic drugs

Class Summary

Benzimidazoles have efficacy on E granulosus and E multilocularis larval stages. Mebendazole (MBZ) and albendazole (ABZ) are the only benzimidazoles effective in experimental models, but their efficacy is related to the clinical condition. These drugs bind to the free beta-tubulin of the parasite, thereby inhibiting both polymerization of tubulin and microtubule-dependent uptake of glucose. In E multilocularis infection, MBZ and ABZ are not parasiticidal, but they do reduce protoscolex viability in vitro and in vivo and inhibit the growth and development of germinal cells in vivo. Because of better bioavailability, better observance, and commercial availability and authorization worldwide, ABZ is usually the preferred drug. Although praziquantel is more effective against protoscoleces than benzimidazole, it is not indicated alone in the treatment of alveolar echinococcosis because it is totally ineffective against larval growth.

Mebendazole (Vermox)

Systemic bioavailability is low because MBZ is poorly absorbed and is subject to significant first-pass metabolism. Administering with a fatty meal enhances the extent and rate of absorption; resultant plasma concentration is 8 times higher than in fasting state. The decarboxylated inactive metabolite is excreted in urine and bile. Considerable between-patient variability in MBZ plasma concentrations. Measure MBZ radioimmunoassay and HPLC with ultraviolet or electrochemical detection. Individualize dosage by measuring plasma levels 4 h after administering the drug. Target MBZ concentration 4 h after morning dose averages 250 nmol/L (74 ng/mL).

Albendazole (Albenza)

Poorly and variably absorbed and subject to significant first-pass metabolism, resulting in a sulfoxide metabolite (ASOX) that may be the active form of the drug. Administering with fatty meal enhances extent and rate of absorption; resultant plasma concentrations are 4-5 times higher than in a fasting state. Considerable interindividual/intraindividual variation in ASOX plasma concentration/time curves. Continuous therapy has better efficacy without marked increase in adverse effects and is currently recommended in all cases of alveolar echinococcosis.

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Other Antifungal/antiparasitic drugs

Class Summary

Although these drugs have not been formally authorized for use in this indication, evidence of their efficacy against E multilocularis in vitro and data from pilot trials in humans may support their use in rare cases in which inefficacy or contraindication of benzimidazoles is demonstrated. Only 2 such drugs may be proposed: amphotericin B and nitazoxanide. Among them, data are available only for amphotericin B; a pilot trial of nitazoxanide in Europe was unsuccessful.

Amphotericin B (Amphocin, Fungizone)

Produced with a strain of Streptomyces nodosus, amphotericin B is a broad-spectrum antifungal drug but also has diverse antiprotozoal activity against Leishmania and Trypanosoma species. Its destructive mechanism against E multilocularis, shown in vitro, could be explained by formation of complexes with membrane phospholipids, which are major components of E multilocularis larval membrane; furthermore, amphotericin B affects membrane-bound enzymes and binds to sterols, thereby forming transmembrane channels. Importantly, amphotericin B is parasitostatic against only E multilocularis. In addition, IV administration and various side effects limit its use to salvage treatment in otherwise untreatable alveolar echinococcosis.

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Immunomodulating agents

Class Summary

Immune modulation of parasitic growth in alveolar echinococcosis has been demonstrated, with a markedly unbalanced Th1/Th2 profile. Efficacy of interferon gamma, which has been tested in the mouse model of alveolar echinococcosis and in a few patients, has not been demonstrated. Recombinant interleukin 12 (IL-12) is fairly efficient in E multilocularis –infected mice but may not be used in humans. Recombinant interferon alpha-2a was able to shrink alveolar echinococcosis lesions size in a patient with a combination hepatitis C and E multilocularis infection and was proven to protect infected mice against the development of alveolar echinococcosis lesions. No clinical trials are available yet.

Interferon alfa 2a (Roferon-A)

Protein produced by recombinant DNA technology. Efficacy in alveolar echinococcosis seems to be due to stimulation of Th1 cytokine production and reversal of the Th1/Th2 unbalance observed in patients with chronic infection by E multilocularis; stimulation of macrophage activation, phagocytosis, and killing has also been shown in experimental studies. Clinical experience with the drug comes from a single observation.

No information is available on interferon alpha-2a/albendazole combined efficacy or side effects.

Given the status of the clinical experience, interferon alpha-2a should be given only for salvage treatment for otherwise untreatable alveolar echinococcosis or as part of a controlled trial.

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