A case for adoption of continuous albendazole treatment regimen for human echinococcal infections

Abstract

Cystic (CE) and alveolar (AE) echinococcosis are chronic, neglected parasitic diseases burdened by high morbidity and, for AE, by high mortality, if left untreated. CE and AE have a widespread distribution, including Europe. Albendazole (ABZ), a broad-spectrum benzimidazole drug widely used to treat parasitic infections, is the drug of choice for the management of CE and AE, and is parasitostatic on echinococcal metacestodes. In Europe, ABZ is licensed for interrupted “cyclic” treatment, for a maximum of 3 cycles. However, better efficacy with no increased side effects has been shown when the drug is administered continuously and for longer periods. Current international recommendations, on the basis of clinical, pharmacological, and biological studies, recommend continuous administration of ABZ for months to years for the treatment of CE and AE, and this schedule has been widely in use for the past 20 years. However, in Europe this internationally recommended schedule, with the exception of France, is technically “off-label”, and, as such, requires an informed consent by the patient and, in some countries, even precludes the reimbursement of the drug cost. Adding to the very high cost of the drug, frequent “out-of-stock” situation, and packaging format impractical for long therapies, these conditions put patients with CE and AE regularly at risk of treatment discontinuation and disease progression. European regulations envisage variations to marketing authorization, but postauthorization studies should be carried out by the holder of the license of the drug, in the form of randomized controlled trials. While such studies do not seem feasible and would probably not be ethically justified for CE and AE, European regulations envisage other possibilities in particular situations, which apply to CE and AE, but there is limited interest to invest in this perspective. We urge a coordination between stakeholders to find effective and feasible ways to take action to revise the benzimidazole dosage regimens for CE and AE and to ensure a fair, regular, and easy access to the appropriate treatment to those suffering from these serious diseases.

Alveolar Echinococcosis—A Challenging Task for the Hepatobiliary Surgeon

“…Cyclic dosing is considered inferior to continuous BMZ intake. While continuous intake, has never been officially approved by the Food and Drug Administration (FDA) or European Medicines Agency (EMA) it is now considered the gold standard of medical treatment by all experts [34]. Reuter et al presented their own experience with continuous and cyclic dosing and found no differences in toxicity [35] for which the drug was originally recommended to be interrupted every 28 days.…”

Hepatic Alveolar Echinococcosis

“…In case of inextirpable AE lesion(s), albendazole (ABZ) will theoretically be given for life, sometimes in association with instrumental procedures. Continuous ABZ administration is superior to intermittent administration, 88,95 at a daily dose of 800 mg bid. Reduced doses are recommended in case of cholestasis and/or biliary cirrhosis, to avoid toxicity.…”

Unveiling the incidences and trends of the neglected zoonosis cystic echinococcosis in Europe: a systematic review from the MEmE project

“…Such rates of hospi talisation from these three highly endemic countries suggests that sequelae and improper clinical manage ment might increase the disease burden of cystic echinococcosis. 18,38 Such morbidity should be taken in account for further research on the clinical burden of disease at the national level.…”