Pancytopenia from Albendazole
Abstract & Commentary
With Comment by Michele Barry MD, FACP, Professor of Medicine; Co-Director, Tropical Medicine and International Travelers’ Clinic, Yale University School of Medicine, and Associate Editor, Travel Medicine Advisor.
Synopsis: A man died with pancytopenia following a course of albendazole in preparation for the excision of an echinococcal cyst. Is this a potential complication of therapy with this commonly used agent?
Sources: Opatrny L, et al. Death Related to Albendazole-Induced Pancytopenia: Case Report and Review. Am J Trop Med Hyg. 2005;72:291-294.
Opatrny and colleagues describe a death that they attribute to albendazole-induced pancytopenia in a man with Child-Pugh class B cirrhosis. The patient was a 68-year-old Peruvian man with a 9 cm echinococcal lung cyst containing an air fluid level, a crescent sign and layering in a dependent position. Surgical resection was planned, so oral albendazole, 400 mg twice daily, was begun for 4 weeks prior to his elective surgery. The patient’s blood counts prior to surgery included a platelet count of 118 × 109/L, a white blood count of 5.96 × 109/L, hemoglobin concentration of 132 g/L, and an INR of 2.27. Sixteen days after starting treatment with albendazole, the patient presented to the Canadian hospital’s emergency department—hypotensive with Klebsiella sepsis and pneumonia, as well as CT confirmation of a larger air fluid level and pericystic inflammation indicating leakage of the cyst. WBC was 0.05 × 109/L, hemoglobin 68 g/L, and platelet count 11 × 109/L. Seven days into admission, after meropenem and gentamicin therapy, granulocyte colony stimulating factor and intravenous gammaglobulin were administered, but the patient expired from a massive esophageal variceal bleed without evidence of any marrow recovery. Autopsy did not indicate either a lymphoproliferative process or infectious process in his marrow, and so albendazole marrow toxicity was inferred.
Comment
Albendazole, a benzamidazole compound, is commonly used for treatment of echinococcal cysts prior to surgical resection, as well as for curative therapy via a prolonged or cyclical treatment pattern. It undergoes virtually 100% passive first-pass metabolism in the liver, and is known to have a significantly increased serum half-life in patients with liver disease. Neutropenia and pancytopenia have been observed in animal models at high doses. However, the overall incidence of neutropenia during long duration of use has been less than 1%.
Bioavailability varies dramatically, increasing especially with fatty meals and grapefruit ingestion. Although this patient probably had the complicating co-factor of potential marrow suppression caused by severe sepsis at the time of his presentation, his severe liver dysfunction probably resulted in reduced metabolic conversion of albendazole and very high serum levels resulting in inhibition of microtubule-dependent processes such as cell division in the marrow. Tubulin polymer inhibition is the mechanism by which antihelminthic action occurs. Albendazole’s low toxicity record might engender complacency among practitioners prescribing long courses of weeks to months. Despite the potential for sepsis having contributed to marrow suppression, this case serves as a reminder that severe hepatic dysfunction is a relative contraindication to albendazole use and mandates close follow-up of serial blood counts and liver functions testing, if no other treatment alternatives are available. In addition, as albendazole levels cannot be routinely obtained, consideration should be given to lower dosing in patients with hepatic dysfunction.
A man died with pancytopenia following a course of albendazole in preparation for the excision of an echinococcal cyst. Is this a potential complication of therapy with this commonly used agent?
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