Drug Topics - March 10, 2008 - (Page 20) 20 DRUG TOPICS MARCH 10, 2008 www.drugtopics.com Rx Care IDSA updates aspergillosis treatment guide Heidi Belden, Pharm.D. ractitioners treating immunocompromised patients for life-threatening aspergillosis infections now have a new guide to aid them in choosing appropriate therapy. The Infectious Diseases Society of America (IDSA) recently published new practice guidelines for management of aspergillosis infections, an update to its 2000 recommendations. “With an expanding armamentarium of diagnostic and therapeutic modalities, the choices available to practitioners have expanded dramatically in recent years,” said Melissa D. Johnson, Pharm.D., Melissa Johnson MHS, assistant professor of medicine at welcomes new ISDA guidelines to Duke University Medical Center’s Divitreat aspergillosis sion of Infectious Diseases and International Health. The guidelines help to put use of newer antifungal agents into perspective, and to make choices which are critical in the case of aspergillosis, given its associated high risk of mortality, she explained. According to IDSA, patients with prolonged neutropenia, advanced HIV infection, inherited immunodeficiency, and those who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) and/or lung transplantation are at risk for infection with aspergillosis. The new guideline focuses on three major forms: invasive aspergillosis, chronic (and saprophytic) types, and allergic aspergillosis. IDSA recommends voriconazole (Vfend, Pfizer) as primary treatment of invasive aspergillosis for most patients. According to the new guide, only a few randomized trials exist that discuss the treatment of invasive aspergillosis, but the largest trial demonstrates that voriconazole is superior to deoxycholate amphotericin B (D-AMB) as a first-line treatment. The study compared voriconazole with D-AMB and other licensed antifungal agents. Voriconazole was shown to be the most effective, followed by D-AMB, and then the other antifungals. Survival at 12 weeks was 71% for voriconazole-treated patients versus 58% of those treated with D-AMB. The voriconazole group also experienced fewer drug-related side effects. “Initial use of voriconazole was associated with improved survival and treatment response,” Johnson said. However, she pointed out that since pulmonary nodules can be somewhat nonspecific, and voriconazole lacks P activity against zygomycetes, it is important to establish the diagnosis when voriconazole is to be used. IDSA does point out, however, that, given that the risk of mortality is so high among patients with invasive mycoses, treatment should not be delayed in the absence of a solid diagnosis when aspergillosis is suspected. Voriconazole should be dosed as 6 mg/kg IV every 12 hours for two doses, followed by 4 mg/kg every 12 hours. Intravenous therapy can be transitioned to oral therapy—typically 200 mg every 12 hours for stable adults. “However, IV voriconazole is generally not recommended for those with creatinine clearance <50 ml/ min. Issues related to organ function, adverse effects, and/or drug interactions may make it difficult to administer voriconazole in some patients,” Johnson added. Liposomal amphotericin B (L-AMB) is an alternative for treating invasive aspergillosis in some patients. According to the new guide, prophylaxis with posaconazole (Noxafil, Schering-Plough) is appropriate in HSCT patients with graft-versus-host disease who are at high risk for invasive aspergillosis and in neutropenic patients with acute myelogenous leukemia or myelodysplastic syndrome, also at high risk. Management of chronic or saprophytic forms of aspergillosis varies depending on the condition. Pulmonary aspergillomas may be best managed by surgical resection, as the role of medical therapy is uncertain. However, alternative therapies include itraconazole or voriconazole. The IDSA guidelines make the point that, while the penetration of amphotericin B into pre-existing cavities may be minimal, it is excellent for itraconazole. With chronic cavitary pulmonary aspergillosis however, surgical resection may lead to significant complications, and therefore itraconazole or voriconazole is recommended and long-term therapy may be warranted. When treating chronic necrotizing pulmonary aspergillosis, a protracted course of therapy is required and an oral triazole, such as voriconazole or itraconazole, would be preferred to a parenteral. First-line treatment for allergic bronchopulmonary aspergillosis is itraconazole along with corticosteroids, which are a cornerstone of therapy. IDSA pointed out that itraconazole has a demonstrable corticosteroidsparing effect. The IDSA guidelines can be accessed online at www. journals.uchicago.edu/doi/pdf/10.1086/525258. DT http://www.drugtopics.com http://www.journals.uchicago.edu/doi/pdf/10.1086/525258
For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.