Cryptococcal Meningitis Treatment Strategies Affected by the Explosive Cost of Flucytosine in the United States: A Cost-effectiveness Analysis

Background. In the United States, cryptococcal meningitis causes approximately 3400 hospitalizations and approximately 330 deaths annually. The US guidelines recommend treatment with amphotericin B plus flucytosine for at least 2 weeks, followed by fluconazole for a minimum of 8 weeks. Due to generic drug manufacturer monopolization, flucytosine currently costs approximately $2000 per day in the United States, with a 2-week flucytosine treatment course costing approximately $28 000. The daily flucytosine treatment cost in the United Kingdom is approximately $22. Cost-effectiveness analysis was performed to determine the value of flucytosine relative to alternative regimens. Methods. We estimated the incremental cost-effectiveness ratio (ICER) of 3 cryptococcal induction regimens: (1) amphotericin B deoxycholate for 4 weeks; (2) amphotericin and flucytosine (100 mg/kg/day) for 2 weeks; and (3) amphotericin and fluconazole (800 mg/day) for 2 weeks. Costs of care were calculated using 2015 US prices and the medication costs. Survival estimates were derived from a randomized trial and scaled relative to published US survival data. Results. Cost estimates were $83 227 for amphotericin monotherapy, $75 121 for amphotericin plus flucytosine, and $44 605 for amphotericin plus fluconazole. The ICER of amphotericin plus flucytosine was $23 842 per quality-adjusted life-year. Conclusions. Flucytosine is currently cost-effective in the United States despite a dramatic increase in price in recent years. Combination therapy with amphotericin and flucytosine is the most attractive treatment strategy for cryptococcal meningitis, though the rising price may be creating access issues that will exacerbate if the trend of profiteering continues.