OBJECTIVES: To estimate the incremental budgetary change in per-member-per-month (PMPM) medical and pharmacy costs after the introduction of everolimus, a mammalian target of rapamycin inhibitor, for the treatment of subependymal giant-cell astrocytomas  (SEGA) in patients with tuberous sclerosis complex. In a phase I/II trial, everolimus was associated with reduced SEGA volume and seizure frequency. METHODS: Two-year budget impact analysis was conducted based on a retrospective, longitudinal study of administrative claims that showed an increase in healthcare costs in the years leading up to and after surgery for SEGA removal.  Based on the aforementioned trial, the model assumed that patients using everolimus did not require surgical intervention; however, to be conservative, no impact on seizure frequency was assumed.  Estimates of SEGA prevalence, adverse events, drug costs, and monitoring costs were based on published sources.  Sensitivity analysis evaluated the impact of estimating annual treatment costs for patients with continuous eligibility only. RESULTS: In a hypothetical 1,000,000-member health plan, an estimated 5.9 patients with growing SEGAs require care.  Prior to introducing everolimus, estimated total cost for the treatment of growing SEGAs was $0.022 PMPM for all plan members.  After introducing everolimus, there were 0.9, 19.8, and 6.6 fewer claims per patient for inpatient hospitalizations, outpatient visits, and other pharmaceutical use, respectively.  While pharmacy cost increased by $0.038 PMPM, the total medical and pharmacy costs increased by only $0.026, due to fewer SEGA surgeries.  Sensitivity analysis showed greater savings in medical spending after the introduction of everolimus, resulting in a total spending increase of $0.022 PMPM. CONCLUSIONS: Increased pharmaceutical spending in the first two years of everolimus use was partially offset by savings in medical costs. Potential additional savings in anti-epileptic drug spending may further offset the costs.