Abstracts

Rationale: Product switching (brand/manufacturer or dose/formulation of the same drug) is associated with non-adherence and breakthrough seizures in patients with epilepsy. Rates of product switching and discontinuation were characterized in patients on levetiracetam (LEV) brands experiencing shortages in Australia, and compared with non-shortage periods to understand how antiseizure medication (ASM) shortages affect product switching and discontinuation in patients with epilepsy. LEV was chosen as the focus due to multiple shortages in the Medicine Shortage Information Initiative (MSII), widespread usage in multiple seizure types and ages, and limited use outside epilepsy.

Methods: Data were obtained from the Australian Therapeutic Goods Administration MSII on all LEV shortages between Jan 2019 and Nov 2020. Shortage dates were cross-referenced with IQVIA-NostraData Longitudinal Dispensation data, which collects pharmacy dispensing data from 25 million patients in Australia with 75% coverage of retail pharmacies nationwide. Patients dispensed a LEV product (brand-formulation-strength combination) appearing in MSII in the 90 days before a shortage were designated as “on therapy.” Patients on therapy and with two consecutive dispensations of a relevant product before start of a shortage were classified as “continuing” (only dispensation of index product throughout shortage), “switching” (dispensation of ≥ 1 different LEV ASM during the shortage), or “discontinuing” (no further LEV dispensations throughout shortage). Switching patterns were compared with the corresponding (non-shortage) period in the prior year to estimate how shortages were associated with rates of product switching and discontinuation.

Results: 118 LEV product shortages were identified and 100% were generic brands. Overlapping shortages of same product were consolidated, leaving 23 distinct shortages (Table 1). Median shortage was 133 days (interquartile range 80, 229.5). Of 11 government funded generic brands of LEV, seven (64%) were affected by shortages over 23 months, representing 93% of total volume of generic LEV dispensed over study period. 46,037 patients had ≥ 1 dispensation for generic LEV over study period. 43,531 (95%) of these patients (non-unique) were affected by shortages. Across all shortages, 24% of patients on therapy at point of shortage continued on therapy across the shortage period vs 46% (non-shortage periods); 68% switched to a different product vs 47% (non-shortage periods); 8% discontinued LEV in shortage periods vs 7% (non-shortage periods) (Table 1).

Conclusions: Shortages affected most brands of generic LEV in Australia, but not the originator brand Keppra. Shortages were associated with increased product switching compared with non-shortage periods. The results suggest that consideration may be necessary when initiating or switching patients to generic ASM brands due to high rates of generic ASMs being in shortage, and associated product switching in shortage periods, which in independent research has been associated with non-adherence and breakthrough seizures.

Funding: Please list any funding that was received in support of this abstract.: UCB Pharma-funded.