(P-214) Real World Evidence in Effectiveness, Safety, and Cost Savings of Generic Levothyroxine: A Systematic Review

Background: Levothyroxine, a narrow therapeutic index (NTI) drug, is among the most prescribed medications in the United States. Generic drugs are approved through bioequivalence studies among healthy volunteers, not patients. Post-marketing evidence in generic equivalence for levothyroxine products is limited.

Objectives: To synthesize existing evidence in effectiveness, safety, and cost savings between real world patients using generic and branded levothyroxine.

Methods: A systematic literature search was conducted using Medline, International Pharmaceutical Abstracts, APA Psychinfo, and CINAHL databases from inception through February 1, 2021. Search teams included a combination of generic and brand names of levothyroxine products, as well as generic switching and substitution. Included studies were limited to post-marketing empirical studies including patients who used levothyroxine products, with direct comparison between generic and brand levothyroxine, and published in English. Risk of bias was assessed using the National Institute of Health Study Quality Assessment Tool.

Results: Among the 342 records searched, six studies meeting inclusion and exclusion criteria were included in the review. The majority (n=5) of included studies used retrospective study designs, and one study was a cross-sectional survey of 199 physicians who were frequent prescribers of levothyroxine. Five (5) studies were of good quality, while the remaining one was of fair quality. One study included children with congenital hypothyroidism while the rest studies focused on the general hypothyroidism patients. Three studies compared clinical outcomes between generic and brand levothyroxine and provided mixed findings. Specifically, two studies found no difference in patient’s TSH and thyrotropin levels between generic and brand levothyroxine users. But one study of physician survey reported potential difference in adverse events and TSH change due to switching from brand to generic levothyroxine. In addition, two studies assessed economic outcomes and highlighted potential savings for Medicaid and Managed Care payers due to lower cost of generic levothyroxine. One study compared medication adherence and found that patients who initiated Synthroid had higher adherence at 6 and 12 months compared to generic levothyroxine initiators.

Conclusions: Real world evidence in effectiveness, safety, and cost savings of generic levothyroxine is very limited. Continuous post-marketing monitoring and assessment of generic levothyroxine and other NTI products are warranted to ensure patient safety.