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Regulatory Focus™ > News Articles > 2020 > 10 > Good real-world outcomes for generic levothyroxine, despite narrow therapeutic index

Good real-world outcomes for generic levothyroxine, despite narrow therapeutic index

Posted 09 October 2020 | By Mary Ellen Schneider 

Good real-world outcomes for generic levothyroxine, despite narrow therapeutic index

Generic versions of levothyroxine – a treatment for hypothyroidism -- are just as effective in restoring thyroid stimulating hormone levels as brand-name drugs in a real-world population, according to a recent study conducted by researchers from the US Food and Drug Administration, Yale University, and the Mayo Clinic.
Generic levothyroxine is prescribed about six-to-one over branded levothyroxine, but that still leaves generic prescriptions lagging behind prescribing rates in other drug categories, the FDA says. Part of the hesitancy to prescribe the generic version of the drug may stem from the fact that levothyroxine has a narrow therapeutic index
Additionally, endocrine professional societies raised safety concerns following FDA’s initial approval of several generic levothyroxine products. The groups called into question FDA’s method for determining bioequivalence for thyroid products. In response, the agency tightened the potency specifications for levothyroxine sodium, changing the potency specification from 90%-110% to 95%-105%.
“This lag may reflect the hesitancy of some prescribers to prescribe generic levothyroxine, but the real-world evidence provided from the study described here should assure clinicians and patients that generic levothyroxine is as effective as brand-name levothyroxine as initial therapy for hypothyroidism,” the agency wrote in a Spotlight article about the study.
The retrospective, longitudinal cohort study included claims data from 17,598 adults with mild thyroid dysfunction who filled prescriptions for either generic or brand-name levothyroxine from 1 Jan. 2008 to 1 Oct. 2017. The findings were published in JAMA Network Open.
There were 15,299 generic prescriptions and 2,299 brand-name prescriptions filled over the course of the study. The researchers compared the effectiveness of generic and brand-name levothyroxine based on thyrotropin levels within 3 months in the outpatient setting. For comparison, patients receiving generics were matched 1-to-1 with patients receiving brand-name drugs.
Among matched pairs of patients, the proportion who achieved a normal thyrotropin value within 3 months was similar between generic and branded drugs at 75.4% versus 76.9%, respectively (P= .23). The findings were also similar for matched pairs who had clinically meaningful abnormal thyrotropin values at 3 months – 4.1% for patients receiving generic drugs and 3.9% for patients receiving branded drugs (P=.65).
These trends continued when researchers evaluated whether patients maintained normal thyrotropin values during the follow-up period. Among the matched cohort who achieved a normal value within 3 months, 82.6% of patients receiving generics maintained that value within the next 3 months, compared with 83.8% of patients received brand-name drugs (P=.62).
“Our results should reassure physicians and patients that generic levothyroxine as initial therapy for mild thyroid dysfunction is as effective as brand-name levothyroxine,” wrote Juan P. Brito, MD, of Mayo Clinic, and his colleagues. “Moreover, prescribing generic compared with brand-name levothyroxine may offer substantial financial benefits to patients and to the health care system.”
The researchers noted that the mean 30-day out-of-pocket cost was $6.20 for generic levothyroxine and $28.65 for the branded drugs in 2017.
The study does not address the issue of interchangeability, specifically switching between formulations. “Additional research should compare the effectiveness of levothyroxine products among patients who switch therapy during the course of their treatment,” the researchers wrote.
Since the study examined comparative effectiveness of generic versus branded treatments in patients with mild thyroid dysfunction, the study also does not address the impact on patients without remaining endogenous thyroid function. However, the researchers noted that the results are “likely generalizable to most patients in the United States who initiate levothyroxine therapy.”
The study was supported by a Center of Excellence in Regulatory Science and Innovation grant to Yale University and Mayo Clinic from the FDA.

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