Advances in Pharmacoepidemiology and Drug Safety

Abstrait

Post-Marketing Change in Dosage and Administrations of FDA-Approved Drugs Between 2000 and 2017

Masako Ashida*, Mamoru Narukawa

Purpose: Relevant information on the change in dosage in the post-marketing stage would be useful in considering future clinical development strategies. Therefore, we investigated the content and timing of post-marketing dosage changes using labeling information for New Molecular Entities (NMEs) approved by the FDA.

Methods: We compiled a list of NMEs approved by the FDA between January 1, 2000, and December 31, 2017, using the FDA’s website, and the descriptions of the section “dosage and administration” in the latest labeling as of December 31, 2018, were compared with that for the initial approval for each drug. The time required for the change in dosage for the main patient population was estimated using survival analysis.

Results: Of the 432 NMEs, 425 (98%) were evaluable. Dosage changes in the initially indicated populations occurred in 178 NMEs (42%). The time required for the change in dosage was shorter for recently approved drugs. Dosage changes for the main patient population, patients with renal/hepatic impairment, and pediatric/adolescent patients accounted for 23%, 27%, and 24% of the total 275 changes, respectively. For dose-related labeling change for the main patients, the earliest change occurred 1 year after approval, and some drugs took more than 10 years before the change.

Conclusion: Over 40% of NMEs approved by the FDA after 2000 underwent a change in dosage after marketing, and over half of the total changes were for special populations. It is necessary to consider ways to accelerate the establishment of appropriate dosages for special populations after marketing.