Label history
Kelsey holds the label versions published on DailyMed, the National Library of Medicine's database of the labeling companies submit to FDA,[1] plus Drugs@FDA[2] and Orange Book editions from 1985. A label that is not held is fetched live from DailyMed where that succeeds. DailyMed itself notes that its labeling may differ from the labeling FDA approved or that was distributed, so a version shows what was published, not which labeling came with a patient's dispensed product.
When the warning appeared
Show the label history of Elmiron.
What comes back: "Warning approved 16 June 2020 (first label version with it: 19 June 2020), in Warnings. The 8 earlier versions (Mar 2010 to Sep 2018) did not mention it." Below it, the sentence that warned:
Pigmentary changes in the retina, reported in the literature as pigmentary maculopathy, have been identified with long-term use of ELMIRON® (see ADVERSE REACTIONS).
A bar runs from Mar 2010 to Sep 2024, split at 16 Jun 2020: "Without the warning, 8 versions without it · Mar 2010 to Sep 2018" and "With the warning, 6 versions with it · Jun 2020 to Sep 2024". Under Sources, the card links the label by month: 12 links for the 14 versions, because the 8 earlier versions fall in six distinct months. Under WHY THIS MATTERS: "The date a warning first appears is the starting point for the notice question: what the reports showed before it, and whether the company could have added it sooner (a company may add a warning itself on newly acquired information, 21 CFR 314.70(c)(6)(iii))."
Each version, with its date
"11 version(s) of the ZOFRAN label are held, from Dec 13, 2000 to Oct 21, 2021." Each row gives the date, the version number, an Open link to the source and "Show the text" for its warning sections. The question asked about one reaction, and the card says at the top: "None of the versions names the reaction group."
The version, opened at its warnings
Clicking the pill opens "ELMIRON label warnings, version 11 (2020-06-19) (Janssen Pharmaceuticals, Inc.)" in the right panel, marked "published 2020-06-19", with a link to dailymed.nlm.nih.gov and "Copy reference". The panel states the set id and "Changed from version 10", then the WARNINGS section with the Retinal Pigmentary Changes sentence highlighted.
Which date is the warning date
The warning date is the day FDA approved the safety-related labeling change that added the warning, when Kelsey holds that change. If it does not, the warning date is the date of the first label version carrying the warning. The card shows both when it has both, as for Elmiron: approved 16 June 2020, first version 19 June 2020.
What counts as a warning
- The sentence sits in the boxed warning, warnings, warnings and precautions or precautions section.
- It names the condition itself. A sentence saying only that the drug slows gastric emptying does not name gastroparesis.
- Negated clauses ("no increased risk of") are masked first.
- A mention in the adverse reactions list or under contraindications counts as a related mention, not the warning.
- If the oldest version held already names the reaction, the card says the first date cannot be established.
Example questions
Which label version was in force when my client started in March 2019, and did it warn?
What comes back: The version in force on that date and its warning text, and the date each relevant warning first appeared. When the history held does not reach back to that date, the answer says so and gives no version.
Was the warning strengthened, moved up a section or boxed, and when?
What comes back: Each version that changed the warning, the section it sits in, and the text before and after.
Sources
- National Library of Medicine, "About DailyMed," https://dailymed.nlm.nih.gov/dailymed/about-dailymed.cfm
- FDA, "Drugs@FDA," https://www.accessdata.fda.gov/scripts/cder/daf/