Evidence map›Paper›PMID 27048352›Full record

ArticleCNS drugs2016

Ghost-Pill-Buster: A Case Study of Intact Levetiracetam Extended-Release Tablets after Dissolution Testing.

Dajun Sun, Hong Wen, Anna Externbrink, Zongming Gao, David Keire, Gregory Krauss, Wenlei Jiang

Abstract read
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In one paragraph

Article in CNS drugs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 6 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Dajun SunUS Food and Drug Administration, Center for Drug Evaluation and Research, Office of Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Hong WenUS Food and Drug Administration, Center for Drug Evaluation and Research, Office of Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Anna ExternbrinkUS Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Testing and Research, Silver Spring, MD, USA.
Zongming GaoUS Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Testing and Research, Silver Spring, MD, USA.
David KeireUS Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Testing and Research, Silver Spring, MD, USA.
Gregory KraussDepartment of Neurology, Johns Hopkins University, Baltimore, MD, USA.
Wenlei JiangUS Food and Drug Administration, Center for Drug Evaluation and Research, Office of Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA. wenlei.jiang@fda.hhs.gov.
United States Food and Drug Administration · USCenter for Drug Evaluation and Research · USJohns Hopkins University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOrally administered medications in extended-release (ER) dosage forms continue to play a pivotal role in the treatment of various central nervous system disorders. For certain ER dosage forms, pharmaceutical scientists have been familiar with the passage of intact tablet-like objects in patients' feces after administration of ER tablets or capsules based on water-insoluble or slowly dissolving excipients. Nevertheless, because of lack of awareness of the "ghost pill" phenomenon, anxiety has ensued among some patients and clinicians, who have less understanding of how drugs are released from these tablets once ingested. It has been brought to the attention of the US Food and Drug Administration (FDA) that epilepsy patients administered with Teva's levetiracetam ER tablets have noticed intact tablets in their stools and been concerned that they were not getting the needed dose of the drug. In response to neurologists' clinical reporting, the FDA has conducted investigations to confirm a minimal risk of incomplete drug release of Teva's drug product.

objectiveThe objective of this study was to evaluate the risks of incomplete drug release associated with the passing of intact levetiracetam ER tablets, by conducting in vitro dissolution testing.

methodsDissolution testing of Teva's drug product was performed in accordance with the US Pharmacopeia monograph for levetiracetam ER tablets in phosphate buffer and bio-relevant buffers at different pH values. In addition, dissolution testing was conducted with split and crushed tablets. At the end of the dissolution testing, all samples were visually inspected for any undissolved pieces.

resultsApproximately 90 % of levetiracetam had been released in all dissolution media after 8 h of dissolution. The levetiracetam ER tablets after dissolution testing remained fully intact in all dissolution media. The rates of drug release were significantly faster from split and crushed tablets than that from whole tablets.

conclusionOn the basis of these findings, Teva's levetiracetam ER tablets may appear intact in the stools but have released the drug successfully. The FDA has requested Teva to revise its product labeling to include remarks regarding the potential passing of intact tablets. Since patients who notice ghost pills in their stools may impetuously crush or split the tablets of subsequent doses on their own, healthcare providers should instruct patients to swallow whole tablets throughout the treatment, in accordance with the drug label.

Indexed as

Administration, OralCapsulesChemistry, PharmaceuticalDelayed-Action PreparationsHumansLevetiracetamPiracetamSolubilityTabletsUnited StatesUnited States Food and Drug AdministrationCapsulesDelayed-Action PreparationsLevetiracetamPiracetamTablets

Identifiers

PMID27048352
OpenAlexW2319069004

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.