Covid-19: The lost lessons of Tamiflu
BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4701 (Published 03 December 2020) Cite this as: BMJ 2020;371:m4701Read our latest coverage of the coronavirus outbreak
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Dear Editor
Thanks, the evocation of prior events in the public domain such as foot and mouth disease management is useful.
There is a ground swell across society to reset the moral barometer and to learn from these events.
The recent publication of ‘Greed is dead‘, covered by the LSE recently and available on YouTube, may prove to be a marker for the decline of the Greed corporate culture.
That Economists can now say the words is the opening of this Pandora’s box.
The determination behind the headlines is building, you have poured oil upon the fire.
But this is only the first phase, we must do more.
Oh, well done you!
John
Competing interests: No competing interests
Dear Editor
The list of promising drugs that have failed to live up to the hype continues to grow, and in addition to remdesivir, one can also add lopinavir/ritonavir, chloroquine, hydroxychloroquine, azithromycin, tocilizumab [1 2] and sarilumab.[2] Over 80,000 articles are now listed on PubMed that refer to covid-19 and one would be hard pressed to find an existing drug where someone hasn’t published a theory on how it might be beneficial in treating this disease.
Off label use before the availability of rigorous published data has been rampant throughout this pandemic and one wonders, in addition to a possible excess in mortality, whether these unwarranted drugs may have also contributed to “long covid” symptoms. Thus, hospitalized patients with covid-19 have had to face two critical challenges: fighting a highly virulent disease, while simultaneously having to metabolize ineffective drugs used in a vain attempt to find that needle in the haystack that may be advantageous. As we search for potential causes for long covid, let us not forget these clinical therapeutic misadventures, as well as the over-the-counter drugs, home remedies or internet-derived cures that patients may use in a quest to combat this illness.
References
1. Li M, Yoo EJ, Baram M, McArthur M, Skeehan C, Awsare B, et al. Tocilizumab in the Management of COVID-19: A Preliminary Report. Am J Med Sci 2020, in press.
2. Cantini F, Goletti D, Petrone L, Najafi Fard S, Niccoli L, Foti R. Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review. Drugs. 2020 Dec;80(18):1929-1946.
Competing interests: No competing interests
A Lost Lesson of Tamiflu
One critical lesion, too often discounted, has been the failure of researchers and journalists to access US Food and Drug Administration (US FDA) product documents. In the case of Tamiflu (oseltamivir), these include the Approval Package for oseltamivir; the current professional product label for the drug, and the archived copy of the oseltamivir’s professional product label from 1999.
The original US FDA professional product label indicated only a modest benefit for oseltamivir in reducing the duration of influenza symptoms:
“… there was a 1.3 day reduction in the median time to improvement …”[1]
Despite the drug’s questionable effectiveness, sales eventually exceeded billions of dollars per year. The US FDA medical reviews for oseltamivir available on the agency’s Web site since 1999 indicated that oseltamivir’s manufacturer did not submit clinical studies showing that the drug reduces the bacterial complications of the influenza:
“ … this application does not contain information on “… effectiveness in preventing complications due to influenza (such as hospitalization, secondary bacterial infections, or mortality) …”[2]
Oseltamivir’s professional product label was amended in 2000 to reflect that there was no evidence that the drug would prevent the bacterial complications of the influenza:
“Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza. TAMIFLU has not been shown to prevent such complications.”[3]
Disclosure and dissemination of this free publically available US FDA information about Tamiflu to patients, researchers, and policy makers may have brought a level of rationality to the pharmaceutical marketplace saving significant economic resources.
Reverences
1. Gilead Sciences, Inc. Professional Product Label Oseltamivir (Tamiflu), October 1999. At http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21087lbl.pdf. Accessed December 5, 2020.
2.Jolson HM. United States Food and Drug Administration, Division Director Memo At https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/21087_Tamiflu_medr...
Accessed December 5, 2020.
3. Gilead Sciences, Inc. Professional Product Label Oseltamivir (Tamiflu), November 2000. At
http://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21087S002lbl.pdf
Accessed December 5, 2020.
Competing interests: No competing interests
Re: Covid-19: The lost lessons of Tamiflu
Dear Editor,
I find myself, perhaps for the first time, agreeing with Fiona Godlee's 'editor's choice' article, 'The lost lessons of Tamiflu'. In particular, her dismay at the lack of public scrutiny of unadultered data from the covid-19 vaccine trials.
Many of these vaccines are made using techniques that are relatively novel and untested, especially at large scale. There has been no mention at all in public media about the possible risks of 'vaccine enhanced disease' or 'antibody-dependent enhancement' of disease seen with some vaccines, including coronavirus vaccines. That is, the enhancement of virus entry into host cells leading to a more severe respiratory disease and acute lung injury.
Surely, this potential risk should be mentioned when consenting patients for the covid-19 vaccines? If not, why not?
Competing interests: No competing interests