Intended for healthcare professionals

Rapid response to:

Analysis

What can we learn from observational studies of oseltamivir to treat influenza in healthy adults?

BMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b5248 (Published 08 December 2009) Cite this as: BMJ 2009;339:b5248

Rapid Response:

Oseltamivir is not only ineffective but also harmful: that's the matter

As I wrote in several rapid responses [1-6] and in a paper on a case
series and overview of adverse reactions to oseltamivir [7], it is not
merely the matter that it is ineffective (at least no proof of efficacy
and effectiveness) to prevent complication for otherwise healthy people
and no proof to prevent complication for people with underling diseases,

More serious problem is the harmful effects of oseltamivir. For
example there is substantial evidence that major psychotic and/or
psychiatric reactions, renal and diabetic complications were significantly
more observed in oseltamivir group when used in the randomized controlled
trials (RCTs) for prevention of influenza targeted otherwise healthy
people [1].

Moreover, early use [2, 3] and late use [4, 5] are both related to
serious harmful effects on survival if users have hypercytokinemia. It
does not depend on the patients' risk situations. However, if they have
severe hypercytokinemia induced in various complications of influenza such
as acute respiratory failure, encephalopathy, sepsis with multi-organ
failures, oseltamivir may affect more seriously: please see the attached
figure of reference [4].

It is risky not only in those people who have complications of
influenza but also in people who have underlying diseases before infection
with influenza. For example, central nervous system may be easily
depressed by the unchanged oseltamivir in patients who have nervous system
disorders resulting in sudden respiratory arrest. Sleep apnea may be
enhanced in extremely obese people resulting sudden death during sleep.
Respiratory failure may be enhanced in patients who are suffering
pulmonary complication and/or cardiac diseases if respiration is depressed
causing hypoxemia. Plasma and brain concentration of unchanged oseltamivir
may increase in patients with liver failure such as liver cirrhosis
because of decreased metabolism of oseltamivir to oseltamivir carboxylate
(OC). Plasma concentration of OC increases six times higher than that in
those who has normal renal function by a single dose in patients who are
under hemodialysis it may cause various complications [7].

Moreover, note that more unweaned animals [7], pregnant
animals and newborn animals that were exposed
to oseltamivir during pregnancy [8, 9] die significantly and dose-
dependently. It is consistent with the results of pregnant women's deaths
[4] reported from the United States [10].

I would like to conclude that it should be remembered that the real
matter is the harm of oseltamivir.

references

1.Hama R. Oseltamivir: psychotic and neurological adverse reactions
in the randomized controlled trials

http://www.bmj.com/cgi/eletters/339/dec07_2/b5106#227187

2.Hama R. Early use of oseltamivir: a case of respiratory depression
after each of two doses, with sudden death. Rapid response:
http://www.bmj.com/cgi/eletters/339/nov13_2/b4831#227027

3.Hama R. Early use of oseltamivir and deaths in 09A-flu
http://www.bmj.com/cgi/eletters/339/dec07_2/b5106#227726

4.Hama R. Oseltamivir: early use and late use are both related to
harmful effects especially in hypercytokinemia in patients with or without
risk.
http://www.bmj.com/cgi/eletters/339/dec07_2/b5106#227363

5.Hama R. Another evidence on association of oseltamivir and death in
09A flu http://www.bmj.com/cgi/eletters/339/dec07_2/b5106#227747

6.Hama R. What can we learn from observational studies of oseltamivir
without examining NSAIDs use?
http://www.bmj.com/cgi/eletters/339/dec07_2/b5248#227268

7.Hama R. Fatal neuropsychiatric adverse reactions to oseltamivir?F
case series and overview of causal relationships. Internat J Risk Safety
Med 2008;20:5-36. : available at : http://npojip.org/english/no11.html

8. Hama R. Oseltamivir (Tamiflu) is harmful for pregnant women (1).
The Informed Prescriber: 2009: 24 (6): 66-70.(in Japanese)

9. Hama R. Oseltamivir (Tamiflu) is harmful for pregnant women (2).
The Informed Prescriber: 2009: 24 (7): 77-82.(in Japanese)

10. Novel Influenza A (H1N1) Pregnancy Working Group. Jamieson DJ,
Honein MA, Rasmussen SA, H1N1 2009 influenza virus infection during
pregnancy in the USA. Lancet. 2009 Aug 8;374(9688):451-8. Epub 2009 Jul
28.

Competing interests:
None declared

Competing interests: No competing interests

18 December 2009
Rokuro Hama
Chairperson: Japan Institute of Pharmacovigilance, Editor: Kusuri-no-Check (a drug bulletin)
#902 Ueshio3-2-17, Tennoji-ku Osaka, Japan 543-0002