All About Oseltamivir

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Flu season is upon us. The decision to treat with a neuraminidase inhibitor requires a risk-benefit analysis, and for many patients, the risks of side effects and the cost may outweigh the potential benefits. A 2014 Cochrane review was finally able to evaluate previously unavailable data [1], and found neuraminidase inhibitors are not all we had hoped.

Major indications:

Oseltamivir can be used for the treatment of influenza to reduce length of symptoms.

In the news:
Recently there has been a lot of controversy surrounding the use and stockpiling of oseltamivir [2,3]. The hope in treating with neuraminidase inhibitors is that treatment could not only reduce symptom duration and severity, but could help reduce the rate of hospitalizations and post-influenza complications such as pneumonia, as well as transmission to others. A Cochrane review of neuraminidase inhibitors performed in 2012 noted a reduction in length of symptoms of 21 hours with use of oseltamivir (from 160 hours to 139 hours). However, the reviewers had significant concerns about the lack of access to much of the data, stating: “We found a high risk of publication and reporting biases in the trial programme of oseltamivir [4].” Roche pharmaceuticals was strongly criticized for failing to publish all their data, and “likely overstating of effectiveness and the apparent under reporting of potentially serious adverse effects [5].” In 2014, an updated Cochrane review was published after previously unpublished data was made available [1]. This newer review reported symptom alleviation with treatment was 16.8 hours sooner compared with placebo (7 vs 6.3 days of symptoms). However, there were no statistically significant differences in rates of hospitalization, or rates of confirmed pneumonias or other complications as was previously thought [6]. Oseltamivir also had significant side effects such as nausea, vomiting, headache, and psychiatric events.

The Cochrane review did find a statistically significant reduction in symptomatic influenza cases among contacts receiving oseltamivir as prophylaxis (NNTB = 33), though there were no difference in rates of asymptomatic influenza (diagnosed by lab tests only) among contacts [1]. The CDC continues to recommend neuraminidase use for all high-risk or seriously ill patients, and recommends considering its use in otherwise healthy flu patients who present within 48 hours of symptom onset [7].

How it works:
Oseltamivir inhibits the viral neuraminidase enzyme, thereby preventing viral budding from the host cell.

Notable history:
Oseltamivir was first approved by the FDA for the treatment of influenza in 1999. After the 2005 H5N1 outbreak in Southeast Asia, and the 2009 H1N1 pandemic, many countries stockpiled reserves of oseltamivir. It is estimated that the United States spent around $1.5 billion stockpiling oseltamivir, money that may have been wasted if the medication does not significantly reduce the severity of illness, hospitalization rate, or mortality [2,8].

Adverse events:
Nausea (NNH 28), headaches (NNH 32), and psychiatric events (NNH 94) are all increased with oseltamivir [1].

Cautions:
It is considered safe in breastfeeding mothers [9] and is pregnancy Class C.

Dose adjustments:
Usual adult treatment dosing is 75mg PO BID for 5 days. Post-exposure prophylaxis dosing is 75mg PO daily for 7-14 days depending on the type of exposure. It can be given for up to 6 weeks for pre-exposure prophylaxis. There are no renal or hepatic dose adjustments defined.

Cost:
10 capsules for a 5-day course of treatment costs around $130.

REFERENCES
1. Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev. 2014;4
2. Jefferson T, Doshi P. Multisystem failure: The story of anti-influenza drugs. BMJ. 2014;348
3. Torjesen I. Cochrane review questions effectiveness of neuraminidase inhibitors. BMJ. 2014;348
4. Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev. 2012;1
5. Kmietowicz Z. Roche should be sued to release data on oseltamivir, says cochrane leader. BMJ. 2012;345
6. Kaiser L, Wat C, Mills T, Mahoney P, Ward P, Hayden F. Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch Intern Med. 2003;163(14):1667-1672
7. Center for Disease Control. Have you heard: CDC recommendations for influenza antiviral medications remain unchanged. http://www.cdc.gov/media/haveyouheard/stories/Influenza_antiviral2.html. Published 04/10/2014. Updated 2014. Accessed 11/18, 2014.
8. Van Noorden R. Report disputes benefit of stockpiling tamiflu. Nature News Web site. http://www.nature.com/news/report-disputes-benefit-of-stockpiling-tamiflu-1.15022. Published 04/10/2014. Updated 2014. Accessed 11/18, 2014.
9. Hale TW. Medications and mothers’ milk: A manual of lactational pharmacology. 12th ed. Amarillo, TX: Hale Publishing L.P.; 2012:1331.

ABOUT THE AUTHOR

Dr. Shenvi is an assistant professor in the department of emergency medicine at the University of North Carolina. She authors RX Pad each month in EPM.

1 Comment

  1. If this drug doesn’t reduce complications or hospitalizations, with only a very marginal benefit at the cost of 130 dlls… I rather drink coffee and some Naproxen, and when I feel better, take my wife for a fancy dinner of 130 dlls. Thank you, but no Tami for me.

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