Tale of Tamiflu
Practicing pharmacy over the years you start to get a feel for what works and what does not. Feedback is constant both welcome and otherwise. Some drugs just seem to work for a wide range of people. Amoxicillin, cefdinir, and azithromycin are just a few of our greatest hits from behind the counter. On the opposite side we have drugs that despite approval and mass marketing never really seemed to take off. Tamiflu is a great example. It was hailed and marketed as a cure for the flu and there was a point due to demand, I would spend an inordinate amount of time opening capsules to compound it into a suspension for younger patients when the commercial product would go on back order. Despite dispensing a lot of it the rave reviews never seemed to follow and it would be prescribed less and less. The most loaded question in healthcare is how was your day and I recall once quipping to another pharmacist “just another day padding Roche’s bottom line how about you”.
Tamiflu’s story would become more complicated as a multiyear effort spearheaded by the British Medical Journal would highlight many problems with clinical transparency that still resonate today. Approval of Tamiflu and subsequent billions spent by world governments stockpiling it for a potential swine flu pandemic was all based upon recommendations by the CDC, WHO, and EMA. None of which ever actually vetted the primary data and took it at face value. A Cochrane review would conclude after a four-year legal fight to obtain the primary data that there was no clear evidence to support the claims that Tamiflu improved influenza complications or infections but did raise concerns about side effects like nausea, vomiting, headaches, hallucinations and depression.
None of these shenanigans are the fault of the drug, oseltamivir phosphate the generic name for Tamiflu is an effective antiviral but studies have shown it needs to be started early and even a 24-hour delay in therapy causes a significant decrease in benefit. In reality once the patient had sought care, obtained a positive flu test and filled a prescription it was likely to late to be of any benefit. Like many drugs though it may still prove useful for other purposes and a recent study has shown that it may be an alternative therapy for liver cancer.
We now know that the toxicity from oseltamivir occurs as the drug hangs around in the GI tract waiting to be absorbed. Increasing the rate of absorption has been proposed to reduce its associated toxicity. A potential new formulation of oseltamivir that replaces the phosphate salt with an organic salt ethoxysuccinate has been proposed. The new formulation retained its antiviral properties and due to its increased rate of absorption expressed less toxicity compared to the phosphate version. Since changing the salt would be a new product don’t be surprised to see oseltamivir come back again with a new name and a fresh patent.
Jacob Hyatt Pharm D.
Father of three, Husband, Pharmacist, Realtor, Landlord, Independent Health and Medicine Reporter
https://substack.com/discover/pharmacoconuts
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Further reading and references
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8673668/
Kositpantawong N, Surasombatpattana S, Siripaitoon P, Kanchanasuwan S, Hortiwakul T, Charernmak B, Nwabor OF, Chusri S. Outcomes of early oseltamivir treatment for hospitalized adult patients with community-acquired influenza pneumonia. PLoS One. 2021 Dec 15;16(12):e0261411. doi: 10.1371/journal.pone.0261411. PMID: 34910777; PMCID: PMC8673668.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651232/
Huang PJ, Chiu CC, Hsiao MH, Yow JL, Tzang BS, Hsu TC. Potential of antiviral drug oseltamivir for the treatment of liver cancer. Int J Oncol. 2021 Dec;59(6):109. doi: 10.3892/ijo.2021.5289. Epub 2021 Dec 3. PMID: 34859259; PMCID: PMC8651232.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549332/
Wiemken TL, Furmanek SP, Carrico RM, Peyrani P, Hoft D, Fry AM, Ramirez JA. Effectiveness of oseltamivir treatment on clinical failure in hospitalized patients with lower respiratory tract infection. BMC Infect Dis. 2021 Oct 27;21(1):1106. doi: 10.1186/s12879-021-06812-2. PMID: 34702188; PMCID: PMC8549332.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6464969/#CD008965-sec1-0004
Jefferson T, Jones MA, Doshi P, Del Mar CB, Hama R, Thompson MJ, Spencer EA, Onakpoya I, Mahtani KR, Nunan D, Howick J, Heneghan CJ. Neuraminidase inhibitors for preventing and treating influenza in adults and children. Cochrane Database Syst Rev. 2014 Apr 10;2014(4):CD008965. doi: 10.1002/14651858.CD008965.pub4. PMID: 24718923; PMCID: PMC6464969.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475347/
Kalashnikov AI, Sonina EG, Kulagina DA, Sysolyatin SV, Prokop'eva EA, Sherstoboev EY. Promising New Salt of Oseltamivir. Pharm Chem J. 2021 Sep 25:1-4. doi: 10.1007/s11094-021-02456-3. Epub ahead of print. PMID: 34602660; PMCID: PMC8475347.
