Tamiflu®: Globally Endorsed in the Treatment and Prevention of Influenza.
Tamiflu® ( oseltamivir INN) is an orally administered anti-influenza drug of worldwide proven value in the in the treatment and prevention of Influenza A and Influenza B. Tamiflu® is a member of a small class of drugs called neuraminidase inhibitors which have largely superseded the older, less effective anti- influenza agents, the adamantanes (1,2,3,4).
Both Influenza A and Influenza B remain a major worldwide health concern with well documented seasonal epidemics and, in particular with Influenza A, pandemics. Which cause significant morbidity and mortality to hundreds of thousands, if not millions during pandemics, along with social and economic hardship and human misery (5, 6, 7). The constantly changing antigenic nature of the influenza virus has hampered effective vaccine production and vaccine scientists are often locked into a game of catch up with the virus's changing immunological appearance. These factors in the context of our ever increasingly fluid world population mean Influenza remains a real and present world health threat (2, 5, 6, 7).
Tamiflu® was the product of a rational drug design project undertaken by C U Kim and his team at Gilead Sciences® and which was subsequently marketed by Roche®. Tamiflu is a pro-drug which is de-esterified within the liver to the free carboxylate. This bio-transformed drug is a competitive inhibitor of influenza neuraminidase, an enzyme essential for viral release and cellular dissemination, and so inhibits influenza viral reproduction (1, 7). Tamiflu® is the only orally administered neuraminidase inhibitor available to date; and this, along with its established efficacy, simple dosing schedules and safety profile has ensured it has remained an integral component of both national and international influenza control strategies and World Health Organisation public health directives(7, 8, 9, 10).
Reputable, well designed and independent clinical trials of Tamiflu have clearly established the significant benefit of Tamiflu® in the treatment of influenza in a wide variety of medical settings and patient groups including children and the medically vulnerable. Tamiflu® was shown to reduce symptom severity and duration, shorten recovery and convalescence times, reduce complication rates and reduce virus secretion in influenza infected patients (11, 13, 14, 15, 16, 17, 18, 19, 20). Tamiflu® was shown to be an effective prophylactic agent when administered to individual at risk of influenza infection in both community and residential settings and was well tolerated, even in patients where clinical circumstances dictated prolonged administration (11, 13, 16, 18, 19, 20).
Though Tamiflu® was never intended as a replacement for vaccination, however in the absence of an effective vaccine, limited vaccine availability and other instances of population vulnerability to influenza the use of Tamiflu®, notably in the current H1N1 Swine Flu pandemic and the H5N1 Avian Flu outbreaks, has ensured we have had an effective pharmaceutical defence in addition to other public health measures with which to combat the continuing national and world influenza threats. Where indicated, Tamiflu® can be co-administered with trivalent influenza vaccine without impairing vaccine response and providing antiviral cover while immunity develops in influenza at risk individuals (11, 21).
The World Health Organisation, the American Centre for Disease Control and European Medical agency, largely as a result of the current pandemic flu threat, have all revised their anti- influenza drug guidelines. And a central tenet of their policy is ensuring adequate supplies of Tamiflu® are readily available and the recommendation that adequate drug stocks be held in reserve worldwide. Additionally, drug safety and clinical trial data were scrutinised which resulted in the extension Tamiflu's product licence to include children aged 1 year or greater along with pregnant and breastfeeding women (7, 8, 9, 10, 11).
In response to concerns about possible worldwide shortages of Tamiflu®, Roche®, the international product licence holder, has sublicensed the manufacture of Tamiflu to a number of pharmaceutical companies throughout the globe to ensure sustainable, adequate production and supply of the drug in the event of further world influenza contingencies(22).
