Tamiflu Vs. Relenza
Both Tamiflu (Oseltamivir) and Relenza (Zanamivir) are antiviral medicines used primarily in the prevention and cure of influenza, commonly referred to as the flu. If given during the first 48 hours, they can reduce the duration of the illness by a day or two and accelerate recovery.
During the last decade they have become particularly important, both medically and commercially, amidst the threats of an influenza pandemic. As the only anti-viral drugs reasonably effective for influenza, they are being vigorously studied by researchers, while their manufacturers compete with each other to gain a larger share of commercial sales and profits. Recently, Glaxo Smith Kline, the manufacturer of Relenza, launched a 3 year clinical study that will compare the efficacy of intravenous Zanamivir (Relenza) with oral Oseltamivir (Tamiflu) in treating hospitalized patients of influenza across 20 countries.
Tamiflu is the trade name under which the Oseltamivir compound is marketed by its manufacturer, Hoffmanne-la-Roche. Tamiflu was developed by three researchers, C.U. Kim, W. Lew, and X. Chen of Gilead Sciences, a US based concern, which licensed it to Roche. Since 1999, it has been the most commonly prescribed drug for influenza, and its demand has skyrocketed.
Relenza is the trade name under which the Zanamivir compound is marketed by its manufacturer, Glaxo Smith Kline. Relenza was developed in 1989 by a team of scientists, led by Mark von Itzstein at the Monash University, in a research funded by an Australian biochemical company, Biota, which licensed the patent rights to Glaxo in 1990, which began marketing it in 1999.
Tamiflu and Relenza : A comparison
Tamiflu and Relenza can be compared across several parameters like clinical efficacy, mode of action, drug formulation, side effects, viral resistance, stockpiling of the drug and commercial issues.
Mode of action & Clinical efficacy
Both Tamiflu and Relenza have a similar action by which they bring relief to a patient of influenza. They are both Neuraminidase inhibitors. They combine with the Neuraminidase enzyme of the influenza virus, thereby preventing it from replicating and spreading further throughout the body. Their clinical efficacy is also very similar. In patients of seasonal influenza, they accelerate the recovery by one or two days if given within the first 48 hours, and reduce the severity and complications. Given the fact that there are epidemics of seasonal influenza every year, Tamiflu and Relenza are the only effective antiviral drugs available, and in addition to vaccination shots, the only treatment available in our fight against influenza.
Tamiflu is marketed as oral tablets of 75mg, 45mg and 30 mg strengths as well as in the form of a syrup, making it easier for a patient to take. On the contrary, Relenza is marketed as powder that has to be inhaled, requiring an inhaler. The more convenient formulation of Tamiflu is considered one of the main reasons why the demand and sales of Tamiflu have usually exceeded Relenza till recently.
Major Side Effects
During the early trials and immediately after being marketed, Relenza was observed to worsen asthma and other obstructive lung diseases, sometimes even leading to Bronchospasm, a side effect not associated with Tamiflu. This led to Public Health Advisory warnings by the U.S. Food and Drug Administration (FDA) regarding use of Relenza in patients with respiratory diseases. Along with the inconvenience associated with inhaling Relenza, this was probably the other factor, which led to its lessening popularity among physicians. As a result, Tamiflu was generally considered the drug of choice for seasonal flu until recently, in spite of the fact that both had similar actions and were equally effective in treating influenza.
Both Tamiflu and Relenza are generally well tolerated with less than 1% cases reporting side effects like nausea, vomiting, abdominal pain, diarrhea, headache, rash and allergic reactions. More toxic side effects have been rare with both drugs though hepatitis, seizure, confusion, aggravation of diabetes, and hemorrhagic colitis are reported in rare cases.
Since 2007, Japan, which is the single largest consumer of Tamiflu, has reported many cases of abnormal behaviour, hallucinations and disturbed consciousness associated with use of Tamiflu, leading to a warning by Japanese Health Ministry that Tamiflu should be avoided in the age group of 10 to 19 years, wherein the maximum such cases were observed. Since then, abnormal behavior has also been considered as one of the possible side effects of both Tamiflu and Relenza.
Influenza virus is a constantly mutating virus. Because of its high frequency of mutations, leading to change of its structure, it escapes immunity that humans develop against the virus. Recently, it has also been reported to have developed resistance to anti-viral drugs. So far, cases of viral resistance have been reported only against Tamiflu, whereas no viral resistance has been observed against Relenza, a finding that can have very significant implications in favor of Relenza in the long run.
Reports of viral resistance against Tamiflu have been surfacing sporadically since 2005, when Lancet published an article in its August 13 issue reporting resistance in 18% patients taking Tamiflu and none in the case of Relenza. More Recently, both the Center for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have acknowledged in their reports that there is widespread resistance to Tamiflu in treating the H1N1 virus, the strain that caused the 2009 flu pandemic, with almost 99.6 % samples being resistant, against only 12% resistance an year earlier. The high incidence of viral resistance in the case of Tamiflu will make it less useful for treating influenza, a fact that can tilt the priorities in favor of Relenza, which has so far been free of the viral resistance problem.
Protective Stockpiling and Commercial Issues
The market demand for Tamiflu and Relenza has often skyrocketed in face of threats of influenza epidemics, and led to higher profits for their manufacturers. During the earlier years, preference for Tamiflu largely overshadowed Relenza. In 2000, Tamiflu outsold Relenza three times. In the first half of 2006, Roche sold Tamiflu worth $770 million, whereas Glaxo Smith Kline’s sales of Relenza were not even one-tenth of this amount. However, subsequently, with rising awareness among Governments about the possible threat of influenza pandemic, and their strategic stockpiling of these drugs, the demand for both the drugs has grown by leaps and bounds. In recent times, there have been some reports suggesting that sales of Relenza have at times even surpassed those of Tamiflu. However, Tamiflu still remains the preferred drug for fighting influenza in most parts of world. Since many countries are likely to continue with their strategic stock-piling, the demand for both drugs will continue to be healthy in immediate future, though the frenzy of 2009 may not be seen unless we face another influenza pandemic scare.
Tamiflu and Relenza are the only pharmaceutical remedies against influenza. In most cases, seasonal influenza or the common flu is self limiting. Both Tamiflu and Relenza, only accelerate the recovery by a day or so, leading to suggestions that it may be better to use them more selectively in very sick patients. Due to the more convenient oral tablet form of Tamiflu and the worsening of respiratory symptoms by Relenza inhalation, Tamiflu has generally been preferred over Relenza. Recent reports of abnormal behavior associated with Tamiflu and the higher degree of viral resistance against it has again tilted the scale somewhat in favor of Relenza. However, the current global demand of both antiviral drugs, arising primarily from protective stock piling of medicines against influenza pandemic, is high enough to absorb the production of both Tamiflu and Relenza in the near future.