Xofluza Vs. Tamiflu: What Is The Difference?

Sandra asked

Can you tell me the differences between Xofluza and Tamiflu? Is one better than the other?

Answer

Xofluza (Baloxavir Marboxil) is the first new oral antiviral for treating influenza to be approved by the FDA in nearly 20 years (Tamiflu was approved in 1999).

With its arrival to the market, it is important to understand its place in therapy and compare it to Tamiflu, the most commonly prescribed antiviral for the flu (i.e. influenza).

There are many key differences between Xofluza and Tamiflu, most notably:

• Dosing: For the treatment of the flu, Xofluza requires only one dose while Tamiflu is dosed twice daily for 5 days.
• Side Effect Profile: Tamiflu and Xofluza are both well tolerated but Xofluza may cause less nausea and vomiting.
• Mechanism Of Action: Xofluza and Tamiflu are both antivirals but work via different mechanisms.
• Indications: Xofluza is only approved in those 12 years of age and older while Tamiflu is indicated for all age groups (neonates to adults).
• Cost: Xofluza is only available as a brand name while Tamiflu is available generically as oseltamivir. There are coupons available for Xofluza that can reduce out-of-pocket cost.
• Efficacy: Xofluza has superior antiviral activity to Tamiflu but time to flu-symptom alleviation is the same.

All of the above are discussed in more detail below.

Dosing 

Dosing for Xofluza is far simpler than Tamiflu.

Xofluza is given as a single dose. One dose is all it takes. Dosing is weight-based:

• 40 to 79 kg = 40 mg as a single dose
• Over 80 kg = 80 mg as a single dose

Tamiflu, on the other hand, is dosed as one capsule, twice daily, for 5 days (for the treatment of flu... for prophylaxis it is dosed once daily for 10 days).

Both Xofluza and Tamiflu are only indicated to be used in those who have had flu symptoms for less than 48 hours. Neither are thought to be effective if taken more than 48 hours after symptoms start.

Even though both are indicated and should provide benefit if taken within 48 hours, the sooner you begin therapy with either, the better.

One study that evaluated Xofluza, published in the New England Journal Of Medicine, showed that individuals who took the drug within 24 hours of flu-symptom onset had their symptoms alleviated more quickly than those who took it later (between 24 and 48 hours after developing flu symptoms):

In the phase 3 trial, the difference in the time to alleviation of symptoms between the baloxavir [Xofluza] group and the placebo group was greater in patients who initiated the trial regimen early (≤24 hours) after symptom onset than in those who initiated it later...

Both Xofluza and Tamiflu can be taken with or without food.

However, certain foods and supplements should be avoided with Xofluza, as they can significantly reduce the absorption of the drug. These include:

• Dairy or products that are fortified with calcium.
• Aluminum-containing products.
• Iron-containing products.
• Polyvalent cation-containing laxatives (e.g. magnesium laxatives).
• Antacids or oral supplements that contain calcium, iron, magnesium, selenium, or zinc

Mechanism Of Action

Xofluza and Tamiflu are both antivirals, which work by preventing viral replication. They do have a different mechanism of action, however.

Xofluza is classified as a 'Polymerase Acidic (PA) Endonuclease Inhibitor Antiviral'. It works by targeting and inhibiting the activity of an influenza virus-specific enzyme known as the polymerase acidic (PA) protein. This inhibition prevents viral gene transcription and viral replication.

Tamiflu is classified as a 'Neuraminidase Inhibitor Antiviral'. It binds to viral neuraminidase, which results in inhibition of the enzyme. This inhibits viral replication.

As Xofluza and Tamiflu work differently, there doesn't appear to be a risk of 'cross-resistance'. This means if a specific influenza virus is resistant to one drug, it shouldn't be innately resistant to the other:

Cross-resistance between baloxavir [Xofluza] and neuraminidase (NA) inhibitors [e.g. Tamiflu], or between baloxavir and M2 proton pump inhibitors (adamantanes), is not expected, because these drugs target different viral proteins.

Therefore, if an individual has a strain of influenza known to be resistant to one drug, the other may be an effective option.

Side Effects

Xofluza and Tamiflu have similar side effect profiles and are both generally well tolerated. However, based on the information listed in the prescribing information for both drugs, Tamiflu has a higher incidence of both nausea and vomiting.

All of the side effects listed for Xofluza show an incidence rate less than or equal to those experienced with placebo treatment:

With Tamiflu, nausea occurred in 8-10% of study participants and vomiting occurred in 2-8% of participants, as shown below:

Efficacy

Data indicates that Xofluza and Tamiflu are just about equally effective in reducing the length of flu symptoms (by about 24 hours). On average, they reduce the length of flu symptoms from slightly over 3 days down to around 2 days.

For specifics, we can look at the clinical trial data provided in the prescribing information for Xofluza:

To summarize:

• For individuals 12 years of age and older, it took 54 hours for flu symptoms to be alleviated after dosing with Xofluza compared with 78 hours after taking a placebo. This is a reduction of 28 hours.
• For individuals 12 years of age and older, it took 50 hours for flu symptoms to be alleviated after dosing with Xofluza compared with 80 hours after taking a placebo. This is a reduction of 26 hours.

The prescribing information for Xofluza goes on to say there was no significant difference in time to alleviation of flu symptoms with Tamiflu vs. Xofluza:

In Trial 2, there was no difference in the time to alleviation of symptoms between subjects who received XOFLUZA (54 hours) and those who received oseltamivir [Tamiflu] (54 hours).

Although both Tamiflu and Xofluza appear to be equally efficacious in reducing the duration of flu symptoms, studies show that Xofluza has superior anti-viral activity and reduces viral load more. From the study:

Single-dose baloxavir [Xofluza] was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza.

It may seem somewhat counterintuitive that Xofluza is more effective in reducing viral load but doesn't seem to reduce the length of flu symptoms better than Tamiflu. The study addressed this:

It is unclear why the time to alleviation of symptoms was similar in the baloxavir [Xofluza] group and the oseltamivir group even though baloxavir showed greater antiviral activity. The findings suggest that the symptom benefit of antiviral agents may have a ceiling in self-limited influenza illness in adults, perhaps because viral replication levels are decreasing by the time of presentation and illness pathogenesis is linked to host proinflammatory responses.

It has been theorized that since Xofluza reduces viral load more than Tamiflu, it may be associated with a reduced risk of virus transmission from individual to individual. This hasn't been tested, however.

When talking about how effective these drugs are, it is important to note that Tamiflu is indicated not only for the treatment of the flu but also for prophylaxis for individuals coming in close contact with infected individuals. Xofluza is only indicated for the treatment of the flu.

Indications

There are key differences between Xofluza and Tamiflu when it comes to uses and FDA approved indications:

• Xofluza is approved only for healthy individuals 12 years of age and older.


• Tamiflu can be used in children, adults, and infants as young as two weeks. Additionally, it is indicated for use in 'high-risk' individuals (e.g. immunocompromised).


• Tamiflu has more safety data when it comes to use during pregnancy.


• Tamiflu has more safety data for use in high-risk or severely ill individuals.


• Xofluza is specifically listed for the treatment of 'uncomplicated influenza'.


• Tamiflu is indicated both for the treatment and prophylaxis of influenza.


• Xofluza is indicated only for the treatment of influenza.

Cost

The retail price of Xofluza is around $150. However, Genentech, the manufacturer, offers coupons to reduce cost. If your insurance covers Xofluza, your co-pay could be as low as $30. If you are paying out-of-pocket (i.e. 'cash), the coupon will bring the price down to around $90.

The coupon can be downloaded from the manufacturer website: Xofluza Manufacturer Coupon

Tamiflu is available generically. It costs about $100 for 5 days of generic oseltamivir if you are paying out-of-pocket and, if covered by insurance, should be on your generic tier for copays.

Additional Information

Tamiflu is available as both a liquid and capsule. Xofluza is only available as a tablet.

Going back to the original question of 'which is better', they are both equally effective and the choice of product will come down to the differences discussed above. For example:

• If the medication is for someone less than 12 years old, Tamiflu is the only choice. Similarly, only Tamiflu is indicated for 'complicated' flu cases

• If you prefer the ease of taking a single dose, Xofluza is a better choice.

• Your insurance may only cover only Tamiflu or vice-versa.

Be sure to ask your doctor about your options if you prefer one over the other.