Peramivir IV for Influenza: Will It Aid In-Hospital Care?
Editor’s Note: On December 22, 2014, the US Food and Drug Administration (FDA) approved RAPIVAB™ (peramivir injection), an intravenous neuraminidase inhibitor, for the treatment of acute uncomplicated influenza in patients 18 years and older. See our news story, FDA Approves Peramivir (Rapivab) for Influenza.
Hello. This is Paul Auwaerter with Medscape Infectious Diseases, speaking from the Johns Hopkins Division of Infectious Diseases. For many of us, the challenge of treating very ill patients with influenza sometimes includes whether or not to administer the neuraminidase inhibitor oseltamivir (Tamiflu®). The question is whether it can be effectively absorbed, as it's only available to be given by an enteric route.
The US Food and Drug Administration (FDA) will be considering a new neuraminidase inhibitor, an injectable agent—peramivir—for approval. I'd like to relay some data that the FDA will likely consider when deciding whether it should be approved. This drug has been used and approved in both Japan and South Korea since 2010. The drug was developed, in part, with considerable grants—almost $235 million—from US agencies because of the need for an injectable drug for hospitalized patients.
How well does this drug work? Observational studies have been done in general practice with children in Southeast Asia. Recently, at IDWeek in October 2014, Dr Rich Whitley presented a poster that reviewed four studies in adults. These were all cases of uncomplicated influenza, and the drug was administered within 48 hours of hospital admission and compared with placebo. The drug was given as an injection either into the muscle or into the vein, at a dose of 150, 300, or 600 mg, and compared with placebo.
Whitley and his colleagues found that, on average, with this kind of early treatment, overall symptoms decreased between 24.8 and 28.3 hours, so in about a day. This included a reduction in fever.
Dr Sylvia Dobo presented a companion poster that reviewed safety data. The drug has seemed quite safe: There was little difference in overall adverse drug reactions compared with placebo. And looking at the adverse events of gastrointestinal upset and diarrhea, those seemed to be less with peramivir than what is typically experienced with oseltamivir.
Unfortunately, an unanswered question remains: Does peramivir really help hospitalized patients? Many of these patients have had symptoms for more than 48 hours when they are admitted. Will the drug have an impact on them?
We know from studies, most observational and retrospective, that the neuraminidase inhibitors may well have an impact on patients who are severely ill. But the biggest impact seems to be for patients who have had symptoms for fewer than 3 days. Perhaps peramivir also has some effect for up to 5 days, but this has never been closely examined.
Certainly with peramivir we don't have much information. The drug was used on a compassionate and emergency basis during the H1N1 pandemic, and the experience was published in Clinical Infectious Diseases a few years ago. For the 42 patients treated, it appeared to be relatively well tolerated. But little could be said about efficacy because these patients obviously were very ill, many of them with acute respiratory distress syndrome. The 14-day survival was 76.7%, which you could argue maybe was a little better than what one might expect for such severely ill patients. But many of them, of course, only got the drug after a considerable delay.
I think the drug is another option and appears safe. Whether peramivir truly has an impact on influenza after the first few days—in other words, for most patients who have been hospitalized with severe influenza—remains a question in many people's minds.
Other drugs currently being studied may also be submitted for FDA approval. One example is an intravenous form of zanamivir, which is currently only available in an inhaled form. This drug, at least in vitro, appears to have even broader activity than peramivir, in particular against avian strains.
So there may be some additional new options. It's time, because it has been over a decade since there have been any new anti-influenza drugs.
Thanks very much for listening. I look forward to your comments.
Editor’s Note: On December 22, 2014, the US Food and Drug Administration (FDA) approved RAPIVAB™ (peramivir injection), an intravenous neuraminidase inhibitor, for the treatment of acute uncomplicated influenza in patients 18 years and older. See our news story, FDA Approves Peramivir (Rapivab) for Influenza.
Hello. This is Paul Auwaerter with Medscape Infectious Diseases, speaking from the Johns Hopkins Division of Infectious Diseases. For many of us, the challenge of treating very ill patients with influenza sometimes includes whether or not to administer the neuraminidase inhibitor oseltamivir (Tamiflu®). The question is whether it can be effectively absorbed, as it's only available to be given by an enteric route.
The US Food and Drug Administration (FDA) will be considering a new neuraminidase inhibitor, an injectable agent—peramivir—for approval. I'd like to relay some data that the FDA will likely consider when deciding whether it should be approved. This drug has been used and approved in both Japan and South Korea since 2010. The drug was developed, in part, with considerable grants—almost $235 million—from US agencies because of the need for an injectable drug for hospitalized patients.
How well does this drug work? Observational studies have been done in general practice with children in Southeast Asia. Recently, at IDWeek in October 2014, Dr Rich Whitley presented a poster that reviewed four studies in adults. These were all cases of uncomplicated influenza, and the drug was administered within 48 hours of hospital admission and compared with placebo. The drug was given as an injection either into the muscle or into the vein, at a dose of 150, 300, or 600 mg, and compared with placebo.
Whitley and his colleagues found that, on average, with this kind of early treatment, overall symptoms decreased between 24.8 and 28.3 hours, so in about a day. This included a reduction in fever.
Dr Sylvia Dobo presented a companion poster that reviewed safety data. The drug has seemed quite safe: There was little difference in overall adverse drug reactions compared with placebo. And looking at the adverse events of gastrointestinal upset and diarrhea, those seemed to be less with peramivir than what is typically experienced with oseltamivir.
Unfortunately, an unanswered question remains: Does peramivir really help hospitalized patients? Many of these patients have had symptoms for more than 48 hours when they are admitted. Will the drug have an impact on them?
We know from studies, most observational and retrospective, that the neuraminidase inhibitors may well have an impact on patients who are severely ill. But the biggest impact seems to be for patients who have had symptoms for fewer than 3 days. Perhaps peramivir also has some effect for up to 5 days, but this has never been closely examined.
Certainly with peramivir we don't have much information. The drug was used on a compassionate and emergency basis during the H1N1 pandemic, and the experience was published in Clinical Infectious Diseases a few years ago. For the 42 patients treated, it appeared to be relatively well tolerated. But little could be said about efficacy because these patients obviously were very ill, many of them with acute respiratory distress syndrome. The 14-day survival was 76.7%, which you could argue maybe was a little better than what one might expect for such severely ill patients. But many of them, of course, only got the drug after a considerable delay.
I think the drug is another option and appears safe. Whether peramivir truly has an impact on influenza after the first few days—in other words, for most patients who have been hospitalized with severe influenza—remains a question in many people's minds.
Other drugs currently being studied may also be submitted for FDA approval. One example is an intravenous form of zanamivir, which is currently only available in an inhaled form. This drug, at least in vitro, appears to have even broader activity than peramivir, in particular against avian strains.
So there may be some additional new options. It's time, because it has been over a decade since there have been any new anti-influenza drugs.
Thanks very much for listening. I look forward to your comments.
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