When to use antivirals for swine flu

We've gotten the question here fairly frequently: If antivirals (Tamiflu, Relenza) for swine flu work best when given early but shouldn't be given to people who aren't really that sick, how do you balance waiting for them to get sick and have the drugs not work well with giving it when you don't need to? There is no absolutely right answer to this difficult question. Early in the pandemic antivirals were being given prophylactically to stop spread, then they were being given only when a diagnosis of swine flu was confirmed. Then only to the sickest patients. We're all on a learning curve. The latest recommendations from CDC try to walk the narrow line between over use and under use, taking into account that missing early treatment could endanger the lives of some patients who go on to serious illness. So the trick is to initiate early treatment for those at highest risk, even if some, or any, test results aren't available or aren't positive. For those patients, "empiric antiviral treatment" is indicated. Empiric treatment means use the drugs and ask questions later. From CDC's Health Alert Network for health departments and clinicians:

The 2009 pandemic H1N1 influenza virus continues to be the dominant influenza virus in circulation in the U.S. The benefit of antiviral treatment is greatest when it is initiated as early as possible in the clinical course. Several recent reports have indicated two problems related to antiviral treatment: (1) some patients with suspected influenza who are at higher risk of developing severe complications, including hospitalized patients, were not treated at all with antiviral medications because of a negative rapid influenza diagnostic test result and (2) initiation of treatment was delayed for some patients with suspected influenza who are at higher risk of developing severe complications, including hospitalized patients, because clinicians were waiting for results of real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay. (CDC Health Alert Network)

Who are the people at higher risk? Let's start with the opposite. Who are the people who have or might have flu that CDC doesn't think need immediate initiation of antiviral therapy? Most flu cases:

Most healthy persons (i.e., those without a condition which puts them at higher risk for complications) who develop an illness consistent with uncomplicated influenza do not need to be treated with antiviral medications and will recover without complications. However, clinical judgment should be the ultimate guide in making antiviral treatment decisions for ill persons who are not at higher risk for complications from influenza.

The main point about this. Treat the patient, not the lab tests. If you are otherwise healthy and have flu-like symptoms but don't feel that bad, you don't need antivirals. But whenever you feel really sick or have trouble breathing or have symptoms in your chest, regardless of how healthy you were before, you should see someone and probably get antivirals. If you didn't feel so bad but now are getting worse, that is an indication, too. Age is not a factor, young or old. If you aren't offered antivirals you should probably ask for them.

What are the categories of people who, when they get flu-like symptoms -- fever or respiratory symptoms in the chest or sore throat or cough without other obvious cause -- should be treated pre-emptively with antivirals? If you are sick enough to be hospitalized for suspect influenza, you should be started immediately on antivirals (Tamiflu or Relenza). If you not not sick enough for the hospital, here is the rest of CDC's list of those for whom early empirical (independent of test results) antiviral treatment should be considered:

  • Children younger than 2 years old
  • Adults 65 years and older
  • Pregnant women
  • Persons with the following conditions:
  • Chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), or metabolic disorders (including diabetes mellitus);
  • Disorders that can compromise respiratory function or the handling of respiratory secretions or that can increase the risk for aspiration (e.g., cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders)
  • Immunosuppression, including that caused by medications or by HIV;
  • Persons younger than 19 years of age who are receiving long-term aspirin therapy, because of an increased risk for Reye syndrome.

These are not automatic or easy decisions to make, either for health care providers or for patients. It would be wrong not to admit there are substantial uncertainties. The advice CDC is giving here seems the most rational and reasonable given what we know at this time. It is even possible it could save your life.

There's a self-assessment tool at www.flu.gov and advice for parents and pregnant women that might be useful.

Here are some CDC links on the topic:

Updated Interim Recommendations for the Use of Antiviral Medications in the Treatment and Prevention of Influenza for the 2009-2010 Season: http://www.cdc.gov/H1N1flu/recommendations.htm

Interim Recommendations for Clinical Use of Influenza Diagnostic Tests During the 2009-10 Influenza Season: http://www.cdc.gov/h1n1flu/guidance/diagnostic_tests.htm

Questions & Answers:
Antiviral Drugs, 2009-2010 Flu Season:http://www.cdc.gov/h1n1flu/antiviral.htm

Influenza Diagnostic Testing: http://www.cdc.gov/h1n1flu/diagnostic_testing_clinicians_qa.htm

Updated Interim Recommendations for Obstetric Health Care Providers Related to Use of Antiviral Medications in the Treatment and Prevention of Influenza for the 2009-2010 Season: http://www.cdc.gov/H1N1flu/pregnancy/antiviral_messages.htm

Antiviral Drugs: Summary of Side Effects: http://www.cdc.gov/flu/protect/antiviral/sideeffects.htm

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Difficult dilemma indeed. As a physician on the front line in the ER, I am getting hammered by the public regarding my failure to prescribe an antiviral when they or one of their loved ones shows up with ILI. Now with the H1N1 2009 vaccine in very short supply the hysteria will likely increase so I think we will see a spike in antiviral prescribing. The CDC--as always--is in a dammed if they do dammed if they don't position on this one. There is no real way to predict who will become real sick with the flu and who wont. Clinical signs lag behind the disease course because of the great organ reserve our bodies have. I say this with 15 years active clinical experience in busy teaching hospital Emergency Departments and scholarly interest in infectious diseases. Truth be told : I have on occasion this past 6 months caved into angry demands. If I don't cave in I then recommend what my Grandmother used to: rest, fluids, and elderberry extract.

By BostonERdoc (not verified) on 21 Oct 2009 #permalink

A little off topic, but what criteria should doctors be using to test for swine flu. I ask because I just recently had the swine flu, Iâm pretty sure I got it from my wife. However when we both went to see the same doctor on the same day, our doctor decided to test me but diagnose on the spot a respiratory infection with my wife. I tested positive and when we called the doc, she still didn't want to test her, she just changed her prescription from and antibiotic to tamiflu. And judging from that I think that doctor is simply prescribing tamiflu to anyone with swine flu.

My own experience was that I went into a nighttime clinic with flu symptoms on Saturday night, and despite the negative rapid flu test, the doctor diagnosed the flu and put me on both Tamiflu and an antibiotic. (I tested positive for strep.) I suspect part of this is that I'm asthmatic, and part is that I was pretty obviously sick.

I assume this really was the flu, though I guess if there's any vaccine left after everyone else has theirs, I may still get it, just in case this wasn't swine flu. (I had the seasonal flu vaccine, but that doesn't guarantee anything.)

By albatross (not verified) on 21 Oct 2009 #permalink

And off topic in another direction... considering some other recent news, should a study be seeing if tamiflu would help those with Chronic Fatigue Syndrome, or does tamiflu not affect the virus now implicated?

From Revere's post: "...waiting for results of real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay..."

Waiting? For the results of a real-time assay? Isn't that an oxymoron? (This is not sarcasm, it's a genuinely stupid question.)

By Wicked Lad (not verified) on 21 Oct 2009 #permalink

Revere,

I posted last week. My 5 year old son had swine flu positive diagnosis and was treated with tamiflu. I then came down with flu like symptoms but had a negative rapid flu test. But my illness turned into pneumonia. Luckily, I recovered, but I was treated with Tamiflu for it. So, now is my son immune and does not need the vaccine? The pediatrician stated he does not need it. But I read somewhere if you were treated with Tamiflu during your illness, then you won't be immune and still need the vaccine. Thoughts on this? Any research to support this?

I was surprised yesterday while at a well check, my doctor looked alarmed when I told her I was dealing with a very mild stomach bug -- mild digestive symptoms, body aches, fatigue, NO fever, chills, or respiratory symptoms. She immediately put me (and I think unnecessarily so) on Tamiflu.

On the one hand, I'm grateful to know that if I do catch H1N1 she'll be happy to prescribe it. On the other, I'm concerned that if doctors start throwing Tamiflu at anything that aches, our supplies will run short for those who need it most.

Wicked: The "real time" part refers to the type of PCR, not that the results are available in real time.

Laura: If your son had flu he likely has some immunity. There is a question whether Tamiflu affects the tests for the antibodies. This has come up in the studies that look for antibodies as a measure of infection or whether Tamiflu treatment affects some of the PCR results. This is a judgment call. I think my judgment would be to get the vaccine anyway.

It is a particular mess for us pediatricians. Fever cough uri ... common enough under any circumstances for kids under 2 years old and usually when those parents call we often talk them through a cold with a fever and only have them come in if the fever goes beyond 3 days (or of course if the parent feels the child is acting sicker than a regular cold) ... now we need to see these kids and decide if we should label them as probable H1N1 and give Tamiflu. We can choose between over-prescribing and giving out scripts to kids whose cough, cold, and fever is of a more mundane cause, in order to not miss the early opportunity with H1N1, or underprescribing and missing some. We will not howver be able to get it just right. There is no way to really tell.

Meanwhile many of us are not so convinced that the effect of Tamiflu is all that draatic and some do worry about whether or not the Japaneses concern over neuropsychiatric side effects is justified or not.

Bleh.

If you aren't offered antivirals you should probably ask for them.

Revere, that is hard to interpret. Who is "you" here? I can't figure out exactly what you are trying to say.

An unanswered question is how well the CDC's advice is making it into clinical practice. Do most primary care providers offer treatment to those in high risk groups for whom treatment is recommended? Are these patients obtaining treatment quickly, given the time required to get an appointment, get a prescription and buy the antivirals? Are clinicians really understanding the point that although early treatment is the most effective, individuals with severe symptoms (even if they have been sick for several days) will likely benefit from treatment and should be treated?

I've heard anecdotes suggesting not all these points are being translated into practice -- but it's a hard question to answer quantitatively.

By Marc Lipsitch (not verified) on 21 Oct 2009 #permalink

Marc: You're right. Probably could have been written more clearly. What I wanted to say was that if your health care provider doesn't offer you antivirals on her/his own when it looks to be indicated, for example, when you feel lousy or are feeling much worse suddenly or have a risk factor, you should ask them for it. The question you raised as to how much practitioners were heeding this advice is too early to say as it was just issued on Monday and there is a lot of confusion out there, including frankly erroneous advice being given to patients by their own doctors and their pediatricians.

have had a 2 days of flu (up to 40 degrees fever, but almost no other symptoms, despite headache). I called the NHS hotline to ask for advice and they told me to get Tamiflu, which I have been taken since, even though I feel a lot better (my only problem at the moment is a stuffed/runny nose). Is this appropriate procedure or should I stop taking it?

But if you stop, aren't you risking possibly allowing a Tamiflu-resistant strain (of whatever sort of flu it may be!) to develop (and possibly, depending how isolated you are for awhile, to spread)?

Disclaimer: I'm an Emergency Physician practicing in an Urgent Care setting.

With regard to testing: We are not longer testing for influenza (with rare exceptions). When testing, the PCR is the test to rely upon; rapid flu testing has been notoriously unreliable (high rate of false negatives) for novel H1N1.

With regard to antiviral treatment: I carefully discuss CDC recommendations as reviewed above with my patient. I will prescribe Tamiflu if a patient still wants the drug. I feel my role as a provider, in this circumstance, is to educate the patient to the best of my ability, but the choice is the patient's to make. I try to be clear that they do not meet CDC criteria, that treatment reduces symptoms only by one-half to two days at best, that antiviral treatment does not appear to reduce complications including hospitalization or death, and that therapy is expensive and not without unpleasant side-effects in a proportion of patients.

Matt wrote: "that antiviral treatment does not appear to reduce complications including hospitalization or death".

Hmmmm. . . I didn't know that !

I'd like to second Gilmore's surprise on Matt's "antiviral treatment does not appear to reduce complications including hospitalization or death." Anyone have more information on this?

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Thanks Paula,

I thought that was one of the main reasons to start antivirals. Sure you want to shorten the length of illness, but stopping / slowing the chance of it spiraling into "ventilator time" was a given for me.
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Re: Matt's Oct. 25 remark re antivirals, "that antiviral treatment does not appear to reduce complications including hospitalization or death"--thank you, Gilmore, I too wonder, and am wondering when Matt is going to provide us a reply on this. Matt?

Isnt' the purpose of the antiviral to stop the virus from reproducing thus not getting anyworse than it already is?????

I'm quite curious as well as to Matt's remarks about antivirals. From personal experience, I've seen how quickly Tamiflu has helped. Once started on it, my kids made a rapid recovery from the swine flu. I myself am taking it now. I went down with flu Saturday evening -- quick onset -- fatigue, chills, headache, sore throat, upper repiratory, followed soon after by lengthy fever, coughing. Aware of the symptoms, I immediately started on Tamiflu. The first 24 hrs I didn't notice any improvement. But the second day was much better. Right now I am at the 2.5 day mark and feel much improved, no fever, chills, sinus congestion gone, body aches are greatly reduced too. Still have sore throat, some coughing, fatigue, and night sweating. I can only attribute this reduction in severity and scope of symptoms, and their duration, to Tamiflu