An ongoing dialogue on HIV/AIDS, infectious diseases,
December 15th, 2019
Should Oseltamivir Become an Over-the-Counter Drug?
News broke last week that oseltamivir — most commonly known by its clever (expired) brand name, Tamiflu — may be heading to pharmacies soon as an over-the-counter (OTC) drug, available without a prescription.
After hearing this, I immediately thought of several reasons both supporting and opposing this change — an ideal question for a poll!
Oseltamivir (brand name Tamiflu) may soon become an over-the-counter medication, available without a prescription. How do you vote, #IDTwitter and other clinicians, and why?
— Paul Sax (@PaulSaxMD) December 14, 2019
Clearly, way more ID-oriented clinicians support the status quo, with oseltamivir remaining available by prescription only. This 70%/30% split shows they feel even more strongly about it than the Brits did in their opposition to Jeremy Corbin.
(Too soon? Sorry.)
But even more fascinating than the poll results were the comments after the poll, many of them thoughtful and backed by clinical and scientific data. These were evident on both sides of the question.
I’ll summarize some of the more interesting opinions below. First, the NAY votes:
- Does the drug even work? A longstanding controversy, linked to concerns that the initial publications included only favorable data. Many cite various Cochrane Reviews (there have been several) as a reason to consider oseltamivir only modestly effective at best. Symptom improvement of only 1 day, or even less than that? Big deal, take some analgesics, curl up in bed, and wait it out.
- Most people have little idea what influenza actually is, using the term “flu” for all kinds of symptoms. “Stomach flu”, for example, is a commonly used lay term. Clearly
oseltamivir would do nothing for this illness. - “Flu-like symptoms” are a common harbinger for several severe infections, and people who start themselves on oseltamivir will delay seeking attention for these conditions that need alternative treatments. Some of these might be respiratory infections such as pneumonia; others are systemic infections that cause fevers and chills first (such as pyelonephritis, streptococcal skin infections, and endocarditis).
- Some will jump the gun and think they need to start oseltamivir at the first sniffle, when all they have is a cold. Distinguishing influenza from other respiratory viral illnesses can be challenging — and the common cold (mostly from the zillions of rhinoviruses out there) is way more common (naturally) than influenza, especially when it isn’t flu season.
- Not only that — if people take it for a common cold or a “stomach flu”, they’ll be both wasting their money and risking side effects for no benefit. We don’t know what OTC oseltamivir will cost, but suspect it won’t be cheap — and this is an out-of-pocket cost, no insurance, with costs passed on to the patient. And no drug is 100% safe. Systematic reviews cite nausea and vomiting as the most common side effects of oseltamivir, but headache and psychiatric symptoms also may occur.
- Increasing access to oseltamivir will breed influenza resistance to it. A huge worry, one that we see globally already with ready access to antibacterial drugs. Do we want to risk this with oseltamivir and influenza? Of course not.
- We have enough trouble getting people to take their flu shot — now it will be even harder since they can get ready access to flu treatment. It’s like statin drugs and an unhealthy diet, right? License to ignore good medical advice.
Now, the YAY votes:
- Oseltamivir works best if started soon after the onset of flu symptoms — hence improving access to the drug is critical. Clearly sooner is better — the package insert says it should be started within 48 hours after symptoms start; studies show the greatest benefits if started in the first 6-12 hours. And who can reach their provider that quickly? What if it’s a weekend? What if your provider doesn’t believe it works? (See above.)
- Just the fact that there’s a controversy about whether it works shows it must work better than existing OTC “cough and cold” drugs, which are widely used. Can’t argue with that, as most of the colorful pills, liquids, and lozenges in that aisle are useless.
- The most rigorous and comprehensive overviews of the oseltamivir studies demonstrate conclusively the benefits of treatment. The key strength of this widely cited Lancet paper is that it used individual patient level data from the trials, which are much more reliable than aggregate study results. Those at high risk for influenza complications appear to benefit the most, reducing the need for antibiotics or hospitalization. (Addendum: And now I can link this recently published trial as additional evidence!)
- If people can get the drug easily at a pharmacy, it will limit the time they spend in doctors’ offices or hospital emergency rooms, reducing the risk they’ll spread flu to vulnerable other people. The elderly, the immunocompromised, those with multiple comorbid medical conditions (especially cardiac and pulmonary), pregnant women — they frequently visit health care settings, and the last thing they need is to spend time in waiting rooms with someone who has active influenza. Many hospitals (ours included) advise people to stay home if they have flu symptoms (unless of course they also have shortness of breath, difficulty staying hydrated, or other worrisome issues). “Sharing Isn’t Always Caring” say the signs in our hospital — clever.
- Making it over-the-counter doesn’t mean it needs to be in the aisle with the cough and cold “remedies” — a pharmacist could release it based on a symptom questionnaire or other screening tool. New Zealand and Japan have taken this approach — the drug is “behind the counter”, so not literally OTC — and this strategy apparently limits inappropriate use.
- There is no evidence that use of oseltamivir in people without influenza selects for influenza resistance. Indeed, without influenza being actually the diagnosis, the drug may not be doing any good — but it’s not leading to resistance. And in the countries that have it without prescription already, resistance to oseltamivir has not (yet) led to more local resistance.
- Influenza resistance to antivirals is unpredictable (to say the least), and not necessarily triggered by overuse. Take a look at this slide set reviewing the issue! Quoting Dr. Marc Lipsitch (who shared the slides): “The usual paradigm of use driving resistance doesn’t appear to hold.”
So where do I stand on the issue?
Gosh, this one is complicated.
While all the YAY and NAY votes make sense, for their own reasons, ultimately I thought about what I currently do in clinical practice.
When a patient calls me during flu season saying that they have fevers, chills, muscle aches, dry cough, and a runny nose, and that this illness “hit them like a truck” — I call in a prescription for oseltamivir rather than ask them to come in for an exam, blood tests, or a flu swab.
Why put them through this punishing trip to the hospital? Why expose other patients and health care providers?
Sure, it could be something else. And sure, it’s important to screen for other symptoms, and to tell them to come in if they’re not improving.
But the call to me seems like an unnecessary barrier; a good pharmacist can conduct the appropriate symptom screen and save people the hassle of reaching their providers by phone. They wouldn’t recommend osteltamivir for symptoms of “stomach flu”, or for a runny nose only, would they?
So bring on behind the counter oseltamivir, available without a prescription! Under the guidance of a wise pharmacist!
And remember — Tamiflu was selected as the one of the greatest expired (it’s now generic) antimicrobial brand names ever by Dr. Raphy Landovitz in this important podcast.
So go ahead, listen again to the whole thing.
And now that you’ve read this far, how would you vote?
Thanks to those who offered the numerous thoughtful responses and insights offered in the original poll. Let’s see what this one shows.
25 Responses to “Should Oseltamivir Become an Over-the-Counter Drug?”
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
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Couldn’t agree more! Pharmacists are an untapped healthcare workforce in many areas (including PrEP)!
I voted no. This resonated with my primary care experience: “‘Flu-like symptoms’ are a common harbinger for several severe infections, and people who start themselves on oseltamivir will delay seeking attention for these conditions that need alternative treatments.” Additionally, some very serious drug reactions, such as Stevens-Johnson syndrome, start with non-specific, flu-like symptoms.
Many patients report having had the flu, but when I question them, they say they felt achey and coughed for a few days. Not the flu! If someone calls me and says they feel like a truck ran them over, they were fine one hour and down for the count the next, every bone, muscle and joint hurts, their head is pounding, etc., I will gladly send in an Rx for oseltamivir and keep them out of the waiting room. After telling them that it’s likely to reduce their symptom duration by only a day or so, of course.
That said, I would be open to pharmacists dispensing it “behind the counter” after an appropriate screening. (I wish this strategy had been adopted when Primatene Mist inhalers were put back on the market as an OTC drug; the tablet form is a “behind the counter” drug, however.) Hopefully, their for-profit big-box drugstore employer won’t pressure them to dispense oseltamivir to all who ask for it. But put it in the aisle with other cough and cold remedies? Not my preferred strategy for sure.
I’m a little skeptical about most patients’ ability to self-diagnose influenza. My health system (northern California Kaiser Permanente) monitors flu activity and updates docs weekly on the status of the flu season, including recommendations about when, and in whom, to use antivirals. There is generally good access to care, and at the very least, a same-day telephone visit can help a patient decide if they need oseltamivir, nothing, testing, or an in-person evaluation. (I guess I’m agreeing with Loretta.) The argument for the necessity of rapid access due to delays in reaching the doctor is less relevant when patients have access to care. I think that is a better solution than an antiviral free-for-all, but in many practice settings, it is hard to achieve.
All the NAY positions are very interesting from a theoretical point of view. However, what is their incidence? E.g. Suppose your decision-making is based on your assumptions about client’s habits. A good (and very basic) research question would be: are my assumptions based on reality or just stereotypes?
Many a time treatment was withheld from self-administration out of fear someone would “abuse it”… Out of fear, yes, because later introduction in the broader market proved that abuse rose only in the early stages of dissemination and then soared.
Interesting post….I always find it interesting that many posts like this fail to note the harm that oseltamivir can cause. For the chance of a few hours of potential benefit, they might also have the chance to experience nausea, vomiting, insomnia, and hallucinations. The harm that this medication causes should also be considered in this decision.
An emphatic yay! Pharmacies in many states are already helping patients sort through their signs and symptoms during influenza season. Pharmacists collect vital signs, HPIs’ and if there is influenza in the community and the patient has signs consistent with ILI they perform a rapid influenza test. (These tests have undergone significant FDA review lately to ensure improved performance.) When the tests are positive the pharmacists have been dispensing oseltamivir. When patients at high risk for complication are identified they are discharged from the pharmacy and referred to their PCP. Of note, about 40% of individuals that use these services do not identify a PCP and are encouraged by the pharmacist to establish a medical home. Wen tests are negative, patients are managed symptomatically. All patients are typically called within 24-48 hours after their encounter to follow-up. This model was highly effective last year in relieving stress in offices when influenza was especially hard in our community. Physicians were actually referring patients to the pharmacies.
The idea of talking with patients before they come to clinic, to screen them and possibly prescribing Tamiflu, seems good, but how many physicians, realistically, communicate with patients before they’re in exam rooms? I imagine some clinic practice structures (e.g., Kaiser’s) have the infrastructure and appropriately trained staff to do it well but I expect many do not. Therefore, I like the behind-the-counter pharmacist-dispensed option.
If it becomes available without prescription, it would be important to find out what actually happens. For instance, what percent of people purchasing the drug actually have the flu? In some respects, we can treat the decision to purchase as a test. So, what would be the positive predictive value of that test? Clearly, it would depend in part on the pre-test probability, but what would we do if, during the flu season, we found that 90% or 10% of the purchasers had influenza? What level of actual precision would be acceptable?
2 reasons why I vote nay:
1. patients perceive that over the counter medications are safe – or at least safer than prescription medications. We’re seeing this as we try to tell patients to take a statin instead of their aspirin. They tell me they would prefer to stay on the aspirin and not start the statin because they’re worried about the statin side effects, but believe aspirin is a safe drug with no potential adverse effects.
2. many insurance carriers won’t cover drugs that are available over the counter. As a result, our high-risk patients who may not be able to afford the out of pocket cost of an OTC medication may not be able to access it when needed. I already have patients trying to quit smoking who can’t afford their nicotine patches or who have severe seasonal allergies who can’t treat them with the nasal steroids and antihistamines I recommend.
Yes to OTC, that way it can begin sooner with wider availability. Have you tried to find Tamiflu during a pandemic? Impossible!! When it is given OTC status it will be more widely available, come down in price and be accessible for those even exposed for prophylaxis! I remember OCT 2009 too well still. H1N1 was horrible in Chicago and across the nation. Ibuprofen used to be RX only and it is riskier than Tamiflu.
All for behind the counter.
One concern for me is that patients already use Tamiflu in lieu of influenza vaccination. “ I don’t believe in flushots, but I want Tamiflu because I have been exposed to the flu”. The cost issue is real as insurers don’t cover OTC’s.
No, this snake oil scam should not be encouraged further.
Very thoughtful discussion. However my vote is nay because
1) have you been to a pharmacy lately? Every pharmacy I’ve been to appears understaffed and the pharmacists overextended. And the pharmacy is no better than a doctors waiting room in terms of contagion.
2) as a primary care physician, people are always coming in telling me they have the flu but they are rarely correct. It’s usually the common cold.
3) In the last couple of years, the pharmacies have run out of tamiflu. If there is a run on tamiflu during flu season, will we run out of it for the patients who need it most? How do we prevent that?
Re: number 1 – speaking as a pharmacist, thank you! Given the way things have been going in the retail pharmacy world (especially at the bigger chains *cough* CVS), I have a lot of trouble imagining any retail pharmacy will have the resources to adequately screen patients prior to dispensing tamiflu. I also would doubt these companies would get behind paying for rapid flu screens to be kept in the pharmacy, to say nothing of paying to train their pharmacists to use them properly. Hell, even if they did, most retail pharmacists are often too busy filling scripts to adequately screen prescriptions, take histories and counsel their patients (ie to be actual pharmacists).
As such, even though I agree with behind the counter tamiflu in principle, I would have a hard time supporting it in practice.
…
Thank the gods I work in hospital…
I agree that a trial of this should be run first. I predict no significant overall benefit or harm.
In the population I serve this won’t make a big difference. Patients and pharmacists will misdiagnose influenza even more than physicians and take medication inappropriately and excessively. Some will delay care hoping their self treatment will keep them out of the hospital. And some might be kept out of the hospital and some will end up in the hospital with a delay in treating their pneumonia.
A third of my patients need renal dose adjustments and so they will all overdose oseltamivir. I am against OTC oseltamivir if there is significant toxicity from minor overdoses.
Patients often come to physicians because our prescribing authority makes us the gatekeepers for the medication they want rather than our expertise in diagnosing and treating disease. This might put the emphasis more on our expertise rather than our prescribing power.
Have you familiar with the literature on RDT and early access to medication with pharmacist involvement? Clearly there is a need for scrutiny and clarity of how pharmacists would perform the evaluation, but these are generally done with a physician CPA. Don’t be afraid of more effective forms of healthcare.
In the late 1990s we lost amantadine in a single season due to overnight development if antiviral resistance. The CDC and DOH test for the emergence of Tamiflu resistance. There is clearly a risk of development of antiviral resistance.
I do not see a good reason to promote antimicrobial use without a diagnosis. We have rapid PCR testing available for the flu that is fast and reliable. Why would stewards promote use of antimicrobial medications without a diagnosis and treatment based alone on symptoms alone?
The symptoms of influenza are non specific. Even at the peak of the influenza season, at least 1/3 of highly sensitive NAAT influenza tests are negative. For the week ending 12/15/2019, in our organization located Seattle Washington, there were 900 NAAT influenza tests performed of which 208 were positive. If all 600 patient with influenza like symptoms were treated, 392 would have been treated with Tamiflu who did not have influenza.
I see little difference between treatment of flu like symptoms and a sore throat. Most providers concerned about antimicrobial stewardship would not prescribe otc antibiotics/PCN/Amoxi without a positive strep test. Why should we recommend prescribing otc Tamiflu without a positive test?
I’m a pharmacist. We have a protocol to administer a rapid flu test and prescribe Oseltamivir, zanamivir or Xofluza off a positive screen.
As for “OTC reducing the price”- yeah I don’t know. I had a supplier call me yesterday offering 20 count boxes for $8 a pop and suspension for $14 a bottle. I very much doubt that OTC retailers will charge less than $25 for a box retail price, and potentially even more.
Also OTC switches lead to immediate removal from all insurance formularies (except some Medicaid plans).
I agree with the point made by the author that “a good pharmacist can conduct the appropriate symptom screen and save people the hassle of reaching their providers by phone.” One of the challenges for pharmacists in practice in the United States is based in our model for provision of pharmacy services. Basically, dispense a drug and the pharmacy receives revenue from the prescription.
A question persists as to what is the value of the cognitive service provided? If the cognitive service provides some inherent value would it not seem logical that the pharmacist would somehow be compensated for this service. As well as there being a value to dispensing a medication, there is value to avoiding the expense and risk of a therapeutic intervention in which the potential benefit is outweighed by the risk. Pharmacists have yet to achieve “provider status” at the federal level in the United States.
Although many states do have provisions for “collaborative practice agreements,” these are grossly underutilized, and beyond immunization, nearly non-existent in practice. Many of the states that have given pharmacists provider status make no provision for payment for the services.
I strongly agree that pharmacists can be an integral part of this process and many others, thereby improving patient access to therapies, streamlining provision of some basic services, saving healthcare costs, avoiding unnecessary therapy, and improving overall outcomes.
I am extremely happy to see comments from our physician colleagues in favor of this approach. I look forward to opportunities to advance this concept and also for the ability for pharmacists to be compensated for the provision of cognitive services and where appropriate even the avoidance of using a medication when one is not warranted.
No, and no real argument
It’s not clear it does anything. Lay people almost always, in my experience, can’t distinguish true flu (isn’t that why we examine/take histories?), and certain groups (ie. pregnant women/elderly) should specifically see an MD if they think they have the flu.
The author casually brushes off “resistance” issues, when NEJM is constantly arguing how MD’s should be limited when and where they use antibiotics due to “resistance” issues!
BTW, where are these “clinical pharmacists” that academic journals love to refer to? I have yet to meet one.
Hi! I’m a clinical pharmacist who works night shift at a community teaching hospital and level 2 trauma center. I have colleagues that work on the floors and in the ICUs/ED on days, seeing patients and assisting with medication regimens, along with providers. There are also clinical pharmacists who work in clinic adjusting medication regimens, which often involves taking labs (e.g. an INR); this is pretty common in the VA setting.
Just because you haven’t met one of us doesn’t mean we don’t exist.
Having worked on the antibiotic resistance crisis for the last five years with some of the worst areas of resistance in the country and having watched the world for pandemic influenza for the last quarter century, I voted an emphatic no. Lipsitch et al had better be 100% certain distribution of this drug won’t promote resistance. It seems we have learned very little and are not paying attention to the very real threat we are seeing in our healthcare facilities right now with MDR, XDR, and PDR organisms.
It would be appropriate to distribute OTC in the context of two conditions: 1) a pandemic warning communication / suspected emergence of pandemic influenza; and 2) release of a universal influenza vaccine that is demonstrated clearly to work.
We have a real problem analyzing the cost / benefit of many systemic level decisions in healthcare- let’s hope this doesn’t become a bad moment of hindsight.
James M Wilson V, MD
CEO / M2 Medical Intelligence
I voted yes, for OTC access but ONLY if behind the counter with prior pharmacist screening for appropriate use to decrease risk of antiviral resistance.
Nay. 1. Valid screening of patients requires hands-on examination as well as PCR testing and thorough history for real risk assessment. Pharmacists in the average major pharmacy have no time for a proper screening of patients including to rule out contraindications to use of antivirals.
2. Drug resistance development is a real phenomenon!
3. Cost. (a). How would the pharmacist be reimbursed for evaluating the patient?
(b). Price of the drug converted to OTC is going to be more affordable? When have we seen that happen? And, the patient will bear the total cost of the drug instead of a nominal co-pay as it will no longer be covered by insurance making it unaffordable to many patients.
4. In my early years experience when ama tadine was given within 6 hours or so it worked completely eliminating symptoms within 6-12 hours. Delay in treatment reduced the benefit significantly. Overuse has totally eliminated its usefulness. Tamiflu works just as well IF given early. This can only happen with widespread patient education and accessibility to prompt physician evaluation must become more widespread than just in the Kaiser model. We must learn from past mistakes of overuse not to hasten the demise of Tamiflu in the same way. Nay to OTC Tamiflu!