Why isn't Zofran OTC?

July 18, 2014 1:56 PM

Why isn't Zofran OTC? Re: this response and a recent bout of norovirus where a tab Zofran, passed along by a pregnant coworker, was a savior.

Other friends in the same outbreak (dinner party with a recently sick host) ended up in the hospital for dehydration and passed it to others. I didn't go to the ER, and I didn't pass it to others, because I never vomited. My recovery was remarkably short compared to friends who did vomit and "got it out of their system" (so much "out of their system" that they infected their coworkers and went to the hospital. healthy!)

If such a great anti-nausea med could both reduce the number of people visiting the ER, and limit outbreaks of a pretty common and miserable illness, why isn't it more widely available? The potential for abuse seems low. And, full disclosure: as an emetophobe, the vision of a world with fewer puking people seems ideal!

The side effects don't seem much more severe than other meds that are freely available without prescriptions. Is this an insurance/"big pharma" conspiracy? Why else wouldn't it be OTC?

posted by magdalemon to Health & Fitness (19 answers total)

Because of the risk of a fatal heart arrhythmia, I assume.
posted by kindall at 2:02 PM on July 18, 2014 [5 favorites]

As someone with chronic nausea I too was amazed that this medication even exists! I didn't even know about it until I couldn't eat after wisdom tooth surgery. Now I get it via RX when I'm sick and hold onto the extras.

I have No idea why it's not OTC but I would guess it's because it's main use is usually related to chemo therapy. And it can cause bad headaches and constipation. I'm so interested in this. But my guess is maybe the constipation side effect has something to do with it.
posted by Crystalinne at 2:05 PM on July 18, 2014

The FDA seems pretty worried about Long QT syndrome which can apparently be triggered by Zofran among other drugs. By making the drug available only with a prescription, doctors can screen patients for a history of arrythmia and steer them to another method if there is a risk.
posted by muddgirl at 2:14 PM on July 18, 2014

Yep it isn't OTC because sometimes you die when you take it.
posted by Justinian at 2:18 PM on July 18, 2014 [2 favorites]

Response by poster: A quick Google of medications that cause Long QT syndrome/fatal heart arrhythmia shows that Ondansetron (Zofran) is risky only at the 32 mg intravenous dose--eight times the standard effective therapeutic dose! What drug doesn't cause negative effects at 8x the recommended dose (and intravenously!)?

Besides that, the list of medications that can cause Long QT syndrome includes many OTCs. So why those, and not this?
posted by magdalemon at 2:20 PM on July 18, 2014

I believe its "labeled" uses are limited to chemo- and radiation-related nausea; using it for pregnancy morning sickness, or for vomiting viral infections and what have you, are off-label uses and not what it's approved for. I believe a whole separate set of studies would have to be done to approve it for "general nausea," which presumably would be the OTC use.

It also works on your central nervous system (it doesn't settle your stomach; it impedes your ability to feel that your stomach is unsettled); when I was pregnant and they gave me Zofran, part of the whole "informed consent" spiel they gave me was about being unclear about certain central nervous system effects, especially at higher doses.

(Also it was fuckin' expensive, even as a generic. My insurance company was very grumpy about it.)
posted by Eyebrows McGee at 2:22 PM on July 18, 2014 [1 favorite]

What list of OTC meds which can cause long QT syndrome are you looking at, magdalemon? I'd like to take a look at it.
posted by Justinian at 2:25 PM on July 18, 2014

Response by poster: Justinian,

This one listing mostly antihistamines (and the rest of the list are pretty clearly rx drugs), but noting "There are many medications that can prolong the QT interval...Do not take over-the-counter medications except for plain aspirin or acetaminophen) without first talking to your health care provider."

And this one, which requires more paging through but again lists antihistamines as the main culprit for OTC's that cause Long QT.

And, I mean, I get it. The pharmaceutical industry is huge on covering their asses and minimizing litigation--in Googling, I found a ton of sites where lawyers want you to join their class-action suit because you were given a high dose of Zofran/Ondansetron and suffered ill effect.

I guess I just don't understand why a baby version (like baby Tylenol, you know?) couldn't be approved for OTC use. The risk of accidentally taking 8 tablets is so very low. The risk of accidentally administering it to yourself intravenously is nonexistent.

And I know AskMefi isn't the FDA, so I'll knock it off with the pleading.
posted by magdalemon at 2:35 PM on July 18, 2014 [1 favorite]

Oh ok. I can answer part of that.

You mention antihistamines specifically. That's actually an example of stuff NOT being OTC because of this. The antihistamines which are most closely associated with long QT syndrome are astemizole and terfenadine.

Get ready for it... BOTH of those drugs were pulled because they could cause long QT syndrome.
posted by Justinian at 2:43 PM on July 18, 2014

And I don't mean they were pulled from OTC to prescription, I mean they are no longer available so far as I am aware.

So, yeah, long QT is taken very seriously and it really is why Zofran isn't available OTC. If a significant link between Zofran and long QT continues to be supported I suspect it will get a "Black Box" warning which is the strongest warning the FDA can provide before yanking it completely.
posted by Justinian at 2:44 PM on July 18, 2014 [1 favorite]

To give you another idea of the strength of Zofran: it's used as an antiemetic when medics administer morphine or other EXTREMELY strong painkillers during a significant physical trauma. Depending on protocols and the medical director, it may or may not be available for use in your county, but it's used pretty rarely. Most areas will use Phenergan before Zofran due to possible contraindications and side effects.
posted by sara is disenchanted at 3:12 PM on July 18, 2014

It also works on your central nervous system (it doesn't settle your stomach; it impedes your ability to feel that your stomach is unsettled);

Wouldn't surprise me at all if you're right, Eyebrows, but the Wikipedia article is somewhat at variance with this:

Ondansetron is a highly specific and selective serotonin 5-HT3 receptor antagonist and with low affinity for Dopamine receptors. The 5-HT3 receptors are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. Serotonin is released by the enterochromaffin cells of the small intestine in response to chemotherapeutic agents and may stimulate vagal afferents (via 5-HT3 receptors) to initiate the vomiting reflex. It is not certain whether ondansetron's antiemetic action is mediated centrally, peripherally, or in both sites.

posted by jamjam at 3:29 PM on July 18, 2014 [1 favorite]

Here's the flip side, though: my 7-year-old daughter gets taken out REALLY hard by the throwups every time she gets them. The first time we experienced her terrible escalation of vomiting and abdominal pain, we rushed her to urgent care and she got IV Zofran, which cured her. The second time it happened, I called our doc and they called us in a single dose; the third time it happened, they set up a standard Zofran prescription for her. They never tried Phenergan or Reglan or anything else. When I had some nausea that threatened to take me out of a show that I really, really needed to be in, my doctor called in a Zofran prescription for me as well -- and my dosage is the same as my 48-pound daughter's. So part of me thinks that it has to be pretty dang safe once you get past the first dose.
posted by KathrynT at 3:37 PM on July 18, 2014

I didn't go to the ER, and I didn't pass it to others, because I never vomited. My recovery was remarkably short compared to friends who did vomit and "got it out of their system" (so much "out of their system" that they infected their coworkers and went to the hospital. healthy!)

I think your emetiphobia may be influencing your analysis of why you got better faster - maybe you have a more robust immune system, maybe you got a milder strain than they did. I was with a bicycle team in Cuba years ago where we all got hit with a norovirus on arrival, and it hit everyone differently. I was sick for days but never fainted. My Dad's first symptom was when he passed out, but by the next day he was back to normal.
posted by oh yeah! at 3:38 PM on July 18, 2014 [4 favorites]

Depending on protocols and the medical director, it may or may not be available for use in your county, but it's used pretty rarely. Most areas will use Phenergan before Zofran due to possible contraindications and side effects.

In the medical world, Zofran is used extremely commonly, particularly in the emergency department. It is really no longer just for chemo-induced nausea - it is regularly used for simple gastroenteritis and I often see it used as first line by obstetricians for nausea of pregnancy, even though vitamin B6 and doxylamine (an over the counter antihistamine) are cheaper recommended first line agents. It is absolutely one of my top 5 most prescribed medications. Phenergan, Compazine, and Reglan are also great anti-nausea drugs, but they also have some pretty unfortunate side effects for some people. I would say just based off my experience - watching people who I give anti-emetics to maybe 10 times per day, that I see side effects from Phenergan/Compazine/Reglan in maybe 10% of patients I use them on, including drowsiness (at the most mild), and the occasional case of akathisia (restlessness), which is easy to treat but very uncomfortable for the person experiencing it.

On the other hand, I've given literally thousands of doses of Zofran and I've never seen a single side effect from it. It's true that prolonged QT can cause a fatal arrhythmia, but I actually agree with you - plenty of things sold over the counter can kill you. Zofran is just as safe as many if not most over the counter medications. It should be over the counter. I wouldn't be surprised if it is available over the counter within the next 10 years. I'd lose a lot of business but I wouldn't mind!
posted by treehorn+bunny at 3:55 PM on July 18, 2014 [4 favorites]

Hmmm, we'll see who is right. Because I kind of expect it to be even more restricted as I said.
posted by Justinian at 3:59 PM on July 18, 2014

It is possible we could both be right. NSAIDs have a boxed warning and they are available OTC. Then again, a number of NSAIDs were grandfathered in as OTC while Vioxx did not survive. Still, Zofran is such a popular medication, and it has far more utility than the coxibs.

I should note that I just realized that the comment linked in the question was my own, so I just repeated myself to some extent - obviously this is just my opinion as one doctor who sees a lot of people for whom Zofran is a useful treatment. But based on patterns I've seen in the past 5 years, I definitely feel it's being prescribed more freely as physicians who trained since it went generic go into practice, and I believe that trend will continue even if a boxed warning came out for it.

magdalemon, one thing to keep in mind is that if a person is taking only Zofran, that person may have to take more like a 32mg dose to see risk of prolonged QT. But there is a not insignificant subsegment of the population who would be at risk with a much smaller dose, namely, people with congenital QT prolongation (not all of whom are aware they have this problem) and people on other medications that prolong the QT, such as methadone, hydrochlorothiazide, and furosemide - all very common prescription meds, and as you saw, there are many more examples. This is part of the reason why prescription meds that combine Tylenol with other pain medications recently got a black box warning. People take multiple Tylenol-containing medications without realizing it too frequently, and the resulting liver failure can be fatal. The FDA has to take into account the fact that we have an aging and diverse populace who would be accessing these meds if they were over the counter, we can't expect most people to know whether their combination of medications would be likely to produce a dangerous QT change.
posted by treehorn+bunny at 4:30 PM on July 18, 2014 [1 favorite]

Dystonic reactions are rare, but can occur with a regular dose of Zofran or other prescription anti-emetics (and certain other classes of prescription medications).
posted by wiskunde at 7:12 PM on July 18, 2014

Generic Zofran is still incredibly expensive. Actually, the last time I checked, which was admittedly a couple of years ago, a month's supply of generic Zofran for 8 mg tabs was more than a thousand dollars! Prescription plans can be a bit of a racket, where the consumer is only concerned with the co-pay, but the plan pays the deep costs. Prescription plans buffer the cost with co-pay maximums, so people really are not aware of how much the insurer is actually paying. I'm guessing that as a geneirc consumers would howl at the charges, there would be no insurance buffer and people would not buy it. The return for pharma is more reliable through prescription reimbursement. Would you spend 50 bucks for a single pill?

As to its safety, I was floored that my pregnant daughter was prescribed Zofran for severe nausea. She has great insurance and pays $10.00 for what is probably $1000 per fill. And if you know physicians, you will know they are extremely reluctant to prescribe anything for pregnant women. When I was pregnant with her, I was told to "eat Saltines".
posted by citygirl at 7:21 PM on July 18, 2014