# Why has the FDA disallowed the use of quinine sulfate to prevent leg cramps? **URL:** \ **Category:** Factual Questions\ **Created:** [March 20, 2007, 2:27am UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660 "2007-03-20T02:27:59Z")\ **Posts on this page:** 13\ **Page:** 1
**Author:** ![ladyfoxfyre](https://avatars.discourse-cdn.com/v4/letter/l/ad7895/32.png) [@ladyfoxfyre](https://boards.straightdope.com/u/ladyfoxfyre)\ **Post date:** [March 20, 2007, 2:27am UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/1 "2007-03-20T02:27:59Z")
Very recently the FDA decided that they were basically rescinding their previous authorization for prescribing quinine sulfate for the treatment of night cramps. AFAIK it is still being produced and dispensed, as we in the pharmacy haven’t been told to remove it from our shelves. However, another brand name medication has recently arisen that’s targeted for patients with leg cramps. The ingredient in this brand-only medication? Quinine sulfate. So what gives? The FDA decides that it’s not okay to prescribe quinine sulfate for leg cramps, considering it is a dirt-cheap generic in all strengths, but approves a brand name of quinine sulfate for the treatment of leg cramps? -foxy ---
**Author:** ![Qadgop\_the\_Mercotan](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/qadgop_the_mercotan/32/83_2.png) [@Qadgop\_the\_Mercotan](https://boards.straightdope.com/u/Qadgop_the_Mercotan)\ **Post date:** [March 20, 2007, 2:45am UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/2 "2007-03-20T02:45:26Z")
It was a good move to pull the drug for cramps. I am not aware that the FDA has approved any other quinine products for leg cramps. In fact, the only product they have approved that contains quinine sulfate is used to treat malaria that is resistant to other drugs, and the FDA labelling specifically states it is **not** to be used for leg cramps. It’s also about 50 times more expensive than the old quinine sulfate tabs were. Here’s a PDA file from the FDA explaining the rationale behind their actions to pull quinine sulfate off the market for use for leg cramps. [http://www.fda.gov/cder/drug/unapproved\_drugs/quinineQA.pdf](http://www.fda.gov/cder/drug/unapproved_drugs/quinineQA.pdf) As a physician who’s looked into the matter, I agree with them. Quinine sulfate is a dangerous drug, there is no good evidence that it actually works better than placebo for leg cramps, and there are other meds out there that are safer, and have been shown to be effective for leg cramps. ---
**Author:** ![ladyfoxfyre](https://avatars.discourse-cdn.com/v4/letter/l/ad7895/32.png) [@ladyfoxfyre](https://boards.straightdope.com/u/ladyfoxfyre)\ **Post date:** [March 20, 2007, 10:22pm UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/3 "2007-03-20T22:22:00Z")
I know that Qualaquin is still on the market, but I distinctly remember throwing away (of course :smack: ) a mailed ad about a new brand name medication that had quinine in it as a therapy for leg cramps. If I could just go back a couple days and dig through my blue trash bags of PHI… I could be misinformed, however. Thanks for clearing that up. Would you mind elaborating on why quinine is such a dangerous drug? With the phasing out of it I know there have been patients with good success with clonazepam, but besides that what else is effective for leg cramps? -foxy ETA: I haven’t seen many patients who complained of leg cramps who were taking potassium for their furosemide. Is there a correlation there? ---
**Author:** ![Dewey\_Finn](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dewey_finn/32/4222_2.png) [@Dewey\_Finn](https://boards.straightdope.com/u/Dewey_Finn)\ **Post date:** [March 20, 2007, 10:26pm UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/4 "2007-03-20T22:26:54Z")
I thought that once a drug was approved for prescription use, a doctor could legally prescribe it for any other purpose (so-called “off-label” use). The PDF linked to above mentions that Qualaquin was approved, so couldn’t a doctor prescribe that for leg cramps if he likes? ---
**Author:** ![Dr.Lao](https://avatars.discourse-cdn.com/v4/letter/d/2bfe46/32.png) [@Dr.Lao](https://boards.straightdope.com/u/Dr.Lao)\ **Post date:** [March 20, 2007, 10:29pm UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/5 "2007-03-20T22:29:21Z")
[QUOTE=Dewey Finn] I thought that once a drug was approved for prescription use, a doctor could legally prescribe it for any other purpose (so-called “off-label” use). The PDF linked to above mentions that Qualaquin was approved, so couldn’t a doctor prescribe that for leg cramps if he likes? [/QUOTE] Even if it was over the counter, a doctor could prescribe it for off-label use. The FDA doesn’t regulate a doctor’s practicing of medicine. ---
**Author:** ![ladyfoxfyre](https://avatars.discourse-cdn.com/v4/letter/l/ad7895/32.png) [@ladyfoxfyre](https://boards.straightdope.com/u/ladyfoxfyre)\ **Post date:** [March 20, 2007, 10:53pm UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/6 "2007-03-20T22:53:59Z")
[QUOTE=Dewey Finn] I thought that once a drug was approved for prescription use, a doctor could legally prescribe it for any other purpose (so-called “off-label” use). The PDF linked to above mentions that Qualaquin was approved, so couldn’t a doctor prescribe that for leg cramps if he likes? [/QUOTE] A lot of medications are prescribed for off-label use, that’s how Viagra came about (originally researched as a blood pressure medication) or Topamax (now commonly used for migraines, originally prescribed for seizures). The FDA has said that they are not approving quinine for leg cramps, so there’s a difference between saying that a drug has an off-label use and strictly forbidding it from being prescribed for a certain off-label use. -foxy ---
**Author:** ![Derleth](https://avatars.discourse-cdn.com/v4/letter/d/b9e5f3/32.png) [@Derleth](https://boards.straightdope.com/u/Derleth)\ **Post date:** [March 20, 2007, 11:32pm UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/7 "2007-03-20T23:32:58Z")
**ladyfoxfyre** : From the PDF: > [@](#): > > **What risks are associated with quinine-containing drugs?** > > Serious safety concerns, including fatalities, associated with drug products containing quinine are well-documented in the literature and in adverse drug events reported to the agency. One of these adverse events is quinine toxicity, a cluster of symptoms that includes tinnitus, dizziness, disorientation, nausea, visual changes, and auditory deficits. There is also evidence that quinine causes serious cardiac arrhythmias including torsades de pointes. People taking quinine are at risk of developing hypersensitivity to the drug and experiencing a serious, life-threatening, or fatal reaction as a consequence. Serious adverse reactions associated with quinine use also include severe skin reactions, thrombocytopenia (a decrease in blood platelets that can cause hemorrhage or clotting problems) and other serious hematological events, permanent visual and hearing disturbances, hypoglycemia, renal failure and generalized anaphylaxis. Overall, from 1969 through September 11, 2006, FDA received 665 reports of adverse events with serious outcomes associated with quinine use, including, 93 deaths. Many of the adverse events associated with quinine are dose-related, and because of age-related differences in the rate at which quinine is eliminated from the body, the frequency and severity of adverse effects associated with quinine drug products may be greater in the elderly. ---
**Author:** ![Ike\_Witt](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/ike_witt/32/283_2.png) [@Ike\_Witt](https://boards.straightdope.com/u/Ike_Witt)\ **Post date:** [March 21, 2007, 12:02am UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/8 "2007-03-21T00:02:00Z")
From the passage that **Derleth** quoted: > [@](#): > > Overall, from 1969 through September 11, 2006, FDA received 665 reports of adverse events with serious outcomes associated with quinine use, including, 93 deaths. Seriously? 93 deaths in 37 years? I don’t know for sure but doesn’t seem overly worrysome. How many people died from Aspirin in the same period? ---
**Author:** ![gazpacho](https://avatars.discourse-cdn.com/v4/letter/g/6f9a4e/32.png) [@gazpacho](https://boards.straightdope.com/u/gazpacho)\ **Post date:** [March 21, 2007, 12:05am UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/9 "2007-03-21T00:05:29Z")
> [@](#): > > quinine toxicity, a cluster of symptoms that includes tinnitus, dizziness, disorientation, nausea, visual changes, and auditory deficits. All this time I though it was the gin causing these. ---
**Author:** ![ladyfoxfyre](https://avatars.discourse-cdn.com/v4/letter/l/ad7895/32.png) [@ladyfoxfyre](https://boards.straightdope.com/u/ladyfoxfyre)\ **Post date:** [March 21, 2007, 12:27am UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/10 "2007-03-21T00:27:18Z")
Thanks, **Derleth** , for the excerpt and **Qadgop** for the link. So what I’m wondering now is, does quinine have an actual therapeutic value for nocturnal leg cramps, and is there a possibility of it being resubmitted with a New Drug Application? Or is the FDA just concerned with the fact that it hasn’t been demonstrated that the harms/benefit ratio of the drug was not widely aware to prescribers? -foxy ---
**Author:** ![Dr.Lao](https://avatars.discourse-cdn.com/v4/letter/d/2bfe46/32.png) [@Dr.Lao](https://boards.straightdope.com/u/Dr.Lao)\ **Post date:** [March 21, 2007, 12:40am UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/11 "2007-03-21T00:40:06Z")
[QUOTE=adam yax] From the passage that **Derleth** quoted: Seriously? 93 deaths in 37 years? I don’t know for sure but doesn’t seem overly worrysome. How many people died from Aspirin in the same period? [/QUOTE] How many more people you suppose took aspirin? Risk isn’t just about raw numbers, but likelihood of an adverse reaction. Also important is the efficacy and the seriousness of the condition it treats. If a drug causes a lot of adverse events, but it cures cancer 100% of the time, it will likely remain approved. If it causes a lot of adverse events and it is supposed to cure leg cramps and it doesn’t even do that very well (and not as well as much safer alternatives), it will get pulled. ---
**Author:** ![Derleth](https://avatars.discourse-cdn.com/v4/letter/d/b9e5f3/32.png) [@Derleth](https://boards.straightdope.com/u/Derleth)\ **Post date:** [March 21, 2007, 6:05am UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/12 "2007-03-21T06:05:28Z")
Again from the PDF (which I can just copy from, as if it were a real text file): > [@](#): > > **Why does the FDA warn against the use of quinine to treat or prevent leg cramps and related conditions?** > > Quinine has been used since at least the 1940’s for the relief of nocturnal leg cramps. However, over the last decade, there has been significant concern regarding its unfavorable risk/benefit ratio for this and related conditions. > > In the 1990s, as part of FDA’s review of over-the-counter (OTC) drugs, the Agency evaluated OTC quinine products sold without applications for leg cramps, reviewing extensive information from studies and adverse drug events reported to the agency regarding the safety and efficacy of quinine drugs. Citing numerous safety concerns associated with use of quinine and concluding that the data were not adequate to establish that quinine is effective for prevention and/or treatment of nocturnal leg muscle cramps, the Agency concluded that these products could not continue to be sold OTC for leg cramps without approved applications. Drug Products for the Treatment and/or Prevention of Nocturnal Leg Muscle Cramps for Over-The-Counter Human Use, 59 Fed. Reg. 43234, (August 22, 1994) > > The labeling for Mutual’s approved prescription quinine sulfate includes numerous warnings regarding the use of the product for the treatment or prevention of nocturnal leg cramps. For instance the “Indications and Usage” section notes that “Quinine sulfate oral capsules are not approved for the treatment or prevention of nocturnal leg cramps.” In a paragraph entitled “Use of Quinine Sulfate for Treatment or Prevention of Nocturnal Leg Cramps” in the “Warnings” section, the labeling states: > > Quinine sulfate may cause unpredictable serious and life-threatening hypersensitivity reactions, QT prolongation, serious cardiac arrhythmias including torsades de pointes, and other serious adverse events requiring medical intervention and hospitalization. Fatalities have also been reported. The risk associated with the use of quinine sulfate in the absence of evidence of its effectiveness for treatment or prevention of nocturnal leg cramps, outweighs any potential benefit in treating and/or preventing this benign, self-limiting condition. > > Similar information regarding use of quinine sulfate for leg cramps is included in information designed for patients that is part of the approved labeling. > > Although adverse events associated with quinine drugs also can occur when it is used to treat the approved indication, because untreated malaria, unlike leg cramps, is life-threatening, these risks may be justified. Because of the risks associated with use of quinine drugs, Mutual will be providing written information to physicians regarding the drug’s unfavorable risk/benefit for treatment of nocturnal leg cramps, as compared with its favorable risk/benefit ratio for treatment of uncomplicated P. falciparum malaria. As a matter of policy, FDA does not ordinarily interfere in the practice of medicine. In the exercise of their professional judgment, physicians may generally prescribe approved drugs for unapproved uses. These warnings regarding quinine drugs do not change that policy. So the drug is not extremely effective against craps, and certainly not effective enough to keep using for that purpose in the face of the risks involved. Personally, I used it for my leg cramps and I never got toxicity. I also have no real evidence it helped. (I _ **HATE** _ it when people rely on anecdotal evidence when something really matters, especially when there is real evidence to hand.) ---
**Author:** ![DrDeth](https://avatars.discourse-cdn.com/v4/letter/d/b487fb/32.png) [@DrDeth](https://boards.straightdope.com/u/DrDeth)\ **Post date:** [March 21, 2007, 6:23am UTC](https://boards.straightdope.com/t/why-has-the-fda-disallowed-the-use-of-quinine-sulfate-to-prevent-leg-cramps/396660/13 "2007-03-21T06:23:24Z")
[QUOTE=Derleth] So the drug is not extremely effective against craps, [/QUOTE] I don’t think it is used as an anti-diarretic, Derleth. 😛 However, Quinine water aka Tonic does contain Quinine and apparently in a low enough dose to be safe. > **[Quinine](https://en.wikipedia.org/wiki/Quinine)** > > Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to Plasmodium falciparum that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg cramps, quinine is not recommended for this purpose due to the risk of serious side effects. It can be taken by mouth or intravenously. Malaria resistance to quinine occurs in certain areas of the world. Quinine is also used as an ingredient in to Common side eff... "Quinine is a flavour component of tonic water, bitter lemon, and vermouth. According to tradition, the bitter taste of anti-malarial quinine tonic led British colonials in India to mix it with gin, thus creating the gin and tonic cocktail, which is still popular today in both India and Great Britain, and in other former British colonies. In the United States, the Food and Drug Administration limits tonic water quinine to 83 ppm, which is one-half to one-quarter the concentration used in therapeutic tonic." " of mild cinchonism (which may occur from standard therapeutic doses of quinine) include flushed and sweaty skin, ringing of the ears (tinnitus), blurred vision, impaired hearing, confusion, reversible high-frequency hearing loss, headache, abdominal pain, rashes, lichenoid photosensitivity [1], vertigo, dizziness, dysphoria (feeling uneasy), nausea and vomiting, and diarrhea. Large doses of quinine may lead to severe symptoms of cinchonism: skin rashes, deafness, somnolence, diminished visual acuity or blindness, anaphylactic shock, and disturbances in cardiac rhythm or conduction, death from cardiotoxicity. Quinine overdose can also result in a rare form of hypersensitivity reaction termed blackwater fever that results in massive hemolysis, hemoglobinemia, hemoglobinuria, and renal failure. Patients treated with quinine may also suffer from hypoglycemia (especially if administered intravenously) and hypotension (low blood pressure). In very high doses (higher than those used to treat malaria) during the first trimester of pregnancy quinine may act as an abortifacient, or cause birth defects, especially deafness. Most symptoms of cinchonism (except in severe cases) are reversible and disappear once quinine is withdrawn."