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Quinine for night-time leg cramps no longer recommended

Last updated: April 2009

If you have nocturnal (nighttime) leg cramps, your doctor might prescribe quinine (Qualaquin)-even though the U.S. Food and Drug Administration has approved it for only one purpose: to treat malaria (although doctors can legally prescribe most medications for any type of treatment they deem appropriate).

Leg cramps are uncontrolled muscle contractions that can be so painful they can waken you from sleep. They occur in many adults and are reported more often by women, and especially pregnant women.

Since the 1940s, doctors have been prescribing quinine for leg cramps because there are no other reliable treatments. The practice has continued despite multiple alerts from the FDA about the risks of quinine and its limited effectiveness.

Prescribing remains high despite warnings

The FDA has issued warnings about quinine since 1994 and more recently about its minimal effectiveness in treating leg cramps. In 2006, it banned the sale of all unapproved drugs that contained quinine except the branded drug, Qualaquin, because of the risk of serious side effects or death. Yet in the first six months of 2008, more than 124,000 people in the U.S. received close to 300,000 prescriptions for Qualaquin, according to the FDA. Since the Centers for Disease Control and Prevention reports that only about 1,500 individuals were diagnosed with malaria last year, it appears that quinine is still frequently prescribed off-label.

Indeed, from January 2006 to June 2008, 62 percent of Qualaquin prescriptions were for musculoskeletal symptoms, mainly for nocturnal leg cramps. Of the 38 reports of serious adverse events received by the FDA in roughly the same time period, over half (55 percent) were from people who had taken quinine for leg cramps.

What is the evidence for use of quinine to treat leg cramps?

There is little convincing scientific evidence for prescribing quinine for leg cramps. Studies of patients with nocturnal leg cramps have been small, were not randomized, controlled trials, and had other shortcomings. Not surprisingly, the FDA recently reported again that the risk of severe side effects from quinine outweighed any potential benefit for the following conditions:

Nocturnal leg cramps. Two meta-analyses (results pooled from a number of studies) were completed before the FDA ban addressed the lack of efficacy and safety issues of quinine for leg cramps. The first, from 1995, using published studies from 1964 to 1994, found that although taking quinine resulted in decreased frequency of leg cramps, it did not reduce the severity or duration of a given episode. Since longer use seemed to produce a greater reduction in the number of cramps, the authors concluded that quinine must be taken for at least four weeks on a regular basis before its effectiveness could be evaluated in a patient.

But the second meta-analysis, which included the earlier studies plus additional, unpublished research from the FDA, found that while quinine use did reduce the number of leg cramps, it didn't occur as often as previously reported-only 3.6 fewer instances in a four-week period vs. 8.83 instances.

The FDA recently reiterated that "there are no data indicating that quinine is effective for the treatment of nocturnal leg cramps or other musculoskeletal disorders, and given the potential for life-threatening adverse events, [practitioners] should use extreme caution in off-label prescribing."

Some doctors do suggest a carefully monitored four- to six-week trial of quinine for patients whose leg cramps are not relieved by other means. If your doctor does, and you decide to try quinine, make sure that you're not at increased risk for serious side effects because of your health or other medications you may be taking (see risks and precautions below). Also be aware that the appropriate dosage for leg cramps is unknown, though it is typically much lower than that recommended for the treatment of malaria. The typical dose of quinine used in studies to treat leg cramps is about 300 mg at bedtime.

And since only one prescription version of the drug is available in the U.S., you should consider the cost (the retail price for 90 324 mg capsules could run as high as $370), particularly since it may not be covered by your insurance for off-label use.

Restless Legs Syndrome. Unlike leg cramps, RLS is a neurological disorder characterized by an uncontrollable impulse to keep moving your legs even when you are sitting trying to go to sleep. Drugs originally developed to treat Parkinson's disease, including ropinirole (Requip and generics) and pramipexole (Mirapex), are generally prescribed to treat moderate to severe forms of this condition. But, no evidence suggests that quinine is effective for RLS.

Other cramping conditions. Some evidence suggests that quinine can reduce the severity and occurrence of leg cramps in people on dialysis for kidney disease. But there is no evidence to support use of the drug to treat diarrhea cramps, muscle cramps, or neuropathy (nerve pain).

Additional considerations

Before starting any treatment for nighttime leg cramps, your doctor should rule out any underlying diseases or drug side effects that might be causing them. Conditions such as movement disorders (dystonia); problems with the amount of minerals and fluids in the body (electrolyte imbalance); diabetes; nerve damage or pain; inflammation in various parts of the body; liver or thyroid disease; or disease of the blood vessels can trigger leg cramps. Cramps can also be caused by certain medications or entire groups of drugs including:

Individual drugs

  • lithium
  • nicotinic acid (Niacin)
  • nifedipine (Adalat, Nifedical, Procardia and generics)
  • raloxifene (Evista)
  • terbutaline

Classes of drugs

  • statins—used to treat high cholesterol (e.g. atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin)
  • corticosteroids—such as prednisone, used to reduce inflammation for conditions like arthritis, asthma lupus, and rashes
  • diuretics—such as hydrochlorothiazide and furosemide (Lasix and generics) used to treat high blood pressure and heart failure
  • phenothiazines—tranquilizing drugs

Drinking alcohol can also trigger leg cramps.

Other potential treatments

Botulinum toxin (Botox); carisoprodol (Soma and generics); gabapentin (Neurontin and generics); orphenadrine (Norflex and generics); verapamil (Calan, Verelan, and generics); and even vitamin E have also been tried, but there is limited evidence to support their use. Drinking tonic water, which contains quinine, is unlikely to trigger the worrisome adverse effects that may occur when you take Qualaquin pills. Even if you choose a tonic water high in quinine, however, you'd have to consistently drink almost two liters a day to reach an effective level. If the cause of your leg cramping isn't clear, you can try stretching your calf muscles before bedtime. Although a few small studies suggest that stretching may not reduce the recurrence or severity of leg cramps, some people do find them helpful. You can also try using a pillow to prop up your feet, or dangling your feet over the edge of your bed at night.

What are the risks of using quinine for leg cramps?

Most of the serious side effects reported from the use of quinine have been in patients taking it off-label to treat leg cramps or RLS. Some of the more serious ones that can result in hospitalization, serious illness, and death include:

  • thrombocytopenia—decreased blood platelets (cells that help the blood to clot)
  • cardiac problems, including an abnormal heart rhythm (too fast, too slow or irregular)
  • rashes and other allergic reactions
  • thrombotic thrombocytopenic purpura—a rare, often fatal blood condition that causes clotting throughout the body
  • hearing problems
  • eye problems
  • electrolyte imbalance (the amount of minerals and fluids in the body)
  • kidney failure
  • lung toxicity

Quinine can also interact with other medications, including antiarrhythmics (e.g. amiodarone, disopyramide, dofetilide, quinidine, sotalol); digoxin; blood thinners; drugs to control seizures; and neuromuscular-blocking drugs (used during surgery).

You should not take quinine if you have certain hereditary heart conditions, such as a prolonged QT interval (a rare problem that may cause fainting or an irregular heartbeat); an abnormal electrocardiogram (ECG; a test that measures the electrical activity of the heart); or if you have or have ever had G-6-PD, or glucose-6-phosphate dehydrogenase, deficiency (an inherited blood disease). Additionally, you should avoid quinine if you have myasthenia gravis (a condition that causes weakness of certain muscles), or optic neuritis (inflammation of the optic nerve that may cause sudden changes in vision), or if you have had an allergic reaction to quinine or similar medicines such as mefloquine or quinidine.

Side effect symptoms to watch out for:

Indicating low blood sugar (hypoglycemia)

  • shakiness
  • dizziness or lightheadedness
  • sweating
  • nervousness or irritability
  • sudden changes in behavior or mood
  • headaches
  • numbness or tingling around the mouth
  • weakness
  • pale skin
  • hunger
  • clumsy or jerky movements


Severe symptoms related to low blood sugar (hypoglycemia)

  • confusion
  • seizures
  • loss of consciousness

Serious side effects
Call your doctor immediately if you experience any of the following:

  • rash
  • hives
  • itching
  • hoarseness
  • difficulty breathing or swallowing
  • swelling of the face, throat, lips, eyes, hands, feet, ankles, or lower legs
  • fever
  • blisters
  • stomach pain
  • vomiting
  • diarrhea
  • blurriness or changes in color vision
  • inability to hear or see
  • faintness
  • easy bruising
  • unusual bleeding
  • blood in the urine
  • dark or tarry stools
  • nosebleeds
  • sore throat
  • changes in heartbeat
  • chest pain


Other side effects
Tell your doctor if any of these symptoms are severe or do not go away:

  • nausea
  • restlessness
  • difficulty hearing or ringing in the ears
  • confusion
  • nervousness


Bottom line. Quinine is widely prescribed to treat leg cramps (and less frequently, other cramping disorders) even though the FDA and the drug's prescribing information specifically caution that it should not be prescribed for those conditions. CR medical advisers suggest: Talk with your doctor about all drug and nondrug treatments for leg cramps. The risk of serious or life-threatening side effects from quinine and the lack of convincing evidence for its use outweigh the potential benefit of the drug for any condition except malaria.

This off-label drug use report is made possible through a collaboration between Consumer Reports Best Buy Drugs and the American Society of Health-System Pharmacists. This is the eighth in a series based on professional reports prepared by ASHP.

These materials were made possible by a grant from the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by a multistate settlement of consumer fraud claims regarding the marketing of the prescription drug Neurontin (gabapentin).
   

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