Cochrane for Clinicians
Putting Evidence into Practice
Quinine for Leg Cramps
Am Fam Physician. 2016 Feb 1;93(3):177-178.
Author disclosure: No relevant financial affiliations.
Are quinine-based agents safe and effective in treating muscle cramps?
Quinine is moderately effective in decreasing the frequency and intensity of muscle cramps, but it is also associated with an increase in minor adverse effects. In addition, there is a risk of rare but serious adverse effects. (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)
Muscle cramps affect between 50% and 60% of adults.1 Little is known about their pathophysiology, so many remedies are used empirically. A crystalline alkaloid powder extracted from the bark of the South American cinchona tree, quinine is well known for its use in treating malaria and providing the bitter flavor for tonic water. Quinine has been used by the Quechua of South America for medicinal purposes for centuries, and has been researched since the 1930s and 1940s as a cure for muscle cramps.2 However, quinine is not without adverse effects, and the U.S. Food and Drug Administration withdrew the indication for treatment of muscle cramps because of reports of serious adverse effects such as hemolytic uremic syndrome, disseminated intravascular coagulation, and arrhythmias.3 Despite this, many patients still request quinine and many clinicians continue to use it off label.
This Cochrane review addresses the safety and effectiveness of quinine for muscle cramps and includes 23 studies comparing quinine to various agents: placebo, vitamin E, a combination of quinine and vitamin E, a combination of quinine and theophylline, and xylocaine injection. Dosages of quinine ranged from 200 to 500 mg, divided, once or twice daily. Thirteen studies were pooled to compare quinine vs. placebo with respect to the number of cramps over a two-week period (n = 952). Patients taking quinine had 2.5 fewer cramps than those taking placebo (95% confidence interval [CI], 1.4 to 3.5). Likewise, in seven studies (n = 666), those who took quinine also had decreased cramp intensity (−0.12 units on a three-point scale; 95% CI, −0.20 to −0.05), but this difference does not meet the usual criteria for a minimal clinically important difference. In seven studies (n = 842), quinine also decreased the number of days with cramps in two weeks (−1.2 days; 95% CI, −1.9 to −0.4). There was no difference in duration of muscle cramps. Patients taking quinine had more minor adverse effects, including gastrointestinal distress and tinnitus (risk difference = 0.03; 95% CI, 0 to 0.06). There was no significant difference in major adverse effects.
There was no statistically significant difference between quinine and vitamin E with respect to number of cramps, intensity or duration of cramps, or adverse effects, although patients taking quinine had a reduction in number of days with cramps (−2.8; 95% CI, −3.3 to −2.4) when compared with vitamin E. When quinine was compared with a quinine/vitamin E combination, there was no difference in number of cramps, intensity or duration of cramps, number of days with cramps, or adverse effects. The quinine/theophylline combination was found to be more effective than quinine alone on multiple measures, but these results are based on a single pharmaceutical-sponsored study of 164 patients. In another small study of 24 patients, xylocaine injection was found to provide better relief than quinine four weeks after the cessation of treatment.
Quinine is available for malaria treatment in the United States and is still readily available for leg cramps in many parts of the world. Tonic water is one good source of quinine; 1 L of tonic water contains approximately 60 to 70 mg of quinine.4 Quinine remains part of the National Health System formulary in Great Britain and is available in brand-name and generic forms in Canada. Physicians should encourage patients to follow the American Academy of Neurology guidelines, which recommend that patients with disabling cramps try nonpharmacologic treatments first and reserve quinine for use only after other agents have failed.2
The practice recommendations in this activity are available at http://summaries.cochrane.org/CD005044.
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Army, the U.S. Air Force, or the Department of Defense.
El-Tawil S, Al Musa T, Valli H, et al. Quinine for muscle cramps. Cochrane Database Syst Rev. 2015;(4):CD005044.
REFERENCESshow all references
1. Allen RE, Kirby KA. Nocturnal leg cramps. Am Fam Physician. 2012;86(4):350–355....
2. Katzberg HD, Khan AH, So YT. Assessment: symptomatic treatment for muscle cramps (an evidence-based review): report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology. Neurology. 2010;74(8):691–696.
3. U.S. Food and Drug Administration. Questions and answers about FDA's enforcement action against unapproved quinine products. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/SelectedEnforcementActionsonUnapprovedDrugs/ucm119653.pdf. Accessed June 16, 2015.
4. Ohira A, Yamaguchi S, Miyagi T, et al. Fixed eruption due to quinine in tonic water: a case report with high-performance liquid chromatography and ultraviolet A analyses. J Dermatol. 2013;40(8):629–631.
These are summaries of reviews from the Cochrane Library.
This series is coordinated by Corey D. Fogleman, MD, Assistant Medical Editor.
A collection of Cochrane for Clinicians published in AFP is available at https://www.aafp.org/afp/cochrane.
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