Quinine for Leg Cramps.

Practice Pointers 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. Cochrane for Clinicians