David R Guay1. 1. Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA. guayx001@umn.edu
Abstract
OBJECTIVE: To review the efficacy and tolerability profiles of quinine in nocturnal and dialysis-associated leg cramps and to examine potential alternative agents. DATA SOURCES: Selection and extraction: a MEDLINE/PubMed, English-language literature search from 1966 to the present using quinine, leg cramps, vitamin E, verapamil, muscle relaxants, gabapentin as search terms. DATA SYNTHESIS: Quinine, an alkaloid originally isolated from the cinchona tree, has been used for many years to treat/prevent leg cramps. In the mid-1990s, the Food and Drug Administration (FDA) banned over-the-counter availability of quinine and marketing of prescription quinine products for leg cramps. In early 2007, FDA banned all prescription quinine products other than Qualaquin. FDA acted in this manner because of a perception that quinine is not effective for this condition and that its risk potential far exceeds its efficacy potential. Efficacy trials for quinine in leg cramps have numerous design flaws that have resulted in poor quality data, producing both positive and negative findings. Two meta-analyses have reached different conclusions. Superimposed on the questionable efficacy of quinine is the well-known toxicity profile of the drug, involving the hematologic, renal, neurologic, cardiac, and endocrine systems. CONCLUSION: Are there any alternatives to quinine for leg cramps? Data are available supporting the potential efficacy of verapamil, gabapentin, carisoprodol, and orphenadrine in the general population, and vitamin E in the dialysis population. One or more of these agents should be tried before resorting to a time-limited (four- to six-week) trial of quinine for the treatment/prevention of leg cramps.
OBJECTIVE: To review the efficacy and tolerability profiles of quinine in nocturnal and dialysis-associated leg cramps and to examine potential alternative agents. DATA SOURCES: Selection and extraction: a MEDLINE/PubMed, English-language literature search from 1966 to the present using quinine, leg cramps, vitamin E, verapamil, muscle relaxants, gabapentin as search terms. DATA SYNTHESIS: Quinine, an alkaloid originally isolated from the cinchona tree, has been used for many years to treat/prevent leg cramps. In the mid-1990s, the Food and Drug Administration (FDA) banned over-the-counter availability of quinine and marketing of prescription quinine products for leg cramps. In early 2007, FDA banned all prescription quinine products other than Qualaquin. FDA acted in this manner because of a perception that quinine is not effective for this condition and that its risk potential far exceeds its efficacy potential. Efficacy trials for quinine in leg cramps have numerous design flaws that have resulted in poor quality data, producing both positive and negative findings. Two meta-analyses have reached different conclusions. Superimposed on the questionable efficacy of quinine is the well-known toxicity profile of the drug, involving the hematologic, renal, neurologic, cardiac, and endocrine systems. CONCLUSION: Are there any alternatives to quinine for leg cramps? Data are available supporting the potential efficacy of verapamil, gabapentin, carisoprodol, and orphenadrine in the general population, and vitamin E in the dialysis population. One or more of these agents should be tried before resorting to a time-limited (four- to six-week) trial of quinine for the treatment/prevention of leg cramps.