2 About 60 percent of patients with cirrhosis reportedly have leg cramps, most of whom are older patients with advanced disease. A study of outpatient veterans reported leg cramps in 75 percent of those with peripheral vascular disease, 63 percent of those with hypokalemia, and 62 percent of those with coronary artery disease. Several medical conditions are associated with leg cramps ( Table 2). 12 Diuretics, such as hydrochlorothiazide, are commonly believed to cause leg cramps secondary to electrolyte abnormalities, but they have not been implicated in evidence-based reviews. However, the study was complicated by worsening disease states (such as vascular disease) and by increased patient-physician contact. A recent study found an association between leg cramps and the use of quinine in the year following new prescriptions for diuretics, statins, and inhaled long-acting beta 2 agonists. 11 Leg cramps also have been reported in studies of medications such as clonazepam (Klonopin), citalopram (Celexa), celecoxib (Celebrex), gabapentin (Neurontin), and zolpidem (Ambien), which, ironically, are used to treat leg cramps. Medication-related leg cramps are most commonly associated with intravenous iron sucrose, conjugated estrogens, raloxifene (Evista), naproxen (Naprosyn), and teriparatide (Forteo), although the overall incidence is very low ( Table 1). Muscle cramps are reported as an adverse effect for hundreds of medications, but only a few are specific to the legs. Quinine is no longer recommended to treat leg cramps. Limited evidence supports treating nocturnal leg cramps with exercise and stretching, or with medications such as magnesium, calcium channel blockers, carisoprodol, or vitamin B 12. Laboratory evaluation and specialized testing usually are unnecessary to confirm the diagnosis. A history and physical examination are usually sufficient to differentiate nocturnal leg cramps from other conditions, such as restless legs syndrome, claudication, myositis, and peripheral neuropathy. Medications that are strongly associated with leg cramps include intravenous iron sucrose, conjugated estrogens, raloxifene, naproxen, and teriparatide. Nocturnal leg cramps are associated with vascular disease, lumbar canal stenosis, cirrhosis, hemodialysis, pregnancy, and other medical conditions. The exact mechanism is unknown, but the cramps are probably caused by muscle fatigue and nerve dysfunction rather than electrolyte or other abnormalities. The recurrent, painful tightening usually occurs in the calf muscles and can cause severe insomnia. Up to 60 percent of adults report that they have had nocturnal leg cramps.
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