Randomised controlled trial of hydroquinine in muscle cramps

Abstract

of the risk of gynaecomastia associated with cimetidine, omeprazole and other antiulccr medications. BM J 1994; 308: 503-06. Jick H, Jick SS, Gurewich V, Myers MW, Vasilakis C. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 1995; 346: 1589-93. Methods This randomised, double-blind, placebo-controlled, parallel-group trial consisted of three consecutive 2-week periods: qualification, treatment, and washout. 68 women and 44 men who had at least three muscie cramps per week w ere e n ro lle d . D uring th e tre a tm e n t period, participants were randomly assigned 300 mg daily dose of hydroquinine hydrobromide dihydrate (54 participants) or placebo (58). The frequency, severity (1-10), duration, and location of muscle cramps, as well as any side-effects, were recorded by participants in daily diaries. The primary outcome measures were the number of muscle cramps and the number of days during which the participants had muscle cramps (cramp-days).Findings We excluded five participants from both groups from the analysis. Thus, data from 49 hydroqulnine-group p a rticip a n ts and 53 placebo-group p a rtic ip a n ts were analysed. In both groups the to ta l number of muscle cramps and the number of cramp-days decreased during the tre a tm e n t period compared w ith the qualification period. However, these improvements were greater in the hydroquinine group th a n in th e placebo group. The Correspondence to: Prof A L M Verbeek hydroquinine-group participants reported a median of 8 (95% Cl 7-12) fewer cramps and median of 3 (1-4) fewer cramp-days, whereas those on placebo reported only 3 (0-5) fewer cramps and 1 (0-5) fewer cramp-days. 32 (65%) of participants in the hydroquinine group had a 50% or greater reduction in the number of muscle cramps. After the onset of cramps, hydroquinine did not reduce the severity or duration of cramps. We also found a sustained effect after treatment had stopped. Hydroquinine was well tolerated, and resulted in only mild side-effects. InterpretationIn our study, 300 mg hydroquinine was safe to take in the short-term and significantly more effective than placebo in the prevention of frequent, ordinary muscle cramps. This therapeutic effect outlasted the duration of treatment.

Assessment: Symptomatic treatment for muscle cramps (an evidence-based review)

“…A randomized trial in 1997 assessed the efficacy of hydroquinine hydrobromide dihydrate 300 mg at night in 112 patients. 11 The trial showed a greater reduction in median number of cramps in treated patients compared to placebo (5 fewer cramps, 95% confidence interval [CI] 2-8 cramps) and a reduction of cramp days in treated patients compared to placebo (1 fewer cramp day, 95% CI 0 -3 cramp days) during the 3-week study period. The mean number of cramps was reduced by 37%.…”

Use of quinine and mortality‐risk in patients with heart failure—a Danish nationwide observational study

“…As the effect of quinine on leg cramps has been shown to be sustained for at least two weeks after treatment cessation, and to avoid "false breaks" during treatment, all treatment periods were lengthened by 14 days. 15 We used loop diuretic dosages as a proxy for severity of heart failure and updated loop diuretic dosages continuously. We used an algorithm similar to that described for quinine to calculate dosages.…”

Effects ofMHRAdrug safety advice on time trends in prescribing volume and indices of clinical toxicity for quinine

“…The bulk of quinine prescribing in the UK, however, occurs in primary care and is almost entirely for muscle cramps affecting the legs. Clinical trials and meta-analyses, however, have shown limited additional benefits from quinine for this indication over those associated with placebo use [2][3][4]. The use of quinine, especially in overdose, carries a risk of significant morbidity and mortality.…”

“…The use of quinine, especially in overdose, carries a risk of significant morbidity and mortality. In clinical trials, adverse effects commonly associated with quinine included headache, nausea and vomiting, tinnitus, dizziness, fever and pruritus [2][3][4]. Severe toxicity may include altered consciousness, convulsions, hypoglycaemia, deafness, peripheral visual field constriction, reduced visual acuity, blindness and cardiac arrhythmias [5,6].…”

“…Despite its limited efficacy and potential toxicity in therapeutic use and in overdose [2][3][4][6][7][8], quinine prescribing for muscle and leg cramps has been increasing. As a result, the UK Medicines and Healthcare products Regulatory Agency (MHRA) issued a Drug Safety Update article on the use of quinine for the treatment of leg cramps in June 2010.…”