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Clinician Article

Quinine for muscle cramps.



  • El-Tawil S
  • Al Musa T
  • Valli H
  • Lunn MP
  • Brassington R
  • El-Tawil T, et al.
Cochrane Database Syst Rev. 2015 Apr 5;2015(4):CD005044. doi: 10.1002/14651858.CD005044.pub3. (Review)
PMID: 25842375
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Disciplines
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 6/7
    Newsworthiness - 6/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 6/7
    Newsworthiness - 6/7
  • Geriatrics
    Relevance - 5/7
    Newsworthiness - 5/7
  • Nephrology
    Relevance - 5/7
    Newsworthiness - 4/7
  • Public Health
    Relevance - 5/7
    Newsworthiness - 4/7
  • Special Interest - Pain -- Physician
    Relevance - 5/7
    Newsworthiness - 4/7

Abstract

BACKGROUND: Muscle cramps can occur anywhere and for many reasons. Quinine has been used to treat cramps of all causes. However, controversy continues about its efficacy and safety. This review was first published in 2010 and searches were updated in 2014.

OBJECTIVES: To assess the efficacy and safety of quinine-based agents in treating muscle cramps.

SEARCH METHODS: On 27 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE. We searched reference lists of articles up to 2014. We also searched for ongoing trials in November 2014.

SELECTION CRITERIA: Randomised controlled trials of people of all ages with muscle cramps in any location and of any cause, treated with quinine or its derivatives.

DATA COLLECTION AND ANALYSIS: Three review authors independently selected trials for inclusion, assessed risk of bias and extracted data. We contacted study authors for additional information. For comparisons including more than one trial, we assessed the quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

MAIN RESULTS: We identified 23 trials with a total of 1586 participants. Fifty-eight per cent of these participants were from five unpublished studies. Quinine was compared to placebo (20 trials, n = 1140), vitamin E (four trials, n = 543), a quinine-vitamin E combination (three trials, n = 510), a quinine-theophylline combination (one trial, n = 77), and xylocaine injections into the gastrocnemius muscle (one trial, n = 24). The most commonly used quinine dosage was 300 mg/day (range 200 to 500 mg). We found no new trials for inclusion when searches were updated in 2014.The risk of bias in the trials varied considerably. All 23 trials claimed to be randomised, but only a minority described randomisation and allocation concealment adequately.Compared to placebo, quinine significantly reduced cramp number over two weeks by 28%, cramp intensity by 10%, and cramp days by 20%. Cramp duration was not significantly affected.A significantly greater number of people suffered minor adverse events on quinine than placebo (risk difference (RD) 3%, 95% confidence interval (CI) 0% to 6%), mainly gastrointestinal symptoms. Overdoses of quinine have been reported elsewhere to cause potentially fatal adverse effects, but in the included trials there was no significant difference in major adverse events compared with placebo (RD 0%, 95% CI -1% to 2%). One participant suffered from thrombocytopenia (0.12% risk) on quinine.A quinine-vitamin E combination, vitamin E alone, and xylocaine injections into gastrocnemius were not significantly different to quinine across all outcomes, including adverse effects. Based on a single trial comparison, quinine alone was significantly less effective than a quinine-theophylline combination but with no significant differences in adverse events.

AUTHORS' CONCLUSIONS: There is low quality evidence that quinine (200 mg to 500 mg daily) significantly reduces cramp number and cramp days and moderate quality evidence that quinine reduces cramp intensity. There is moderate quality evidence that with use up to 60 days, the incidence of serious adverse events is not significantly greater than for placebo in the identified trials, but because serious adverse events can be rarely fatal, in some countries prescription of quinine is severely restricted.Evidence from single trials suggests that theophylline combined with quinine improves cramps more than quinine alone, and the effects of xylocaine injections into gastrocnemius are not significantly different to quinine across all outcomes. Low or moderate quality evidence shows no significant difference between quinine and vitamin E or quinine and quinine-vitamin E mixture. Further research into these alternatives, as well other pharmacological and non-pharmacological treatments, is thus warranted.There is no evidence to judge optimal dosage or duration of quinine treatment. Further studies using different dosages and measurement of serum quinine levels will allow a therapeutic range to be defined for muscle cramp. Because serious adverse events are not common, large population studies are required to more accurately inform incidence. Longer lengths of follow-up in future trials will help determine the duration of action following cessation of quinine as well as long-term adverse events. The search for new therapies, pharmacological and nonpharmacological, should continue and further trials should compare vitamin E, quinine-vitamin E combination, and quinine-theophylline mixture with quinine.


Clinical Comments

Family Medicine (FM)/General Practice (GP)

Leg muscle cramps, especially at night, are a common enough concern that I wish we had therapy to recommend. When the FDA advised against prescribing quinine for nocturnal leg cramps, many patients were unhappy that I would no longer prescribe this medication. http://www.fda.gov/ForHealthProfessionals/ArticlesofInterest/ucm317811.htm That there is enough evidence to support the use of quinine is major news to me.

Geriatrics

Quinine probably doesn't help much for muscle cramps but in rare circumstances, if overused, can cause problems. I think that we all knew this, but now we really do.

Geriatrics

-

Nephrology

This is an update on a meta-analysis done by same group in 2010 but there were no new studies included. As before, the conclusion was based on relatively poor quality evidence. More importantly, quinine is no longer available in USA for use to treat cramps and this restriction is unlikely to change without any better study. Nephrologists and patients with cramps are eagerly waiting for an effective safe RX but quinine does not seem to be the answer.

Nephrology

Quinine is still widely prescribed for patients with cramps including those on dialysis with weak evidentiary support. The potential for harm is likely higher in the high risk ESRD populations who may have impaired metabolism of the drug and hence increased risk of adverse events. This meta-analysis does not allow one to evaluate this subset of patients specifically.

Public Health

Muscle cramps are a relatively common symptom in various chronic diseases, especially in chronic renal failure. However, the treatment of cramps offers no clear answer, and many approaches have been used, often with disappointing results. The interest of this systematic review is to show, albeit with a relatively low level of evidence, that quinine at low doses and for short periods, reduces the frequency and intensity of cramps without causing major side effects. Minor side effects, however, are more frequent than with placebo. Because of its potentially serious side effects, treatment of cramps with quinine should be closely monitored. New and better studies should be conducted to clarify the value of this treatment alone or in combination with other substances.

Special Interest - Pain -- Physician

The relevance is hindered by safety concerns regarding quinine including FDA actions. The usefulness of the information is limited because most clinicians are aware of modest benefits from its use. This Cochrane review confirmed what is largely known.

Special Interest - Pain -- Physician

The main conclusion is that quinine could be useful for decreasing cramps but the main reason for not recommending it (fatal side_effects) is not explored. The FDA took the view that risk/benefit ratio was most unfavourable and banned its use. Atypical haemolytic uraemic syndrome was the concern.

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