Quinine for muscle cramps linked to increased mortality

Long-term use of quinine for nocturnal leg cramps may increase the risk of mortality, a study of UK GP prescribing published in JAMA has found.

Quinine has been used in the UK for the treatment of nocturnal leg cramps for many years. | SCIENCE PHOTO LIBRARY
Quinine has been used in the UK for the treatment of nocturnal leg cramps for many years. | SCIENCE PHOTO LIBRARY
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Researchers from the UK and France used data from the Health Improvement Network database from general practices in the UK. Of 175,195 patients included in their analysis, approximately a quarter (44,699) had been prescribed quinine for idiopathic muscular cramps or restless leg syndrome for at least one year.

The median daily quinine dose was 203mg. Over a median follow-up period of 5.7 years, quinine exposure was associated with 4.2 deaths per 100 personyears, compared with a rate of 3.2 deaths per 100 personyears for unexposed individuals (adjusted hazard ratio 1.24, CI 1.21–1.27). These findings suggest the risk of death could be significantly increased with long-term use of quinine. 

Poor riskbenefit ratio

The authors acknowledge that their findings could reflect unmeasured confounders that may predispose patients to higher mortality. However, they concluded, "the benefits of quinine in reducing cramps should be balanced against the risks."

Owing to the poor benefit-to-risk ratio, both NICE CKS and the MHRA advise that quinine should not be considered a routine treatment for nocturnal leg cramps, and should only be considered when self-care measures fail and cramps cause regular disruption of sleep.

If GPs choose to prescribe quinine for this indication, CKS recommends a dose of 200300mg at bedtime for 46 weeks. If this is beneficial, treatment may be continued with review every 36 months.


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