Quinine: not to be used routinely for nocturnal leg cramps

Quinine should only be considered when cramps cause regular disruption of sleep.

Article date: June 2010

Quinine has been used in the UK for the treatment of nocturnal leg cramps for many years. Although patient response may vary, overall efficacy is modest. A meta-analysis of eight randomised placebo controlled trials reported that the mean number of cramps in a 4-week period while taking placebo was 17·08 and the absolute reduction in cramps while taking quinine was 3·6 (95% CI 2·2–5·1). Hence patients had around 20% fewer cramps in this period—around 1 episode a week difference—when taking quinine compared with placebo.1

The licensed dose for the treatment and prevention of nocturnal leg cramps in adults is 200–300 mg at night for quinine sulphate (recommended starting dose 200 mg), and is 300 mg at night for the bisulphate. The quinine salt should always be stated when prescribing because 200 mg quinine sulphate is equivalent to around 300 mg quinine bisulphate.

Patient selection and clinical monitoring

Quinine should not be considered a routine treatment for nocturnal leg cramps, and should only be considered when cramps cause regular disruption of sleep. Before use for nocturnal leg cramps, the risks should be carefully considered relative to the potential benefits. Quinine should only be considered:

  • when cramps are very painful or frequent
  • when other treatable causes of cramp have been ruled out
  • when non-pharmacological measures have not worked (eg, passive stretching exercises)

A reduction in frequency of leg cramps may take up to 4 weeks to become apparent. Patients should be monitored closely during the early stages of treatment for adverse effects. After an initial trial of 4 weeks, treatment should be stopped if there is no benefit. Treatment should be interrupted approximately every 3 months to reassess the benefit. In patients taking quinine long term, a trial discontinuation may be considered.

Summaries of product characteristics and patient information leaflets are being updated, and should be consulted for safety information.

Safety summary

Quinine tablets are generally well tolerated at the doses used for treatment of leg cramps. However, adverse events may include:

  • tinnitus
  • impaired hearing
  • headache *nausea
  • disturbed vision
  • confusion
  • flushing
  • abdominal pain.

Treatment should be stopped if these occur.

A rarer but more serious adverse reaction is thrombocytopenia, thought to be a hypersensitivity reaction. A small number of deaths linked to thrombocytopenia have been reported in patients taking quinine for the treatment of leg cramps, including two cases in the UK Yellow Card database. Quinine should not be prescribed to patients who have previously experienced any adverse reaction to quinine, including that found in tonic water or other beverages. Patients should be instructed to stop treatment and consult a physician if signs of thrombocytopenia occur, such as unexplained petechiae, bruising, or bleeding.

Quinine has a number of potentially significant drug interactions, including with digoxin and warfarin. It also has significant toxicity in overdose, which can result in death or permanent visual loss.

Advice for healthcare professionals:

  • quinine is not a routine treatment for nocturnal leg cramps, and should only be used when cramps regularly disrupt sleep
  • before use of quinine for nocturnal leg cramps, the risks should be carefully considered relative to the potential benefits
  • after a trial of at least 4 weeks, treatment should be stopped if there is no benefit. If treatment continues, the benefits should be assessed around every 3 months
  • patients should be warned not to exceed the recommended dose. Serious side effects including irreversible blindness and death may occur with overdose
  • thrombocytopenia is a rare but potentially life-threatening adverse reaction associated with quinine. Patients should be instructed to stop treatment and consult a physician if signs of thrombocytopenia occur, such as unexplained petechiae, bruising, or bleeding
  • quinine should not be prescribed or given to patients who have previously experienced any adverse reaction to quinine, including that found in beverages

Article citation: Drug Safety Update June 2010, vol 3 issue 11: 3.

  1. Man-Son-Hing M, et al. J Gen Intern Med 1998; 13: 600–06

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