Trip Answers

Question answered:05/02/08 Warning! this question is over two years old.

The CKS guideline on leg cramps gives the following prescribing instructions for quinine:

 

• “Quinine 200–300 mg at bedtime is effective in reducing the frequency of nocturnal leg cramps. It may take up to 4 weeks for improvement to become apparent, and the treatment is then given regularly if there is benefit [BNF 49, 2005].
• Treatment should be interrupted at intervals of about 3 months to assess the need for further quinine treatment [BNF 49, 2005]. Some people who found quinine beneficial were able to stop it without any major problems [Coppin et al, 2005].
• People should be monitored closely during the early stages for adverse effects as well as for benefit [BNF 49, 2005].”

 

Concerning the safety of quinine, CKS states:

 

• “Adverse effects of quinine have been reported, but these do appear to be dose-related.
o There is no good study of the risk of adverse effects when using the low doses that are prescribed for leg cramps, although a recent meta-analysis showed that tinnitus was the only adverse effect occurring with significantly greater frequency than found with placebo [Man-Son-Hing et al, 1998].
o Adverse effects of quinine are reported at the high doses received during treatment of malaria namely tinnitus, headache, nausea, visual disturbance, fever, digestive disorders, thrombocytopenia, and pruritus [Mackie and Davidson, 1995; DTB, 1996; Reddy et al, 2004].
• Hypersensitivity reactions are not uncommon, with symptoms usually limited to fever and rashes. However, angioedema, thrombocytopenia and asthma have been reported [Dukes and Aronson, 2000; Brasic, 2001].
• Drinking tonic water is unlikely to be effective in managing leg cramps, as large quantities would need to be consumed to achieve therapeutic levels. Tonic water contains up to 80 mg/l, and other soft drinks (e.g. bitter lemon) contain up to 40 mg/l, of quinine hydrochloride [Worden et al, 1987].
• Prolonged QT interval has been noted with quinine. However, clinically significant effects are generally only seen with very high doses or following overdose [Thomas, 1997; Dukes and Aronson, 2000]. Consider the risk–benefit ratio when prescribing quinine with other drugs that may prolong the QT interval, as they may have a synergistic effect.
• Overdose of quinine may lead to permanent visual impairment, cardiac arrhythmias, and death [DTB, 1996; BNF 49, 2005].”

 

CKS also discusses contraindications to quinine:

 

• “A woman who is pregnant or who might become pregnant. Pregnancy in someone with malaria is not generally regarded as a contraindication to the use of quinine. As malaria infection is potentially serious during pregnancy and poses a threat to the mother and fetus, there is little justification in withholding treatment in the absence of a suitable alternative. However, quinine should not be used for cramps during pregnancy.
• Someone who has previously had a hypersensitive reaction to quinine or who has had thrombocytopenic purpura associated with quinine.
• Quinine is contraindicated in someone with a history of haemolytic anaemia, G6PD deficiency, haemoglobinuria, myasthenia gravis, or optic neuritis.
• Quinine should only be used after a risk–benefit assessment in a person with heart disease.” [1]

 

Two other sources recommend quinine be prescribed at a dosage of 200-300 mg at night for the prevention of leg cramps.

 

The BNF notes:

 

“Quinine salts (section 5.4.1) 200 –300 mg at bedtime are effective in reducing the frequency of nocturnal leg cramps by about 25% in ambulatory patients. It may take up to 4 weeks for improvement to become apparent and long-term quinine is then given if there is benefit. Patients should be monitored closely during the early stages for adverse effects as well as for benefit. Treatment should be interrupted at intervals of approximately 3 months to assess the need for further quinine treatment. Quinine is very toxic in overdosage and accidental fatalities have occurred in children (see also below).” [2]

 

In addition, GPNotebook states in its entry on the management of night cramps:

 

“Specific causes should be sought and treated appropriately.
Otherwise, consider:
•... pharmacological:
o quinine - 200-300 mg nocte; benefits may be delayed for 4 weeks - there is evidence from the Netherlands that hydroquinine (the only quinine derivative in that country licensed for the prevention of muscle cramps) is effective in preventing leg cramps. Hydroquinine therapy does not reduce their duration or severity - note that in the USA, the Food and Drugs Administration has abandoned the use of quinine in the treatment of leg cramps because of potentially fatal immune-allergic reactions... [3]

 

References
1. CKS. Leg cramps. July 2005. (http://www.cks.library.nhs.uk/leg_cramps/)
2. BNF No. 54. September 2007. (http://www.bnf.org.uk/bnf/bnf/current/31767.htm)
3. GPNotebook. Leg cramps: management. (http://www.gpnotebook.co.uk/simplepage.cfm?ID=-1241120744&linkID=11146&cook=yes)

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