Side Effects of Quinine for Muscle Cramps Linked to Increased Risk of Death: Study

Treatments for muscle cramps and restless leg syndrome that involve drugs with quinine may increase an individuals risk of death, according to the findings of new research.

In a study published this week in the Journal of the American Medical Association (JAMA), researchers found that taking doses of quinine above 300 mg/day for idiopathic muscle cramps may increase an individuals risk of death by 83%. Similarly, people consuming large quantities of bar drinks containing quinine may also be at risk.

Quinine has been used since the 1930s to treat muscle cramps and restless leg syndrome. While it is FDA approved as an anti-malaria drug, sold under the brand Qualaquin, it has also been prescribed “off-label” to treat muscle cramps and restless leg syndrome.

In 2006, the FDA issued a warning for off-label use of Qualaquin and other quinine drugs, citing safety issues. The FDA indicated that it had received more than 660 reports of problems linked to side effects of quinine, causing nearly 100 deaths. Despite the warnings, it continues to be widely used for muscle cramps and more complex conditions, like thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome.

Researchers warn quinine is also an ingredient in many popular bar drinks, such as bitter lemon and tonic waters, which may also place individuals at risk unnecessarily. The FDA does limit the quinine content of those products to 83mg/L.

This new study used data from The Health Improvements Network (THIN), which is a primary care database in the U.K. Data, examining information from January 1990 to December 2014. Researchers compared mortality rates among adults prescribed quinine salt for at least one year, for muscle cramps and restless leg syndrome.

Researchers compared three unexposed people for every quinine exposed person. More than 175,000 people over the age of 70 were included and followed for nearly six years. Most were exposed to an average of 203 mg/day of quinine, or more.

Overall, nearly 12,000 people died who were exposed to quinine. This was among nearly 45,000 people in total who were exposed. Among the 130,000 control subjects who were unexposed, nearly 27,000 people died.

Researchers determined patients under 50 had the most significant death risk. Additionally, a dose-effect was indicated.

Patients who took between 200 to 299 mg/day had a 25 percent increased risk of death. Those who took 300 to 399 mg/day had an 83 percent increased risk of death. Patients taking over 400 mg/day had the highest risk compared to those taking less than 200 mg/day.

Researchers warn that a review of evidence in 2015 found “low quality evidence” to indicate quinine treatment of 200 mg to 500 mg daily reduced muscle cramp frequency, and “moderate quality evidence” that quinine reduced cramp intensity. The review indicates using quinine off-label may not only be ineffective, but also quite risky.