FDA warns of serious hematologic reactions with off-label use of quinine sulfate for night-time leg cramps

On July 8, FDA released a "Drug Safety Communication" warning that off-label use of quinine sulfate (Qualaquin, AR Scientific) to treat night-time leg cramps has been found to result in serious and life-threatening adverse effects.

Key Points

On July 8, FDA released a "Drug Safety Communication" warning that off-label use of quinine sulfate (Qualaquin, AR Scientific) to treat night-time leg cramps has been found to result in serious and life-threatening adverse effects. At present, quinine sulfate is only approved for use in the United States to treat uncomplicated malaria caused by the parasite Plasmodium falciparum.

The safety communication notes that a review of reports submitted to FDA's Adverse Event Reporting System (AERS) between April 2005 and October 1, 2008, found 38 serious adverse effects associated with the use of quinine sulfate (median time-to-onset of adverse events after starting quinine was 13.5 days). The majority of cases (nearly 66%) were in patients taking quinine sulfate for night-time leg cramps and not as an anti-malarial. Among these 38 reports, there were 24 hematologic events (including thrombocytopenia [low platelet count], hemolytic uremic syndrome and thrombotic thrombocytopenic purpura [a blood disorder resulting in clots in small blood vessels and potentially impairment of kidney function]), 4 cardiovascular events, and 10 miscellaneous adverse events (eg, gastrointestinal symptoms, hearing loss, rash, electrolyte imbalance, and drug interaction). While many of the patients recovered when quinine was discontinued and other therapeutic interventions were initiated, 2 patients died (one due to hemolysis and the other thrombotic thrombocytopenic purpura) and others developed permanent kidney impairment and/or required hospitalization.

In addition to the safety communication, FDA is imposing a Risk Evaluation and Mitigation Strategy (REMS) that will require all patients be given a medication guide explaining what quinine sulfate is and is not approved for, as well as the potential side effects of the drug. In addition, the REMS will require that the manufacturer (AR Scientific, Philadelphia, PA) distribute a Dear Health Care Provider Letter warning of the risk of serious and life-threatening hematologic (blood-related) reactions.