Jansen PHP, Verbeek ALM, et al
Randomised controlled trial of hydroquinine in muscle
(Feb) 349:528-532 1997
This paper is best summarized from the Lancet Press Release:
MUSCLE-CRAMP DRUG FOUND TO BE EFFECTIVE (pp 528-32)
For more than 50 years, doctors have been giving patients with muscle cramps
quinine and its derivatives hydroquinine and quinidine. Although these
popular, it was not clear how well they worked, or if they worked at all.
trials with these drugs did not have controls, so the placebo effect could
ruled out, and more recent trials have been small or had design faults.
Verbeek and colleagues from the Netherlands did a randomised, double-blind,
placebo-controlled trial of hydroquinine in a group of otherwise healthy
had at least three muscle cramps a week. Their findings are published in this
issue of The Lancet.
In the trial, 112 participants were randomly assigned 300 mg hydroquinine a
participants) or inactive placebo pills (58 participants). All the
a diary to record the frequency, severity, duration and location of any
well as any side-effects they might notice.
"In both groups the total number of muscle cramps and the number of cramp
decreased", the researchers report. "However, these improvements were greater
hydroquinine group". For example, the patients taking hydroquinine reported
to have a
median of eight fewer cramps and a median of three fewer cramp days, while
placebo reported only three fewer cramps and one fewer cramp days. Two-thirds
hydroquinine group saw a 50% or greater reduction in the number of muscle
The only side-effects which were definitely related to taking hydroquinine
bitter taste or dry mouth, which affected ten patients, and a ringing in the
called tinnitus, which occurred in one patient. "In our study", the
conclude, "300 mg of hydroquinine was safe to take in the short term and
significantly more effective than placebo in the prevention of frequent,
Contact: Professor ALM Verbeek, Department of Medical Informatics,
Statistics, Catholic University of Nijmegen, Nijmegen, Netherlands; tel +31
A related story appeared in the July-August 1995 FDA Consumer
FDA Orders Stop to Marketing Of Quinine for Night Leg Cramps
Less than a year after ordering a halt to the marketing of over-the-counter
quinine sulfate for night leg cramps based on its serious risks, FDA ordered
to the marketing of prescription quinine for this use because even under a
care, its risks outweigh any possible benefits.
In January, FDA sent warning letters to 44 companies stating that it is
market their quinine sulfate products for night leg cramp relief because FDA
approved the drug for this use. By the end of March, all major manufacturers
distributors had stopped labeling their products for this use, including
Merrell Dow, the manufacturer of the original and best-known quinine drug,
From 1969 through June 1992, FDA received 157 reports of health problems
quinine use, including 23 that resulted in death. Nonserious problems
temporary sight and hearing disturbances, dizziness, fever, nausea, vomiting,
diarrhea. Serious problems included thrombocytopenia, a destruction of blood
platelets that can lead to massive bleeding and sometimes death.
After weighing the benefits and risks of OTC quinine sulfate for night leg
FDA concluded that quinine is not safe and effective for this use
* No studies demonstrate that quinine is effective against night leg
* Night leg cramps are not a threat to life or health.
* Health risks outweigh any small potential benefits.
Based on this finding, the agency published a rule in the Aug. 22, 1994,
Register prohibiting OTC marketing of the drug for leg cramps.
FDA also proposed to stop OTC marketing of quinine for another use--to
treat malaria. The public has until July 3 to comment on the proposal,
the April 19, 1995, Federal Register. The agency based the proposal on its
that physician monitoring is essential to the safe and effective treatment of
serious, potentially life-threatening disease. Written comments may be sent
Dockets Management Branch (HFA-305), Rockville, MD 20857.
The lack of availability of quinine to nephrologists is a real problem. Many
are convinced of its efficacy. There have been a few small trials that
have been well designed showing efficacy; e.g., Roca, ASAIO J, 1992, although
efficacy was found in that study for vitamin E, which is admittedly much
nephrologists have to resort to suggesting tonic water for their patients
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