HDCN Article Review/Hyperlink

Jansen PHP, Verbeek ALM, et al

Randomised controlled trial of hydroquinine in muscle cramps

Lancet (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 the drug quinine and its derivatives hydroquinine and quinidine. Although these remedies were popular, it was not clear how well they worked, or if they worked at all. Early trials with these drugs did not have controls, so the placebo effect could not be ruled out, and more recent trials have been small or had design faults. Professor ALM Verbeek and colleagues from the Netherlands did a randomised, double-blind, placebo-controlled trial of hydroquinine in a group of otherwise healthy adults who had at least three muscle cramps a week. Their findings are published in this week's issue of The Lancet.

In the trial, 112 participants were randomly assigned 300 mg hydroquinine a day (54 participants) or inactive placebo pills (58 participants). All the participants kept a diary to record the frequency, severity, duration and location of any cramps as well as any side-effects they might notice.

"In both groups the total number of muscle cramps and the number of cramp days decreased", the researchers report. "However, these improvements were greater in the 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 those on placebo reported only three fewer cramps and one fewer cramp days. Two-thirds of the hydroquinine group saw a 50% or greater reduction in the number of muscle cramps.

The only side-effects which were definitely related to taking hydroquinine were a bitter taste or dry mouth, which affected ten patients, and a ringing in the ears, called tinnitus, which occurred in one patient. "In our study", the researchers conclude, "300 mg of hydroquinine was safe to take in the short term and significantly more effective than placebo in the prevention of frequent, ordinary muscle cramps".

Contact: Professor ALM Verbeek, Department of Medical Informatics, Epidemiology, and Statistics, Catholic University of Nijmegen, Nijmegen, Netherlands; tel +31 24 3619132

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 (OTC) quinine sulfate for night leg cramps based on its serious risks, FDA ordered a stop to the marketing of prescription quinine for this use because even under a doctor's care, its risks outweigh any possible benefits.

In January, FDA sent warning letters to 44 companies stating that it is unlawful to market their quinine sulfate products for night leg cramp relief because FDA has not approved the drug for this use. By the end of March, all major manufacturers and distributors had stopped labeling their products for this use, including Marion Merrell Dow, the manufacturer of the original and best-known quinine drug, Quinamm.

From 1969 through June 1992, FDA received 157 reports of health problems related to quinine use, including 23 that resulted in death. Nonserious problems included temporary sight and hearing disturbances, dizziness, fever, nausea, vomiting, and 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 cramps, FDA concluded that quinine is not safe and effective for this use because:
* No studies demonstrate that quinine is effective against night leg cramps.
* 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, Federal Register prohibiting OTC marketing of the drug for leg cramps.

FDA also proposed to stop OTC marketing of quinine for another use--to prevent or treat malaria. The public has until July 3 to comment on the proposal, published in the April 19, 1995, Federal Register. The agency based the proposal on its conclusion that physician monitoring is essential to the safe and effective treatment of this serious, potentially life-threatening disease. Written comments may be sent to: FDA Dockets Management Branch (HFA-305), Rockville, MD 20857.

The lack of availability of quinine to nephrologists is a real problem. Many of us are convinced of its efficacy. There have been a few small trials that appear to have been well designed showing efficacy; e.g., Roca, ASAIO J, 1992, although equal efficacy was found in that study for vitamin E, which is admittedly much safer. Many nephrologists have to resort to suggesting tonic water for their patients (which contains quinine).

The press release on this paper is available from the Lancet. However, you must register at the Lancet site first (you can get there via the home page of HDCN). Once you have registered, click on this link.