By Ann Saul
FLORENCE, Italy -- September 23, 2009 -- Reconsideration should be given to the use of oral dantrolene sodium capsules for the treatment of spasticity, according to new data presented here at the 13th Congress of the European Federation of Neurological Societies (EFNS).
Willem J. Meijler, MD, PhD, University Hospital Groningen, Amsterdam, who presented the study on September 13, noted that "oral dantrolene sodium is a well-established oral muscle relaxant that has been used for more than 30 years for the treatment of spasticity."
Over the years, rare cases of fatal hepatotoxicity have been reported with this agent. "These cases may have been caused by the use of concentrations that were too high," explained Dr. Meijler. "In recent years, risk factors have been identified, monitoring guidelines have been published, and there have been no fatalities."
The study included an analysis of all reports of adverse events related to dantrolene sodium derived from the Periodic Safety Update Reports, published scientific literature, and other sources for a period of 12 months. The patient exposure for oral dantrolene sodium was 7,593 patient-years during 2008 and 39,268 patient-years for the period 2004 to 2008. For the intravenous formulation, there were 10,602 patients in 2008 and 46,216 patients from 2004 to 2008.
The most frequently reported serious adverse drug reactions during 2008 were: general disorders and administration-site conditions (15.5%); gastrointestinal disorders (14.7%); hepatobiliary disorders (10.3%); and nervous system disorders 10.3%). There were no serious hepatotoxicity cases reported that were related to the use of dantrolene.
The most common undesirable effects included diarrhoea, dizziness, drowsiness, fatigue, malaise, and weakness. Events reported less often included anorexia, abdominal pain, nausea and/or vomiting, liver function test disturbances, hepatotoxicity, pericarditis, pleural effusion with associated eosinophilia, acne-like rash, skin eruptions, speech disturbances, seizure, headache, visual disturbance, respiratory depression, and chills or fever.
Hepatic disorders are mainly reported with chronic use of dantrolene sodium capsules. Three risk factors for hepatic events have been clearly identified: higher daily doses, female gender, and increasing patient age. Regular hepatic monitoring of transaminases (alanine aminotransferase/ aspartate transaminase), bilirubin, gamma-glutamyltransferase, and alkaline phosphatases must take place before and during dantrolene therapy.
"Dantrolene sodium capsules are effective at low doses, and pose no increased hazard to the patient," concluded Dr. Meijler.
In most cases, the highest daily dose reached after the 5- to 6-week titration period is 300 mg. The maximal recommended daily dose is 400 mg.
Since the establishment of current guidelines, there has been no serious hepatotoxicity directly and solely related to the use of dantrolene sodium. This updated safety information suggests that the use of dantrolene sodium capsules should be reconsidered in situations where there are few alternatives.
Funding for this study was provided by SpePharm.
[Presentation title: Safety Update of Dantrolene Sodium, a Muscle Relaxant for the Treatment of Spasticity. Poster 1584]
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