Safety of low-dose oral dantrolene sodium on hepatic function

Objective: To investigate the incidence of hepatobiliary dysfunction after administration of low-dose dantrolene sodium. Design: A retrospective survey of medical records. Setting: One secondary and 2 tertiary hospitals. Participants: Patients (N=243; 144 men, 27 children; mean age ± SD, 47.8±19.7y) who were administered dantrolene at a daily dose of 12.5 to 400mg for more than 4 weeks. Interventions: Not applicable. Main Outcome Measures: Liver function test (LFT) results, including serum total bilirubin, aspartate transaminase, alanine transaminase, and alkaline phosphatase, were recorded before and at least 1 month after the initial dose of dantrolene. In cases of treatment cessation, the reason was investigated. Significantly elevated LFT levels were defined as < to 2 times the upper limit of the normal range. Results: Treatment duration was 268.0±428.5 days with a daily dose of 65.2±44.7mg. At the end of the investigation, 95 patients (39.1%) had been lost to follow-up, and 105 (43.2%) had stopped treatment. The reasons for cessation were improved spasticity (42.9%), no effect of the medication (27.6%), weakness (6.7%), and other medical problems (5.7%). Patients with weaknesses did not have elevated LFT values. A 32-year-old man with head injuries and multiple trauma developed hepatic dysfunction 82 days after the initial dose and 43 days after a dose increment to 400mg/d. Other patients did not experience significant LFT abnormalities. Conclusions: One case of hepatic dysfunction was recorded in 243 cases after at least 4 weeks of low-dose oral dantrolene administration. Low-dose dantrolene can be used safely with meticulous clinical and laboratory monitoring.