Dantrolene has a direct action on skeletal muscle. Dantrolene depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor 1, and decreasing intracellular calcium concentration. Ryanodine receptors mediate the release of calcium from the sarcoplasmic reticulum, an essential step in muscle contraction.
For Use in Chronic Spasticity: It is important that the dosage be titrated and individualized for maximum effect. The lowest dose compatible with optimal response is recommended. Each dosage level should be maintained for seven days to determine the patient’s response. If no further benefit is observed at the next higher dose, dosage should be decreased to the previous lower dose.
Adults: 25 mg once daily for seven days, then 25 mg t.i.d. for seven days, 50 mg t.i.d. for seven days, 100 mg t.i.d.
Pediatric Patients: 0.5 mg/kg once daily for seven days, then 0.5 mg/kg t.i.d. for seven days, 1 mg/kg t.i.d. for seven days, 2 mg/kg t.i.d. Therapy with a dose four times daily may be necessary for some individuals. Doses higher than 100 mg four times daily should not be used.
The long-term safety of Dantrolene in pediatric patients under the age of 5 years has not been established.
For Malignant Hyperthermia:
Preoperatively: 4 to 8 mg/kg/day of oral Dantrolene in 3 or 4 divided doses for one or two days prior to surgery, with the last dose being given approximately 3 to 4 hours before scheduled surgery with a minimum of water.
Post Crisis Follow-up: Oral Dantrolene should also be administered following a malignant hyperthermia crisis, in doses of 4 to 8 mg/kg per day in four divided doses, for a one to three day period to prevent recurrence of the manifestations of malignant hyperthermia.