Chronic spasticity
Malignant hyperthermia

Acts directly on skeletal muscle by interfering with release of calcium ion from the sarcoplasmic reticulum; prevents or reduces the increase in myoplasmic calcium ion concentration that activates the acute catabolic processes associated with malignant hyperthermia

Absorption: Oral: 70% (Allen 1988)
Distribution: Vd: 36.4 ± 11.7 L
Metabolism: Hepatic; major metabolites are 5-hydroxy dantrolene and an acetylamino metabolite of dantrolene.
Half-life elimination:
Neonates (at birth): ~20 hours (Shime 1988)
Children 2 to 7 years: 10 hours (range: 8.1 to 14.8 hours) (Lerman 1989)
Adults: 4 to 11 hours
Time to peak: IV: 1 minute post-dose (dantrolene); 24 hours post-dose (5-hydroxy dantrolene)
Excretion: Feces (45% to 50%); urine (25% as unchanged drug and metabolites)

IV: There are no contraindications listed within the manufacturer's labeling.
Oral: Active hepatic disease (eg, cirrhosis, hepatitis); when spasticity is used to maintain upright posture/balance in locomotion or to obtain/maintain increased function

C(FDA)

Low amounts of dantrolene are present in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends that a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother. In a case report, the half-life of dantrolene in breast milk was calculated to be 9 hours; the highest milk concentration was 1.2 mcg/mL following a maternal IV dose; however, the maternal serum concentrations were not reported.

Cardiovascular: Flushing (intravenous: 27%), atrioventricular block (intravenous: 3%), tachycardia (3%), cardiac failure, phlebitis, variable blood pressure
Central nervous system: Drowsiness (17%; drowsiness may persist for 48 hours post dose), voice disorder (intravenous: 13%), feeling abnormal (intravenous: 10%), dizziness (3%), headache (3%), myasthenia (3%), chills, choking sensation, confusion, depression, fatigue, insomnia, malaise, nervousness, seizure, speech disturbance
Dermatologic: Acneiform eruption (capsules), diaphoresis, eczematous rash, erythema (intravenous), hair disease (abnormal growth), pruritus, urticaria
Gastrointestinal: Dysphagia (10%; use caution at meal time on day of administration as swallowing may be difficult), nausea (10%), vomiting (3%), abdominal cramps, anorexia, constipation, diarrhea, dysgeusia, gastric irritation, gastrointestinal hemorrhage, sialorrhea

Malignant hyperthermia (MH):
Preoperative prophylaxis:
IV: 2.5 mg/kg ~11/4 hours prior to anesthesia and infused over at least 1 minute (Ryanodex) or 1 hour (Dantrium) with additional doses as needed and individualized
Crisis: IV: 2.5 mg/kg (MHAUS recommendation, available at www.mhaus.org); continuously repeat dose until symptoms subside or a cumulative dose of 10 mg/kg is reached (rarely, some patients may require up to 30 mg/kg for initial treatment). Note: Manufacturer's labeling suggests an initial minimum dose of 1 mg/kg.

Chronic spasticity: Children ?5 years and Adolescents: Oral:
Note: Dose should be titrated and individualized for maximum effect; use the lowest dose compatible with optimal response. Some patients may not respond until a higher daily dosage is achieved; each dose level should be maintained for 7 days to determine patient response. If no further benefit observed with the higher dose level, then decrease dosage to previous dose level. Because of the potential for hepatotoxicity, stop therapy if benefits are not evident within 45 days.
Initial: 0.5 mg/kg/dose once daily for 7 days; increase to 0.5 mg/kg/dose 3 times daily for 7 days, increase to 1 mg/kg/dose 3 times daily for 7 days, and then increase to 2 mg/kg/dose 3 times daily; some patients may require 2 mg/kg/dose 4 times daily; maximum dose: 400 mg/day
Malignant hyperthermia (MH): Infants, Children, and Adolescents: Refer to adult dosing.

Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling.

Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; use of oral dantrolene in patients with active liver disease (hepatitis or cirrhosis) is contraindicated.