Section 09 · Monograph

Dantrolene

Reviewed Nov 2026FDA label

DantriumRyanodine receptor antagonist

Black Box Warning

Hepatotoxicity: Symptomatic hepatitis, including fatal and non-fatal cases, has occurred at various dosage levels of oral dantrolene. Idiosyncratic and clinically overt hepatotoxicity appears to be dose related, with higher incidence in patients taking 800 mg/day or more, and in those on the drug longer than 60 days. Risk of fatal hepatic injury appears higher in females, patients over 35 years old, and those taking other medications concomitantly.
Dantrolene should be used only in patients who are being carefully monitored and in whom spasticity limits function or in whom spasticity is necessary to sustain posture/balance during locomotion, or when relief of muscle spasm is otherwise significant enough to outweigh hepatotoxic risk.
Liver function tests must be obtained at baseline and monitored periodically (frequent SGOT/SGPT determinations recommended) throughout therapy; discontinue if no clinical benefit is observed within 45 days of therapy.

Oral (Dantrium): control of clinical spasticity resulting from upper motor neuron disorders such as spinal cord injury, cerebral palsy, multiple sclerosis, and stroke.FDA-labeled
IV formulations (Dantrium IV, Revonto, Ryanodex): treatment of malignant hyperthermia (MH) crises in conjunction with appropriate supportive measures; also used preoperatively for prophylaxis in patients known/suspected to be MH-susceptible.FDA-labeled

Neuroleptic malignant syndrome (NMS) — used adjunctively (often with bromocriptine) for severe rigidity/hyperthermia, based on case series and expert consensus, not a formal FDA indication.Off-label
Severe serotonin syndrome / exertional heat stroke with life-threatening hyperthermia and rigidity (limited evidence, used in refractory cases).Off-label

Direct-acting skeletal muscle relaxant — unlike other agents in this class, dantrolene acts peripherally at the level of the skeletal muscle itself, not on the CNS.
Dissociates excitation-contraction coupling, most likely by interfering with the release of calcium ion (Ca2+) from the sarcoplasmic reticulum via antagonism of the ryanodine receptor (RyR1).
Decreases the force of skeletal muscle contraction without affecting nerve conduction, neuromuscular transmission, or muscle membrane electrical excitability.
This mechanism underlies its unique utility in malignant hyperthermia (uncontrolled Ca2+ release from sarcoplasmic reticulum via mutated RyR1).

Adult, chronic spasticity (oral): begin 25 mg once daily for 7 days; increase to 25 mg three times daily for 7 days; then 50 mg three times daily for 7 days; then 100 mg three times daily.
May increase further to 100 mg four times daily if needed; doses above 100 mg four times daily are rarely required and increase hepatotoxicity risk.
Discontinue if no observable benefit occurs within 45 days of dantrolene therapy.
Malignant hyperthermia crisis (IV, for MH management — not spasticity): 1 mg/kg IV rapid push, repeated as needed to a cumulative dose up to 10 mg/kg, until symptoms subside; followed by post-crisis oral or IV maintenance per protocol to prevent recurrence.
MH prophylaxis (preoperative, IV): typically 2.5 mg/kg infused over ~1 hour, completed shortly before anesthesia, per current MH-susceptible patient protocols.

Renal/hepatic impairment: use with caution; contraindicated in active hepatic disease; no formal renal dosage adjustment established but caution advised.

Active hepatic disease, e.g., hepatitis or cirrhosis.
Should not be used where spasticity is utilized to sustain upright posture and balance in locomotion, or to sustain increased function.
Known hypersensitivity to dantrolene sodium or any component of the formulation.

CNS depressants (alcohol, sedatives, opioids, benzodiazepines) — additive drowsiness/sedation.
Estrogens — concomitant use, particularly in women over 35, is associated with a higher reported incidence of hepatotoxicity.
Calcium channel blockers (notably verapamil) — case reports of cardiovascular collapse (hyperkalemia, myocardial depression) when IV dantrolene given with verapamil during MH treatment; avoid this combination.
Neuromuscular blocking agents (e.g., vecuronium) — dantrolene may potentiate neuromuscular blockade.
Other hepatotoxic drugs — increased risk of liver injury with concomitant use.

Very common: drowsiness/somnolence, dizziness, generalized muscle weakness, malaise, fatigue.
Common: diarrhea (can be severe, occasionally requiring discontinuation), nausea/vomiting, headache.
Serious: hepatotoxicity (idiosyncratic hepatitis, potentially fatal — see boxed warning), pleural effusion with pericarditis, hematologic abnormalities (aplastic anemia, thrombocytopenia, leukopenia), seizures, photosensitivity, and, rarely, respiratory depression.

Baseline liver function tests (AST/ALT, alkaline phosphatase, bilirubin) prior to initiation and periodically throughout therapy.
Clinical signs/symptoms of hepatitis (jaundice, malaise, anorexia, dark urine).
Assess clinical benefit at regular intervals — discontinue if no improvement within 45 days.
CBC periodically for hematologic abnormalities.
Pulmonary status if pleural effusion/pericarditis suspected.
Renal function and vital signs during IV administration for malignant hyperthermia.

Pregnancy: adequate and well-controlled studies in pregnant women have not been conducted; animal reproduction data are limited. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus; dantrolene crosses the placenta.
Lactation: dantrolene is excreted in human breast milk. Labeling states dantrolene should not be used in nursing mothers, or a decision should be made to discontinue nursing or discontinue the drug given potential for adverse effects in the infant.