DANTROLENE SODIUM

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Dantrolene sodium dissociates the excitation-contraction coupling in skeletal muscle by inhibiting calcium release from the sarcoplasmic reticulum via ryanodine receptor blockade.

What the body does with it

Metabolism	Hepatic metabolism via oxidative and reductive pathways; minor renal excretion.
Excretion	Primarily hepatic metabolism; approximately 25% excreted in urine as metabolites, 45-50% in feces via bile; less than 1% unchanged in urine.
Half-life	Terminal elimination half-life is approximately 8-10 hours in adults; may be prolonged to 12-15 hours in elderly or patients with hepatic impairment. Steady-state achieved in 3-4 days.
Protein binding	Approximately 90-95% bound to plasma proteins, primarily albumin.
Volume of Distribution	Apparent Vd is 0.5-1.0 L/kg, indicating distribution into total body water and some tissue binding.
Bioavailability	Oral: 70% (range 20-90% due to first-pass metabolism). Not applicable for IV.
Onset of Action	Oral: 2-4 hours for decrease in muscle spasticity; IV: within 5-10 minutes for malignant hyperthermia crisis.
Duration of Action	Oral: 6-12 hours with clinical effects lasting up to 24-48 hours; IV: duration sufficient to control malignant hyperthermia, typically several hours.

Classification & Brands

Dosing & administration

25 mg orally once daily for 7 days; then 25 mg three times daily for 7 days; then 50 mg three times daily for 7 days; then 100 mg three times daily. Maximum daily dose: 400 mg. For malignant hyperthermia: 1 mg/kg intravenously, may repeat up to cumulative dose of 10 mg/kg.

Dosage form	CAPSULE
Renal impairment	No specific adjustment required for chronic use; caution in renal impairment as dantrolene is hepatically metabolized and renally excreted. For malignant hyperthermia, use standard dosing.
Liver impairment	Contraindicated in active hepatic disease (Child-Pugh class C). For Child-Pugh class A or B, reduce dose by 50% and monitor liver function; do not exceed 100 mg/day.
Pediatric use	For spasticity in children ≥5 years: initial 0.5 mg/kg orally once daily for 7 days, then 0.5 mg/kg three times daily for 7 days, then increase by 0.5 mg/kg increments every 7 days up to maximum 3 mg/kg/dose three times daily or 100 mg four times daily, whichever is less. For malignant hyperthermia: 1 mg/kg intravenously, may repeat.
Geriatric use	Initiate at 25 mg orally once daily, increase slowly with monitoring for hepatic and CNS effects. Higher risk of hepatotoxicity and muscle weakness. For malignant hyperthermia, use standard dosing.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

CNS depressants and estrogens may enhance hepatotoxicity Can cause hepatotoxicity and muscle weakness.

Breastfeeding	Limited data; dantrolene is excreted into breast milk in small amounts. Milk-to-plasma ratio is not established. Monitor infant for adverse effects (muscle weakness, sedation). Consider alternative therapy if available.
Teratogenic Risk	Dantrolene sodium is not associated with major congenital malformations; however, data are limited. In animal studies, doses above human therapeutic range caused fetal toxicity (reduced fetal weight, increased resorptions). Use during pregnancy only if clearly needed, weighing benefits against potential risks.

Warnings & precautions

■ FDA Black Box Warning

Hepatotoxicity: Active liver disease or hepatic impairment (e.g., hepatitis, cirrhosis) is a contraindication. Risk is dose-dependent; discontinue if no benefit within 45 days.

Side Effect Profile

Common Effects	spasticity
Serious Effects

Absolute Contraindications

["Active hepatic disease (e.g., hepatitis, cirrhosis)","Known hypersensitivity to dantrolene","Symptomatic muscle weakness where spasticity is needed to maintain function"]

Clinical Precautions

Precautions

["Hepatotoxicity: monitor liver function tests (LFTs) at baseline and periodically; discontinue if LFTs elevated or symptoms of hepatitis.","Muscle weakness: may impair ability to walk or perform tasks; caution in patients with compromised pulmonary function.","Carcinogenesis: increased incidence of benign and malignant tumors in animal studies; clinical significance unknown.","Photosensitivity: avoid sun exposure; use sunscreen."]

Clinical Tips & Counseling

Drug interactions

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