DANTROLENE SODIUM
Clinical safety rating
safeAnimal studies have demonstrated safety
Dantrolene sodium dissociates the excitation-contraction coupling in skeletal muscle by inhibiting calcium release from the sarcoplasmic reticulum via ryanodine receptor blockade.
| 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. |
| Molecular Weight | 336.31 |
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. |
| 1st trimester | Limited human data; animal studies show increased fetal death and malformations at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | No well-controlled studies. Potential risk of maternal hepatotoxicity. Use only if clearly needed. |
| 3rd trimester | Risk of uterine relaxation and maternal hemorrhage. Avoid near term unless necessary for malignant hyperthermia. |
Clinical note
CNS depressants and estrogens may enhance hepatotoxicity Can cause hepatotoxicity and muscle weakness.
| Placental transfer | Crosses the placenta; fetal serum levels reach approximately 40% of maternal levels. |
| Breastfeeding | Dantrolene is excreted into breast milk in low concentrations (milk:plasma ratio ~0.2). However, no reports of adverse effects in infants. Caution if infant has hepatic impairment or neuromuscular disease. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| Fetal Monitoring | Monitor liver function tests (LFTs) regularly due to risk of hepatotoxicity. Monitor for signs of respiratory depression or muscle weakness in both mother and fetus/nconate. |
| Fertility Effects | No adequate data on fertility impairment in humans; animal studies showed no significant effects on reproductive performance. |
■ 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.
| Common Effects | spasticity |
| Serious Effects |
Active hepatic disease (e.g., hepatitis, cirrhosis)Hepatic impairment with elevated liver enzymesConcurrent use with verapamil or calcium channel blockers due to risk of hyperkalemia and myocardial depression
| 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. |
| Food/Dietary | Avoid excessive alcohol consumption due to risk of hepatotoxicity. No specific food restrictions; however, maintain adequate hydration to prevent constipation, a common side effect. |
| Clinical Pearls | Dantrolene sodium is a direct-acting skeletal muscle relaxant that inhibits calcium release from the sarcoplasmic reticulum. It is the drug of choice for malignant hyperthermia crisis, requiring rapid IV administration at 2.5 mg/kg. For chronic spasticity, start with 25 mg orally daily, titrate slowly to avoid hepatotoxicity; monitor LFTs at baseline and monthly for 3 months, then periodically. Avoid in patients with active liver disease. Dantrolene may cause muscle weakness, including respiratory muscles; caution in patients with compromised pulmonary function. |
| Patient Advice | Take dantrolene exactly as prescribed; do not increase dose without consulting your doctor. · Report any signs of liver problems: yellowing of skin/eyes, dark urine, abdominal pain, or unexplained fatigue. · Avoid driving or operating heavy machinery until you know how dantrolene affects you; it may cause dizziness or drowsiness. · Do not abruptly stop taking dantrolene; tapering is needed to prevent rebound spasticity. · Inform all healthcare providers you are taking dantrolene, especially before surgery. · Store at room temperature away from moisture and heat. |
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