RYANODEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RYANODEX (RYANODEX).
Ryanodine receptor agonist; stabilizes the ryanodine receptor (RyR1) channel in skeletal muscle, reducing calcium leakage and improving excitation-contraction coupling.
| Metabolism | Hydrolyzed by esterases in plasma and tissues (including red blood cells) to dantrolene and then to 5-hydroxydantrolene via CYP3A4 oxidation. |
| Excretion | Primarily hepatic metabolism; <1% excreted unchanged in urine. Biliary/fecal excretion of metabolites accounts for the majority of elimination. |
| Half-life | Terminal elimination half-life is approximately 1.5-2 hours in healthy adults; prolonged in patients with hepatic impairment. |
| Protein binding | Approximately 90-95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution: 200-300 L (approximately 3-4 L/kg) indicating extensive tissue distribution. |
| Bioavailability | Not applicable; only administered intravenously. Oral bioavailability is negligible (<5%) due to extensive first-pass metabolism. |
| Onset of Action | Intravenous administration: Onset of action within 1-2 minutes for malignant hyperthermia treatment; maximal effect seen within 5 minutes. |
| Duration of Action | Duration of therapeutic effect: 30-60 minutes after intravenous administration for malignant hyperthermia; may be shorter in hypermetabolic states. |
Dantrolene sodium: 2.5 mg/kg IV bolus, repeated as needed up to a cumulative dose of 10 mg/kg, then 1 mg/kg IV every 6 hours for 24-48 hours following malignant hyperthermia crisis.
| Dosage form | FOR SUSPENSION |
| Renal impairment | No specific dose adjustment recommended; monitor for hyperkalemia and fluid overload. Use with caution in renal impairment. |
| Liver impairment | Contraindicated in active hepatic disease (e.g., hepatitis, cirrhosis). No Child-Pugh based adjustments; avoid use in hepatic impairment. |
| Pediatric use | Same as adult: 2.5 mg/kg IV bolus, repeat as needed up to 10 mg/kg total, then 1 mg/kg IV every 6 hours. No weight-based adjustment beyond mg/kg. |
| Geriatric use | Use with caution; increased sensitivity and risk of adverse effects (e.g., muscle weakness, hepatotoxicity). No specific dose reduction; monitor closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RYANODEX (RYANODEX).
| Breastfeeding | No data on excretion in human milk; M/P ratio unknown. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment. |
| Teratogenic Risk | Animal studies have not been conducted; no human data available. Ryanodine is a plant alkaloid with potential teratogenicity; avoid in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to dantrolene or any component of the formulation","Concurrent use with verapamil or other calcium channel blockers (risk of hyperkalemia and cardiac depression)"]
| Precautions | ["Risk of respiratory depression and muscle weakness, particularly in patients with compromised respiratory function.","Caution in patients with hepatic impairment due to potential for hepatotoxicity.","May cause drowsiness, dizziness, or blurred vision; caution with driving or operating machinery.","Contains propylene glycol; monitor for adverse effects in patients with renal impairment or those receiving high doses."] |
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| Monitor maternal vital signs, cardiac function, electrolytes, and signs of malignant hyperthermia. Fetal monitoring is not routine due to limited data; consider fetal heart rate monitoring if used near term. |
| Fertility Effects | No human data; animal studies not reported. Theoretical risk of impaired fertility due to effects on calcium signaling in reproductive tissues. |