DANTRIUM
Clinical safety rating
cautionComprehensive clinical and safety monograph for DANTRIUM (DANTRIUM).
Dantrolene inhibits calcium release from the sarcoplasmic reticulum by binding to the ryanodine receptor (RyR1), thereby reducing intracellular calcium concentration and decreasing muscle contraction.
| Metabolism | Metabolized in the liver via microsomal enzymes (CYP3A4 and others) to 5-hydroxydantrolene (active metabolite) and other metabolites. Undergoes enterohepatic recirculation. |
| Excretion | Renal: ~65% as unchanged drug; biliary/fecal: ~15% as metabolites; remainder metabolized and eliminated via urine. |
| Half-life | Terminal elimination half-life: 8.7-14.4 hours in adults; longer with hepatic dysfunction. |
| Protein binding | ~90% bound to albumin. |
| Volume of Distribution | Vd: 0.8-1.2 L/kg; suggests extensive tissue distribution. |
| Bioavailability | Oral: ~70% (first-pass metabolism reduces from ~90% absorbed). |
| Onset of Action | IV: 2-4 minutes; Oral: 1-2 hours. |
| Duration of Action | IV: 30-60 minutes; Oral: 4-6 hours; prolonged in hepatic impairment. |
| Molecular Weight | 336.4 |
Initially 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 400 mg/day in divided doses. For malignant hyperthermia crisis: IV bolus 1 mg/kg, repeated as needed up to 10 mg/kg cumulative dose.
| Dosage form | CAPSULE |
| Renal impairment | No specific guidelines; use with caution in renal impairment due to potential accumulation. Monitor renal function and reduce dose if toxicity occurs. |
| Liver impairment | Contraindicated in active hepatic disease (elevated AST/ALT, hepatitis, cirrhosis). For Child-Pugh A: reduce dose by 50%; Child-Pugh B: reduce dose by 75%; Child-Pugh C: avoid use. |
| Pediatric use | Spasticity: 0.5 mg/kg/dose twice daily, titrate up to 0.5-2 mg/kg/dose three times daily; maximum 100 mg four times daily for children >5 years. Malignant hyperthermia: IV 1 mg/kg, repeated as needed. |
| Geriatric use | Start at lower end of dosing range (25 mg daily), titrate slowly. Increased risk of sedation, muscle weakness, and hepatic toxicity. Monitor liver function frequently. |
| 1st trimester | Limited human data; animal studies suggest risk. Use only if benefit outweighs risk. |
| 2nd trimester | Limited human data; potential for maternal hepatotoxicity. Use only if clearly needed. |
| 3rd trimester | Avoid near term due to risk of uterine relaxation and postpartum hemorrhage. |
Clinical note
Comprehensive clinical and safety monograph for DANTRIUM (DANTRIUM).
| Placental transfer | Crosses placenta in humans; concentrations in cord blood are similar to maternal levels. |
| Breastfeeding | Excreted into breast milk in small amounts; monitor infant for drowsiness and hypotonia. Use caution. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Dantrolene (Dantrium) is classified as FDA Pregnancy Category C. Animal studies have shown an increased incidence of fetal resorptions and delayed ossification at doses ≥ 30 mg/kg/day in rats and 45 mg/kg/day in rabbits. There are no adequate and well-controlled studies in pregnant women. Potential risks include skeletal anomalies and embryotoxicity. Use only if potential benefit justifies potential risk to fetus. |
| Fetal Monitoring | Monitor liver function tests (LFTs) periodically due to risk of hepatotoxicity. Assess for signs of muscle weakness, respiratory depression, or extrapyramidal effects in mother. In pregnancy, fetal monitoring with ultrasound for growth and development if exposure during first trimester. Non-stress testing if late pregnancy exposure. |
| Fertility Effects | No specific human data; animal studies suggest no significant impact on fertility at clinically relevant doses. However, dantrolene may cause testicular atrophy in male rats at high doses; relevance unknown. Effects on female fertility not well studied. |
■ FDA Black Box Warning
Hepatotoxicity: Dantrolene can cause fatal hepatitis, especially with long-term use (≥60 days) and at doses >300 mg/day. Liver function must be monitored before and during therapy. Risk is increased in females, patients >35 years, and those on other hepatotoxic medications.
| Serious Effects |
Active hepatic disease (e.g., hepatitis, cirrhosis)Pre-existing muscle weakness or central nervous system depressionConditions requiring neuromuscular transmission integrity (e.g., myasthenia gravis)
| Precautions | Monitor liver function tests (LFTs) before and during therapy; discontinue if hepatic injury suspected., May cause muscle weakness, impair ability to drive or operate machinery., Caution in patients with compromised respiratory function or impaired cardiac function due to negative inotropic effects., Photosensitivity reactions possible., Risk of pleural effusion and pericarditis with long-term use., Use with caution in renal impairment (no dosage adjustment needed, but monitor). |
| Food/Dietary | No specific food interactions are established. Avoid alcohol due to additive CNS depression. |
| Clinical Pearls | Monitor liver function tests before and during therapy; hepatotoxicity risk increases with doses >300 mg/day. Do not use in patients with pre-existing hepatic disease. Abrupt discontinuation may precipitate hyperthermia and spasticity rebound. Use with caution in patients with impaired pulmonary function due to potential respiratory muscle weakness. |
| Patient Advice | Take exactly as prescribed; do not increase dose without consulting your doctor. · Report signs of liver problems: yellow skin/eyes, dark urine, abdominal pain, unusual fatigue. · Do not stop taking suddenly; dose must be tapered to avoid withdrawal symptoms. · May cause drowsiness or dizziness; avoid driving or operating machinery until you know how you react. · Avoid alcohol and other CNS depressants while taking this medication. · Use sun protection as photosensitivity may occur. |
Loading safety data…