Dantrium (Dantrolene Sodium) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Sprague-Dawley female rats fed Dantrium for 18 months at dosage levels of 15, 30, and 60 mg/kg/day showed an increased incidence of benign and malignant mammary tumors compared with concurrent controls. At the highest dose level (approximately the same as the maximum recommended daily dose on a mg/m² basis), there was an increase in the incidence of benign hepatic lymphatic neoplasms. In a 30-month study in Sprague-Dawley rats fed dantrolene sodium, the highest dose level (approximately the same as the maximum recommended daily dose on a mg/m² basis) produced a decrease in the time of onset of mammary neoplasms. Female rats at the highest dose level showed an increased incidence of hepatic lymphangiomas and hepatic angiosarcomas.

The only drug-related effect seen in a 30-month study in Fischer-344 rats was a dose-related reduction in the time of onset of mammary and testicular tumors. A 24-month study in HaM/ICR mice revealed no evidence of carcinogenic activity.

The significance of carcinogenicity data relative to use of Dantrium in humans is unknown.

Dantrolene sodium has produced positive results in the Ames S. Typhimurium bacterial mutagenesis assay in the presence and absence of a liver activating system.

Dantrolene sodium administered to male and female rats at dose levels up to 45 mg/kg/day (approximately 1.4 times the maximum recommended daily dose on a mg/m² basis) showed no adverse effects on fertility or general reproductive performance.

Pregnancy

Pregnancy Category C

Dantrium has been shown to be embryocidal in the rabbit and has been shown to decrease pup survival in the rat when given at doses seven times the human oral dose. There are no adequate and well-controlled studies in pregnant women. Dantrium Intravenous should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

OVERDOSAGE

Because Dantrium Intravenous must be administered at a low concentration in a large volume of fluid, acute toxicity of Dantrium could not be assessed in animals. In 14-day (subacute) studies, the intravenous formulation of Dantrium was relatively non-toxic to rats at doses of 10 mg/kg/day and 20 mg/kg/day. While 10 mg/kg/day in dogs for 14 days evoked little toxicity, 20 mg/kg/day for 14 days caused hepatic changes of questionable biologic significance.

Symptoms which may occur in case of overdose include, but are not limited to, muscular weakness and alterations in the state of consciousness (e.g., lethargy, coma), vomiting, diarrhea, and crystalluria.

For acute overdosage, general supportive measures should be employed.

Intravenous fluids should be administered in fairly large quantities to avert the possibility of crystalluria. An adequate airway should be maintained and artificial resuscitation equipment should be at hand. Electrocardiographic monitoring should be instituted, and the patient carefully observed. The value of dialysis in Dantrium overdose is not known.

CONTRAINDICATIONS

None.