Dantrolene

Dantrolene Sodium for Injection is indicated, along with appropriate supportive measures, for the management of the fulminant hypermetabolism of skeletal muscle characteristic of malignant hyperthermia crises in patients of all ages. Dantrolene Sodium for Injection should be administered by continuous rapid intravenous push as soon as the malignant hyperthermia reaction is recognized (i.e., tachycardia, tachypnea, central venous desaturation, hypercarbia, metabolic acidosis, skeletal muscle rigidity, increased utilization of anesthesia circuit carbon dioxide absorber, cyanosis and mottling of the skin, and, in many cases, fever). …

• As soon as the malignant hyperthermia reaction is recognized, all anesthetic agents should be discontinued; the administration of 100% oxygen is recommended
• Dantrolene Sodium for Injection should be administered by continuous rapid intravenous push beginning at a minimum dose of 1 mg/kg, and continuing until symptoms subside or the maximum cumulative dose of 10 mg/kg has been reached
• If the physiologic and metabolic abnormalities reappear, the regimen may be repeated
• It is important to note that administration of Dantrolene Sodium for Injection should be continuous until symptoms subside
• The effective dose to reverse the crisis is directly dependent upon the individual's degree of susceptibility to malignant hyperthermia, the amount and time of exposure to the triggering agent, and the time elapsed between onset of the crisis and initiation of treatment
• Pediatric Dose Experience to date indicates that the dose of Dantrolene Sodium for Injection for pediatric patients is the same as for adults
• Preoperatively Dantrolene Sodium for Injection and/or Dantrolene Sodium Capsules may be administered preoperatively to patients judged malignant hyperthermia susceptible as part of the overall patient management to prevent or attenuate the development of clinical and laboratory signs of malignant hyperthermia
• The recommended prophylactic dose of Dantrolene Sodium for Injection is 2.5 mg/kg, starting approximately 1-1/4 hours before anticipated anesthesia and infused over approximately 1 hour. …

None.

Dantrolene sodium is metabolized by the liver, and it is theoretically possible that its metabolism may be enhanced by drugs known to induce hepatic microsomal enzymes. However, neither phenobarbital nor diazepam appears to affect dantrolene sodium metabolism. Binding to plasma protein is not significantly altered by diazepam, diphenylhydantoin, or phenylbutazone. Binding to plasma proteins is reduced by warfarin and clofibrate and increased by tolbutamide. Cardiovascular collapse in association with marked hyperkalemia has been reported in patients receiving dantrolene in combination with calcium channel blockers. …

The use of Dantrolene Sodium for Injection in the management of malignant hyperthermia crisis is not a substitute for previously known supportive measures. These measures must be individualized, but it will usually be necessary to discontinue the suspect triggering agents, attend to increased oxygen requirements, manage the metabolic acidosis, institute cooling when necessary, monitor urinary output, and monitor for electrolyte imbalance. …

There have been occasional reports of death following malignant hyperthermia crisis even when treated with intravenous dantrolene; incidence figures are not available (the pre-dantrolene mortality of malignant hyperthermia crisis was approximately 50%). Most of these deaths can be accounted for by late recognition, delayed treatment, inadequate dosage, lack of supportive therapy, intercurrent disease and/or the development of delayed complications such as renal failure or disseminated intravascular coagulopathy. In some cases there are insufficient data to completely rule out therapeutic failure of dantrolene. …

Pregnancy Pregnancy Category C Dantrolene sodium 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. Dantrolene Sodium for Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Because Dantrolene Sodium for Injection must be administered at a low concentration in a large volume of fluid, acute toxicity of dantrolene sodium could not be assessed in animals. In 14-day (subacute) studies, the intravenous formulation of dantrolene sodium 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. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.