RYANODEX® (dantrolene sodium) for injectable suspension is a treatment for malignant hyperthermia (MH) along with other previously known supportive measures.1 MH is a potentially fatal disorder triggered when susceptible individuals come in contact with certain anesthetic products, such as succinylcholine and volatile anesthetics.4 RYANODEX® is supplied as 250 mg vials of dantrolene sodium in lyophilized powder form.1 It is reconstituted with 5 mL of sterile water for injection (non-bacteriostatic).  Its formulation allows for reconstitution and administration in less than 1 minute to patients experiencing MH.2 Upon reconstitution, RYANODEX® is a suspension of dantrolene sodium which should be administered by intravenous push.1  The MHAUS recommended loading dose is 2.5 mg/kg.3  If MH symptoms continue, additional doses should be given.1

Dantrolene sodium is the standard of care for malignant hyperthermia (MH) treatment, and for the past 35 years has been the only treatment available to reverse an MH episode. The following chart provides an overview of the primary differences between RYANODEX® (dantrolene sodium) for injectable suspension and other dantrolene sodium IV products:

Attribute RYANODEX®1 Existing Dantrolene Sodium Products9,10
Loading Dose (2.5 mg/kg) of Dantrolene Sodium Needed Per Average Patient (will vary based on patient’s weight)
  • 1 vial contains 250 mg of dantrolene sodium
  • 1 vial per patient
  • Each vial only contains 20 mg of dantrolene sodium
  • Multiple vials per patient (eg, 13 vials for a 100 kg subject)
Time to Reconstitute
  • Less than 1 minute to reconstitute and administer 1 vial
  • Between 15 to 20 minutes to reconstitute 13 vials
Water for Injection
  • 5 mL sterile water for injection (non-bacteriostatic) per vial
  • 1 mL contains 50 mg dantrolene sodium as a uniform nanoparticle suspension*
  • 60 mL per vial (750 mL for 250 mg of dantrolene sodium)
  • 1 mL contains 0.33 mg dantrolene sodium as a solution
Amount of Mannitol
  • 125 mg mannitol/vial
  • 3000 mg mannitol/vial (39,000 mg for 13 vials of older dantrolene sodium products)

*RYANODEX® (upon reconstitution) is a uniform suspension of dantrolene sodium. Dissolution is extremely rapid in whole blood/plasma.

Administration to conscious subjects is associated with loss of grip strength and weakness in the legs, as well as drowsiness and dizziness. Other common adverse reactions may include nausea, thrombophlebitis, tissue necrosis secondary to extravasation, urticaria, erythema, and injection site reactions (pain, erythema, swelling).

Each vial of RYANODEX® (dantrolene sodium) for injectable suspension contains only 125 mg (which is subtherapeutic in terms of diuretic effects) of mannitol compared to 3000 mg of mannitol in each vial of other dantrolene sodium for injection products.1,9,10 This allows the medical practitioner to better manage diuresis.

The existing formulation of dantrolene sodium for injection is a lyophilized (dry), fluffy, light orange powder. RYANODEX® (dantrolene sodium) for injectable suspension differs from this in that it is a deep orange lyophilized (dry) cake with a lightened meniscus edge.

RYANODEX® VialDantrium® Vial

Attribute RYANODEX® Other Dantrolene Sodium Products
Dry Reconstituted Dry Reconstituted
Color Deep orange with a lightened miniscus edge Opaque bright orange Light orange Translucent light yellow/orange
Texture Cake Nanoparticle suspension Fluffy Solution
Lyophilized? yes N/A yes N/A

MHAUS recommends stocking a minimum of 720 mg dantrolene sodium, which is supplied in only 3 vials of RYANODEX® (dantrolene sodium) for injectable suspension (in contrast to the 36 vials required to obtain 720 mg with other dantrolene sodium IV products).12 Data suggest that the average patient uses a median dose of 5.9 mg/kg of dantrolene sodium in a crisis.13 For many patients, this is more than the recommended 720 mg. Check with your accrediting body and MHAUS.org for additional information.

RYANODEX® (dantrolene sodium) for injectable suspension has a shelf life of 33 months.

RYANODEX® (dantrolene sodium) for injectable suspension may be ordered beginning in August through your regional or national wholesaler. RYANODEX® will begin shipping in September 2014.

RYANODEX® (dantrolene sodium) for injectable suspension should be reconstituted with 5 mL sterile water for injection (without a bacteriostatic agent).1 Shake the vial until RYANODEX® is mixed thoroughly (should take less than 10 seconds). Suspension should be a uniform orange suspension.  Please refer to the preparation section (2.4) of the prescribing information.

Reconstituted RYANODEX® (dantrolene sodium) for injectable suspension should be used within 6 hours after reconstitution.1 Store reconstituted suspension at controlled room temperature 20°C to 25°C (68ºF to 77ºF).  Protect from light.

RYANODEX® (dantrolene sodium) for injectable suspension should be reordered as soon as possible after use or about 1 to 2 months before expiration. Similar to other dantrolene sodium IV products, RYANODEX® cannot be returned for credit. Eagle believes in education and suggests that if your facility permits, the expired RYANODEX® be used for a mock drill, in which your team can become familiar with reconstituting RYANODEX® in an MH crisis situation.

Eagle has developed a reconstitution and administration video, a reconstitution and administration dosing card, and other informational tools to educate medical practitioners on how to use RYANODEX® (dantrolene sodium) for injectable suspension. Go to RYANODEX.com/resources for more information.

Store unreconstituted product at 20°C to 25°C (68ºF to 77ºF) [see USP Controlled Room Temperature] and avoid prolonged exposure to light.1

Malignant hyperthermia (MH) is a hypermetabolic condition that can be triggered when genetically susceptible individuals come in contact during surgery with certain inhaled (volatile) anesthetics or the muscle relaxant succinylcholine.4 Symptoms of MH include truncal and/or masseter muscle rigidity, elevated end tidal CO2, tachycardia, elevated body temperature, acidosis, rhabdomyolysis, hypercarbia, and hyperkalemia.  If not treated immediately, MH can be fatal.

For more information on MH, visit the Malignant Hyperthermia Association of the United States’ (MHAUS) website: http://www.mhaus.org/.

The general signs of malignant hyperthermia (MH) include truncal and/or masseter muscle rigidity, elevated end tidal CO2, tachycardia, elevated body temperature (may exceed 110°F), acidosis, rhabdomyolysis, hypercarbia, and hyperkalemia.4

Epidemiologic studies reveal that malignant hyperthermia (MH) complicates 1 in approximately 100,000 surgeries in adults and 1 in 30,000 surgical procedures in children.5 Additionally, about 1 in 2,000 patients harbor a genetic change that makes them susceptible to MH.

 

Susceptibility to malignant hyperthermia (MH) is a genetically inherited condition where, upon exposure to triggering agents (volatile and succinylcholine), a hypermetabolic condition results.4 The majority of people who are susceptible to MH are completely unaware of their risk unless they or a family member have previously experienced MH, or they have been tested for the condition.

Dantrolene sodium is the only known antidote for malignant hyperthermia induced by inhalational anesthetics in humans and is recognized as the only standard treatment for MH. The use of RYANODEX® (dantrolene sodium) for injectable suspension in the management of malignant hyperthermia crises 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. Patients who receive IV dantrolene sodium preoperatively should have vital signs monitored. For more information about dantrolene, visit: http://www.mhaus.org/faqs/category/frequently-asked-questions-about/dantrolene/.

For additional information, please refer to the full Prescribing Information.

For additional background information on malignant hyperthermia, please visit http://MHAUS.org/.

During an MH crisis, additional advice can be obtained by calling 1.800.MH.HYPER.

To report a RYANODEX® related adverse event, or for other information on RYANODEX®, please contact Eagle Customer Service Team: 800.720.1650.