Ryanodex 250mg Sdv Inj, 1 Vial
It is used in certain patients to relax muscles.It is used to treat or prevent a health problem called malignant hyperthermia.
Drug Class
Skeletal muscle relaxant; Agent for malignant hyperthermia
Pharmacologic Class
Direct-acting skeletal muscle relaxant; Ryanodine receptor antagonist
Pregnancy Category
Category C
FDA Approved
Jul 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Dantrolene is a medication given intravenously (into a vein) to treat a rare and life-threatening condition called malignant hyperthermia (MH). MH causes a rapid increase in body temperature, severe muscle stiffness, and other dangerous symptoms, usually triggered by certain anesthetics or muscle relaxants during surgery. Dantrolene works by relaxing the muscles and helping to lower body temperature, counteracting the effects of MH.
How to Use This Medicine
To use this medication correctly, follow your doctor's instructions and carefully read all accompanying information. Take this medication exactly as directed, and follow all instructions provided. This drug is administered via intravenous injection.
If you need to store this medication at home, consult with your doctor, nurse, or pharmacist to determine the proper storage procedure.
In the event that you miss a dose, contact your doctor for guidance on the appropriate course of action.
If you need to store this medication at home, consult with your doctor, nurse, or pharmacist to determine the proper storage procedure.
In the event that you miss a dose, contact your doctor for guidance on the appropriate course of action.
Lifestyle & Tips
- Not applicable for acute IV use in MH crisis. For patients with a history of MH, avoid known trigger agents (e.g., volatile anesthetics, succinylcholine) and inform all healthcare providers of MH susceptibility.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Malignant Hyperthermia (MH) Crisis: Initial 2.5 mg/kg IV push. Repeat as needed until symptoms subside or avoid recurrence. MH Prophylaxis: 2.5 mg/kg IV over 1 hour, 30-60 minutes prior to anesthesia.
Dose Range:
2.5 - 10 mg
Condition-Specific Dosing:
Malignant Hyperthermia Crisis:
Initial 2.5 mg/kg IV push. May repeat as needed until symptoms subside or up to a cumulative dose of 10 mg/kg. Higher doses may be required based on clinical response. Post-crisis management: 1 mg/kg IV every 4-6 hours for 24-48 hours or longer as clinically indicated.
Malignant Hyperthermia Prophylaxis:
2.5 mg/kg IV infused over 1 hour, approximately 30-60 minutes prior to anticipated anesthesia. An additional 2.5 mg/kg may be administered during surgery if signs of MH appear.
Pediatric Dosing
Neonatal:
Not established (use with caution, based on individual risk/benefit)
Infant:
Malignant Hyperthermia Crisis: Same as adult (2.5 mg/kg IV push, repeat as needed). MH Prophylaxis: Same as adult (2.5 mg/kg IV over 1 hour).
Child:
Malignant Hyperthermia Crisis: Same as adult (2.5 mg/kg IV push, repeat as needed). MH Prophylaxis: Same as adult (2.5 mg/kg IV over 1 hour).
Adolescent:
Malignant Hyperthermia Crisis: Same as adult (2.5 mg/kg IV push, repeat as needed). MH Prophylaxis: Same as adult (2.5 mg/kg IV over 1 hour).
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment, use with caution.
Moderate:
No specific dose adjustment, use with caution and monitor renal function.
Severe:
No specific dose adjustment, use with caution and monitor renal function. Elimination may be prolonged.
Dialysis:
Not well studied. Use with caution. Dantrolene is highly protein-bound and not significantly removed by dialysis.
Hepatic Impairment:
Mild:
No specific dose adjustment for acute use, but monitor liver function tests (LFTs).
Moderate:
Use with caution. Monitor LFTs closely. Elimination may be prolonged.
Severe:
Use with extreme caution. Contraindicated in patients with active hepatic disease. Monitor LFTs closely. Elimination may be significantly prolonged.
Pharmacology
Mechanism of Action
Dantrolene acts directly on skeletal muscle by interfering with the release of calcium from the sarcoplasmic reticulum. It binds to the ryanodine receptor (RyR1) channel, inhibiting the efflux of calcium ions from the sarcoplasmic reticulum into the myoplasm. This uncouples excitation-contraction, reducing muscle contraction and heat production, which is critical in malignant hyperthermia.
Pharmacokinetics
Absorption:
Bioavailability:
100% (IV administration)
Tmax:
Immediate (IV administration)
FoodEffect:
Not applicable (IV administration)
Distribution:
Vd:
Approximately 0.6 L/kg
ProteinBinding:
Approximately 90% (primarily to albumin)
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 4 to 8 hours
Clearance:
Not precisely quantified for IV, but primarily hepatic metabolism and renal/biliary excretion.
ExcretionRoute:
Primarily urine (25%) and bile/feces (45-50%)
Unchanged:
Less than 1% (in urine)
Pharmacodynamics
OnsetOfAction:
Minutes (IV)
PeakEffect:
Minutes (IV)
DurationOfAction:
Variable, typically 4-6 hours, requiring continued dosing to prevent recurrence in MH.
Safety & Warnings
Side Effects
Serious Side Effects: Seek Medical Help Right Away
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Note: In rare cases, allergic reactions can be fatal.
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Choking
Trouble swallowing
Shortness of breath
If the medication leaks from the vein, it can cause tissue damage. Inform your nurse immediately if you experience:
+ Redness
+ Burning
+ Pain
+ Swelling
+ Blisters
+ Skin sores
+ Leaking of fluid at the injection site
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms that bother you or do not go away, contact your doctor:
Feeling sleepy
Dizziness
Flushing
Upset stomach
Change in voice
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Note: In rare cases, allergic reactions can be fatal.
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Choking
Trouble swallowing
Shortness of breath
If the medication leaks from the vein, it can cause tissue damage. Inform your nurse immediately if you experience:
+ Redness
+ Burning
+ Pain
+ Swelling
+ Blisters
+ Skin sores
+ Leaking of fluid at the injection site
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms that bother you or do not go away, contact your doctor:
Feeling sleepy
Dizziness
Flushing
Upset stomach
Change in voice
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Recurrence of MH symptoms (e.g., muscle stiffness, high fever, rapid heart rate, dark urine) after initial treatment.
- Signs of liver problems (though rare with acute IV use): yellowing of skin or eyes (jaundice), dark urine, unusual fatigue, nausea, vomiting, abdominal pain, loss of appetite.
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the symptoms you experienced.
If you have liver disease, as this may affect how your body processes the medication.
If you are taking a calcium channel blocker, such as diltiazem, nifedipine, or verapamil. If you are unsure whether your medication falls into this category, consult with your doctor or pharmacist.
If you are breastfeeding or plan to breastfeed. It is recommended that you do not breastfeed while taking this medication, and you may need to avoid breastfeeding for a period after your last dose. Your doctor will advise you on the necessary precautions.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health conditions with your doctor and pharmacist. They will help you determine whether it is safe to take this medication in conjunction with your other treatments and health issues. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the symptoms you experienced.
If you have liver disease, as this may affect how your body processes the medication.
If you are taking a calcium channel blocker, such as diltiazem, nifedipine, or verapamil. If you are unsure whether your medication falls into this category, consult with your doctor or pharmacist.
If you are breastfeeding or plan to breastfeed. It is recommended that you do not breastfeed while taking this medication, and you may need to avoid breastfeeding for a period after your last dose. Your doctor will advise you on the necessary precautions.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health conditions with your doctor and pharmacist. They will help you determine whether it is safe to take this medication in conjunction with your other treatments and health issues. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
After surgery, you may experience muscle weakness, which can manifest as weak grip strength or weak leg muscles, and dizziness. These effects can persist for up to 48 hours. To ensure your safety, avoid driving and engaging in activities that require alertness for at least 48 hours after surgery.
You may require assistance with standing and walking until your strength returns to normal. Exercise caution when navigating stairs. Additionally, be careful when eating meals on the day this medication was administered, as difficulty swallowing and choking have been reported. If you experience any concerns, discuss them with your doctor.
Before consuming alcohol, marijuana, or other forms of cannabis, or taking prescription or over-the-counter drugs that may impair your actions, consult with your doctor.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
If you are pregnant or planning to become pregnant, inform your doctor, as you will need to discuss the benefits and risks of using this medication during pregnancy.
After surgery, you may experience muscle weakness, which can manifest as weak grip strength or weak leg muscles, and dizziness. These effects can persist for up to 48 hours. To ensure your safety, avoid driving and engaging in activities that require alertness for at least 48 hours after surgery.
You may require assistance with standing and walking until your strength returns to normal. Exercise caution when navigating stairs. Additionally, be careful when eating meals on the day this medication was administered, as difficulty swallowing and choking have been reported. If you experience any concerns, discuss them with your doctor.
Before consuming alcohol, marijuana, or other forms of cannabis, or taking prescription or over-the-counter drugs that may impair your actions, consult with your doctor.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
If you are pregnant or planning to become pregnant, inform your doctor, as you will need to discuss the benefits and risks of using this medication during pregnancy.
Overdose Information
Overdose Symptoms:
- Generalized muscle weakness
- Respiratory depression
- CNS depression (drowsiness, confusion, coma)
- Nausea
- Vomiting
- Diarrhea
- Tachycardia
- Hypotension
What to Do:
Treatment is primarily supportive. Maintain a patent airway and assist ventilation as needed. Administer IV fluids. Monitor vital signs, ECG, and electrolytes. Gastric lavage may be considered if oral overdose. Dialysis is unlikely to be effective due to high protein binding. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Major Interactions
- Calcium Channel Blockers (especially verapamil): Concomitant use with dantrolene has been associated with hyperkalemia, myocardial depression, and cardiovascular collapse in animal models. Avoid concurrent use if possible, particularly in MH crisis.
Moderate Interactions
- Hepatotoxic Agents: Increased risk of hepatotoxicity when co-administered with other potentially hepatotoxic drugs. Monitor liver function closely.
- Neuromuscular Blocking Agents (non-depolarizing): May potentiate or prolong the neuromuscular blockade.
- Estrogens (oral): May increase the risk of hepatotoxicity, particularly in women over 35 years of age receiving chronic oral dantrolene.
Minor Interactions
- CNS Depressants: May cause additive CNS depression.
Monitoring
Baseline Monitoring
Liver Function Tests (ALT, AST, ALP, Bilirubin)
Rationale: To establish baseline hepatic function, as dantrolene is hepatically metabolized and can cause liver injury.
Timing: Prior to initiation, especially if prolonged therapy is anticipated or patient has pre-existing liver conditions.
Serum Electrolytes (Potassium, Calcium)
Rationale: To establish baseline and monitor for imbalances, particularly in MH crisis where hyperkalemia can occur.
Timing: Prior to initiation.
Renal Function (BUN, Creatinine)
Rationale: To assess baseline kidney function, as metabolites are renally excreted.
Timing: Prior to initiation.
Routine Monitoring
Vital Signs (Heart Rate, Blood Pressure, Temperature, Respiratory Rate)
Frequency: Continuously during MH crisis, then every 1-4 hours during post-crisis management.
Target: Within normal physiological limits; resolution of hyperthermia and tachycardia.
Action Threshold: Persistent hyperthermia, tachycardia, or other signs of MH recurrence; significant hemodynamic instability.
End-tidal CO2 (ETCO2)
Frequency: Continuously during MH crisis and post-crisis management.
Target: Normal range (e.g., 35-45 mmHg); resolution of hypercapnia.
Action Threshold: Rising ETCO2 despite increased ventilation, indicating ongoing hypermetabolism.
Arterial Blood Gases (ABGs)
Frequency: As clinically indicated during crisis, then every 4-6 hours during post-crisis management.
Target: Resolution of acidosis (pH > 7.35, HCO3 > 22 mEq/L).
Action Threshold: Persistent metabolic acidosis.
Serum Electrolytes (Potassium, Calcium)
Frequency: Every 4-6 hours during crisis and post-crisis management.
Target: Within normal limits (e.g., K 3.5-5.0 mEq/L, Ca 8.5-10.5 mg/dL).
Action Threshold: Hyperkalemia, hypocalcemia.
Creatine Kinase (CK)
Frequency: Every 6-12 hours during crisis and post-crisis management.
Target: Decreasing trend towards normal.
Action Threshold: Persistent elevation or rising CK, indicating ongoing muscle damage/rhabdomyolysis.
Urine Output and Color
Frequency: Hourly during crisis, then every 2-4 hours.
Target: >0.5 mL/kg/hr; clear urine.
Action Threshold: Oliguria, dark/cola-colored urine (suggesting myoglobinuria).
Liver Function Tests (ALT, AST, ALP, Bilirubin)
Frequency: Daily for first 3-5 days, then as clinically indicated, especially if prolonged therapy.
Target: Stable or decreasing trends.
Action Threshold: Significant elevation (e.g., >2-3x ULN) or rising trend, indicating potential liver injury.
Symptom Monitoring
- Muscle rigidity (generalized or localized)
- Hyperthermia (rapidly rising body temperature)
- Tachycardia (unexplained rapid heart rate)
- Tachypnea (unexplained rapid breathing)
- Hypercapnia (elevated end-tidal CO2)
- Metabolic acidosis
- Arrhythmias
- Cyanosis
- Mottled skin
- Sweating
- Dark urine (myoglobinuria)
- Signs of liver dysfunction (jaundice, dark urine, fatigue, nausea, abdominal pain) if prolonged use.
Special Patient Groups
Pregnancy
Category C. Animal studies have shown adverse effects on the fetus. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus, particularly in a life-threatening situation like MH crisis.
Trimester-Specific Risks:
First Trimester:
Potential for fetal harm based on animal data; use only if critically indicated.
Second Trimester:
Potential for fetal harm based on animal data; use only if critically indicated.
Third Trimester:
Potential for fetal harm based on animal data; use only if critically indicated. May cause transient muscle weakness in the neonate if administered close to delivery.
Lactation
Dantrolene is excreted into breast milk. Caution should be exercised when dantrolene is administered to a nursing mother. The amount excreted is generally low, but potential for infant muscle weakness or sedation exists. Monitor breastfed infant for signs of weakness or lethargy.
Infant Risk:
Low to Moderate (L3). Potential for infant muscle weakness, lethargy, or gastrointestinal upset. Monitor infant closely.
Pediatric Use
Dosing for malignant hyperthermia crisis and prophylaxis is weight-based and similar to adult dosing. Safety and efficacy have been established in pediatric patients. Neonates should be treated with caution due to immature hepatic and renal function.
Geriatric Use
No specific dose adjustments are generally required for elderly patients. However, use with caution due to potential for age-related decreases in hepatic and renal function. Monitor liver function and overall clinical status closely.
Clinical Information
Clinical Pearls
- Ryanodex (dantrolene sodium for injection) is the only specific pharmacologic treatment for malignant hyperthermia (MH) crisis.
- Rapid reconstitution and administration are critical in an MH crisis. Ryanodex reconstitutes significantly faster (approx. 10 seconds) and requires less diluent (5 mL sterile water for injection) compared to older dantrolene formulations, making it advantageous in emergencies.
- The initial dose for MH crisis is 2.5 mg/kg IV, which should be repeated until symptoms subside. There is no absolute maximum dose; some patients may require cumulative doses exceeding 10 mg/kg.
- Continue dantrolene therapy for at least 24-48 hours after the MH crisis to prevent recurrence, typically at 1 mg/kg IV every 4-6 hours.
- Monitor for signs of MH recurrence (e.g., rising ETCO2, hyperthermia, muscle rigidity) during the post-crisis period.
- Avoid calcium channel blockers (especially verapamil) in conjunction with dantrolene due to the risk of hyperkalemia and myocardial depression.
- Ensure adequate hydration and monitor urine output to prevent renal complications from rhabdomyolysis.
Alternative Therapies
- There is no direct pharmacological alternative to dantrolene for the specific treatment of malignant hyperthermia crisis. Management primarily involves dantrolene administration and aggressive supportive care (e.g., cooling, correction of acidosis, management of hyperkalemia, treatment of arrhythmias).
Cost & Coverage
Average Cost:
$2,000 - $4,000+ per 250mg vial
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (Tier 4 or 5) for outpatient use; typically covered under medical benefit for inpatient use.
General Drug Facts
If your symptoms or health problems persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others, and do not take medication prescribed for someone else. Store all medications in a secure location, out of reach of children and pets, to prevent accidental ingestion. Dispose of unused or expired medications properly. Unless instructed otherwise, do not flush medications down the toilet or drain. If you are unsure about the correct disposal method, consult your pharmacist, who can also inform you about potential drug take-back programs in your area. Some medications may come with an additional patient information leaflet; check with your pharmacist for more information. If you have any questions or concerns about your medication, discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide details about the medication taken, the amount, and the time it occurred.