Dosing and uses of Dantrium, Ryanodex (dantrolene)
Adult dosage forms and strengths
capsule
- 25mg
- 50mg
- 100mg
powder for injection
- 20mg/vial (Dantrium, Revonto)
- 250mg/vial (Ryanodex)
Malignant Hyperthermia (Per MHAUS)
2.5 mg/kg rapid IV bolus, repeat PRn
Sometimes >10 mg/kg (cumulative dose) is necessary (up to 30 mg/kg)
Maintenance: 1 mg/kg IV q4-6hr OR 0.25 mg/kg/hr IV infusion
Continue at least for 36 hr
MHAUS: Malignant Hyperthermia Association of the United States, guideline 2008
Malignant Hyperthermia, Prevention
NOT recommended by MHAUs
1-3 days before surgery: 4-8 mg/kg/day PO divided q6hr
75 minutes before anesthesia: 2.5 mg/kg IV once over 60 minutes; administer additional doses PRn
Spasticity
25 mg PO qDay for 7 days, THEn
25 mg PO q8hr for 7 days, THEn
50 mg PO q8hr for 7 days, THEn
100 mg PO q8hr, not to exceed 100 mg PO q6hr
Discontinued if no benefits within 6-7 weeks
Neuroleptic Malignant Syndrome (Off-label)
25 mg/day IV; gradually increase to 150 mg/day
Succinylcholine-induced Fasciculations & Post-op Muscle Pain (Off-label)
<45 kg: 100 mg PO 2 hr pre-op
≥45 kg: 150 mg PO 2 hr pre-op
Monitor: LFTs, bilirubin
Wolfram Syndrome (Orphan)
Orphan designation for treatment of Wolfram Syndrome
Sponsor
- Washington University in St. Louis; 660 S. Euclid Avenue, Campus Box 8127; St. Louis, Missouri 63110
Other Indications & Uses
Off-label: Muscle pain in Duchenne muscular dystrophy, muscle pain in phosphorylase deficiency (exercise), to reduce succinylcholine-induced fasciculations & post-op muscle pain, NMs
Pediatric dosage forms and strengths
capsule
- 25mg
- 50mg
- 100mg
powder for injection
- 20mg/vial (Dantrium, Revonto)
- 250mg/vial (Ryanodex)
Malignant Hyperthermia (Per MHAUS)
2.5 mg/kg rapid IV bolus, repeat PRn
Sometimes >10 mg/kg (cumulative dose) is necessary (up to 30 mg/kg)
Maintenance: 1 mg/kg IV q4-6hr OR 0.25 mg/kg/hr IV infusion
Continue at least for 36 hr
MHAUS: Malignant Hyperthermia Association of the United States, guideline 2008
Malignant Hyperthermia, Prevention
NOT recommended by MHAUs
1-3 days before surgery: 4-8 mg/kg/day PO divided q6hr
75 minutes before anesthesia: 2.5 mg/kg IV once over 60 minutes; administer additional doses PRn
Spasticity
Monitor: LFTs, bilirubin
≥5 Years
- 0.5 mg/kg PO qDay for 7 days, THEN
- 0.5 mg/kg PO q8hr for 7 days, THEN
- 1 mg/kg PO q8hr for 7 days, THEN
- 2 mg/kg PO q8hr, not to exceed 100 mg PO q6hr
<5 Year
- Initial: 1 mg/kg/day PO divided q12hr
- Maximum maintenance: 12 mg/kg/day PO divided q6hr
- Not to exceed 3 mg/kg PO q6-12hr OR 400 mg/24 hr PO
Geriatric dosage forms and strengths
See adult dosing
Spontaneous reports suggest a higher proportion of hepatic events with fatal outcome in elderly patients
Dantrium, Ryanodex (dantrolene) adverse (side) effects
Frequency not defined
Increased serum AST (SGOT), ALT (SGPT), alkaline phosphatase, LDH, BUN, and total serum bilirubin concentrations
Fatal/nonfatal hepatitis
Diarrhea
Anorexia
Nausea
Vomiting
Gastric irritation
Abdominal cramps
Constipation
Dysphagia
GI bleeding
Adynamic ileus
Speech disturbance
Headache
Visual disturbances
Dysgeusia
Mental depression
Confusion
Auditory/visual hallucinations
Increased nervousness
Insomnia
Drooling
Exacerbation/precipitation of seizures
Muscle weakness
Drowsiness
Dizziness
Urinary frequency/incontinence
Nocturia
Difficult urination/urinary retention
Crystalluria, hematuria
Difficult erection
Abnormal hair growth
Acneiform rash
Eczematoid eruption
Pruritus, urticaria
Sweating
Tachycardia
Erratic blood pressure
Phlebitis
Heart failure
Aplastic anemia
Anemia
Leukopenia
Lymphocytic
Lymphoma
Thrombocytopenia
Respiratory depression
Pleural effusion with associated eosinophilia
Warnings
Black box warnings
The incidence of symptomatic (fatal and nonfatal) hepatitis is lower with doses up to 400 mg daily compared to >800 mg daily
Overt hepatitis has been most frequently observed during third and twelfth months, but may occur at anytime. Risk higher in females and patients >35 years, and with concurrent therapy
Use only in conjunction with liver monitoring
Should not be used in conditions other than those recommended; discontinue therapy if benefits not observed within 45 days in chronic spasticity
Contraindications
NO CONTRAINDICATIONS for IV use in MH management/prophylaxis
Hypersensitivity
Impaired hepatic, cardiac or pulmonary function
Upper motor neuron disorder
Patients in whom spasticity is utilized to maintain upright posture & balance
Cautions
Possibility of severe hepatotoxicity
Risk of muscle weakness
Risk of photosensitivity reactions
Females, >35 years, receiving other drugs, history of liver disease
Not indicated in muscle spasms due to rheumatic disorder or musculoskeletal trauma
Ineffective in ALs
Use caution when administering oral therapy in patients with severely impaired cardiac function resulting from myocardial disease
Use caution when administering oral therapy in patients with impaired pulmonary function
In combination with calcium channel blockers IV dantrolene may increase risk for hyperkalemia and cardiac arrest (combination not recommended)
Severely impaired cardiac function due to myocardial disease
Associated with pleural effusion with associated eosinophilia
Pregnancy and lactation
Pregnancy category: C
Lactation: enters breast milk/not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Dantrium, Ryanodex (dantrolene)
Mechanism of action
Interferes with calcium release within skeletal muscle cells (from sarcoplasmic reticulum)
Pharmacokinetics
Peak plasma time: 5 hr
Concentration: 100 to >600 ng/mL
Half-life elimination: 4-8hr
Duration: 3 hr or longer
Protein Bound: substantiaL
Metabolism: Liver
Metabolites: 5-hydroxy derivative
Excretion: Urine (25%); feces (45-50%)
Administration
IV Compatibilities
Sterile water for injection (SWI)
IV Incompatibilities
Dextrose solutions
0.9% NaCL
Other acidic solutions
IV Preparation
Ryanodex
- Reconstitute each 250 mg vial by adding 5 mL of SWI (not bacteriostatic water for injection)
- Shake the vial to ensure an orange-colored uniform suspension Visually inspect the vial for particulate matter and discoloration prior to administration
Dantrium, Revonto
- Reconstitute each 20 mg vial by adding 60 mL of SWI (not bacteriostatic water for injection)
- Shake vial for about 20 seconds or until solution is clear
- Do not transfer reconstituted solutions to large glass bottles for prophylactic infusion due to precipitate formation
- May transfer to larger volume sterile IV empty plastic bag
IV Administration
Therapeutic or emergency dose can be administered with rapid IV push
Follow-up doses should be administered over 2-3 min
36 vials (20 mg/vial) are needed for adequate hyperthermia therapy
Ryanodex
- Administer the reconstituted suspension either:
- -Into the IV catheter while an IV infusion of 0.9% NaCal or 5% dextrose injection is freely running; or
- -Into the indwelling catheter after assuring its patency without a freely running infusion
- Flush the IV line to assure that there is no residual drug that remains in the catheter
Storage
Unreconstituted vials
- Store controlled room temperature 20-25° C (68-77° F)
- Avoid prolonged exposure to light
Reconstituted vials
- Should be used immediately, but reconstituted solution may be stored at controlled room temperature 20-25° C (68-77° F) and used within 6 hr
- Protect from direct light
