Dantrolene Dosage

Medically reviewed by Drugs.com. Last updated on May 1, 2023.

Usual Adult Dose for Malignant Hyperthermia

TREATMENT of Malignant Hyperthermia (MH): 1 mg/kg IV push

• Additional IV boluses up to 10 mg/kg should be given if physiologic and metabolic abnormalities continue

Maximum Cumulative dose: 10 mg/kg

If Physiologic and Metabolic Abnormalities of MH Reappear: Repeat dosing starting with 1 mg/kg IV

Institute the following supportive measures with dantrolene therapy:

• Discontinue use of MH triggering anesthetic agents (i.e., volatile anesthetic gases and succinylcholine)
• Manage metabolic acidosis
• Institute cooling when necessary
• Administer diuretics to prevent late kidney injury due to myoglobinuria (the amount of mannitol in injectable suspension is insufficient to maintain diuresis)

Comments:

• 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.

PREVENTION of Malignant Hyperthermia (MH):
Preoperatively:

• IV: 2.5 mg/kg IV over at least 1 minute approximately 75 minutes prior to surgery; if surgery is prolonged, additional individualized doses may be needed
• Oral: 4 to 8 mg/kg/day orally in 3 or 4 divided doses for 1 or 2 days prior to surgery (last dose being given with a minimum of water approximately 3 to 4 hours before scheduled surgery)

Postoperatively:

• Following a MH Crisis: 4 to 8 mg/kg per day orally in 4 divided doses

Duration of Therapy: 1 to 3 days

Comments:

• Use for the prevention of MH should include avoiding agents that trigger MH.
• Dose adjustment of oral therapy may be made within the recommended dosage range to avoid incapacitation (weakness, drowsiness, etc.) or excessive gastrointestinal irritation (nausea and/or vomiting).

Uses:

• For the treatment of malignant hyperthermia in conjunction with appropriate supportive measures (IV)
• For the prevention of malignant hyperthermia in patients at high risk (IV and oral)

Usual Adult Dose for Chronic Spasticity

Dosage should be titrated and individualized for maximum effect; the lowest dose compatible with optimal response is recommended: therapy should be stopped if benefits are not evident within 45 days

Initial dose: 25 mg orally once a day for 7 days, then
25 mg orally 3 times a day for 7 days
50 mg orally 3 times a day for 7 days
100 mg orally 3 times a day
Maximum dose: 100 mg orally 4 times a day

Comments:

• Maintain each dose level for 7 days during titration to determine patient's response; some patients will do better with dosing 4 times a day.
• Some patients will not respond until a higher daily dosage is achieved; improvement can be expected to manifest as a decrease in severity of spasticity that restores the ability to perform a daily function not quite attainable without therapy.
• If no further benefit is observed with the next higher dose, a decrease to the previous lower dose is recommended.
• This drug is not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders.

Use: For use controlling the manifestations of clinical spasticity resulting from upper motor neuron disorders such as spinal cord injury, stroke, cerebral palsy, or multiple sclerosis.

The decision to continue therapy on a long-term basis is justified if this drug produces a significant reduction in painful and/or disabling spasticity such as clonus, permits a significant reduction in the intensity and/or degree of nursing care required, or eliminates annoying manifestations of spasticity considered important by the patient.

Usual Pediatric Dose for Malignant Hyperthermia

TREATMENT of Malignant Hyperthermia (MH): 1 mg/kg IV push

• Additional IV boluses up to 10 mg/kg should be given if physiologic and metabolic abnormalities continue

Maximum Cumulative dose: 10 mg/kg

If Physiologic and Metabolic Abnormalities of MH Reappear: Repeat dosing starting with 1 mg/kg IV

Institute the following supportive measures with dantrolene therapy:

• Discontinue use of MH triggering anesthetic agents (i.e., volatile anesthetic gases and succinylcholine)
• Manage metabolic acidosis
• Institute cooling when necessary
• Administer diuretics to prevent late kidney injury due to myoglobinuria (the amount of mannitol in injectable suspension is insufficient to maintain diuresis)

Comments:

• 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.

PREVENTION of Malignant Hyperthermia (MH):
Preoperatively:

• IV: 2.5 mg/kg IV over at least 1 minute approximately 75 minutes prior to surgery; if surgery is prolonged, additional individualized doses may be needed
• Oral: 4 to 8 mg/kg/day orally in 3 or 4 divided doses for 1 or 2 days prior to surgery (last dose being given with a minimum of water approximately 3 to 4 hours before scheduled surgery)

Postoperatively:

• Following a MH Crisis: 4 to 8 mg/kg per day orally in 4 divided doses

Duration of Therapy: 1 to 3 days

Comments:

• Use for the prevention of MH should include avoiding agents that trigger MH.
• Dose adjustment of oral therapy may be made within the recommended dosage range to avoid incapacitation (weakness, drowsiness, etc.) or excessive gastrointestinal irritation (nausea and/or vomiting).

Uses:

• For the treatment of malignant hyperthermia in conjunction with appropriate supportive measures (IV)
• For the prevention of malignant hyperthermia in patients at high risk (IV and oral)

Usual Pediatric Dose for Chronic Spasticity

5 years or older:

Dosage should be titrated and individualized for maximum effect; the lowest dose compatible with optimal response is recommended: therapy should be stopped if benefits are not evident within 45 days

Initial dose: 0.5 mg/kg orally once a day for 7 days, then
0.5 mg/kg orally 3 times a day for 7 days
1 mg/kg orally 3 times a day for 7 days
2 mg/kg orally 3 times a day
Maximum dose: 100 mg orally 4 times a day

Comments:

• Maintain each dose level for 7 days during titration to determine patient's response; some patients will do better with dosing 4 times a day.
• Some patients will not respond until a higher daily dosage is achieved; improvement can be expected to manifest as a decrease in severity of spasticity that restores the ability to perform a daily function not quite attainable without therapy.
• If no further benefit is observed with the next higher dose, a decrease to the previous lower dose is recommended.
• This drug is not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders.

Use: For use controlling the manifestations of clinical spasticity resulting from upper motor neuron disorders such as spinal cord injury, stroke, cerebral palsy, or multiple sclerosis.

The decision to continue therapy on a long-term basis is justified if this drug produces a significant reduction in painful and/or disabling spasticity such as clonus, permits a significant reduction in the intensity and/or degree of nursing care required, or eliminates annoying manifestations of spasticity considered important by the patient.

Renal Dose Adjustments

No adjustments recommended

Liver Dose Adjustments

Chronic Spasticity:

• Active hepatic disease (including hepatitis and cirrhosis): Contraindicated

Dose Adjustments

Elderly: Dose selection should be cautious; use the lowest dose compatible with optimal response

Precautions

US BOXED WARNINGS: HEPATOTOXICITY (Capsules)

• This drug has the potential for hepatotoxicity, and should not be used in conditions other than those recommended. Symptomatic hepatitis (fatal and non-fatal) has been reported at various dose levels. The incidence reported in patients taking 400 mg per day is much lower than in those taking 800 mg or more per day. Even sporadic short courses of these higher dose levels within a treatment regimen markedly increased the risk of serious hepatic injury.
• Liver dysfunction as evidenced by liver enzyme elevations, has been observed in patients exposed to this drug for varying periods of time. Overt hepatitis has occurred at varying intervals after initiation of therapy, but has been most frequently observed between the 3rd and 12th month of therapy.
• The risk of hepatic injury appears to be greater in females, in patients over 35 years of age, and in patients taking other medications in addition to this drug. Spontaneous reports suggest a higher proportion of hepatic events with fatal outcome in elderly patients; however, the majority of these cases were complicated with confounding factors such as intercurrent illnesses and/or concomitant potentially hepatotoxic medications.
• This drug should be used only in conjunction with appropriate monitoring of hepatic function, including frequent determination of AST and ALT. If no observable benefit is derived after 45 days of use, therapy should be discontinued. The lowest possible effective dose for the individual patient should be prescribed.

CONTRAINDICATIONS: Oral Therapy:

• Active hepatic disease (e.g., hepatitis, cirrhosis)
• When spasticity is sustaining upright posture and balance in locomotion or maintaining increased function

CONTRAINDICATIONS: Intravenous Therapy

• None

Safety and efficacy of the oral capsules have not been established in patients younger than 5 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
IV administration; Use care to prevent extravasation into surrounding tissues

Storage requirements:

• Unreconstituted vials: Store at room temperature; avoid prolonged exposure to light
• Reconstituted vials: Store at room temperature; Use within 6 hours

Reconstitution/preparation techniques:

• There are 2 products: consult Product Insert for specific guidance
• Reconstitute vials using sterile water for injection (20 mg solution: 60 mL; 250 mg suspension: 5 mL)
• Shake vial to obtain orange-colored uniformed suspension (Ryanodex[R]) or clear solution (Dantrium[R]).
• Do not dilute or transfer the reconstituted suspension to another container to infuse (Ryanodex[R])

General:

• Prior to using this drug for chronic spasticity, it is important to establish a therapeutic goal; dose should be increased until the maximum performance compatible with dysfunction due to underlying disease is achieved.
• Because of the potential for liver damage, this drug should be stopped if benefits are not evident within 45 days.
• Ryanodex(R) injectable suspension contains mannitol 125 mg per 250 mg vial; Dantrium(R) intravenous containers 3000 mg per vial; these amounts of mannitol are insufficient to maintain diuresis, but should be taken into account.

Monitoring:

• Oral therapy: Obtain baseline liver function tests (ALT, AST, alkaline phosphatase, total bilirubin); follow AST and ALT during therapy

Patient advice:

• Patients/caregivers should understand that muscle weakness, difficulty swallowing, dizziness and somnolence may occur; patients should be provided with assistance standing and walking until their strength returns; patients should be observed while eating until risk of dysphagia has passed.
• Patients should not drive or perform other hazardous activity for up to 48 hours after IV therapy as lightheadedness may occur.
• Patients receiving oral therapy should be advised to limit sun exposure as photosensitivity reactions may occur.
• Patients/caregivers should understand the risk of hepatotoxicity and should be instructed to promptly report signs and symptoms of hepatitis.

Further information

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