Dantrolene

Dantrolene

ADMINISTRATION ROUTES:

  • IV, PO

ALTERNATIVE NAMES:

  • Dantrium

ICU INDICATIONS:

  1. malignant hyperthermia (IV therapy only)
  2. control of chronic spasticity (PO therapy)

PRESENTATION AND ADMINISTRATION:

  • IV:
    Reconstitute each 20mg vial with 60ml of Water for Injection and shake vigorously until solution is clear (concentration is 0.333mg/ml). A large bore, vented needle (as found in the malignant hyperthermia box in theatre) will hasten the transfer of diluent and reconstituted solution.
    Inspect carefully for cloudiness or precipitation before administration.
    Compatible only with Water from Injection. Do not mix with other fluid or drugs.
    Reconstituted solution should be stored at room temperature and must be protected from direct light. Use solution within 6 hours of reconstitution.
  • PO:
    Dantrium 25mg and 50mg capsules (orange / tan)

DOSAGE:

  • IV:
    Administer solution by continuous IV push beginning at 1mg/kg and continuing until response is achieved or a maximum cumulative dose of 10mg/kg is reached. May repeat if required.
  • PO:
    Oral therapy is not appropriate for treatment of malignant hyperthermia. The usual dose for chronic spasticity is between 25mg daily and 50mg four times a day.

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

  • Dose as in normal renal function

DOSAGE IN PAEDIATRICS:

  • IV:
    Administer solution by continuous IV push beginning at 1mg/kg and continuing until response is achieved or a maximum cumulative dose of 10mg/kg is reached. May repeat if required.
  • PO:
    For spasticity: 0.5mg/kg-3mg/kg 6 hourly

CLINICAL PHARMACOLOGY:

  • In skeletal muscle, Dantrium dissociates the excitation-contraction coupling, probably by interfering with the release of Ca++ from the sarcoplasmic reticulum. It is hypothesized that addition of Dantrium to the “triggered” malignant hyperthermic muscle cell reestablishes a normal level of ionized calcium in the myoplasm. Inhibition of calcium release from the sarcoplasmic reticulum by Dantrium reestablishes the myoplasmic calcium equilibrium, increasing the percentage of bound calcium.

CONTRAINDICATIONS:

  • None.

WARNINGS

  • The use of Dantrium IV 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.

PRECAUTIONS

  • General:
    Care must be taken to prevent extravasation of Dantrium solution into the surrounding tissues due to the high pH of the intravenous formulation. Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may occur with Dantrium therapy.
  • Laboratory Tests:
    No tests in addition to routine ICU test are indicated
  • Drug/Laboratory Test Interactions:
    None of note

IMPORTANT DRUG INTERACTIONS FOR THE ICU

  • The combination of therapeutic doses of IV dantrolene sodium and verapamil in anesthetized swine has resulted in ventricular fibrillation and cardiovascular collapse in association with marked hyperkalemia. It is recommended that the combination of IV dantrolene sodium and calcium channel blockers, such as verapamil, not be used together during the management of malignant hyperthermia crisis until the relevance of these findings to humans is established. Administration of dantrolene may potentiate vecuronium-induced neuromuscular block.

ADVERSE REACTIONS

  • Body as a whole:
    Erythematous rash, anaphylaxis
  • Central nervous system:
    Weakness
  • Cardiovascular system:
    Pulmonary oedema

None of the serious reactions occasionally reported with long-term oral Dantrium use, such as hepatitis, seizures, and pleural effusion with pericarditis, have been reasonably associated with short-term Dantrium IV therapy.
The following events have been reported in patients receiving oral dantrolene:
Hepatitis, seizures, pericarditis, aplastic anemia, leukopenia, lymphocytic lymphoma, and heart failure.

Critical Care Drug Manual

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