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Vial $148, Capsule $1.01

Dantrolene

Editor: Updated Class:

ADMINISTRATION ROUTES:

IV, PO

ALTERNATIVE NAMES:

Dantrium

ICU INDICATIONS:

  1. Malignant hyperthermia (IV route only)
  2. Control of chronic spasticity (PO route)

PRESENTATION AND ADMINISTRATION:

IV:

Reconstitute each 20 mg vial with 60 mL of Water for Injection and shake vigorously until solution is clear. Resulting concentration is 0.333 mg/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 for 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:

Dantrolene 25mg and 50 mg capsules (orange / tan)

DOSAGE:

IV:

For malignant hyperthermia only

Give as continuous IV push beginning at 1 mg/kg

Continue until response achieved or max dose 10 mg/kg total is given

May repeat if required

PO:

For chronic spasticity only

25 - 50 mg QID

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

Dose as in normal renal function

DOSAGE IN PAEDIATRICS:

IV:

For malignant hyperthermia only

Give as continuous IV push beginning at 1 mg/kg

Continue until response achieved or max dose 10 mg/kg total is given

PO:

For chronic spasticity only

0.5 - 3 mg/kg QID

CLINICAL PHARMACOLOGY:

In skeletal muscle, dantrolene dissociates the excitation-contraction coupling, probably by interfering with the release of Ca++ from the sarcoplasmic reticulum. It is hypothesised that addition of dantrolene to the 'triggered' malignant hyperthermic muscle cell reestablishes a normal level of ionised calcium in the myoplasm. Inhibition of calcium release from the sarcoplasmic reticulum by dantrolene re-establishes the myoplasmic calcium equilibrium, increasing the percentage of bound calcium

CONTRAINDICATIONS:

None

WARNINGS:

The use of dantrolene IV in the management of malignant hyperthermia crisis is not a substitute for previously known supportive measures. These measures must be individualised, 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 dantrolene 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 dantrolene therapy.

Laboratory Tests:

No tests in addition to routine ICU test are indicated

Drug/Laboratory Test Interactions:

None of note

IMPORTANT DRUG INTERACTIONS IN ICU:

The combination of therapeutic doses of IV dantrolene sodium and verapamil in anaesthetised pigs has resulted in ventricular fibrillation and cardiovascular collapse in association with marked hyperkalaemia. 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 dantrolene use such as hepatitis, seizures, and pleural effusion with pericarditis, have been reasonably associated with short-term dantrolene IV therapy.

The following have been reported in patients receiving oral dantrolene: hepatitis, seizures, pericarditis, aplastic anaemia, leukopaenia, lymphocytic lymphoma, and heart failure