Dantrolene Sodium

Skeletal muscle relaxant.108 109

General

Spasticity

• Establish therapeutic goal before initiating therapy.109 Use lowest possible effective dosage.109 Discontinue drug if beneficial effects are not attained within 45 days.109 (See Boxed Warning.)

• Subjective impressions of improvement may sometimes be confirmed by withdrawal of the drug for 2–4 days.109

Malignant Hyperthermia Crisis

• Immediately discontinue all anesthetic agents and institute IV dantrolene as soon as malignant hyperthermia crisis is recognized.108

• Monitor vital signs; employ the usual precautions associated with surgery in susceptible patients, since malignant hyperthermia may only be attenuated rather than prevented.108

Administration

Administer orally or by continuous IV infusion or rapid IV injection.108 109

Oral Administration

Administer orally 1–4 times daily.109

To prepare oral suspension containing 25 mg of dantrolene sodium per 5 mL, empty 5 100-mg capsules in 50 mL of Syrup NF, then add a solution containing 150 mg of citric acid in 10 mL of water followed by a sufficient volume of Syrup NF to make 100 mL.c Mix thoroughly before use.c

IV Administration

For solution compatibility information, see Compatibility under Stability.

For IV infusion, transfer reconstituted solution from the appropriate number of vials to plastic infusion bag.109 Do not use large glass containers; precipitate formation observed with some glass containers.108

Avoid extravasation (injection has high pH).108

Add 60 mL of sterile water for injection (without bacteriostatic agent) to vial containing 20 mg of dantrolene sodium.108 Shake vial until solution is clear.108

Although reconstituted solutions are stable for 6 hours,108 infusions preferably should be prepared immediately before use.a

Preoperative prophylaxis: Infuse IV over approximately 1 hour beginning about 1.25 hours before anticipated anesthesia.108

Treatment of malignant hyperthermia syndrome: Rapid IV injection.108

Dosage

Available as dantrolene sodium; dosage expressed in terms of the salt.108 109

Pediatric Patients

Children ≥5 years of age: 0.5 mg/kg once daily for 7 days, followed by 0.5 mg/kg 3 times daily for 7 days, then 1 mg/kg 3 times daily for 7 days, and then 2 mg/kg 3 times daily, if necessary.109 Some patients may require doses 4 times daily.109

If no additional benefit is observed at the next higher dosage, decrease dosage to the previous (lower) dosage.109

4–8 mg/kg daily in 3 or 4 divided doses for 1–2 days prior to surgery; give the last dose approximately 3–4 hours before surgery with small amount of water.109

2.5 mg/kg infused over approximately 1 hour beginning about 1.25 hours before anticipated anesthesia; may give additional individualized doses intraoperatively, if necessary.108

Initially, 1 mg/kg or more by rapid IV injection.108 Repeat dose as necessary until physiologic and metabolic abnormalities subside or a maximum total dosage of 10 mg/kg is reached.108

Average total dosage: 2.5 mg/kg.a

Repeat regimen if physiologic and metabolic abnormalities reappear.108

4–8 mg/kg daily in 4 divided doses for up to 3 days after the crisis.109

Initially, 1 mg/kg or more as clinically indicated.108 Individualize subsequent doses.108

Adults

Initially, 25 mg once daily for 7 days, followed by 25 mg 3 times daily for 7 days, then 50 mg 3 times daily for 7 days, and then 100 mg 3 times daily, if necessary.109 Some patients may require doses 4 times daily.109

If no additional benefit is observed at the next higher dosage, decrease dosage to the previous (lower) dosage.109

4–8 mg/kg daily in 3 or 4 divided doses for 1–2 days prior to surgery; give the last dose approximately 3–4 hours before surgery with small amount of water.109

2.5 mg/kg infused over approximately 1 hour beginning about 1.25 hours before anticipated anesthesia; may give additional individualized doses intraoperatively, if necessary.108

Initially, 1 mg/kg or more by rapid IV injection.108 Repeat dose as necessary until physiologic and metabolic abnormalities subside or a maximum total dosage of 10 mg/kg is reached.108

Average total dosage: 2.5 mg/kg.a

Repeat regimen if physiologic and metabolic abnormalities reappear.108

4–8 mg/kg daily in 4 divided doses for up to 3 days after the crisis.109

Initially, 1 mg/kg or more as clinically indicated.108 Individualize subsequent doses.108

Prescribing Limits

Pediatric Patients

Maximum 100 mg 4 times daily.109

Maximum 10 mg/kg.108

Adults

Maximum 100 mg 4 times daily.109

Maximum 10 mg/kg.108

Absorption

Bioavailability

Absorption following oral administration is incomplete and slow but consistent.109

Distribution

Extent

Readily crosses the placenta, with maternal and fetal whole blood concentrations approximately equal at delivery; neonatal concentrations then fall approximately 50% per day for 2 days before declining sharply.108

Plasma Protein Binding

Substantially bound to plasma proteins (mostly albumin); binding is readily reversible.108

Elimination

Metabolism

Specific metabolic pathways not established.108 May undergo hydrolysis and subsequent oxidation forming nitrophenylfuroic acid.108

Elimination Route

Specific pathways not established.108

Half-life

Approximately 4–8 hours following IV administration.108

Approximately 9 hours following oral administration in adults.109

• Causes skeletal muscle relaxation through a direct effect on skeletal muscle, probably by interfering with release of calcium from the sarcoplasmic reticulum.108 109

• Interference with calcium release from the sarcoplasmic reticulum may prevent the increase in myoplasmic calcium that activates acute catabolism of skeletal muscle cells in patients with anesthesia-induced malignant hyperthermia.108

• Has little or no effect on the contraction of cardiac or intestinal smooth muscle, except possibly at concentrations higher than those required for effects on skeletal muscle contraction.a

• Risk of hepatoxicity with oral dantrolene.108 109

• Risk of dizziness and muscle weakness; use caution when driving or operating machinery.108 109 Do not drive or operate machinery within 48 hours of receiving IV dantrolene.109

• Risk of choking and difficulty swallowing; exercise caution during meals.108

• Risk of photosensitivity reactions; limit exposure to sunlight.109

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.108 109

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, alcohol consumption, and any concomitant illnesses.108 109

• Importance of informing patients of other important precautionary information.108 109 (See Cautions.)