Muscle relaxants

Intrathecal: Test dose: 50-100 mcg, doses >50 mcg should be given in 25 mcg increments, separated by 24 hours. A screening dose of 25 mcg may be considered in very small patients. Patients not responding to screening dose of 100 mcg should not be considered for chronic infusion/implanted pump. Maintenance: After positive response to test dose, a maintenance intrathecal infusion can be administered via an implanted intrathecal pump. Initial dose via pump: Infusion at a 24-hourly rate dosed at twice the test dose. Avoid abrupt discontinuation.

Supplied: Injection (soln) intrathecal [preservative free] (Lioresal®): 50 mcg/mL (1 mL); 500 mcg/mL (20 mL); 2000 mcg/mL (5 mL). Tablet: 10 mg, 20 mg

PK: Onset of action: 3-4 days. Peak effect: 5-10 days.

HEPATIC IMPAIRMENT
Mild: 5 mg 3 times/day; use with caution and titrate slowly.
Moderate to severe: Use not recommended.

PK: Onset of action: ~1 hour.

For POST CRISIS FOLLOW-UP OF MALIGNANT HYPERTHERMIA, if oral dantrolene cannot be administered, intravenous dantrolene beginning with 1 milligram/kilogram is recommended. This may be increased as the clinical situation dictates.

Spasticity: Oral: 25 mg/day to start, increase frequency to 2-4 times/day, then increase dose by 25 mg every 4-7 days to a maximum of 100 mg 2-4 times/day or 400 mg/day.

Malignant hyperthermia:
- Preoperative prophylaxis: Oral: 4-8 mg/kg/day in 4 divided doses, begin 1-2 days prior to surgery with last dose 3-4 hours prior to surgery. I.V.: 2.5 mg/kg ~1.25 hours prior to anesthesia and infused over 1 hour with additional doses as needed and individualized.
- Crisis: I.V.: 2.5 mg/kg; may repeat dose up to cumulative dose of 10 mg/kg; if physiologic and metabolic abnormalities reappear, repeat regimen.

- Postcrisis follow-up: Oral: 4-8 mg/kg/day in 4 divided doses for 1-3 days; I.V. dantrolene may be used when oral therapy is not practical; individualize dosage beginning with 1 mg/kg or more as the clinical situation dictates.

Neuroleptic malignant syndrome (unlabeled use): IV: 1 mg/kg; may repeat dose up to maximum cumulative dose of 10 mg/kg, then switch to oral dosage. Administration - IV: Therapeutic or emergency dose can be administered with rapid continuous I.V. push. Follow-up doses should be administered over 2-3 minutes.

Supplied: 25 mg, 50 mg, 100 mg capsule. Injection (powder for reconstitution): 20 mg vial.

Drug UPDATES:  RYANODEX ® (dantrolene sodium) for injectable suspension, for intravenous use.
Initial U.S. Approval: 1974
[Drug information  /  PDF]  
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

U.S. Approval:  2014

Mechanism of Action: In isolated nerve-muscle preparation, dantrolene has been shown to produce relaxation by affecting the contractile response of the muscle at a site beyond the myoneural junction. In skeletal muscle, dantrolene dissociates the excitation-contraction coupling, probably by interfering with the release of Ca++ from the sarcoplasmic reticulum.

In the anesthetic-induced malignant hyperthermia syndrome, evidence points to an intrinsic abnormality of skeletal muscle tissue. In affected humans, it has been postulated that "triggering agents" (e.g., general anesthetics and depolarizing neuromuscular blocking agents) produce a change within the cell which results in an elevated myoplasmic calcium. This elevated myoplasmic calcium activates acute cellular catabolic processes that cascade to the malignant hyperthermia crisis.
The addition of dantrolene to the "triggered" malignant hyperthermic muscle cell may reestablish a normal level of ionized calcium in the myoplasm. Inhibition of calcium release from the sarcoplasmic reticulum by dantrolene reestablishes the myoplasmic calcium equilibrium, increasing the percentage of bound calcium. In this way, physiologic, metabolic, and biochemical changes associated with the malignant hyperthermia crisis may be reversed or attenuated.

INDICATIONS AND USAGE:
RYANODEX is a skeletal muscle relaxant drug indicated for:
Treatment of malignant hyperthermia in conjunction with appropriate supportive measures.
Prevention of malignant hyperthermia in patients at high risk.
HOW SUPPLIED: For injectable suspension: 250 mg of lyophilized powder in a single-use vial for reconstitution

Dosing: ELDERLY — Muscle spasm: Oral: Initial: 500 mg 4 times/day; titrate to response

Tetanus: I.V.: Initial dose: 1-3 g; may repeat dose every 6 hours until oral dosing is possible; injection should not be used for more than 3 consecutive days

Administration:  (Injection:)
I.M.: A maximum of 5 mL can be administered into each gluteal region.
I.V.: Maximum rate: 3 mL/minute; should not be used for more than 3 consecutive days; may be administered undiluted. Monitor closely for extravasation. Administer I.V. while in recumbent position. Maintain position 15-30 minutes following infusion.