No

Skeletal Muscle Relaxant

Treatment of spasticity associated with spinal cord injury, stroke, cerebral palsy, or multiple sclerosis; also used as treatment of malignant hyperthermia

C

Active hepatic disease; should not be used where spasticity is used to maintain posture or balance

Use with caution in patients with impaired cardiac function or impaired pulmonary function; has potential for hepatotoxicity; overt hepatitis has been most frequently observed between the third and twelfth month of therapy; hepatic injury appears to be greater in females and in patients >35 years of age

>10%:

Central nervous system: Drowsiness, dizziness, lightheadedness, fatigue

Dermatologic: Rash

Gastrointestinal: Diarrhea (mild), nausea, vomiting

Neuromuscular & skeletal: Muscle weakness

1% to 10%:

Cardiovascular: Pleural effusion with pericarditis

Central nervous system: Chills, fever, headache, insomnia, nervousness, mental depression

Gastrointestinal: Diarrhea (severe), constipation, anorexia, stomach cramps

Ocular: Blurred vision

Respiratory: Respiratory depression

<1%: Seizures, confusion, hepatitis

Symptoms of overdose include CNS depression, hypotension, nausea, vomiting

For decontamination, lavage/activated charcoal with cathartic; do not use ipecac; hypotension can be treated with isotonic I.V. fluids with the patient placed in the Trendelenburg position; dopamine or norepinephrine can be given if hypotension is refractory to above therapy

Increased toxicity: Estrogens (hepatotoxicity), CNS depressants (sedation), MAO inhibitors, phenothiazines, clindamycin (increased neuromuscular blockade), verapamil (hyperkalemia and cardiac depression), warfarin, clofibrate and tolbutamide

Reconstitute vial by adding 60 mL of sterile water for injection USP ( not bacteriostatic water for injection); protect from light; use within 6 hours; avoid glass bottles for I.V. infusion

Acts directly on skeletal muscle by interfering with release of calcium ion from the sarcoplasmic reticulum; prevents or reduces the increase in myoplasmic calcium ion concentration that activates the acute catabolic processes associated with malignant hyperthermia

Absorption: Slow and incomplete from GI tract

Metabolism: Slowly in liver

Half-life: 8.7 hours

Elimination: 25% excreted in urine as metabolites and unchanged drug, 45% to 50% excreted in feces via bile

Spasticity: Oral:

Children: Initial: 0.5 mg/kg/dose twice daily, increase frequency to 3-4 times/day at 4- to 7-day intervals, then increase dose by 0.5 mg/kg to a maximum of 3 mg/kg/dose 2-4 times/day up to 400 mg/day

Adults: 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: Children and Adults:

Oral: 4-8 mg/kg/day in 4 divided doses

Preoperative prophylaxis: Begin 1-2 days prior to surgery with last dose 3-4 hours prior to surgery

I.V.: 1 mg/kg; may repeat dose up to cumulative dose of 10 mg/kg (mean effective dose is 2.5 mg/kg), then switch to oral dosage

Preoperative: 2.5 mg/kg ~11/4 hours prior to anesthesia and infused over 1 hour with additional doses as needed and individualized

Alcohol: Additive CNS effects, avoid use

Motor performance should be monitored for therapeutic outcomes; nausea, vomiting, and liver function tests should be monitored for potential hepatotoxicity; intravenous administration requires cardiac monitor and blood pressure monitor

serum AST (SGOT), ALT (SGPT), alkaline phosphatase, LDH, BUN, and total serum bilirubin

Drowsiness is common; may cause insomnia, nervousness, confusion, or depression

Concurrent use with psychotropic may result in additive sedation; use to treat neuroleptic malignant syndrome

No information available to require special precautions

No effects or complications reported

Take exactly as directed. Do not increase dose or discontinue without consulting prescriber. Do not use alcohol, prescriptive or OTC antidepressants, sedatives, or pain medications without consulting prescriber. You may experience drowsiness, dizziness, lightheadedness (avoid driving or engaging in tasks that require alertness until response to drug is known); nausea or vomiting (small, frequent meals, frequent mouth care, or sucking hard candy may help); or diarrhea (buttermilk, boiled milk, or yogurt may help). Report excessive confusion; drowsiness or mental agitation; chest pain, palpitations, or difficulty breathing; skin rash; or vision disturbances. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

36 vials needed for adequate hyperthermia therapy; exercise caution at meals on the day of administration because difficulty swallowing and choking has been reported; avoid extravasation as is a tissue irritant

Capsule, as sodium: 25 mg, 50 mg, 100 mg

Powder for injection, as sodium: 20 mg

A 5 mg/mL suspension may be made by adding five 100 mg capsules to a citric acid solution (150 mg citric acid powder in 10 mL water) and then adding syrup to a total volume of 100 mL; stable 2 days in refrigerator

Britt BA, "Dantrolene," Can J Anaesth, 1984, 31(1):61-75.

Guerrero RM and Shifrar KA, "Diagnosis and Treatment of Neuroleptic Malignant Syndrome," Clin Pharm, 1988, 7(9):697-701.

May DC, Morris SW, Stewart RM, et al, "Neuroleptic Malignant Syndrome: Response to Dantrolene Sodium," Ann Intern Med, 1983, 98(2):183-4.

Nahata MC and Hipple TF, Pediatric Drug Formulations, 1st ed, Harvey Whitney Books Co, 1990.

Rosenberg MR and Green M, "Neuroleptic Malignant Syndrome. Review of Response to Therapy," Arch Intern Med, 1989, 149(9):1927-31.

Rubin AS and Zablocki AD, "Hyperkalemia, Verapamil, and Dantrolene," Anesthesiology, 1987, 66(2):248-9.

Tayeb OS, "A Serious Interaction of Dantrolene and Theophylline," Vet Hum Toxicol, 1990, 32(5):442-3.

Ward A, Chaffman MO, and Sorkin EM, "Dantrolene: A Review of Its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Use in Malignant Hyperthermia, the Neuroleptic Malignant Syndrome and an Update of Its Use in Muscle Spasticity," Drugs, 1986, 32(2):130-68.