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dantrolene (Dantrium)
Tradename: Dantrium.
Indications:
- control of muscle spasticity & myalgias
a) upper motor neuron disorders
1] stroke
2] spinal cord injury
3] multiple sclerosis
4] cerebral palsy
b) malignant hyperthermia
- neuroleptic malignant syndrome
c) Duchenne muscular dystrophy [5]
Contraindications:
1) active hepatic disease
2) do NOT use when spasticity is necessary to maintain posture
Dosage:
1) spasticity (adults)
a) start 25 mg PO QD for 4-7 days
b) increase to 25 mg BID-QID
c) max 400 mg/day divided BID/QID.
d) discontinue if benefits not seen within 45 days
2) spasticity (children)
a) 0.5 mg/kg PO BID
b) increase to 0.5 mg/kg TID-QID
c) increase by 0.5 mg/kg to a max of 3 mg/kg BID-QID
d) maximum daily dose of 400 mg
3) surgery
a) 4-8 mg/kg/day PO in 3-4 divided doses for 1-2 days prior to surgery
b) last oral dose 3-4 hours prior to surgery
c) 2.5 mg/kg IV 1-2 hours prior to surgery infused over 1 hour
d) additional IV doses may be given PRN
4) malignant hyperthermia
a) discontinue anesthetics
b) 100% oxygen
c) 1 mg/kg rapid IV push
d) continue IV pushes until symptoms subside or cumlutative dose of 10 mg/kg is reached
Tabs: 25, 50, 100 mg.
Powder for injection: 20 mg.
Monitor: liver function tests, baseline & throughout therapy
Pharmacokinetics:
1) highly bound to plasma proteins
2) metabolized by liver to 5-OH dantrolene
3) elimination 1/2life
a) 9 hours after oral dose
b) 4-8 hours after IV dose
Adverse effects:
1) common (> 10%)
- diarrhea (mild), drowsiness, dizziness, fatigue, nausea/vomiting
2) less common (1-10%)
- blurred vision, fever/chills, severe diarrhea, constipation, headache, anorexia, insomnia, nervousness, respiratory depression, mental depression, pleural effusion with pericarditis, abdominal cramps
3) uncommon (< 1%)
- seizures, confusion, hepatitis
4) other
- hypersensitivity reactions (may be fatal)
- hirsuitism (uncommon)
- slurred speech (uncommon)
- after IV administration
- pulmonary edema
- thrombophlebitis
- urticaria
Drug interactions:
1) concurrent administration of verapamil increases risk of hyperkalemia & myocardial depression
2) estrogens increase hepatotoxicity
3) coumadin may displace dantrolene from plasma proteins
Laboratory:
1) specimen: serum
2) methods: fluorometry (measures 5-hydroxydantrolene), HPLC
Mechanism of action:
1) direct action on skeletal muscle
2) produces muscle relaxation by effecting contractile response
3) dissociates excitation-contraction coupling by interfering with release of Ca+2 from sarcoplasmic reticulum
Related
malignant hyperthermia/hyperthermia of anesthesia
General
antispasmodic
hydantoin; glycolylurea
skeletal muscle relaxant (tranquilizer)
Properties
MISC-INFO: elimination route LIVER
KIDNEY
1/2life 4-9 HOURS
therapeutic-range 1.0-3.0 UG/ML
toxic-range >5.0 UG/ML
pregnancy-category C
safety in lactation -
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998
Department of Veterans Affairs, VA National Formulary
- restricted to spinal cord injury, neurology, & rehabilitation
- Kaiser Permanente Northern California Regional Drug
Formulary, 1998
- Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed.,
W.B. Saunders, 1995
- Deprecated Reference