dantrolene (Dantrium)

Introduction

Tradename: Dantrium.

Indications

• control of muscle spasticity & myalgias
  • upper motor neuron disorders
    • stroke
    • spinal cord injury
    • multiple sclerosis
    • cerebral palsy
  • malignant hyperthermia
    • neuroleptic malignant syndrome
  • Duchenne muscular dystrophy

Contraindications

• active hepatic disease
• do NOT use when spasticity is necessary to maintain posture

pregnancy category = c

safety in lactation = -

Dosage

• spasticity (adults)
  • start 25 mg PO QD for 4-7 days
  • increase to 25 mg BID-QID
  • max 400 mg/day divided BID/QID.
  • discontinue if benefits not seen within 45 days
• spasticity (children)
  • 0.5 mg/kg PO BID
  • increase to 0.5 mg/kg TID-QID
  • increase by 0.5 mg/kg to a max of 3 mg/kg BID-QID
  • maximum daily dose of 400 mg
• surgery
  • 4-8 mg/kg/day PO in 3-4 divided doses for 1-2 days prior to surgery
  • last oral dose 3-4 hours prior to surgery
  • 2.5 mg/kg IV 1-2 hours prior to surgery infused over 1 hour
  • additional IV doses may be given PRN
• malignant hyperthermia
  • discontinue anesthetics
  • 100% oxygen
  • 1 mg/kg rapid IV push
  • 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.

Pharmacokinetics

• highly bound to plasma proteins
• metabolized by liver to 5-OH dantrolene
• elimination 1/2life
  • 9 hours after oral dose
  • 4-8 hours after IV dose

elimination via liver

elimination via kidney

1/2life = 4-9 hours

Monitor

liver function tests, baseline & throughout therapy

Adverse effects

• common (> 10%)
  • diarrhea (mild), drowsiness, dizziness, fatigue, nausea/vomiting
• 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
• uncommon (< 1%)
  • seizures, confusion, hepatitis
• other
  • hypersensitivity reactions (may be fatal)
  • hirsuitism (uncommon)
  • slurred speech (uncommon)
  • after IV administration
    • pulmonary edema
    • thrombophlebitis
    • urticaria

Drug interactions

• concurrent administration of verapamil increases risk of hyperkalemia & myocardial depression
• estrogens increase hepatotoxicity
• coumadin may displace dantrolene from plasma proteins

Laboratory

• specimen: serum
• methods: fluorometry (measures 5-hydroxydantrolene), HPLC

Mechanism of action

• direct action on skeletal muscle
• produces muscle relaxation by effecting contractile response
• dissociates excitation-contraction coupling by interfering with release of Ca+2 from sarcoplasmic reticulum

More general terms

• antispasmodic
• skeletal muscle relaxant (tranquilizer)
• hydantoin; glycolylurea

Additional terms

• malignant hyperthermia/hyperthermia of anesthesia

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2951
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2952
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=32731