tolcapone (Tasmar)

Indications

• adjunct agent used with Sinemet for treatment of Parkinson's disease with sign/symptoms of end of dose "wearing off"
• parkinsonism

Dosage

• start 100 mg PO QD
• increase to 100-200 mg PO TID
• keep 1st daily L-dopa dose the same
• generally decreases total L-dopa dose by 20-30%

Pharmacokinetics

• bioavailability is 10-20%
• protein binding > 99%
• elimination 1/2life is 2-3 hours

Monitor

• liver function tests every 2 weeks for the 1st year, monthly for the next 6 months, every 2 months thereafter

Adverse effects

• fulminant hepatotoxicity associated with death
  • 3 deaths reported as of 2004
  • risk is < 1 in 20,000
• other
  • dyskinesia, nausea, sleep disorder, dystonia, anorexia, muscle cramps, orthostasis, somnolence, diarrhea, confusion, dizziness, headache, hallucinations, vomiting, constipation, fatigue, upper respiratory tract infection, falls, sweating, urinary tract infection, xerostomia, abdominal pain, urine discoloration

Drug interactions

• avoid non-selective MAO inhibitors (selegiline, MAO-B inhibitor is OK)
• drugs metabolized by COMT
  • isoproterenol, epinephrine, norepinephrine, dopamine, dobutamine, alpha-methyldopa, apomorphine, isoetharine, bitolterol

Mechanism of action

• inhibits catechol-O-methyltransferase
• decreases L-dopa clearance
• both peripheral & central actions
• more potent than entacapone

More general terms

• pharmacologic agents for treatment of Parkinson's disease
• enzyme inhibitor

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4659569
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=71361