entacapone (Comtan)

Indications

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

Dosage

• 200 mg with sinemet
• maximum 1600 mg/day

Tablets: 200 mg.

Pharmacokinetics

• rapidly absorbed; unaffected by food
• bioavailability 35%
• protein binding 96-98%, mainly albumin
• metabolized by isomerization to cis isomer followed by glucuronidation
• t1/2 of 2.4 hours

Adverse effects

• cardiovascular:
  • orthostatic hypotension, syncope
  • no increased risk of cardiovascular events
• central nervous system: dizziness, fatigue, hallucinations, anxiety, somnolence, agitation, hyperpyrexia & confusion (resembling neuroleptic malignant syndrome)
• neuromuscular: dyskinesia, hyperkinesia, hypokinesia, back pain, weakness, rhabdomyolysis
• gastrointestinal: nausea, diarrhea, abdominal pain, constipation, vomiting, xerostomia, dyspepsia, flatulence, gastritis, taste disturbance*
• genitourinary: urine discoloration (orange), retroperitoneal fibrosis
• skin: purpura
• respiratory: dyspnea, pulmonary fibrosis

* no hepatotoxicity demonstrated

Overdose: no reported cases

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
• drugs which interfere with glucuronidation:
  • probenecid, cholestyramine, erythromycin, rifampicin, ampicillin, chloramphenicol

Mechanism of action

• reversible inhibitor of catechol-O-methyltransferase (COMT)
• decreases peripheral L-dopa clearance (no central action)
• inhibits cyt P450 isozymes only at high concentrations

More general terms

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

Component of

• carbidopa/entacapone/levodopa (Stalevo)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5281081
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60804