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entacapone (Comtan)

Indications: - Parkinson's disease - adjunct agent used with Sinemet for sign/symptoms of end of dose "wearing off" - parkinsonism Dosage: 1) 200 mg with sinemet 2) maximum 1600 mg/day Tablets: 200 mg. Pharmacokinetics: 1) rapidly absorbed; unaffected by food 2) bioavailability 35% 3) protein binding 96-98%, mainly albumin 4) metabolized by isomerization to cis isomer followed by glucuronidation 5) t1/2 of 2.4 hours Adverse effects: 1) cardiovascular: - orthostatic hypotension, syncope - no increased risk of cardiovascular events [4] 2) central nervous system: dizziness, fatigue, hallucinations, anxiety, somnolence, agitation, hyperpyrexia & confusion (resembling neuroleptic malignant syndrome) 3) neuromuscular: dyskinesia, hyperkinesia, hypokinesia, back pain, weakness, rhabdomyolysis 4) gastrointestinal: nausea, diarrhea, abdominal pain, constipation, vomiting, xerostomia, dyspepsia, flatulence, gastritis, taste disturbance [3]* 5) genitourinary: urine discoloration (orange), retroperitoneal fibrosis 6) skin: purpura 7) respiratory: dyspnea, pulmonary fibrosis [3] * no hepatotoxicity demonstrated Overdose: no reported cases [3] Drug interactions: 1) avoid non-selective MAO inhibitors (selegiline, MAO-B inhibitor is OK) 2) drugs metabolized by COMT - isoproterenol, epinephrine, norepinephrine, dopamine, dobutamine, alpha-methyldopa, apomorphine, isoetharine, bitolterol 3) drugs which interfere with glucuronidation: - probenecid, cholestyramine, erythromycin, rifampicin, ampicillin, chloramphenicol Mechanism of action: 1) reversible inhibitor of catechol-O-methyltransferase (COMT) 2) decreases peripheral L-dopa clearance (no central action) 3) inhibits cyt P450 isozymes only at high concentrations

General

enzyme inhibitor pharmacologic agents for treatment of Parkinson's disease

Properties

INHIBITS: catechol O-methyl transferase

Database Correlations

PUBCHEM correlations

References

  1. Kaiser Permanente Pharmacy update
  2. Bronstein J, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
  3. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  4. FDA Safety Alert. Oct 26, 2015 Entacapone: Drug Safety Communication - FDA Review Found No Increased Cardiovascular Risks. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm469162.htm
  5. Department of Veterans Affairs, VA National Formulary - restricted to PADRECC Centers

Component-of

carbidopa/entacapone/levodopa (Stalevo)