Tolcapone

Class: Catechol-O-Methyltransferase (COMT) Inhibitors
VA Class: CN500
Chemical Name: (3,4-Dihydroxy-5-nitrophenyl)(4-methylphenyl)-methanone
Molecular Formula: C14H11NO5
CAS Number: 134308-13-7
Brands: Tasmar

Warning(s)

  • Tolcapone should not be initiated until the clinician has fully explained the risks and the patient (or representative) has provided written informed consent.1

  • Use with caution in patients with severe dystonia or dyskinesia.1 (See Rhabdomyolysis under Cautions.)

  • Hepatotoxicity
  • Risk of potentially fatal, acute fulminant hepatic failure.1 30 31 32 Incidence may be 10- to 100-fold higher than the background incidence in the general population.1 32

  • Generally reserve tolcapone therapy for patients with parkinsonian syndrome receiving levodopa/carbidopa who are experiencing symptom fluctuations and are not responding adequately to or are not candidates for other adjunctive therapies (e.g., ergot- and nonergot-derivative dopamine receptor agonists, selegiline).1 30 31 32

  • Do not initiate tolcapone in patients with clinical evidence of active liver disease, ALT or AST concentrations exceeding the ULN, or any other evidence of hepatocellular dysfunction.1

  • Discontinue tolcapone if the patient does not experience symptomatic improvement within 3 weeks of initiating therapy.1

  • Discontinue tolcapone if aminotransferase concentrations exceed the ULN or if clinical manifestations suggest the onset of hepatic failure (e.g., persistent nausea, fatigue, lethargy, anorexia, jaundice, dark urine, pruritus, upper right quadrant tenderness).1

  • Advise patients of the need for self-monitoring for signs or symptoms of liver disease.1

  • Patients who develop evidence of hepatocellular injury while receiving tolcapone and in whom such therapy is discontinued for any reason may be at increased risk for hepatic injury if tolcapone is reintroduced.1 Retreatment with tolcapone ordinarily should not be considered in such patients.1

  • Perform appropriate tests to exclude hepatic disease prior to initiation of therapy1 and monitor patients receiving tolcapone for evidence of emergent liver injury.1

  • Evaluate serum AST and ALT at baseline, every 2 weeks during the first year of therapy, every 4 weeks during the next 6 months of therapy, and every 8 weeks thereafter.1 If dosage is increased to 200 mg 3 times daily, determine serum AST and ALT prior to increasing the dosage and then at the same frequency as that recommended when therapy is initiated.1

  • Not known whether baseline and periodic monitoring of liver enzymes will prevent the occurrence of fulminant tolcapone-induced hepatic failure; however, frequent laboratory monitoring for evidence of hepatocellular injury is considered essential.1 Early detection of drug-induced hepatic injury along with immediate discontinuance of the suspect drug is believed to enhance the likelihood for recovery.1 Baseline monitoring is recommended, since patients with preexisting liver disease may be more vulnerable to hepatotoxins.1

Introduction

Reversible catechol-O-methyltransferase (COMT) inhibitor.1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17 18 19 28

Uses for Tolcapone

Parkinsonian Syndrome

Adjunct to levodopa/carbidopa therapy for the symptomatic treatment of parkinsonian syndrome; concomitant administration of tolcapone with levodopa and a decarboxylase inhibitor results in more sustained plasma levodopa concentrations compared with administration of levodopa and a decarboxylase inhibitor.1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17 18 19 23 26 28

Slideshow: Parkinson’s Disease - 10 Clinical Fast Facts

Generally reserve therapy for patients with parkinsonian syndrome receiving levodopa/carbidopa who are experiencing symptom fluctuations and are not responding adequately to or are not candidates for other adjunctive therapies (e.g., ergot- and nonergot-derivative dopamine receptor agonists, selegiline).1 31 32 (See Boxed Warning.)

Tolcapone Dosage and Administration

General

  • Symptomatic improvement generally is evident within 3 weeks following initiation of tolcapone.1 7 Discontinue tolcapone if the patient fails to show symptomatic improvement within 3 weeks of initiating therapy.1 (See Boxed Warning.)

  • Concomitant Levodopa/Carbidopa Therapy
  • Administer in conjunction with levodopa/carbidopa (conventional or extended-release preparations).1 9

  • To optimize patient response, reductions in the daily levodopa/carbidopa dosage may be necessary.1 6 7 9 16 28 In clinical trials, most patients receiving levodopa dosages >600 mg daily or with moderate to severe dyskinesia prior to initiation of tolcapone required reduction of levodopa dosage (average reduction: about 30%).1 6 7 9 16 23

  • Discontinuance of Tolcapone
  • Discontinuance or abrupt dosage reduction may lead to reemergence of signs and symptoms of parkinsonian syndrome or a symptom complex resembling neuroleptic malignant syndrome (e.g., hyperpyrexia, confusion).1

  • If tolcapone is discontinued, monitor the patient closely and adjust the dosage of dopaminergic therapy, if needed.1

  • If hyperpyrexia or severe rigidity occurs following drug discontinuance, the differential diagnosis should include the possibility of a symptom complex resembling neuroleptic malignant syndrome.1

  • Tapering the dosage of tolcapone has not been systematically evaluated;1 however, reducing the frequency to twice or once daily prior to discontinuance may not prevent these events, since the duration of COMT inhibition associated with tolcapone therapy is 5–6 hours or longer.1 2 4 5 8

Administration

Oral Administration

Administer orally in 3 equally divided doses daily1 6 7 9 16 23 28 without regard to meals.1

In clinical studies, the first dose of the day was administered together with the first dose of the day of levodopa/carbidopa; subsequent doses of tolcapone are administered 6 and 12 hours later.1 6 7 9 28

Dosage

Adults

Parkinsonian Syndrome
Oral

Usual dosage: 100 mg 3 times daily.1 28

Reserve higher dosage (200 mg 3 times daily) for situations when the anticipated incremental benefit is justified.1 If the patient fails to show the expected clinical benefit while receiving 200 mg 3 times daily for 3 weeks, discontinue the drug.1 (See Hepatic Effects under Cautions.)

Special Populations

Renal Impairment

Dosage adjustment not required in patients with mild to moderate renal impairment (Clcr >30 mL/minute).1 Safety not evaluated in patients with Clcr <25 mL/minute.1

Cautions for Tolcapone

Contraindications

  • Liver disease.1

  • Patients in whom tolcapone was discontinued because of evidence of tolcapone-induced hepatocellular injury.1

  • History of nontraumatic rhabdomyolysis.1

  • History of drug-related hyperpyrexia and confusion.1

  • Known hypersensitivity to tolcapone or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Hepatic Effects

Risk of potentially fatal, acute fulminant hepatic failure.1 30 31 32 (See Boxed Warning.)

Increases in ALT reported more frequently in patients receiving tolcapone 200 mg 3 times daily than in those receiving 100 mg 3 times daily; not known whether the risk of fulminant hepatic failure is increased in patients receiving the higher dosage.1

Frequency of aminotransferase elevations greater in women than men.1

In clinical studies, aminotransferase elevations generally occurred 6 weeks to 6 months following initiation of therapy; concentrations generally returned to baseline within 1–3 months in about 50% of patients who continued tolcapone therapy and within 2–3 weeks up to 1–2 months in patients who discontinued the drug.1 7 16 However, rapid deterioration30 and death1 30 31 32 can occur despite drug discontinuance.30

MAO Inhibitors

Concomitant administration with a nonselective MAO inhibitor (e.g., phenelzine, tranylcypromine) could result in inhibition of the 2 principal pathways of catecholamine metabolism (i.e., metabolism by COMT and MAO1 2 3 4 5 6 7 8 9 10 13 ).1 Avoid concomitant administration with a nonselective MAO inhibitor;1 28 may administer tolcapone concomitantly with a selective inhibitor of MAO-B (e.g., selegiline).1 19 (See Interactions.)

General Precautions

Orthostatic Hypotension and Syncope

Increased occurrence of orthostatic instability1 2 3 6 10 13 15 16 in patients receiving tolcapone in combination with levodopa and a decarboxylase inhibitor relative to patients receiving levodopa and a decarboxylase inhibitor (17 versus 14%).1 16 Mechanism not fully established, but an increase would be expected because dopaminergic therapy in patients with parkinsonian syndrome is associated with orthostatic hypotension and tolcapone increases systemic exposure to levodopa.1

Orthostatic hypotension usually is asymptomatic;1 however, patients with orthostatic instability at baseline are more likely than patients without symptoms to experience orthostatic hypotension.1 No apparent increase in the incidence of orthostatic hypotension in patients receiving a dopamine agonist or selegiline at baseline.1 19

Possible syncope;1 reported more frequently in patients who had an episode of documented hypotension than in those who did not have an episode of documented hypotension.1

Diarrhea

Possible diarrhea,1 2 4 5 7 9 15 16 generally mild to moderate1 7 but can be severe and result in hospitalization.1

Generally occurs during the first 6–12 weeks of therapy but may occur as early as 2 weeks or as late as several months following initiation of therapy.1 7 16

Frequently is associated with anorexia, is dose related, and resolves with continued therapy or following drug discontinuance.1 7 15 16

Patients experiencing persistent diarrhea should be evaluated by appropriate clinical and laboratory studies, including fecal occult blood studies.1

Hallucinations

Hallucinations1 6 9 10 13 15 16 reported in 8–10% of patients receiving tolcapone in clinical studies, required hospitalization in up to 1.7% of patients, and resulted in drug discontinuance in 1–1.4% of patients.1 9 15

Hallucinations generally occur within first 2 weeks of therapy; are commonly accompanied by confusion and, less commonly, insomnia and excessive dreaming; and occur more frequently in patients ≥75 years of age.1

Dyskinesia

Addition of tolcapone may exacerbate levodopa-associated dyskinesias.1 2 6 7 9 15 16 26 Usually occurs within 24 hours after initiating tolcapone and is controlled by reducing the levodopa dosage by 20–30%.1 2 6 7 9 16 26 However, some patients continue to experience frequent dyskinesias after reduction of levodopa dosage.1

Rhabdomyolysis

Severe rhabdomyolysis,1 including multiorgan system failure progressing to death, reported rarely.1 Causal relationship not established.1

Severe, prolonged motor activity (e.g., dyskinesia) may account for rhabdomyolysis; however, some cases included fever, altered consciousness, and muscular rigidity and resembled neuroleptic malignant syndrome.1

Use with caution in patients with severe dystonia or dyskinesia.1

Renal Effects

High incidence of proximal tubule cell damage (degeneraton, single cell necrosis, hyperplasia, karyocytomegaly, atypical nuclei) in rats receiving tolcapone for 1 or 2 years at dosages ≥6 times the recommended human dosage; not associated with changes in clinical chemistry values.1 No established method for monitoring for occurrence of such lesions in humans.1 Species-specific mechanism postulated, but studies to confirm this theory not conducted.1

Possible hematuria.1 28

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome has occurred in patients receiving psychotherapeutic agents and in patients with parkinsonian syndrome during withdrawal of dopaminergic agents (i.e., levodopa, amantadine, bromocriptine).20

Symptom complex resembling neuroleptic malignant syndrome (elevated temperature, muscular rigidity, altered consciousness) reported rarely in association with abrupt withdrawal or dosage reduction of tolcapone.1 28 Creatine kinase concentrations may be increased.1 (See Discontinuance of Tolcapone under Dosage and Administration.)

Fibrosis

Retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, and thickening of pleura reported in patients receiving ergot-derivative dopamine receptor agonists (e.g., bromocriptine, pergolide);1 presumably related to the ergoline structure of these agents.1 However, consider the possibility that non-ergot-derived drugs that increase dopaminergic activity (e.g., tolcapone) may induce similar changes.1

Specific Populations

Pregnancy

Category C.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Use with caution in nursing women.1

Pediatric Use

Safety and efficacy not established.1 No identified potential use in children.1

Geriatric Use

Safety and efficacy in geriatric patients have not been studied specifically to date; however, parkinsonian syndrome, for which safety and efficacy have been established, occurs principally in patients >50 years of age.1 6 7 8 9 Patients ≥75 years of age may be more likely to develop hallucinations but less likely to develop dystonia than younger patients.1

No evidence of age-related differences in tolcapone pharmacokinetics.1 4 5

Hepatic Impairment

Do not initiate therapy in patients with clinical evidence of active liver disease, ALT or AST concentrations exceeding the ULN, or any other evidence of hepatocellular dysfunction.1

Renal Impairment

Use with caution in patients with severe renal impairment.1

Common Adverse Effects

Many CNS and psychiatric disturbances in patients receiving tolcapone in conjunction with levodopa are likely to result from increased levodopa concentrations and CNS bioavailability induced by tolcapone.1 7 9 16 24 33

Dyskinesia, dystonia, nausea, anorexia, sleep disturbances/insomnia, orthostatic instability, muscle cramping, excessive dreaming, somnolence; these are dopaminergic effects associated with levodopa therapy.7 9 15 16 28 Most frequent nondopaminergic adverse effect: diarrhea.7 9 15 16 28 29

Interactions for Tolcapone

Metabolized in part by COMT1 2 27 28 and by CYP3A4 and CYP2A6.1 28

Inhibits COMT; has affinity for CYP2C9 in vitro.1 20

Drugs Metabolized by Hepatic Microsomal Enzymes

Clinically important interactions with drugs metabolized by CYP2C9 and CYP2D6 are not expected to occur.1 In vitro studies did not reveal important interactions with substrates for CYP isoenzymes 2A6, 1A2, 3A4, 2C19, or 2D6.1

Drugs Metabolized by COMT

Tolcapone may alter the metabolism of drugs metabolized by COMT.1

Drugs Affecting CNS Monoaminergic or Cholinergic System

Symptom complex resembling neuroleptic malignant syndrome reported in patients receiving tolcapone in combination with other drugs that affect brain monoaminergic or anticholinergic systems; caution is advised if such combinations are used.1

Specific Drugs

Drug

Interaction

Comments

Antidepressants, SSRIs

Symptom complex resembling neuroleptic malignant syndrome reported in patients receiving tolcapone in combination with other drugs that affect brain monoaminergic systems1

Caution advised if such combinations are used1

Antidepressants, tricyclics

Symptom complex resembling neuroleptic malignant syndrome reported in patients receiving tolcapone in combination with other drugs that affect brain monoaminergic systems1

No alteration of desipramine pharmacokinetics; however, regimens that include tolcapone, levodopa/carbidopa, and desipramine are not tolerated as well as regimens that do not include desipramine1

Caution advised if such combinations are used1

Carbidopa

No alteration of carbidopa pharmacokinetics1

Catecholamines (methyldopa, dobutamine, apomorphine, isoproterenol)

Effect on pharmacokinetics not evaluated1 28

Consider dosage reduction of drugs metabolized by COMT1 28

CNS depressants

Possible additive sedative effects1

Ephedrine

No apparent change in tolerability of ephedrine (hemodynamic parameters or plasma catecholamine concentrations at rest or during exercise)1

Can administer concomitantly1

Levodopa

Levodopa AUC increased 2-fold and half-life increased from 2 hours to 3.5 hours without an increase in peak plasma levodopa concentration or a change in the time to peak plasma concentration; the result is more stable plasma levodopa concentrations and enhanced clinical efficacy1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17 18 19 26

Used for therapeutic effect1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17 18 19 26

Levodopa dosage reduction may be required1 6 7 9 16 23

MAO inhibitors, nonselective (e.g., phenelzine, tranylcypromine)

Possible inhibition of the principal pathways of catacholamine metabolism1 28

Symptom complex resembling neuroleptic malignant syndrome reported in patients receiving tolcapone in combination with other drugs that affect brain monoaminergic systems1

Avoid concomitant administration1 28

MAO-B inhibitors, selective (e.g., selegiline)

Adverse effect profile associated with regimens that include tolcapone, levodopa/carbidopa, and selegiline is similar to that associated with regimens that do not include selegiline1 19

Can be administered concomitantly1 19

Phenytoin

No displacement of phenytoin from protein binding sites in vitro1

Tolbutamide

No effect on tolbutamide pharmacokinetics; no displacement of tolbutamide from protein binding sites in vitro1

Warfarin

Possible increased plasma warfarin concentrations;1 28 33 no displacement of warfarin from protein binding sites in vitro1

Determine PT and INR frequently and adjust dosage, if needed1 28 33

Tolcapone Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability following oral administration is about 65–68%.1 27

Rapidly absorbed following oral administration, with peak plasma concentrations generally attained within 2 hours.1 2 3 4 5 8 14 27 28

Onset

Maximum inhibition of erythrocyte COMT activity is achieved within 1 hour and exceeds 80% following a single oral 200-mg dose in healthy individuals;1 2 4 5 8 maximum inhibition is about 80% following administration of 200 mg 3 times daily for 7 days.1 8

Duration

COMT inhibitory activity persists for 16–24 hours following a single oral 200-mg dose in healthy individuals;1 2 4 5 8 inhibition at trough tolcapone concentrations is 30–45% following administration of 200 mg 3 times daily for 7 days.1 8

Food

Administration within 1 hour before or 2 hours after a meal reduces bioavailability by 10–20% compared with administration in the fasting state.1

Distribution

Extent

Distribution into body tissues and fluids is not fully characterized;1 33 however, the drug is not widely distributed.1 2 13

Distributes into brain tissue.1 2 13

Distributes into milk in rats; not known whether tolcapone distributes into human milk.1

Plasma Protein Binding

>99.9% (principally albumin).1 27

Special Populations

In patients with moderate cirrhotic liver disease (Child-Pugh class B), volume of distribution of unbound tolcapone is reduced almost 50%.1 27

Elimination

Metabolism

Extensively metabolized by a variety of mechanisms:1 27 28 glucuronidation (principal metabolic pathway),1 27 28 metabolism by COMT to catechol-3-O-methyltolcapone,1 2 27 28 hydroxylation followed by oxidation to a carboxylic acid derivative,1 28 and reduction followed by N-acetylation.1 In vitro data indicate that CYP3A4 and CYP2A6 catalyze the oxidation reaction.1 28

Elimination Route

Excreted in urine (60%) and feces (40%);1 minimally excreted in urine as unchanged drug (<0.5%).1 27

Half-life

Terminal elimination half-life of tolcapone: 2–3 hours.2 3 4 5 8 27 28

Terminal elimination half-life of catechol-3-O-methyltolcapone: 30–60 hours (but does not appear to accumulate with multiple dosing because tolcapone inhibits COMT).2 3 4 5 8 27

Special Populations

In patients with moderate cirrhotic liver disease (Child-Pugh class B), clearance of unbound tolcapone reduced almost 50%.1 27

In patients with Clcr of 30–130 mL/minute, pharmacokinetics not altered.1

No evidence of gender-, age-, or weight-related pharmacokinetic differences.1 4 5

Stability

Storage

Oral

Tablets

Tight containers at 20–25°C.1

Actions

  • Selective, potent, peripheral and to a lesser extent central, reversible inhibitor of COMT.1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17 18 19 23 26 28

  • Lacks antiparkinsonian effects when administered as monotherapy.

  • Is believed to act principally by inhibiting COMT in peripheral tissues and altering the plasma pharmacokinetics of levodopa, resulting in more sustained plasma levodopa concentrations (see Specific Drugs under Interactions).1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17 18 19 23 26 28 When levodopa is administered concomitantly with a decarboxylase inhibitor (e.g., carbidopa), COMT is the major enzyme catalyzing the metabolism of levodopa to 3-methoxy-4-hydroxy-l-phenylalanine (3-OMD).1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17 18 19

  • Reductions in circulating 3-OMD that result from decreased peripheral metabolism of levodopa may increase distribution of levodopa into the CNS by reducing the competitive substrate (3-OMD) for transport mechanisms.26

Advice to Patients

  • Risk of hepatic toxicity.1 Necessity of laboratory monitoring of liver enzymes.1 Importance of contacting clinician immediately if signs or symptoms suggestive of hepatic failure (e.g., clay-colored stools, jaundice, fatigue, loss of appetite, lethargy) occur.1

  • Potential for tolcapone to exacerbate levodopa-associated adverse effects (e.g., dyskinesias, dystonia).1 7 9 16

  • Risk of orthostatic hypotension with or without symptoms (e.g., dizziness, nausea, syncope, sweating).1 Avoid rising rapidly after prolonged sitting or lying down, especially during the first few weeks of therapy.1

  • Possible occurrence of hallucinations.1

  • Risk of somnolence; possibility of additive sedative effects if used with other CNS depressants.1 Avoid driving or operating machinery until effects on individual are known.1

  • Risk of nausea, especially during the first 3 months of therapy.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., liver disease).1

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Tolcapone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

100 mg

Tasmar (with povidone)

Valeant

200 mg

Tasmar (with povidone)

Valeant

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Tasmar 100MG Tablets (VALEANT): 90/$980.02 or 270/$2,879.98

Tasmar 200MG Tablets (VALEANT): 90/$660.01 or 270/$1,959.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Roche Laboratories, Inc. Tasmar (tolcapone) tablets prescribing information. Nutley, NJ; 1998 Nov.

2. Gottwald MD, Bainbridge JL, Dowling GA et al. New pharmacotherapy for Parkinson’s disease. Ann Pharmacother. 1997; 31:1205-17. [IDIS 392974] [PubMed 9337447]

3. Dingemanse J, Jorga K, Zürcher G et al. Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone and single-dose levodopa. Br J Clin Pharmacol. 1995; 40:253-62. [IDIS 353472] [PubMed 8527287]

4. Dingemanse J, Jorga KM, Schmitt M et al. Integrated pharmacokinetics and pharmacodynamics of the novel catechol-O-methyltransferase inhibitor tolcapone during first administration to humans. Clin Pharmacol Ther. 1995; 57:508-17. [IDIS 348372] [PubMed 7768073]

5. Dingemanse J, Jorga K, Zürcher G et al. Multiple-dose clinical pharmacology of the catechol-O-methyl-transferase inhibitor tolcapone in elderly subjects. Eur J Clin Pharmacol. 1996; 50:47-55. [IDIS 367583] [PubMed 8739811]

6. Kurth MC, Adler CH, St Hilaire M et al et al. Tolcapone improves motor function and reduces levodopa requirement in patients with Parkinson’s disease experiencing motor fluctuations: a multicenter, double-blind, randomized, placebo-controlled trial. Neurology. 1997; 48:81-7. [IDIS 379257] [PubMed 9008498]

7. Waters CH, Kurth M, Bailey P et al et al. Tolcapone in stable Parkinson’s disease: efficacy and safety of long-term treatment. Neurology. 1997; 49: 665-71.

8. Jorga KM, Sedek G, Fotteler B et al. Optimizing levodopa pharmacokinetics with multiple tolcapone doses in the elderly. Clin Pharmacol Ther. 1997; 62:300-10. [IDIS 394950] [PubMed 9333106]

9. Rajput AH, Martin W, Saint-Hilaire MH et al. Tolcapone improves motor function in parkinsonian patients with the “wearing-off” phenomenon: a double-blind, placebo-controlled, multicenter trial. Neurology. 1997; 49:1066-71. [IDIS 393988] [PubMed 9339691]

10. Agid Y, Destée A, Durif F et al et al. Tolcapone, bromocriptine, and Parkinson’s disease. Lancet. 1997; 350:712-3. [IDIS 390849] [PubMed 9291909]

11. Catechol O-methyltransferase. In: Dorland’s illustrated medical dictionary. 28th ed. Philadlephia, PA: W.B. Saunders Co; 1994:278.

12. Byrne JM, Tipton KF. Nitrocatechol derivatives as inhibitors of catechol-O- methyltransferase. Biochem Soc Trans. 1996; 24:64S. [PubMed 8674740]

13. Kaakkola S, Gordin A, Männistö PT. General properties and clinical possibilities of new selective inhibitors of catechol O-methyltransferase. Gen Pharmacol. 1994; 25:813-24. [PubMed 7835624]

14. Sedek G, Jorga K, Schmitt M et al. Effect of tolcapone on plasma levodopa concentrations after coadministration with levodopa/carbidopa to healthy volunteers. Clin Neuropharmacol. 1997; 20:531-41. [PubMed 9403227]

15. Dupont E, Burgunder JM, Findley LJ et al et al. Tolcapone added to levodopa in stable parkinsonian patients: a double-blind placebo-controlled study. Mov Disord. 1997; 12:928-34. [PubMed 9399217]

16. Baas H, Beiske AG, Ghika J et al. Catechol-O-methyltransferase inhibition with tolcapone reduces the “wearing off” phenomenon and levodopa requirements in fluctuating parkinsonian patients. J Neurol Neurosurg Psychiatry. 1997; 63:421-8. [PubMed 9343116]

17. Männistö PT. Catechol O-methyltransferase: characterization of the protein, its gene, and the preclinical pharmacology of COMT inhibitors. Adv Pharmacol. 1998; 42:324-8. [PubMed 9327906]

18. Zürcher G, Dingemanse J, Da Prada M. Potent COMT inhibition by Ro 40-7592 in the periphery and in the brain: preclinical and clinical findings. Adv Neurol. 1993; 60:641-7. [PubMed 8420203]

19. Davis TL, Roznoski M, Burns RS. Effects of tolcapone in Parkinson’s patients takingl-dihydroxyphenylalanine/carbidopa and selegiline. Mov Disord. 1995; 10:349- 51. [PubMed 7651456]

20. Keyser DL, Rodnitzky RL. Neuroleptic malignant syndrome in Parkinson’s disease after withdrawal or alteration of dopaminergic therapy. Arch Intern Med. 1991; 151:794- 6. [IDIS 280495] [PubMed 1672810]

21. Slaughter RL, Edwards DJ. Recent advances: the cytochrome P450 enzymes. Ann Pharmacother. 1995; 29:619-24. [IDIS 349735] [PubMed 7663035]

22. Gasparini M, Fabrizio E, Bonifati V et al. Cognitive improvement during tolcapone treatment in Parkinson’s disease. J Neural Transm. 1997; 104:887-94. [PubMed 9451720]

23. Nutt JG. Catechol-O-methyltransferase inhibitors for treatment of Parkinson’s disease. Lancet. 1998; 351:1221-22. [IDIS 404933] [PubMed 9643737]

24. Henry C, Wilson JA. Catechol-O-methyltransferase inhibitors in Parkinson’s disease. Lancet. 1998; 351:1965-66. [IDIS 408474] [PubMed 9654299]

25. Xie T, Ho SL. Catechol-O-methyltransferase inhibitors in Parkinson’s disease. Lancet. 1998; 351:1966. [IDIS 408475] [PubMed 9654300]

26. Olanow CW, Watts Rl, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology. 2001; 56:S1-S88.

27. Jorga KM, Kroodsma JM, Fotteler B, et al. Effect of liver impairment on the pharmacokinetics of tolcapone and its metabolites. Clin Pharmacol Ther. 1998;63:646- 54.

28. Anon. Tolcapone for Parkinson’s disease. Med Lett Drugs Ther. 1998; 40:60- 61. [PubMed 9629124]

29. Lang AE, Lozano AM. Parkinson’s disease: second of two parts. N Engl J Med. 1998; 339:1130-1143. [IDIS 414132] [PubMed 9770561]

30. Assal F, Spahr L, Hadengue A et al. Tolcapone and fulminant hepatitis. Lancet. 1998; 352:958. [IDIS 411373] [PubMed 9752821]

31. Anon. New warnings for Parkinson’s drug, Tasmar. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 1998 Nov. 16.

32. Ellison RH. Dear health professional letter regarding appropriate use of Tasmar. Nutley, NJ: Roche Laboratories; 1998 Nov. 16.

33. Reviewers’ comments (personal observations).

Hide
(web3)