(TOLE ka pone)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tasmar: 100 mg
Generic: 100 mg
Brand Names: U.S.
- Anti-Parkinson's Agent, COMT Inhibitor
Tolcapone is a selective and reversible inhibitor of catechol-o-methyltransferase (COMT). In the presence of a decarboxylase inhibitor (eg, carbidopa), COMT is the major degradation pathway for levodopa. Inhibition of COMT leads to more sustained plasma levels of levodopa and enhanced central dopaminergic activity.
Hepatic, via glucuronidation, to inactive metabolite (>99%)
Urine (60% as metabolites; 0.5% as unchanged drug); feces (40%)
Time to Peak
Special Populations: Hepatic Function Impairment
In patients with moderate cirrhotic liver disease, clearance and Vd is reduced about 50%. Do not initiate therapy if the patient exhibits clinical evidence of active liver disease or 2 ALT or AST values greater than the ULN.
Use: Labeled Indications
Adjunct to levodopa and carbidopa for the treatment of signs and symptoms of idiopathic Parkinson's disease in patients with motor fluctuations not responsive to other therapies
Hypersensitivity to tolcapone or any component of the formulation; patients with liver disease or a history of tolcapone-induced hepatocellular injury; history of nontraumatic rhabdomyolysis or hyperpyrexia and confusion potentially related to medication
Note: Tolcapone is only appropriate in patients receiving concomitant carbidopa and levodopa. If clinical improvement is not observed after 3 weeks of therapy (regardless of dose), tolcapone treatment should be discontinued.
Parkinson's disease: Oral: Initial: 100 mg 3 times daily; may increase as tolerated to 200 mg 3 times daily only if clinical benefit is justified (dosage associated with an increased incidence of ALT elevations). Note: Levodopa dose may need to be decreased upon initiation of tolcapone (average reduction in clinical trials was 30%). As many as 70% of patients receiving levodopa doses >600 mg daily required levodopa dosage reduction in clinical trials. Patients with moderate-to-severe dyskinesia prior to initiation are also more likely to require dosage reduction.
Refer to adult dosing.
Dosing: Renal Impairment
Mild-to-moderate impairment (CrCl ≥25 mL/minute): No dosage adjustment necessary.
Severe impairment (CrCl <25 mL/minute): No dosage adjustment provided in manufacturer’s labeling (has not been studied). Use with caution.
Dosing: Hepatic Impairment
Use is contraindicated in patients with liver disease. Discontinue immediately if signs/symptoms of hepatic impairment develop.
May be administered without regard to meals. In clinical studies, the first dose of the day was administered with carbidopa/levodopa, and the subsequent doses were administered 6 hours and 12 hours later.
May be taken without regard to meals.
Store at 20°C to 25°C (68°F to 77°F).
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Monitor therapy
COMT Substrates: COMT Inhibitors may decrease the metabolism of COMT Substrates. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hydrocodone: CNS Depressants may enhance the CNS depressant effect of Hydrocodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
MAO Inhibitors: COMT Inhibitors may enhance the adverse/toxic effect of MAO Inhibitors. Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
Metyrosine: CNS Depressants may enhance the sedative effect of Metyrosine. Monitor therapy
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pipamperone [INT]: COMT Inhibitors may diminish the therapeutic effect of Pipamperone [INT]. Pipamperone [INT] may diminish the therapeutic effect of COMT Inhibitors. Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification
Cardiovascular: Orthostatic hypotension (17%)
Central nervous system: Somnolence (14% to 32%), sleep disorder (24% to 25%), hallucinations (8% to 24%), excessive dreaming (16% to 21%), dizziness (6% to 13%), headache (10% to 11%), confusion (10% to 11%)
Gastrointestinal: Nausea (28% to 50%), diarrhea (16% to 34%; approximately 3% to 4% severe), anorexia (19% to 23%)
Neuromuscular & skeletal: Dyskinesia (42% to 51%), dystonia (19% to 22%), muscle cramps (17% to 18%)
1% to 10%:
Cardiovascular: Syncope (4% to 5%), chest pain (1% to 3%), hypotension (2%), palpitation
Central nervous system: Fatigue (3% to 7%), loss of balance (2% to 3%), agitation (1%), euphoria (1%), hyperactivity (1%), malaise (1%), panic reaction (1%), irritability (1%), mental deficiency (1%), fever (1%), depression, hypoesthesia, tremor, speech disorder, vertigo, emotional lability, hyperkinesia
Dermatologic: Alopecia (1%), bleeding (1%), tumor (1%), rash
Gastrointestinal: Vomiting (8% to 10%), constipation (6% to 8%), xerostomia (5% to 6%), abdominal pain (5% to 6%), dyspepsia (3% to 4%), flatulence (2% to 4%)
Genitourinary: UTI (5%), hematuria (4% to 5%), urine discoloration (2% to 3%), urination disorder (1% to 2%), uterine tumor (1%), incontinence, impotence
Hepatic: Transaminases increased (1% to 3%; 3 times ULN, usually with first 6 months of therapy)
Neuromuscular & skeletal: Paresthesia (1% to 3%), hyper-/hypokinesia (1% to 3%), arthritis (1% to 2%), neck pain (2%), stiffness (2%), myalgia, rhabdomyolysis
Ocular: Cataract (1%), eye inflammation (1%)
Respiratory: Upper respiratory infection (5% to 7%), dyspnea (3%), sinus congestion (1% to 2%), bronchitis, pharyngitis
Miscellaneous: Diaphoresis (4% to 7%), influenza (3% to 4%), burning (1% to 2%), flank pain, injury, infection
<1% (Limited to important or life-threatening): Abnormal stools, abscess, allergic reaction, amnesia, anemia, antisocial reaction, apathy, apnea, arteriosclerosis, arthrosis, asthma, bladder calculus, breast neoplasm, carcinoma, cardiovascular disorder, cellulitis, cerebral ischemia, cerebrovascular accident, chills, cholecystitis, cholelithiasis, choreoathetosis, colitis, cough increased, death, dehydration, delirium, delusions, diabetes mellitus, diplopia, duodenal ulcer, dysphagia, dysuria, ear pain, eczema, edema, encephalopathy, epistaxis, erythema multiforme, esophagitis, extrapyramidal syndrome, eye hemorrhage, eye pain, facial edema, furunculosis, gastroenteritis, gastrointestinal carcinoma, gastrointestinal hemorrhage, glaucoma, hemiplegia, hernia, herpes simplex, herpes zoster, hiccup, hostility, hypercholesteremia, hyperventilation, hypoxia, infection (bacterial), infection (fungal), joint disorder, kidney calculus, lacrimation disorder, laryngitis, leukemia, libido changes, lung edema, manic reaction, meningitis, mouth ulceration, myoclonus, neoplasm, nervousness, neuralgia, neuropathy, nocturia, oliguria, otitis media, ovarian carcinoma, pain, paranoid reaction, parosmia, pericardial effusion, polyuria, prostatic carcinoma, prostatic disorder, pruritus, psychosis, rectal disorder, rhinitis, salivation increased, seborrhea, skin discoloration, skin disorder, stomach atony, surgical procedure, tenosynovitis, thinking abnormal, thirst, thrombocytopenia, thrombosis, tongue disorder, twitching, urinary retention, urinary tract disorder, urticaria, uterine atony, uterine disorder, uterine hemorrhage, vaginitis, viral infection
Concerns related to adverse effects:
• Abnormal thinking/behavioral changes: Abnormal thinking and behavior changes have been reported and may include paranoid ideation, delusions, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.
• Diarrhea: Has been associated with delayed development of diarrhea (onset after 2-12 weeks); use with caution in patients with lower gastrointestinal disease or an increased risk of dehydration.
• Hallucinations: May cause hallucinations (onset within 2 weeks), which may improve with reduction in levodopa therapy; incidence may be increased in patients >75 years of age.
• Impulse control disorders: Dopaminergic agents used for Parkinson’s disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.
• Hepatotoxicity: [U.S. Boxed Warning]: Due to reports of fatal liver injury associated with use of this drug, the manufacturer is advising that tolcapone be reserved for patients who are experiencing inadequate symptom control or who are not appropriate candidates for other available treatments. Patients must provide written consent acknowledging the risks of hepatic injury. Close monitoring for potential hepatotoxicity is required during use. Do not initiate in patients with clinical evidence of liver disease or with two transaminases values greater than the upper limit of normal. Discontinue if signs and/or symptoms of hepatic injury are noted (eg, anorexia, jaundice, lethargy, or transaminases >2 times upper limit of normal) or if clinical improvement is not evident after 3 weeks of therapy. Tolcapone should not be reinitiated in patients who discontinued therapy due to evidence of liver injury; may be at increased risk for liver injury.
• Melanoma: Risk for melanoma development is increased in Parkinson’s disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed.
• Orthostatic hypotension: May cause orthostatic hypotension and syncope; Parkinson's disease patients appear to have an impaired capacity to respond to a postural challenge; use with caution in patients at risk of hypotension (such as those receiving antihypertensive drugs) or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Parkinson's patients being treated with dopaminergic agonists ordinarily require careful monitoring for signs and symptoms of postural hypotension, especially during dose escalation, and should be informed of this risk.
• Pleural/retroperitoneal fibrosis: Dopaminergic agents from the ergot class have been associated with fibrotic complications, such as retroperitoneal fibrosis, pulmonary infiltrates or effusion and pleural thickening. It is unknown whether nonergot, pro-dopaminergic agents like tolcapone confer this risk.
• Rhabdomyolysis: Severe rhabdomyolysis has been reported with use.
• Somnolence: Patients have reported falling asleep while engaging in activities of daily living; this has been reported to occur without significant warning signs. Monitor for daytime somnolence or pre-existing sleep disorder. Use caution with other CNS depressants, sedating agents, psychoactive drugs or ethanol. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Discontinuation of treatment may be required in patients experiencing significant drowsiness.
• Dyskinesia: Use with caution in patients with pre-existing dyskinesias; exacerbation of pre-existing dyskinesia has been reported. Levodopa dosage reduction may be required, particularly in patients with levodopa dosages >600 mg daily or with moderate-to-severe dyskinesia prior to initiation.
• Psychotic disorders: Avoid use in patients with a major psychotic disorder; may exacerbate psychosis.
• Renal impairment: Use with caution in patients with severe renal impairment.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• MAO inhibitors: Concomitant use of tolcapone and nonselective MAO inhibitors should be avoided. Selegiline is a selective MAO type B inhibitor (when given orally at ≤10 mg/day) and can be taken with tolcapone.
• Discontinuation of therapy: Dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome upon withdrawal or abrupt dosage reduction; patients should be monitored closely if therapy is discontinued.
Blood pressure; symptoms of Parkinson's disease; mental status; liver enzymes at baseline and then every 2-4 weeks for the first 6 months of therapy; thereafter, periodic monitoring should be conducted as deemed clinically relevant. If the dose is increased to 200 mg 3 times/day, reinitiate LFT monitoring prior to dose increase and then every 2-4 weeks for 6 months, and then resume periodic monitoring. Discontinue therapy if the ALT or AST exceeds 2 times ULN or if the clinical signs and symptoms suggest the onset of liver failure.
Pregnancy Risk Factor
Adverse events were observed in animal reproduction studies.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, sweating a lot, insomnia, lack of appetite, nausea, vomiting, constipation, urine discoloration, or loss of strength and energy. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), severe fatigue, narcolepsy, confusion, severe diarrhea, blood in urine, severe dizziness, passing out, angina, shortness of breath, behavioral changes, hallucinations, mood changes, muscle pain, muscle rigidity, dark urine, uncontrollable urges, skin growths, mole changes, abnormal movements, or nightmares (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
More about tolcapone
- Other brands: Tasmar