Because of the risk of potentially fatal acute fulminant liver failure, tolcapone should ordinarily be used in patients with Parkinson disease on L-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies.
Because of the risk of liver injury and because tolcapone, when it is effective, provides an observable symptomatic benefit, the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment should be withdrawn from tolcapone.
Tolcapone should not be initiated if the patient exhibits clinical evidence of liver disease or 2 ALT or AST values greater than the upper limit of normal. Patients with severe dyskinesia or dystonia should be treated with caution.
Patients who develop evidence of hepatocellular injury while on tolcapone and are withdrawn from the drug for any reason may be at increased risk for liver injury if tolcapone is reintroduced. Accordingly, such patients should not ordinarily be considered for re-treatment.
Cases of severe hepatocellular injury, including fulminant liver failure resulting in death, have been reported in postmarketing use. As of May 2005, 3 cases of fatal fulminant hepatic failure have been reported from more than 40,000 patient-years of worldwide use. This incidence may be 10- to 100-fold higher than the background incidence in the general population. Underreporting of cases may lead to significant underestimation of the increased risk associated with the use of tolcapone. All 3 cases were reported within the first 6 months of initiation of treatment with tolcapone. Analysis of the laboratory monitoring data in over 3,400 tolcapone patients participating in clinical trials indicated that increases in ALT or AST, when present, generally occurred within the first 6 months of treatment with tolcapone.
A prescriber who elects to use tolcapone in the face of the increased risk of liver injury is strongly advised to monitor patients for evidence of emergent liver injury. Patients should be advised of the need for self-monitoring for both the classical signs of liver disease (eg, clay-colored stools, jaundice) and the nonspecific ones (eg, fatigue, loss of appetite, lethargy).
Although a program of frequent laboratory monitoring for evidence of hepatocellular injury is recommended, it is not clear that periodic monitoring of liver enzymes will prevent the occurrence of fulminant liver failure. However, it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery. Accordingly, the following liver monitoring program is recommended.
Before starting treatment with tolcapone, the health care provider should conduct appropriate tests to exclude the presence of liver disease. In patients determined to be appropriate candidates for treatment with tolcapone, ALT and AST levels should be determined at baseline and then periodically (ie, every 2 to 4 weeks) for the first 6 months of therapy. After the first 6 months, periodic monitoring is recommended at intervals deemed clinically relevant. Although more frequent monitoring increases the chances of early detection, the precise schedule for monitoring is a matter of clinical judgment. If the dose is increased to 200 mg 3 times daily, liver enzyme monitoring should take place before increasing the dose and then be conducted every 2 to 4 weeks for the following 6 months of therapy. After 6 months, periodic monitoring is recommended at intervals deemed clinically relevant.
Tolcapone should be discontinued if ALT or AST exceeds 2 times the upper limit of normal (ULN) or if clinical signs and symptoms suggest the onset of hepatic dysfunction (eg, persistent nausea, fatigue, lethargy, anorexia, jaundice, dark urine, pruritus, right upper quadrant tenderness).
Note: Because of the risk of potentially fatal, acute fulminant liver failure, tolcapone is only appropriate in patients who are experiencing symptom fluctuations while receiving levodopa/carbidopa and who are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies. If clinical improvement is not observed after 3 weeks of therapy (regardless of dose), tolcapone treatment should be discontinued.
Parkinson disease: Oral: Initial: 100 mg 3 times daily always as an adjunct to levodopa/carbidopa; 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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
Use is contraindicated in patients with liver disease. Discontinue immediately if signs/symptoms of hepatic impairment develop.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Tasmar: 100 mg
Generic: 100 mg
Yes
A patient signed consent form acknowledging the risks of hepatic injury should be obtained by the treating physician.
May be administered without regard to meals. In clinical studies, the first dose of the day was administered with levodopa/carbidopa, and the subsequent doses were administered 6 hours and 12 hours later.
Adjunct to levodopa and carbidopa for the treatment of signs and symptoms of idiopathic Parkinson disease in patients with motor fluctuations not responsive to other therapies
Tolcapone may be confused with TOLAZamide, TOLBUTamide, tolmetin, tolterodine
Tolcapone may be confused with Tolcamin, international brand name for ifosfamide.
Tasmar may be confused with Tasmen, international brand name for acetaminophen.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Orthostatic hypotension (17%)
Central nervous system: Drowsiness (14% to 32%), sleep disorder (24% to 25%), hallucination (8% to 24%), dystonia (19% to 22%), increased dream activity (16% to 21%), dizziness (6% to 13%), confusion (10% to 11%), headache (10% to 11%)
Gastrointestinal: Nausea (28% to 50%), diarrhea (16% to 34%; severe: 3% to 4%), anorexia (19% to 23%)
Neuromuscular & skeletal: Dyskinesia (42% to 51%), muscle cramps (17% to 18%)
1% to 10%:
Cardiovascular: Syncope (4% to 5%), chest pain (1% to 3%), hypotension (2%), palpitations
Central nervous system: Fatigue (3% to 7%), loss of balance (2% to 3%), paresthesia (1% to 3%), burning sensation (1% to 2%), agitation (1%), euphoria (1%), hyperactivity (1%), malaise (1%), panic (1%), irritability (1%), mental deficiency (1%), depression, emotional lability, flank pain, hypoesthesia, speech disturbance, vertigo
Dermatologic: Diaphoresis (4% to 7%), alopecia (1%), skin rash
Gastrointestinal: Vomiting (8% to 10%), constipation (6% to 8%), abdominal pain (5% to 6%), xerostomia (5% to 6%), dyspepsia (3% to 4%), flatulence (2% to 4%)
Genitourinary: Urinary tract infection (5%), hematuria (4% to 5%), urine discoloration (2% to 3%), urination disorder (1% to 2%), impotence, urinary incontinence
Hematologic & oncologic: Hemorrhage (1%), skin neoplasm (1%), uterine neoplasm (1%)
Hepatic: Increased serum transaminases (1% to 3%; 3 x ULN, usually with first 6 months of therapy)
Infection: Influenza (3% to 4%), infection
Neuromuscular & skeletal: Hyperkinesia (≤3%), hypokinesia (≤3%), muscle rigidity (2%), neck pain (2%), arthritis (1% to 2%), myalgia, rhabdomyolysis, tremor
Ophthalmic: Cataract (1%), ophthalmic inflammation (1%)
Otic: Tinnitus
Respiratory: Upper respiratory tract infection (5% to 7%), dyspnea (3%), sinus congestion (1% to 2%), bronchitis, pharyngitis
Miscellaneous: Fever (1%), accidental injury
<1%, postmarketing, and/or case reports: Abnormal stools, abnormality in thinking, abscess, altered sense of smell, amnesia, anemia, antisocial behavior, apathy, apnea, arteriosclerosis, arthropathy, asthma, bacterial infection, bladder calculus, brain disease, breast neoplasm, carcinoma, cardiovascular signs and symptoms, cellulitis, cerebral ischemia, cerebrovascular accident, change in libido, chills, cholecystitis, cholelithiasis, choreoathetosis, colitis, cough, dehydration, delirium, delusions, dermatological disease, diabetes mellitus, diplopia, disease of the lacrimal apparatus, duodenal ulcer, dysphagia, dysuria, eczema, edema, epistaxis, erythema multiforme, esophagitis, extrapyramidal reaction, eye pain, facial edema, fungal infection, furunculosis, gastric atony, gastroenteritis, gastrointestinal carcinoma, gastrointestinal hemorrhage, genitourinary disease, glaucoma, hemiplegia, hemophthalmos, hernia, herpes simplex infection, herpes zoster, hiccups, hostility, hypercholesteremia, hypersensitivity reaction, hyperventilation, hypoxia, increased thirst, laryngitis, leukemia, manic reaction, meningitis, myoclonus, neoplasm, nephrolithiasis, nervousness, neuralgia, neuropathy, nocturia, oliguria, oral mucosa ulcer, otalgia, otitis media, ovarian carcinoma, pain, paranoia, pericardial effusion, polyuria, prostate carcinoma, prostatic disease, pruritus, psychosis, pulmonary edema, rectal disease, rhinitis, seborrhea, sialorrhea, skin discoloration, surgery, tenosynovitis, thrombocytopenia, thrombosis, tongue disease, twitching, urinary retention, urticaria, uterine atony, uterine disease, uterine hemorrhage, vaginitis, viral infection
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
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.
• CNS depression: 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 preexisting 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, driving). Discontinuation of treatment may be required in patients experiencing significant drowsiness.
• Diarrhea: Has been associated with delayed development of diarrhea (onset after 2 to 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.
• Hematuria: Has been associated with hematuria; ~2% to 5% of patients experienced hematuria in clinical trials.
• Hepatotoxicity: [US 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.
• Impulse control disorders: Dopaminergic agents used for Parkinson 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.
• Melanoma: Risk for melanoma development is increased in Parkinson 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 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 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.
Disease-related concerns:
• Dyskinesia: Use with caution in patients with preexisting dyskinesias; exacerbation of preexisting 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.
• Hepatic impairment: Avoid in patients who have ALT or AST values exceeding two times the upper limit of normal or any other evidence of hepatocellular dysfunction. Use is contraindicated in patients with hepatic impairment.
• 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.
Other warnings/precautions:
• 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.
Inhibits COMT
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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 at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
COMT Substrates: COMT Inhibitors may increase the serum concentration of COMT Substrates. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: 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. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: COMT Inhibitors may enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Management: Avoid coadministration of COMT inhibitors and nonselective monoamine oxidase inhibitors (MAOIs) (eg, isocarboxazid, phenelzine, tranylcypromine, linezolid, methylene blue) whenever possible. Risk D: Consider therapy modification
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: 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. Risk D: Consider therapy modification
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pipamperone [INT]: COMT Inhibitors may diminish the therapeutic effect of Pipamperone [INT]. Pipamperone [INT] may diminish the therapeutic effect of COMT Inhibitors. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: 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. Risk D: Consider therapy modification
Tolcapone, taken with food within 1 hour before or 2 hours after the dose, decreases bioavailability by 10% to 20%. Management: Administer without regard to meals.
Adverse events were observed in animal reproduction studies.
It is not known if tolcapone is excreted in breast milk. The manufacturer recommends that caution be exercised when administering tolcapone to nursing women.
May be taken without regard to meals.
Blood pressure; symptoms of Parkinson disease; mental status; periodic skin examinations for melanoma; liver enzymes at baseline and then every 2 to 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 to 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.
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.
Absorption: Rapid
Distribution: 9 L
Protein binding: >99.9%
Metabolism: Hepatic, via glucuronidation, to inactive metabolite (>99%)
Bioavailability: ~65%
Half-life elimination: 2 to 3 hours
Time to peak: ~2 hours
Excretion: Urine (60% as metabolites, 0.5% as unchanged drug); feces (40%)
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.
Tablets (Tasmar Oral)
100 mg (per each): $142.25
Tablets (Tolcapone Oral)
100 mg (per each): $52.50 - $117.44
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