TOLCAPONE 100 mg Tablet, 90-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Catechol-O-Methyltransferase Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Tolcapone is used in combination with levodopa and carbidopa to treat the signs and symptoms of Parkinson's disease. This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
Read the full MedlinePlus article ↗- Levodopa is the main treatment for Parkinson's disease, but over time it can wear off between doses, causing your symptoms to return before your next pill. Tolcapone blocks an enzy...
- Why do I need tolcapone if I'm already taking levodopa and carbidopa?
- This is a real and serious risk that you should take seriously. Rare cases of fatal liver failure have been reported, mostly in the first six months of treatment. Your doctor will...
- I heard tolcapone can cause liver problems. How serious is that, and what should I watch for?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Tolcapone — tap one for details:
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII L11K75P92J
A mineral salt made from calcium and phosphate. It acts as a filler and binder in tablets to add bulk and help hold the medicine together in solid form.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII 7Z8S9VYZ4B
Ethylcellulose is a plant-derived thickener and film-former made by chemically modifying cellulose. It's used as a binder to hold tablet ingredients together, a coating to control how quickly medicine is released, or a thickener in liquid formulations.
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UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII U725QWY32X
Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
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UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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UNII 5856J3G2A2
A starch-based powder made from potatoes and processed with sodium. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the medicine can be absorbed.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
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UNII XHX3C3X673
Triacetin is a clear, oily liquid made from glycerin and acetic acid. It works as a plasticizer and solvent in medicines, helping soften coatings and improve how liquids mix together in formulations.
13 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $35.24 | $3,171.65 / 90 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Tasmar 100 mg 00187-0938-01 | Bausch | 90 tablets | — | — | FDA listed | — |
| Tolcapone 100 mgthis 50742-0193-90 | Ingenus | 90 tablets | — | — | FDA listed | — |
| Tolcapone 100 mg 68682-0938-90 | Oceanside | 90 tablets | — | — | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 50742-0193-90 You're viewing this | 90 TABLET in 1 BOTTLE (50742-193-90) | 2018-08-21 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING Because of the risk of potentially fatal, acute fulminant liver failure, tolcapone tablets should ordinarily be used in patients with Parkinson's 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 (see INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION sections). Because of the risk of liver injury and because tolcapone tablets, 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 tablets.
Tolcapone tablets therapy should not be initiated if the patient exhibits clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal. Patients with severe dyskinesia or dystonia should be treated with caution (see PRECAUTIONS: Rhabdomyolysis ). PATIENTS WHO DEVELOP EVIDENCE OF HEPATOCELLULAR INJURY WHILE ON TOLCAPONE TABLETS AND ARE WITHDRAWN FROM THE DRUG FOR ANY REASON MAY BE AT INCREASED RISK FOR LIVER INJURY IF TOLCAPONE TABLETS IS REINTRODUCED.
ACCORDINGLY, SUCH PATIENTS SHOULD NOT ORDINARILY BE CONSIDERED FOR RETREATMENT. 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-to100-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 tablets. All 3 cases were reported within the first six months of initiation of treatment with tolcapone tablets.
Analysis of the laboratory monitoring data in over 3,400 tolcapone tablets-treated patients participating in clinical trials indicated that increases in SGPT/ALT or SGOT/AST, when present,generally occurred within the first 6 months of treatment with tolcapone tablets. A prescriber who elects to use tolcapone tablets in 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 (e.g., clay colored stools, jaundice) and the nonspecific ones (eg, fatigue, loss of appetite, lethargy).
Although a program of periodic 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 tablets, the physician should conduct appropriate tests to exclude the presence of liver disease. In patients determined to be appropriate candidates for treatment with tolcapone tablets, serum glutamic-pyruvic transaminase (SGPT/ALT) and serum glutamic-oxaloacetic transaminase (SGOT/AST) levels should be determined at baseline and periodically (i.e. every 2 to 4 weeks) for the first 6 months of therapy. After the first six 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 tid (see DOSAGE AND ADMINISTRATION section), 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 six months, periodic monitoring is recommended at intervals deemed clinically rele…
🎯 Indications and Usage ▾
INDICATIONS AND USAGE Tolcapone tablets, USP is indicated as an adjunct to levodopa and carbidopa for the treatment of the signs and symptoms of idiopathic Parkinson's disease. Because of the risk of potentially fatal, acute fulminant liver failure, tolcapone tablets, USP should ordinarily be used in patients with Parkinson's 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 tablets, USP, 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 tablets, USP.
The effectiveness of tolcapone tablets, USP was demonstrated in randomized controlled trials in patients receiving concomitant levodopa therapy with carbidopa or another aromatic amino acid decarboxylase inhibitor who experienced end of dose wearing-off phenomena as well as in patients who did not experience such phenomena (see CLINICAL PHARMACOLOGY : Clinical Studies ).
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION Because of the risk of potentially fatal, acute fulminant liver failure, tolcapone tablets should ordinarily be used in patients with Parkinson's 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 (see INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION sections). BECAUSE OF THE RISK OF LIVER INJURY AND BECAUSE TOLCAPONE TABLETS 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 TABLETS Tolcapone tablets therapy should not be initiated if the patient exhibits clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal.
Patients with severe dyskinesia or dystonia should be treated with caution (see PRECAUTIONS : Rhabdomyolysis). Patients who develop evidence of hepatocellular injury while on tolcapone tablets and are withdrawn from the drug for any reason may be at increased risk for liver injury if tolcapone tablets is reintroduced. These patients should not ordinarily be considered for retreatment with tolcapone tablets.
Only prescribe tolcapone tablets for patients taking concomitant carbidopa levodopa therapy. The initial dose of tolcapone tablets is always 100 mg three times per day. The recommended daily dose of tolcapone tablets is also 100 mg tid.
In clinical trials, elevations in ALT occurred more frequently at the dose of 200 mg tid. While it is unknown whether the risk of acute fulminant liver failure is increased at the 200-mg dose, it would be prudent to use 200 mg only if the anticipated incremental clinical benefit is justified (see BOXED WARNING , WARNINGS , PRECAUTIONS : Laboratory Tests ). If a patient fails to show the expected incremental benefit on the 200-mg dose after a total of 3 weeks of treatment (regardless of dose), tolcapone tablets should be discontinued.
In clinical trials, the first dose of the day of tolcapone tablets was always taken together with the first dose of the day of levodopa/carbidopa, and the subsequent doses of tolcapone tablets were given approximately 6 and 12 hours later. In clinical trials, the majority of patients required a decrease in their daily levodopa dose if their daily dose of levodopa was >600 mg or if patients had moderate or severe dyskinesias before beginning treatment. To optimize an individual patient's response, reductions in daily levodopa dose may be necessary.
In clinical trials, the average reduction in daily levodopa dose was about 30% in those patients requiring a levodopa dose reduction. (Greater than 70% of patients with levodopa doses above 600 mg daily required such a reduction.) Tolcapone tablets can be combined with both the immediate and sustained release formulations of levodopa/carbidopa. Tolcapone tablets may be taken with or without food (see CLINICAL PHARMACOLOGY ).
Patients With Impaired Hepatic Function: Tolcapone tablets therapy should not be initiated in any patient with liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal. (See BOXED WARNING , WARNINGS , and CLINICAL PHARMACOLOGY ). Patients With Impaired Renal Function: No dose adjustment of tolcapone tablets is recommended for patients with mild to moderate renal impairment.
However, patients with severe renal impairment should be treated with caution. The safety of tolcapone has not been examined in subjects who had creatinine clearance less than 25 mL/min (see CLINICAL PHARMACOLOGY ). Withdrawing Patients From Tolcapone Tablets: As with any dopaminergic drug, withdrawal or abrupt reduction in the tolcapone tablets dose may lead to emergence of signs and symptoms of Parkinson's disease or Hyperpyrexia and Confusion, a syndrome complex resembling the neuroleptic malignant syndrome (see PRECAUTIONS : Events Rep…
⛔ Contraindications ▾
CONTRAINDICATIONS Tolcapone tablets are contraindicated in patients with liver disease, in patients who were withdrawn from tolcapone tablets because of evidence of tolcapone tablets-induced hepatocellular injury or who have demonstrated hypersensitivity to the drug or its ingredients. Tolcapone tablets is also contraindicated in patients with a history of nontraumatic rhabdomyolysis or hyperpyrexia and confusion possibly related to medication (see PRECAUTIONS : Events Reported With Dopaminergic Therapy ).
⚠️ Warnings ▾
WARNINGS (SEE BOXED WARNING) Because of the risk of potentially fatal, acute fulminant liver failure, tolcapone tablets should ordinarily be used in patients with Parkinson's 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 (see INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION sections). Because of the risk of liver injury and because tolcapone tablets, 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 tablets.
Tolcapone tablets therapy should not be initiated if the patient exhibits clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal. Patients with severe dyskinesia or dystonia should be treated with caution (see PRECAUTIONS : Rhabdomyolysis ). Patients who develop evidence of hepatocellular injury while on tolcapone tablets and are withdrawn from the drug for any reason may be at increased risk for liver injury if tolcapone tablets is reintroduced.
Accordingly, such patients should not ordinarily be considered for retreatment. In controlled Phase 3 trials, increases to more than 3 times the upper limit of normal in ALT or AST occurred in approximately 1% of patients at 100 mg tid and 3% of patients at 200 mg tid. Females were more likely than males to have an increase in liver enzymes (approximately 5% vs 2%).
Approximately one third of patients with elevated enzymes had diarrhea. Increases to more than 8 times the upper limit of normal in liver enzymes occurred in 0.3% at 100 mg tid and 0.7% at 200 mg tid. Elevated enzymes led to discontinuation in 0.3% and 1.7% of patients treated with 100 mg tid and 200 mg tid, respectively.
Elevations usually occurred within 6 weeks to 6 months of starting treatment. In about half the cases with elevated liver enzymes, enzyme levels returned to baseline values within 1 to 3 months while patients continued tolcapone tablets treatment. When treatment was discontinued, enzymes generally declined within 2 to 3 weeks but in some cases took as long as 1 to 2 months to return to normal.
Monoamine oxidase (MAO) and COMT are the two major enzyme systems involved in the metabolism of catecholamines. It is theoretically possible, therefore, that the combination of tolcapone tablets and a non-selective MAO inhibitor (e.g., phenelzine and tranylcypromine) would result in inhibition of the majority of the pathways responsible for normal catecholamine metabolism. For this reason, patients should ordinarily not be treated concomitantly with tolcapone tablets and a non-selective MAO inhibitor.
Tolcapone can be taken concomitantly with a selective MAO-B inhibitor (e.g., selegiline). Falling Asleep During Activities of Daily Living and Somnolence Tolcapone increases plasma levels of levodopa in patients taking concomitant carbidopa levodopa products [see Dosage and Administration]. Patients taking carbidopa levodopa products alone or with other dopaminergic medications have reported suddenly falling asleep without prior warning of sleepiness while engaged in activities of daily living (includes the operation of motor vehicles).
Some of these episodes resulted in automobile accidents. Although many of these patients reported somnolence while on tolcapone tablets, some did perceive that they had no warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some patients reported these events one year after the initiation of treatment.
The risk for somnolence was increased with tolcapone tablets treatment (tolcapone tablets 100 mg -18 %, 200 mg-14 %, vs placebo-13 %) compared to placebo treatment. In clinical trials, discontinuation due to somnolence occurred in 1 % of patients treated with 200 mg tolcapone tablets and 0 % o…
🤒 Adverse Reactions ▾
ADVERSE REACTIONS 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.
All 3 cases were reported within the first six months of initiation of treatment with tolcapone tablets. Analysis of the laboratory monitoring data in over 3,400 tolcapone tablets-treated patients participating in clinical trials indicated that increases in SGPT/ALT or SGOT/AST, when present, generally occurred within the first 6 months of treatment with tolcapone tablets. The imprecision of the estimated increase is due to uncertainties about the base rate and the actual number of cases occurring in association with tolcapone tablets.
The incidence of idiopathic potentially fatal fulminant hepatic failure (i.e., not due to viral hepatitis or alcohol) is low. One estimate, based upon transplant registry data, is approximately 3/1,000,000 patients per year in the United States. Whether this estimate is an appropriate basis for estimating the increased risk of liver failure among tolcapone tablets users is uncertain.
Tolcapone tablets users, for example, differ in age and general health status from candidates for liver transplantation. Similarly, underreporting of cases may lead to significant underestimation of the increased risk associated with the use of tolcapone tablets. During the premarketing development of tolcapone, two distinct patient populations were studied, patients with end-of-dose wearing-off phenomena and patients with stable responses to levodopa therapy.
All patients received concomitant treatment with levodopa preparations, however, and were similar in other clinical aspects. Adverse reactions are shown for these two populations combined. The most commonly observed adverse reactions in the double-blind, placebo-controlled trials (N=892), with a difference in incidence (tolcapone tablets minus Placebo) of at least 5 % or greater in the 100 mg or 200 mg tolcapone tablets- treated groups compared to placebo, were dyskinesia, nausea, diarrhea, anorexia, sleep disorder, vomiting, urine discoloration, somnolence, hallucination, dystonia, and sweating.
Approximately 16% of the 592 patients who participated in the double-blind, placebo- controlled trials discontinued treatment due to adverse reactions compared to 10% of the 298 patients who received placebo. Diarrhea was by far the most frequent cause of discontinuation (approximately 6% in tolcapone patients vs. 1% on placebo).
Adverse Reaction Incidence in Controlled Clinical Studies: Table 4 lists treatment emergent adverse reactions that occurred in at least 1% of patients treated with tolcapone participating in the double-blind, placebo-controlled studies and were numerically more common in at least one of the tolcapone groups. In these studies, either tolcapone or placebo was added to levodopa/carbidopa (or benserazide). The prescriber should be aware that these figures cannot be used to predict the incidence of adverse reactions in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical studies.
Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. However, the cited figures do provide the prescriber with some basis for estimating the relative contribution of drug and nondrug factors to the adverse reactions incidence rate in the population studied. Table 4.
Summary of Patients With Adverse Reactions After Start of Trial Drug Administration(At Least 1% in Tolcapone Tablets Group and at Least One Tolcapone Tablets Dose Group greater than Placebo) Placebo Tolcapone tid N = 298 100 mg N = 296 200…
🆘 Overdosage ▾
OVERDOSAGE The highest dose of tolcapone administered to humans was 800 mg tid, with and without levodopa/carbidopa co-administration. This was in a 1-week study in elderly, healthy volunteers. The peak plasma concentrations of tolcapone at this dose were on average 30 mcg/mL (compared to 3 mcg/mL and 6 mcg/mL with 100 mg and 200 mg tolcapone, respectively).
Nausea, vomiting and dizziness were observed, particularly in combination with levodopa/carbidopa. The threshold for the lethal plasma concentration for tolcapone based on animal data is >100 mcg/mL. Respiratory difficulties were observed in rats at high oral (gavage) and intravenous doses and in dogs with rapidly injected intravenous doses.
Management of Overdose: Hospitalization is advised. General supportive care is indicated. Based on the physicochemical properties of the compound, hemodialysis is unlikely to be of benefit.
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY Mechanism of Action: Tolcapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). In mammals, COMT is distributed throughout various organs. The highest activities are in the liver and kidney.
COMT also occurs in the heart, lung, smooth and skeletal muscles, intestinal tract, reproductive organs, various glands, adipose tissue, skin, blood cells and neuronal tissues, especially in glial cells. COMT catalyzes the transfer of the methyl group of S-adenosyl-Lmethionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, epinephrine) and their hydroxylated metabolites.
The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa catalyzing the metabolism to 3-methoxy-4 hydroxy-L-phenylalanine (3-OMD) in the brain and periphery. The precise mechanism of action of tolcapone is unknown, but it is believed to be related to its ability to inhibit COMT and alter the plasma pharmacokinetics of levodopa.
When tolcapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that these sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson's disease in patients as well as increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa.
Tolcapone enters the CNS to a minimal extent, but has been shown to inhibit central COMT activity in animals. Pharmacodynamics COMT Activity in Erythrocytes: Studies in healthy volunteers have shown that tolcapone reversibly inhibits human erythrocyte catechol- O - methyltransferase (COMT) activity after oral administration. The inhibition is closely related to plasma tolcapone concentrations.
With a 200-mg single dose of tolcapone, maximum inhibition of erythrocyte COMT activity is on average greater than 80%. During multiple dosing with tolcapone (200 mg tid), erythrocyte COMT inhibition at trough tolcapone blood concentrations is 30% to 45%. Effect on the Pharmacokinetics of Levodopa and its Metabolites: When tolcapone is administered together with levodopa/carbidopa, it increases the relative bioavailability (AUC) of levodopa by approximately twofold.
This is due to a decrease in levodopa clearance resulting in a prolongation of the terminal elimination half-life of levodopa (from approximately 2 hours to 3.5 hours). In general, the average peak levodopa plasma concentration (C max ) and the time of its occurrence (T max ) are unaffected. The onset of effect occurs after the first administration and is maintained during long-term treatment.
Studies in healthy volunteers and Parkinson's disease patients have confirmed that the maximal effect occurs with 100 mg to 200 mg tolcapone. Plasma levels of 3-OMD are markedly and dose-dependently decreased by tolcapone when given with levodopa/carbidopa. Population pharmacokinetic analyses in patients with Parkinson's disease have shown the same effects of tolcapone on levodopa plasma concentrations that occur in healthy volunteers.
Pharmacokinetics of Tolcapone: Tolcapone pharmacokinetics are linear over the dose range of 50 mg to 400 mg, independent of levodopa/carbidopa co-administration. The elimination half-life of tolcapone is 2 to 3 hours and there is no significant accumulation. With tid dosing of 100 mg or 200 mg, C max is approximately 3 mcg/mL and 6 mcg/mL, respectively.
Absorption: Tolcapone is rapidly absorbed, with a T max of approximately 2 hours. The absolute bioavailability following oral administrati…
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Tolcapone tablets USP, 100 mg is supplied as pale yellow to yellow color biconvex, oval shaped film-coated, unscored tablets, debossed with 'RA' on one side and '10' on other side. Tolcapone tablets USP, 100 mg: bottles of 90 (NDC 50742-193-90). Storage: Store in tight containers at 20°C-25°C (68°F-77°F); excursions permitted to 15°C- 30°C (59°F-86°F) [See USP Controlled Room Temperature].
PATIENT ACKNOWLEDGMENT OF RISKS ASSOCIATED WITH TOLCAPONE TABLETS TREATMENT The following is important information that patients should know about tolcapone tablets. ● Tolcapone tablets should not be used until you and your doctor (insert physician name here: ______________________________________) have had a complete discussion about the risks and benefits associated with the use of tolcapone tablets. ● Reports of potentially life-threatening cases of severe hepatocellular injury, including fulminant liver failure resulting in death, have been reported in association with use of tolcapone tablets. ● There are no laboratory tests that will predict in advance which patients are at an increased risk for liver failure or death from liver failure. ● Patients should have the recommended liver blood tests before treatment with tolcapone tablets is begun and periodically for the first 6 months of therapy.
After the first six months, periodic liver blood tests should be performed as directed by your physician. If the dose of tolcapone tablets is to be increased, the liver blood tests should be checked before increasing the dose and repeated periodically as described earlier. Liver blood tests may help detect if liver failure has occurred but they may do so only after significant damage, that may not go away, has already occurred. ● Patients must immediately report any unusual symptoms to their physician and be especially aware of persistent nausea, fatigue, lethargy, decreased appetite, jaundice (yellowing of skin or the whites of the eyes), dark urine, itchiness or right- sided abdominal pain.
The above points of information, possibly along with other information, have been explained to me and I have been able to ask my physician questions and discuss risks and benefits associated with tolcapone tablets treatment. Patient or Patient Caregiver Signature: ___________________________________________________ Date: ________________________________ NOTE TO PHYSICIAN : It is strongly recommended that you retain a signed copy of this form with the patient's medical records. SUPPLY OF PATIENT ACKNOWLEDGEMENT FORMS : A supply of Patient Acknowledgement forms is available, free of charge, from your local Ingenus Pharmaceuticals representative, or by calling at 1-877-748-1970.
Permission to use the above Patient Acknowledgement form by photocopy reproduction is also hereby granted by Ingenus Pharmaceuticals, LLC. U.S.A. Rx only Manufactured for: Ingenus Pharmaceuticals, LLC Orlando, FL 32839-6408 Made in India Rev: 08/2018
📋 Description ▾
DESCRIPTION Tolcapone tablets, USP is available as tablets containing 100 mg tolcapone, USP. Tolcapone, an inhibitor of catechol-O-methyltransferase (COMT), is used in the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa therapy. It is a yellow, non-hygroscopic, fine powder or fine powder with lumps with a relative molecular mass of 273.24.
The chemical name of tolcapone is 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone. Its empirical formula is C 14 H 11 NO 5 and its structural formula is: Inactive ingredients: Core: lactose monohydrate, microcrystalline cellulose, dibasic calcium phosphate anhydrous, sodium starch glycolate, povidone, talc and magnesium stearate.Film coating: hydroxypropyl methylcellulose, titanium dioxide, talc, ethyl cellulose, triacetin,and sodium lauryl sulfate, with the following dye system: yellow iron oxide. Structure