Tolcapone Side Effects

Medically reviewed by Drugs.com. Last updated on Jul 10, 2023.

Applies to tolcapone: oral tablet.

Warning

Oral route (Tablet)

Because of the risk of potentially fatal, acute fulminant liver failure, tolcapone should ordinarily be used in patients with Parkinson disease on levodopa/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the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from tolcapone.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 therapy should not be initiated if the patient exhibits clinical evidence of liver disease or 2 SGPT/ALT or SGOT/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 Patients who develop evidence of hepatocellular injury while on tolcapone and are withdrawn from the drug for any reason may be at increased risk for liver injury if tolcapone is reintroduced.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 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- 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 3400 tolcapone-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.A prescriber who elects to use tolcapone 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 (eg, 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, the physician should conduct appropriate tests to exclude the presence of liver disease. In patients determined to be appropriate candidates for treatment with tolcapone, serum glutamic-pyruvic transaminase (SGPT/ALT) and serum glutamic-oxaloacetic transaminase (SGOT/AST) levels should be determined at baseline and 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 judgement. If the dose is increased to 200 mg 3 times a day, liver enzyme monitoring should take place before increasing the dose 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 SGPT/ALT or SGOT/AST exceeds 2 times the upper limit of normal or if clinical signs and symptoms suggest the onset of hepatic dysfunction (persistent nausea, fatigue, lethargy, anorexia, jaundice, dark urine, pruritus, and right upper quadrant tenderness) .

Serious side effects of Tolcapone

Along with its needed effects, tolcapone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking tolcapone:

Incidence not known

Dark urine
itching
light-colored stools
loss of appetite
nausea (continuing)
tenderness in upper right part of abdomen
unusual drowsiness, dullness, or feeling sluggish
unusual tiredness or weakness
yellow eyes or skin

Check with your doctor as soon as possible if any of the following side effects occur while taking tolcapone:

More common

Abdominal pain
cough
diarrhea
dizziness
dizziness or lightheadedness when getting up from a lying or sitting position
drowsiness
fainting
fever
hallucinations (seeing, hearing, or feeling things that are not there)
headache
nasal congestion (stuffy nose)
nausea
runny nose
sneezing
sore throat
trouble in sleeping
twitching, twisting, or other unusual body movements
vomiting

Less common

Absence of or decrease in body movement
blood in urine
chest pain
chills
confusion
falling
general feeling of discomfort or illness
hyperactivity
loss of balance control
muscle pain
troubled breathing

Rare

Agitation
bloody or cloudy urine
burning of feet
burning, prickling, or tingling sensations
chest discomfort
difficult or painful urination
difficulty in thinking or concentrating
frequent urge to urinate
irritability
joint pain, redness, or swelling
low blood pressure
muscle cramps
neck pain
stiffness

Other side effects of Tolcapone

Some side effects of tolcapone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Constipation
dryness of mouth
excessive dreaming
increased sweating

Less common

Bleeding
difficulty in sleeping
excessive muscle tone
fever
heartburn
gas
muscle stiffness
muscle tension or tightness
trouble in holding or releasing urine

After you stop using this medicine, it may still produce some side effects that need attention. During this period of time, Check with your doctor immediately if you notice the following side effects:

Confusion
fever
muscle rigidity

For Healthcare Professionals

Applies to tolcapone: oral tablet.

General

The more commonly reported adverse events have included dyskinesia, nausea, sleep disorder, orthostatic complaints, and diarrhea.^[Ref]

Hepatic

Cases of severe hepatocellular injury, including fulminant liver failure resulting in death, have been reported. As of 5-2005, 3 cases of fulminant hepatic failure had been reported from more than 40,000 patient years of worldwide use. This incidence may be 10 to 100-fold higher than the incidence in the general population. All 3 cases were reported within the first 6 months of treatment initiation. Analysis of laboratory monitoring indicates that when present, transaminase elevations generally occur within the first 6 months. It is not clear whether periodic monitoring will prevent the occurrence of fulminant liver failure, but it is believed that early detection and immediate withdrawal enhances the likelihood for recovery.

During clinical trials, transaminase elevations to greater than 3 times the upper limit of normal (3 x ULN) occurred in 1% and 3% of patients receiving 100 mg or 200 mg three times a day, respectively. Females were more likely than males to have elevated liver enzymes (5% vs 2%). Approximately 33% of patients with elevated liver enzymes had diarrhea. Liver enzyme elevations to greater than 8 x ULN occurred in 0.3% and 0.7% of patients receiving 100 mg or 200 mg three times a day, respectively.^[Ref]

Common (1% to 10%): ALT increases

Uncommon (0.1% to 1%): Hepatocellular injury^[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 35%), diarrhea (up to 18%), vomiting (up to 10%)

Common (1% to 10%): Constipation, xerostomia, abdominal pain, dyspepsia, flatulence, tooth disorder

Uncommon (0.1% to 1%): Dysphagia, gastrointestinal hemorrhage, gastroenteritis, mouth ulceration, increased salivation, abnormal stools, esophagitis, cholelithiasis, colitis, tongue disorder

Rare (0.01% to 0.1%): Cholecystitis, duodenal ulcer, gastrointestinal carcinoma, stomach atony^[Ref]

In clinical trials, diarrhea developed in approximately 16%, and 18%, of patients receiving 100 mg or 200 mg three times a day, respectively. Diarrhea was generally regarded as mild to moderate, however, severe diarrhea occurred in 3% to 4% of patients and hospitalization was needed in 0.7% and 1.7% of patients receiving 100 mg or 200 mg, respectively. Diarrhea was the most common adverse reaction resulting in discontinuation. No consistent mechanism for tolcapone-induced diarrhea is known.^[Ref]

Musculoskeletal

Very common (10% or more): Muscle cramps (up to 18%)

Common (1% to 10%): Neck pain, flank pain, myalgia

Uncommon (0.1% to 1%): Tenosynovitis, arthrosis, joint disorder^[Ref]

Cardiovascular

Very common (10% or more): Orthostatic complaints (up to 17%)

Common (1% to 10%): Syncope, palpitation

Uncommon (0.1% to 1%): Hypertension, vasodilation, angina pectoris, heart failure, atrial fibrillation, tachycardia, migraine, aortic stenosis, arrhythmia, arteriospasm, bradycardia, coronary artery disorder, heart arrest, myocardial infarct, myocardial ischemia, edema

Rare (less than 0.1%): Arteriosclerosis, cardiovascular disorder, pericardial effusion, thrombosis^[Ref]

This drug enhances levodopa bioavailability and therefore can increase the occurrence of orthostatic hypotension. During clinical trials, orthostatic hypotension occurred at least once in 14% and 13% of patients receiving 100 mg or 200 mg three times a day, respectively. At least one episode of syncope was reported in 4% and 3% of patients, respectively. Approximately 0.7% of patients discontinued therapy due to events related to hypotension.^[Ref]

Psychiatric

Hallucinations occurred in 8% to 10% of patients receiving this drug in clinical trials compared to 5% in placebo. Hallucinations generally present shortly after therapy initiation and appeared to be responsive to levodopa dose reduction. Postmarketing reports of new or worsening mental status and behavioral changes have included paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.

Very common (10% or more): Sleep disorder (up to 25%), excessive dreaming (up to 21%), confusion (up to 11%), hallucinations (up to 10%)

Common (1% to 10%): Agitation, irritability, mental deficiency, hyperactivity, panic reaction, euphoria, depression, emotional lability

Uncommon (0.1% to 1%): Amnesia, hostility, increased libido, manic reaction, nervousness, paranoid reaction, elusions, libido decreased, apathy, psychosis, abnormal thinking

Rare (less than 0.1%): Antisocial reaction, impulse control disorders

Postmarketing reports: New or worsening mental status and behavioral changes

Nervous system

Very common (10% or more): Dyskinesia (up to 51%), dystonia (up to 22%), somnolence (up to 18%), dizziness (up to 13%), headache (up to 11%),

Common (1% to 10%): Hyperkinesia, hypertonia, hypesthesia, tremor, speech disorder,

Uncommon (0.1% to 1%): Neuralgia, extrapyramidal syndrome, cerebral ischemia, cerebrovascular accident, neuropathy, choreoathetosis, myoclonus, twitching, cerebral hemorrhage

Rare (less than 0.1%): Encephalopathy, hemiplegia, meningitis, delirium, neuroleptic malignant syndrome symptom complex

Female patients may be more likely to develop somnolence than males. Dyskinesia may occur or be exacerbated as this drug potentiates the dopaminergic side effects of levodopa.

Respiratory

Common (1% to 10%): Upper respiratory tract infection, dyspnea, sinus congestion, bronchitis, pharyngitis

Uncommon (0.1% to 1%): Pulmonary embolus, increased cough, rhinitis, asthma, epistaxis, hyperventilation, laryngitis, hiccup

Rare (less than 0.1%): Apnea, hypoxia, lung edema^[Ref]

Genitourinary

Common (1% to 10%): Urinary tract infection, urine discoloration, micturition, urinary incontinence, impotence

Uncommon (0.1% to 1%): Rectal disorder, prostatic disorder, dysuria, nocturia, polyuria, urinary retention, urinary tract disorder, hematuria, kidney calculus, oliguria, uterine atony, uterine disorder, vaginitis

Rare (less than 0.1%): Bladder calculus, uterine hemorrhage^[Ref]

This drug and its metabolites are yellow and can cause a harmless intensification in the color of the urine.^[Ref]

Dermatologic

Common (1% to 10%): Increased sweating, alopecia, rash

Uncommon (0.1% to 1%): Cellulitis, face edema, herpes zoster, pruritus, seborrhea skin discoloration, eczema, erythema multiforme, skin disorder, furunculosis, herpes simplex, urticaria^[Ref]