Summary
Commonly reported side effects of tolcapone include: diarrhea, dyskinesia, insomnia, nausea, orthostatic hypotension, vomiting, confusion, dizziness, dystonia, headache, muscle cramps, anorexia, and increased dream activity. Other side effects include: syncope, abdominal pain, constipation, falling, fatigue, diaphoresis, urine discoloration, and xerostomia. Continue reading for a comprehensive list of adverse effects.
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the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from tolcapone.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 Patients who develop evidence of hepatocellular injury while on tolcapone and are withdrawn from the drug for any reason may be at increased risk for liver injury if tolcapone is reintroduced.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]
Oncologic
Common (1% to 10%): Skin tumor, uterine tumor
Uncommon (0.1% to 1%): Carcinoma, neoplasm, prostatic carcinoma, breast neoplasm
Rare (less than 0.1%): Ovarian carcinoma[Ref]
Ocular
Common (1% to 10%): Cataract, inflamed eye
Uncommon (0.1% to 1%): Diplopia, eye hemorrhage, eye pain, lacrimation disorder,
Rare (less than 0.1%): Glaucoma[Ref]
Other
Common (1% to 10%): Fatigue, falling, loss of balance, malaise, fever, vertigo, accidental injury, tinnitus , ear pain, otitis media, parosmia
Uncommon (0.1% to 1%): Hernia, chills
Rare (0.01% to 0.1%): Death[Ref]
Hypersensitivity
Uncommon (0.1% to 1%): Allergic reaction
Immunologic
Common (1% to 10%): Influenza
Uncommon (0.1% to 1%): Fungal infection, viral infection, bacterial infection, abscess
