Dosing & Uses
Dosage Forms & Strengths
tablet
- 100mg
Parkinson Disease
100 mg PO q8hr
May increase dose to 200 mg q8hr, but increased ALT occurred more frequently
Failure to show the expected incremental benefit on the 200-mg dose after a total of 3 weeks of treatment (regardless of dose), tolcapone should be discontinued
Always use as an adjunct to levodopa/carbidopa
Monitor
Baseline AST, ALT at initiation of treatment, then q2Weeks for 1 year, then q4Weeks for next 6 months, thereafter q8Weeks
Any symptoms of liver injury
Hepatic Impairment
Two SGPT/ALT or SGOT/AST baseline values >ULN: Do not initiate
ALT/AST >2 xULN while taking tolcapone: Discontinue drug
Renal Impairment
CrCl<25 mL/min: Caution, safety and efficacy not established
Amyloidosis (Orphan)
Orphan designation for treatment of transthyretin amyloidosis
Orphan sponsor
- SOM Innovation Biotech SL (SOM Biotech); Baldiri Reixac 4, 08028; Barcelona, Spain
Safety and efficacy not established
Parkinson disease
100-200 mg PO q8hr
Always as an adjunct to levodopa/carbidopa
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Dyskinesia (45-50%)
Nausea (30-35%)
Insomnia (21-25%)
Hallucinations (8-24%)
Excessive dreaming (16-21%)
Diarrhea (16-20%)
Anorexia (16-20%)
Dystonia (16-20%)
Muscle cramping (16-20%)
Somnolence (16-20%)
Orthostatic hypotension (11-15%)
Confusion (10-11%)
Headache (10-11%)
1-10%
Vomiting (8-10%)
Constipation (6-8%)
URI (5-7%)
Fatigue (3-7%)
Abdominal pain (5-6%)
Xerostomia (5-6%)
UTI (5%)
Hematuria (4-5%)
Syncope (4-5%)
Dyspnea (3%)
Loss of balance (2-3%)
Urine discoloration (2-3%)
Chest pain (1-3%)
Hyper/hypokinesia (1-3%)
Parasthesia (1-3%)
Transaminases increased (1-3%, usually 3x ULN in first 6 mos of therapy)
Hypotension (2%)
Neck pain (2%)
Stiffness (2%)
Sinus congestion (1-2%)
<1%
Dysphagia
GI hemorrhage
Gastroenteritis
Mouth ulceration
Salivation increase
Esophagitis
Cholelithiasis
Colitis
Dopaminergic side effects due to increased dopamine levels
Hepatocellular injury, including liver failure
Warnings
Black Box Warnings
Because of risk of potentially fatal, acute fulminant liver failure, reserve use for 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
If substantial benefit not observed within 3 weeks following initiation, withdraw therapy
Do not initiate if clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values >ULN
Discontinue if SGPT/ALT or SGOT/AST levels exceed 2 xULN 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)
Patients with severe dyskinesia or dystonia should be treated with caution
Patients who develop hepatocellular injury while taking tolcapone and are withdrawn from the drug are at increased risk for liver injury if tolcapone reintroduced
Contraindications
Hypersensitivity
Liver disease or history of tolcapone-induced hepatotoxicity
History of: non-traumatic rhabdomyolysis, drug-related hyperpyrexia & confusion
Cautions
Risk of potentially fatal hepatotoxicity; withdraw drug if no improvement in 3 wk
Do not initiate treatment if AST/ALT >ULN; discontinue if liver enzymes >2 xULN
Impulse control/compulsive behaviors: Risk of uncontrollable sexual, gambling or other urges
Orthostatic hypotension, diarrhea, hallucinations, psychotic-like behavior, rhabdomyolysis, renal/hepatic impairment, hematuria, hyperpyrexia, confusion, and fibrotic complications may occur
May be linked to higher melanoma risk in Parkinson's patients
Avoid abrupt withdrawal
May increase risk for falling asleep during activities of daily living
Do not coadminister with nonselective MAO inhibitor (ie, MAO-A inhibitors); combination may result in result in inhibition of the majority of the pathways responsible for normal catecholamine metabolism
Discontinued in Canada
Pregnancy & Lactation
Pregnancy Category: C
Lactation: not known if secreted in breast milk, use caution
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Reversible catechol-O-methyltransferase (COMT) inhibitor that prolongs the half-life of levodopa
Pharmacokinetics
Peak Plasma Time: 2 hr
Concentration (100/200 mg q8hr for7 days): 3.5/6.4 mcg/mL
Excretion: Urine (60%); feces (40%)
Bioavailability: 65-85%
Protein Bound: >99.9%
Half-life elimination: 2-3hr
Vd: 9 L
Metabolism: Liver glucuronidation
Total body clearance: 7 L/hr
Images
Patient Handout
Formulary
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