General

Pronunciation:
tole-ka-pone

Trade Name(s)

• Tasmar

Ther. Class.

antiparkinson agents

Pharm. Class.

catechol o methyltransferase comt inhibitors

Indications

Management of Parkinson's disease with carbidopa/levodopa in patients without severe movement abnormalities who do not respond to other treatment.

Action

• Acts as a selective and reversible inhibitor of the enzyme catechol- O -methyltransferase.
• Inhibition of this enzyme prevents the breakdown of levodopa, greatly increasing its availability to the CNS.

Therapeutic Effect(s):

• Prolongs duration of response to levodopa without end-of-dose motor fluctuations.
• Decreased signs and symptoms of Parkinson's disease.

Pharmacokinetics

Absorption: Rapidly absorbed following oral administration with 65% bioavailability.

Distribution: Unknown.

Protein Binding: >99% bound to plasma proteins.

Metabolism and Excretion: Mostly metabolized by the liver; <0.5% excreted unchanged in urine.

Half-life: 2–3 hr.

TIME/ACTION PROFILE (blood levels)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Concurrent MAO inhibitor therapy;
• Clinical evidence of liver disease.

Use Cautiously in:

• Severe renal impairment (safety not established if CCr <25 mL/min);
• OB:  Lactation: Safety not established.

Adverse Reactions/Side Effects

CV: orthostatic hypotension

Derm: ↑ sweating, melanoma

GI: constipation, diarrhea, ↑ liver enzymes, anorexia, HEPATOTOXICITY, nausea, vomiting

GU: hematuria, yellow discoloration of urine

Neuro: dyskinesia, dystonia, headache, sleep disorder, hallucinations, syncope, urges (gambling, sexual)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• Concurrent use with  MAO inhibitors  is not recommended; both agents inhibit the metabolic pathways of catecholamines.
• May ↑ the effects of  apomorphine,  dobutamine, or  isoproterenol ; dose reduction may be necessary.
• ↑ the bioavailability of  levodopa  by two-fold; this is a desired effect.

Route/Dosage

PO (Adults): 100 mg 3 times daily; may cautiously ↑ to 200 mg 3 times daily if benefit is justified.

Availability (generic available)

Tablets: 100 mg

Assessment

• Assess patient for signs and symptoms of Parkinson's disease (tremor, muscle weakness and rigidity, ataxic gait) prior to and throughout therapy.
• Assess BP periodically during therapy.
• Monitor for signs and symptoms of liver dysfunction (persistent nausea, fatigue, lethargy, anorexia, jaundice, dark urine, pruritus, right upper quadrant tenderness) periodically during therapy.

Lab Test Considerations:

Monitor liver function tests before every 2–4 wk for the first 6 mo following initiation or dose increase and periodically thereafter. Discontinue tolcapone if liver function tests reach two times the upper limit of normal or if jaundice occurs; do not reinstate.

Implementation

• PO Administer 1st dose of the day of tolcapone together with carbidopa/levodopa. Administer subsequent doses 6 and 12 hr later.
  • May be administered without regard to food.

Patient/Family Teaching

• Instruct patient to take medication as directed. Caution patient not to discontinue tolcapone without consulting health care professional. Abrupt discontinuation or rapid dose reduction may result in neuroleptic malignant syndrome (↑ temperature, muscular rigidity, altered consciousness).
• Caution patient to make position changes slowly to minimize orthostatic hypotension, especially at the beginning of therapy.
• May affect mental and/or motor performance. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to avoid taking alcohol or other CNS depressants concurrently with tolcapone.
• Inform patient and caregiver that hallucinations, nausea, dyskinesia, or dystonia may occur during tolcapone therapy.
• Instruct patient to notify health care professional if persistent diarrhea occurs.
• Advise patient to notify health care professional if symptoms of liver failure (clay-colored stools, jaundice, fatigue, loss of appetite, lethargy), suspicious or unusual skin changes, hallucinations, or new or increased gambling, sexual, or other intense urges occur.
• Advise patient to notify health care professional if pregnancy is planned or suspected.
• Emphasize the importance of routine follow-up exams.

Evaluation/Desired Outcomes

Decrease in signs and symptoms of Parkinson's disease.