Tolcapone

Tolcapone is a drug used to treat Parkinson disease. It is typically used in combination with carbidopa-levodopa therapy (Sinemet and Parcopa), as it is not effective at treating Parkinson disease by itself. Tolcapone is useful for people who experience fluctuations in their symptoms, such as "wearing off" of their carbidopa-levodopa before each dose.

The U.S. Food and Drug Administration approved tolcapone on January 29, 1998.

PET scan showing patterns in the brain that assist in the diagnosis of Parkinson Disease. Source: Wikimedia Commons

Other Names

Tolcapone is marketed in the U.S. by Valeant Pharmaceuticals under the brand name Tasmar.

Uses

Tolcapone is used to treat Parkinson disease. It is used in combination with carbidopa-levodopa products, and is useful for people who experience fluctuations in their symptoms, such as "wearing off" of their carbidopa-levodopa before each dose.

How Tolcapone is Taken

Tolcapone is available in 100-mg and 200-mg oral tablets.

Treatment is started at 100 mg three times daily in combination with levodopa/carbidopa therapy.

Liver enzymes are monitored every two to four weeks over the first six months of treatment and at the physician's discretion thereafter. Elevations in liver enzymes occur more frequently at the 200-mg dose three times daily; therefore, the 200-mg dosing regimen is only used if the clinical benefit is justified. If there is no improvement in symptoms on the 200-mg dosing regimen after three weeks of treatment, treatment should be discontinued.

How Tolcapone Works

Tolcapone inhibits the activity of the enzyme catechol-O-methyltransferase (COMT). In the presence of carbidopa, COMT breaks down levodopa in the brain and periphery, which decreases the beneficial effects of levodopa.

Therefore, when tolcapone is given in conjunction with levodopa and carbidopa, circulating levels of levodopa remain higher than if levodopa and carbidopa are given without it. These sustained circulating levels of levodopa lead to an improvement in the signs and symptoms of Parkinson disease.

How the Body Affects Tolcapone

Tolcapone is rapidly absorbed, with peak levels in the bloodstream reached two hours after the drug is taken.

Tolcapone is almost completely metabolized (broken down by the body) prior to excretion, with a small amount (0.5% of the original dose) found unchanged in urine.

After tolcapone pills are taken, 60% of the original dose is excreted in urine and 40% is excreted in feces.

Side Effects

The following are common side effects associated with tolcapone, observed in >5% of patients in clinical trials.

• dyskinesia (involuntary movements)
• nausea
• sleepiness/sleep disorders
• dystonia (involuntary movements)
• anorexia
• muscle cramps
• orthostatic complaints (dizzy spells on standing)
• diarrhea
• confusion
• dizziness
• headache
• hallucination
• vomiting
• constipation
• fatigue
• upper respiratory tract infection
• falling
• increased sweating
• urinary tract infection
• dry mouth
• abdominal pain
• urine discoloration

Risks and Precautions

Because of the risk of liver failure, tolcapone should ordinarily be used in patients with Parkinson disease on levodopa/carbidopa who are not responding satisfactorily to or are not appropriate candidates for other therapies.

Naturally, tolcapone should not be initiated in patients with liver disease. In patients who develop liver damage while on tolcapone and are withdrawn from the drug are at increased risk for liver injury if tolcapone is restarted. Accordingly, such patients should not ordinarily be considered for retreatment.

Drug Interactions

• Tolcapone may influence the metabolism of drugs metabolized by COMT. The effect of tolcapone on the drugs of this class such as α-methyldopa, dobutamine, apomorphine, and isoproterenol has not been studied yet. Physicians may consider reducing the doses of those drugs if they are given with tolcapone.

• Because tolcapone can interfere with the liver's ability to break down certain drugs (specifically, the cytochrome P450 enzyme in the liver called 2C9), tolcapone may interfere with drugs which are broken down via that enzyme, such as warfarin. Tests for whether the blood is thinned enough should be done in patients taking both drugs at once.

• When tolcapone is given together with levodopa/carbidopa and desipramine, the frequency of side effects increases slightly. Therefore, increased monitoring of side effects is necessary when desipramine is given along with tolcapone.

• Monoamine oxidase (MAO) and COMT are the two primary enzyme systems that break down catecholamines (a type of nervous-system substance). It is possible that the combination of tolcapone and a non-selective MAO inhibitor (like phenelzine and tranylcypromine) may result in inhibition of the major pathways responsible for normal catecholamine metabolism. For this reason, patients shouldn't be prescribed tolcapone and a non-selective MAO inhibitor at the same time.

Research

In several clinical trials, tolcapone consistently and significantly reduced "wearing off" and reduced the amount of levodopa needed in patients with Parkinson disease.^[1]

References

1. ↑ Olanow CW, Watkins PB. Tolcapone: an efficacy and safety review (2007). Clin Neuropharmacol. 2007 Sep-Oct;30(5):287-94. Abstract

External Links

FDA: Patient Information Sheet

Drugs.com: Tolcapone

RxList: Tasmar