|Pronunciation||// or //|
|Trade names||Comtan, Comtess, others|
|Drug class||COMT inhibitors|
|Main uses||Parkinson's disease|
|Side effects||Uncontrollable movements, nausea, change in urine color|
|Protein binding||98% (binds to serum albumin)|
|Elimination half-life||0.4–0.7 hours|
|Excretion||Feces (90%), urine (10%)|
|Chemical and physical data|
|Molar mass||305.290 g·mol−1|
|3D model (JSmol)|
Entacapone, sold under the brand name Comtan among others, is a medication used to treat Parkinson's disease. It is used to prevent the wearing off of levodopa/carbidopa before the next dose is due. It is taken by mouth.
Common side effects include uncontrollable movements, nausea, and change in urine color. Other side effects may include abdominal pain, urge to gamble, falling asleep, prostate cancer, low blood pressure with standing, and hallucinations. It works by blocking the enzyme that breaks down levodopa, catechol-O-methyltransferase (COMT).
Entacapone was approved for medical use in Europe in 1998 and the United States in 1999. It is available as a generic medication. In the United Kingdom 100 tablets of 200 mg costs the NHS about £16 as of 2021. This amount in the United States costs about 40 USD.
Entacapone is used in addition to levodopa and carbidopa for people with Parkinson's disease to treat the signs and symptoms of end-of-dose "wearing-off." "Wearing-off" is characterized by the re-appearance of both motor and non-motor symptoms of Parkinson's disease occurring towards the end of a previous levodopa and carbidopa dose. Entacapone has not been shown to slow progression or reverse Parkinson's disease.
There is a high risk for allergic reactions for people who are hypersensitive to entacapone.
Potential limiting conditions to consider before starting entacapone include:
- History of allergic reaction to entacapone
- History of liver disease, liver dysfunction, or alcoholism
- Current or planned pregnancy
- Current or planned surgeries
The following side effects have been reported by people with Parkinson's disease treated with entacapone:
- Abdominal pain
- Dry mouth
- Back ache
The most common side effect of entacapone is movement problems, which occur in 25% of people taking entacapone. This drug may cause or worsen dyskinesia for people with Parkinson's disease treated together with levodopa and carbidopa. In particular, "peak-dose dyskinesias" may occur when levodopa levels are at its peak concentration in the serum plasma.
10% of patients taking entacapone have been shown to experience diarrhea. Diarrhea may occur within 4–12 weeks of initial entacapone use but resolves after discontinuation of the drug. Use of entacapone in the presence of diarrhea can also be associated with weight loss, low potassium levels, and dehydration. In clinical studies, severe diarrhea was the most common reason for discontinuation of entacapone.
10% of people taking entacapone experience a change in urine color to orange, red, brown, or black. This side effect is due to entacapone metabolism and excretion in the urine and shown to not be harmful.
People have reported sudden sleep onset while engaging in daily activities without prior warning of drowsiness. In controlled studies, patients on entacapone had a 2% increased risk of somnolence compared to placebo.
People taking entacapone may experience increased urges to participate in gambling, sexual activities, money spending, and other stimulating reward behaviors.
There are no significant considerations for people with poor kidney function taking entacapone.
Pregnancy and breastfeeding
Although there have been animal studies that showed that entacapone was excreted into maternal rat milk, there have been no studies with human breast milk. Caution is advised for mothers taking entacapone while breastfeeding or during pregnancy.
In studies, entacapone has shown a low potential for interaction with other drugs. In theory, it could interact with MAO inhibitors, tricyclic antidepressants and noradrenaline reuptake inhibitors because they also increase catecholamine levels in the body, with drugs being metabolized by COMT (for example methyldopa, dobutamine, apomorphine, adrenaline, and isoprenaline), with iron because it could form chelates, with substances binding to the same albumin site in the blood plasma (for example diazepam and ibuprofen), and with drugs being metabolized by the liver enzyme CYP2C9 (for example warfarin). None of the medications tested in studies have shown clinically relevant interactions, except perhaps warfarin for which a 13% (CI90: 6–19%) increase in INR was seen when combined with entacapone.
Mechanism of action
Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). COMT eliminates biologically active catechols present in catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. When administered with a decarboxylase inhibitor, COMT acts as the major metabolizing enzyme for levodopa and metabolizes it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and in the periphery.
For the treatment of Parkinson's disease, entacapone is given as an adjunct to levodopa and an aromatic amino acid decarboxylase inhibitor, carbidopa. Entacapone inhibits COMT in the periphery (but not, or at most marginally, in the brain) and the metabolism of levodopa, thus increasing plasma levels of levodopa and causing more constant dopaminergic stimulation in order to reduce the signs and symptoms presented in the disease.
Metabolism and elimination
Entacapone is primarily metabolized to its glucuronide in the liver, and 5% are converted into the Z-isomer. It has a half-life of approximately 0.3–0.7 hours, with only 0.2% being excreted unchanged in the urine.
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