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| Pronunciation | /ˌɛntəkəˈpoʊn/ or/ɛnˈtækəpoʊn/ |
| Trade names | Comtan (single ingredient), Stalevo (multi-ingredient) |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a601236 |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | 35% |
| Protein binding | 98% (binds to serum albumin) |
| Metabolism | Hepatic |
| Eliminationhalf-life | 0.4–0.7 hours |
| Excretion | Feces (90%), urine (10%) |
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| ECHA InfoCard | 100.128.566 |
| Chemical and physical data | |
| Formula | C14H15N3O5 |
| Molar mass | 305.290 g·mol−1 |
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Entacapone, sold under the brand nameComtan among others, is a medication commonly used in combination with other medications for the treatment ofParkinson's disease.[2] Entacapone together withlevodopa andcarbidopa allows levodopa to have a longer effect in the brain and reduces Parkinson's diseasesigns and symptoms for a greater length of time than levodopa and carbidopa therapy alone.[2]
Entacapone is aselective andreversible inhibitor of theenzymecatechol-O-methyltransferase (COMT).[2] When taken together with levodopa (L-DOPA) and carbidopa, entacapone stops COMT frombreaking down levodopa, resulting in an overall increase of levodopa remaining in the brain and body.[2] Entacaponedoes not cross into the brain and hence does not inhibit COMT there.[3]
Carbidopa/levodopa/entacapone (Stalevo), a medication developed byOrion Pharma and marketed byNovartis, is a single tabletformulation that contains levodopa, carbidopa, and entacapone.[4]
Entacapone is usedin addition to levodopa and carbidopa for people with Parkinson's disease to treat the signs and symptoms of end-of-dose "wearing-off."[5] "Wearing-off" is characterized by the re-appearance of bothmotor andnon-motor symptoms of Parkinson's disease occurring towards the end of a previous levodopa and carbidopa dose.[6] In clinical trials, entacapone has not been shown to slow progression or reverse Parkinson's disease.[2][6][7]
Entacapone is anorally active drug that can be taken with or without food.[5][7]
Pregnancy category C: risk is not ruled out.[2]
Although there have been animal studies that showed that entacapone wasexcreted into maternal rat milk, there have been no studies withhuman breast milk. Caution is advised for mothers taking entacapone while breastfeeding or during pregnancy.[2]
Entacapone safety and efficacy have not been assessed ininfants or children.[2]
Biliary excretion is the major route ofexcretion for entacapone. People with liver dysfunction may require additional caution and more frequent liver function monitoring while taking entacapone.[2]
There are no significant considerations for people with poor kidney function taking entacapone.[2]
There is a high risk for allergic reactions for people who are hypersensitive to entacapone.[2]
Potential limiting conditions to consider before starting entacapone include:[7]
The followingside effects have been reported by people with Parkinson's disease treated with entacapone:
The most common side effect of entacapone is movement problems, which occur in 25% of people taking entacapone.[2] This drug may cause or worsendyskinesia for people with Parkinson's disease treated together with levodopa and carbidopa.[2] In particular, "peak-dose dyskinesias" may occur when levodopa levels are at itspeak concentration in theserum plasma.[8][9]
10% of patients taking entacapone have been shown to experiencediarrhea.[2] 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 withweight loss, lowpotassium levels, anddehydration.[2] In clinical studies, severe diarrhea was the most common reason for discontinuation of entacapone.[10]
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.[10]
People have reportedsudden sleep onset while engaging in daily activities without prior warning of drowsiness. In controlled studies, patients on entacapone had a 2% increased risk ofsomnolence compared toplacebo.[2]
Episodes oforthostatic hypotension have been shown to be more common at the start of entacapone use due to increased levels of levodopa.[2]
Post-marketing data shows that entacapone may change or worsenmental status, leading to behaviors such asdelusions, agitation, confusion, anddelirium.[2]
People taking entacapone may experience increased urges to participate in gambling, sexual activities, money spending, and other stimulating reward behaviors.[2]
In studies, entacapone has shown a low potential for interaction with other drugs. In theory, it could interact withMAO inhibitors,tricyclic antidepressants andnoradrenaline reuptake inhibitors because they also increasecatecholamine levels in the body, with drugs being metabolized by COMT (for examplemethyldopa,dobutamine,apomorphine,adrenaline, andisoprenaline), with iron because it could formchelates, with substances binding to the samealbumin site in the blood plasma (for examplediazepam andibuprofen), and with drugs being metabolized by the liver enzymeCYP2C9 (for examplewarfarin). None of the medications tested in studies have shown clinically relevant interactions, except perhaps warfarin for which a 13% (CI90: 6–19%) increase inINR was seen when combined with entacapone.[11]
Entacapone is a selective and reversibleinhibitor of catechol-O-methyltransferase (COMT).[2] COMT eliminates biologically activecatechols present incatecholamines (dopamine,norepinephrine, andepinephrine) and theirhydroxylatedmetabolites. When administered with adecarboxylase inhibitor, COMT acts as the major metabolizing enzyme for levodopa and metabolizes it to3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and in theperiphery.[2]
For the treatment of Parkinson's disease, entacapone is given as an adjunct to levodopa and an aromatic amino acid decarboxylase inhibitor,carbidopa. Entacapone isperipherally selective and inhibits COMT in the body but not in the brain.[3][12] As a result, entacapone inhibits the peripheral metabolism of levodopa, thus increasing plasma levels of levodopa.[3][2] This causes more constant dopaminergic stimulation in order to reduce thesigns and symptoms presented in the disease.[2]
The time to highest blood plasma concentrations is approximately one hour. The substance undergoes extensivefirst-pass metabolism. Absolute oralbioavailability (F) is 35%.[2][11]
Thevolume of distribution (Vd) afterintravenous injection is approximately 20 liters. 98% of the circulating entacapone is bound to serumalbumin, which limits itsdistribution intotissues.[2][11] Entacapone has lowlipophilicity and does not significantly cross theblood–brain barrier.[3] As a result, it is aperipherally selective drug and does not act in thebrain.[3]
Entacapone is primarily metabolized to itsglucuronide in the liver, and 5% are converted into theZ-isomer.[11] It has ahalf-life of approximately 0.3–0.7 hours, with only 0.2% being excreted unchanged in the urine.[2]
Entacapone, in conjunction withlevodopa and carbidopa, was under development for use in the treatment ofrestless legs syndrome (RLS), but development was discontinued.[13][14]
Entacapone is a potent and specific peripheral catechol-O-methyltransferase inhibitor. [...] Entacapone has no antiparkinsonian activity as a sole agent. Therefore, it must be given as an adjunct to LD and a peripherally acting DDC inhibitor, such as carbidopa. Entacapone acts peripherally and does not penetrate the blood-brain barrier (BBB). [...] It is poorly lipophilic and does not penetrate the BBB to any significant extent. Its clinical effects are thus due to peripheral COMT inhibition only (Nutt, 1998; Fahn et al, 2004). [...] Entacapone is poorly lipophilic. Therefore, its clinical effects are due to peripheral COMT inhibition alone. [...] Entacapone is a potent, specific, and reversible COMT inhibitor. The drug has been shown to act peripherally, but not centrally, when given at clinically effective doses.
