Entacapone Carbidopa

Always administer entacapone in combination with levodopa/carbidopa. Entacapone has no antiparkinsonian effect of its own. 

Levodopa + carbidopa + entacapone (Stalevo) Entacapone is a catechol-O-methyltransferase (COMT) inhibitor (see below)... 

The dopamine precursor l-DOPA (levodopa) is commonly used in TH treatment of the symptoms of PD. l-DOPA can be absorbed in the intestinal tract and transported across the blood-brain barrier by the large neutral amino acid (LNAA) transport system, where it taken up by dopaminergic neurons and converted into dopamine by the activity of TH. In PD treatment, peripheral AADC can be blocked by carbidopa or benserazide to increase the amount of l-DOPA reaching the brain. Selective MAO B inhibitors like deprenyl (selegiline) have also been effectively used with l-DOPA therapy to reduce the metabolism of dopamine. Recently, potent and selective nitrocatechol-type COMT inhibitors such as entacapone and tolcapone have been shown to be clinically effective in improving the bioavailability of l-DOPA and potentiating its effectiveness in the treatment of PD. 

Tolcapone (Tasmar) and entacapone (Comtan) are used only in conjunction with carbidopa/L-dopa to prevent the peripheral conversion of L-dopa to dopamine (increasing the area under the curve of L-dopa by approximately 35%). Thus, on time is increased by about 1 hour. These agents significantly decrease off time and decrease L-dopa requirements. Concomitant use of nonselective MAO inhibitors should be avoided to prevent inhibition of the pathways for normal catecholamine metabolism. 

Because entacapone has a shorter half-life, 200 mg is given with each dose of carbidopa/L-dopa up to eight times a day. Dopaminergic adverse effects may occur and are managed easily by reducing the carbidopa/L-dopa dose. Brownish-orange urine discoloration may occur (as with tolcapone), but there is no evidence of hepatotoxicity from entacapone. 

Chlorpromazine is an aliphatic phenothiazine antipsychotic used in schizophrenia and which may exacerbate parkinsonism. Co-careldopa is a combination of levodopa and the peripheral dopa-decarboxylase inhibitor, carbidopa. Co-careldopa, amantadine, entacapone and bromocriptine are all indicated in the management of parkinsonism. 

Parkinson s disease As an adjunct to levodopa/carbidopa to treat patients with idiopathic Parkinson s disease who experience the signs and symptoms of end-of-dose wearing-off. The effectiveness of entacapone has not been systematically evaluated in patients with idiopathic Parkinson s disease who do not experience end-of-dose wearing-off. ... 

The recommended dose of entacapone is one 200 mg tablet administered concomitantly with each levodopa/carbidopa dose to a maximum of 8 times/day (200 mg X 8 = 1600 mg/day). Clinical experience with daily doses greater than 1600 mg is limited. 

Entacapone can be combined with the immediate- and sustained-release formulations of levodopa/carbidopa. 

Pharmacology Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT), which alters the plasma pharmacokinetics of levodopa. When entacapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor (such as carbidopa), plasma levels of levodopa are greater and more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. 

Tablets 12.5 mg carbidopa, 50 mg levodopa, and 200 mg Stalevo 50 entacapone (Novartis)...

Use carbidopa, levodopa, and entacapone combination as a substitute for patients already stabilized on equivalent doses of carbidopa/levodopa and entacapone. Some patients who have been stabilized on a given dose of carbidopa/levodopa may be treated with carbidopa, levodopa, and entacapone combination if a decision has been made to add entacapone. 

The optimum daily dosage of carbidopa, levodopa, and entacapone combination must be determined by careful titration in each patient. Carbidopa, levodopa, and entacapone combination tablets are available in 3 strengths, each in a 1 4 ratio of carbidopa to levodopa and combined with 200 mg of entacapone in a standard... 

Clinical experience with daily doses above 1600 mg of entacapone is limited. It is recommended that no more than 1 carbidopa, levodopa, and entacapone combination tablet be taken at each dosing administration. Thus, the maximum recommended daily dose of carbidopa, levodopa, and entacapone combination is 8 tablets/day. 

Transferring patients currently treated with carbidopa/levodopa and entacapone to carbidopa, levodopa, and entacapone combination tablet ... 

Carbidopa/levodopa - There is no experience in transferring patients currently treated with formulation of carbidopa/levodopa other than immediate release carbidopa/levodopa with a 1 4 ratio (controlled release formulations, or standard release presentations with a 1 10 ratio of carbidopa/levodopa) and entacapone to carbidopa, levodopa, and entacapone combination. 

Entacapone - Patients who are currently treated with entacapone 200 mg tablet with each dose of standard release carbidopa/levodopa, can be directly switched to the corresponding strength of carbidopa, levodopa, and entacapone combination containing the same amounts of levodopa and carbidopa. 

When less levodopa is required, reduce the total daily dosage of carbidopa/levodopa by decreasing the strength of carbidopa, levodopa, and entacapone combination at each administration or by decreasing the frequency of administration by extending the time between doses. 

When more levodopa is required, take the next higher strength of carbidopa, levodopa, and entacapone combination and/or increase the frequency of doses, up to a maximum of 8 times daily and not to exceed the maximum daily dose recommendations as outlined above. 

Addition of other antiparkinsonian medications Standard drugs for Parkinson disease may be used concomitantly while carbidopa, levodopa, and entacapone... 

The two COMT inhibitors in clinical use are tol-capone (Tasmar) and entacapone fComtan). They are used in combination with levodopa-carbidopa. In patients with motor fluctuations, they increase the on time. Adverse effects are similar to those observed with levodopa-carbidopa alone. Tolcapone therapy can cause fatal hepatotoxicity and so should be used only in patients who do not respond to other therapies. Patients taking tolcapone require close monitoring of liver enzymes for signs of hepatic changes. 

Take entacapone with carbidopa and levodopa for best results... 

A commercial preparation named Stalevo consists of a combination of levodopa with both carbidopa and entacapone. It is available in three strengths Stalevo 50 (50 mg levodopa plus 12.5 mg carbidopa and 200 mg entacapone), Stalevo 100 (100 mg, 25 mg, and 200 mg, respectively), and Stalevo 150 (150 mg, 37.5 mg, and 200 mg). Use of this preparation simplifies the drug regimen and requires the consumption of a lesser number of tablets than otherwise. Stalevo is priced at or below the price of its individual components. 

Oral sustained-release (Sinemet CR) 25 mg carbidopa and 100 mg levodopa 50 mg carbidopa and 200 mg levodopa Carbidopa/levodopa/entacapone (Stalevo)... 

Stocchi F, Barbato L, Nordera G, et al. Entacapone improves the pharmacokinetic and therapeutic response of controlled release levodopa/carbidopa in Parkinson s patients. J Neural Transm. 2004 111 173-180. 

COMT inhibitors Entacapone Tolcapone Help prevent breakdown of dopamine in peripheral tissues allows more levodopa to reach the brain. Useful as an adjunct to levodopa/carbidopa administration may improve and prolong effects of levodopa. 

L-dopa is not bound to plasma proteins, and the elimination half-life is about 1 hour. The addition of carbidopa can extend the haff-hfe to 1.5 hours, and the addition of a COMT inhibitor (e.g., entacapone) can extend it to... 

LEVODOPA, SELEGILINE, POSSIBLY RASAGILINE, ENTACAPONE, TOLCAPONE MAOIs Risk of adrenergic syndrome -hypertension, hyperthermia, arrhythmias - and dopaminergic effects with selegiline Levodopa and related drugs are precursors of dopamine. Levodopa is predominantly metabolized to dopamine, and a smaller proportion is converted to epinephrine and norepinephrine. Effects are due to inhibition of MAOI, which breaks down dopamine and sympathomimetics Avoid concurrent use. Onset may be 6-24 hours after ingestion. Carbidopa and benserazide, which inhibit dopa decarboxylase that converts L-dopa to dopamine, is considered to minimize this interaction. However, MAOIs should not be used in patients with Parkinson s disease on treatment with levodopa. Imipramine and amitriptyline are considered safer by some clinicians... 

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