Comtess

Comtess - General Information

Comtess is a catechol-O-methyl transferase inhibitor for the treatment of Parkinson's disease. When administered in conjunction with dopaminergic agents such as L-DOPA, entacapone increases the bioavailability of these compounds by facilitating their passage across the blood-brain barrier.
It is a member of the class of nitrocatechols.
The most frequent undesirable effects caused by entacapone relate to the increased effects of L-DOPA, such as involuntary movements (dyskinesias).These occur most frequently at the beginning of entacapone treatment. Others common side effects are gastrointestinal problems, including diarrhoea, nausea and abdominal pains. The substance may cause urine to turn reddish-brown. This is a harmless side effect and is not a cause for concern. In studies with entacapone, some people have reported experiencing a dry mouth.

Pharmacology of Comtess

Comtess is used in the treatment of Parkinson’s disease as an adjunct to levodopa/carbidopa therapy. Comtess is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). In mammals, COMT is distributed throughout various organs with the highest activities in the liver and kidney. COMT also occurs in the heart, lung, smooth and skeletal muscles, intestinal tract, reproductive organs, various glands, adipose tissue, skin, blood cells and neuronal tissues, especially in glial cells. COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa, catalyzing the metabolism to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery.

Comtess for patients

Patients should be instructed to take C.M. A. only as prescribed.

Patients should be informed that hallucinations can occur.

Patients should be advised that they may develop postural (orthostatic) hypotension with or without symptoms such as dizziness, nausea, syncope, and sweating. Hypotension may occur more frequently during initial therapy. Accordingly, patients should be cautioned against rising rapidly after sitting or lying down, especially if they have been doing so for prolonged periods, and especially at the initiation of treatment with COMTAN.

Patients should be advised that they should neither drive a car nor operate other complex machinery until they have gained sufficient experience on C.M. A. to gauge whether or not it affects their mental and/or motor performance adversely. Because of the possible additive sedative effects, caution should be used when patients are taking other CNS depressants in combination with COMTAN.

Patients should be informed that nausea may occur, especially at the initiation of treatment with COMTAN.

Patients should be advised of the possibility of an increase in dyskinesia.

Patients should be advised that treatment with entacapone may cause a change in the color of their urine (a brownish orange discoloration) that is not clinically relevant. In controlled trials, 10% of patients treated with C.M. A. reported urine discoloration compared to 0% of placebo patients.

Although C.M. A. has not been shown to be teratogenic in animals, it is always given in conjunction with levodopa/carbidopa, which is known to cause visceral and skeletal malformations in the rabbit. Accordingly, patients should be advised to notify their physicians if they become pregnant or intend to become pregnant during therapy.

Entacapone is excreted into maternal milk in rats. Because of the possibility that entacapone may be excreted into human maternal milk, patients should be advised to notify their physicians if they intend to breastfeed or are breastfeeding an infant.

Comtess Interactions

In vitro studies of human CYP enzymes showed that entacapone inhibited the CYP enzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A only at very high concentrations (IC50 from 200 to over 1000 uM; an oral 200 mg dose achieves a highest level of approximately 5 uM in people); these enzymes would therefore not be expected to be inhibited in clinical use.
Protein Binding: Entacapone is highly protein bound (98%). In vitro studies have shown no binding displacement between entacapone and other highly bound drugs, such as warfarin, salicylic acid, phenylbutazone, and diazepam.
Drugs Metabolized by Catechol-O-methyltransferase (COMT):
Hormone levels: Levodopa is known to depress prolactin secretion and increase growth hormone levels. Treatment with entacapone coadministered with levodopa/dopa decarboxylase inhibitor does not change these effects.
No interaction was noted with the MAO-B inhibitor selegiline in two multiple-dose interaction studies when entacapone was coadministered with a levodopa/dopa decarboxylase inhibitor (n=29). More than 600 Parkinson's disease patients in clinical trials have used selegiline in combination with entacapone and levodopa/dopa decarboxylase inhibitor.
As most entacapone excretion is via the bile, caution should be exercised when drugs known to interfere with biliary excretion, glucuronidation, and intestinal beta-glucuronidase are given concurrently with entacapone. These include probenecid, cholestyramine, and some antibiotics (e.g. erythromycin, rifamipicin, ampicillin and chloramphenicol).
No interaction with the tricyclic antidepressant imipramine was shown in a single-dose study with entacapone without coadministered levodopa/dopa-decarboxylase inhibitor.

Comtess Contraindications

COMTAN tablets are contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.

Additional information about Comtess

Comtess Indication: For 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".
Mechanism Of Action: The mechanism of action of entacapone is believed to be through its ability to inhibit COMT and alter 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. It is believed that at a given frequency of levodopa administration, these more sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson's disease.
Drug Interactions: Apomorphine Comtess increases the effect and toxicity of sympathomimetics
Bitolterol Comtess increases the effect and toxicity of sympathomimetics
Dobutamine Comtess increases the effect and toxicity of sympathomimetics
Dopamine Comtess increases the effect and toxicity of sympathomimetics
Epinephrine Comtess increases the effect and toxicity of sympathomimetics
Isocarboxazid Possible hypertensive crisis with this combination
Isoetharine Comtess increases the effect and toxicity of sympathomimetics
Isoproterenol Comtess increases the effect and toxicity of sympathomimetics
Methyldopa Comtess increases the effect and toxicity of sympathomimetics
Norepinephrine Comtess increases the effect and toxicity of sympathomimetics
Phenelzine Possible hypertensive crisis with this combination
Tranylcypromine Possible hypertensive crisis with this combination
Bitolterol Comtess increases the effect and toxicity of sympathomimetics
Food Interactions: Take without regard to meals.
Generic Name: Entacapone
Synonyms: Entacapona [Inn-Spanish]; Entacapone [Usan-Inn]; Entacaponum [Inn-Latin]
Drug Category: Antiparkinson Agents; Antidyskinetics; Central Nervous System Agents; Enzyme Inhibitors
Drug Type: Small Molecule; Approved

Other Brand Names containing Entacapone: Comtan; Comtess;
Absorption: Entacapone is rapidly absorbed (approximately 1 hour). The absolute bioavailability following oral administration is 35%.
Toxicity (Overdose): Side effect include increase the occurrence of orthostatic hypotension, severe rhabdomyolysis, dyskinesia, hallucinations, hyperkinesia, hypokinesia, dizziness, fatigu,e gastrointestinal effects including abdominal pain constipation diarrhea nausea
Protein Binding: 98% (bind to serum albumin)
Biotransformation: Metabolized via isomerization to the cis-isomer, followed by direct glucuronidation of the parent and cis-isomer.
Half Life: 0.4-0.7 hour
Dosage Forms of Comtess: Tablet Oral
Chemical IUPAC Name: (E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide
Chemical Formula: C14H15N3O5
Entacapone on Wikipedia: https://en.wikipedia.org/wiki/Entacapone
Organisms Affected: Humans and other mammals