Comtan

Comtan Uses, Dosage, Side Effects, Food Interaction and all others data.

Comtan decreases the metabolic loss of levodopa to 3-O-methyldopa (3-OMD) through inhibition of COMT enzyme leading to an increased levodopa concentration, thus, extending the duration and effect in the brain.

Comtan is structurally and pharmacologically related to tolcapone, but unlike tolcapone, is not associated with hepatotoxicity. Comtan is used in the treatment of Parkinson’s disease as an adjunct to levodopa/carbidopa therapy. Comtan selectively and reversiblly inhibits 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. COMT is responsible for 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 it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery.

Comtan
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Comtan
Availability	Prescription only
Generic	Entacapone
Entacapone Other Names	Entacapona, Entacapone, Entacaponum
Related Drugs	Gocovri, Rytary, Sinemet, Sinemet CR, ropinirole, pramipexole, benztropine, carbidopa / levodopa, Exelon
Weight	200mg,
Type	Tablet, Film Coated, Oral Tablet
Formula	C₁₄H₁₅N₃O₅
Weight	Average: 305.286 Monoisotopic: 305.101170605
Protein binding	98% (bind to serum albumin)
Groups	Approved, Investigational
Therapeutic Class	Antiparkinson drugs
Manufacturer	Novartis (Bangladesh) Ltd
Available Country	Bangladesh, Canada, Australia, Saudi Arabia, United States, France, Italy, Netherlands, Portugal, Spain, Switzerland,
Last Updated:	September 19, 2023 at 7:00 am

Uses

Adjunct to levodopa treatment in Parkinson's disease

Comtan is also used to associated treatment for these conditions: Parkinson's Disease (PD)

How Comtan works

The mechanism of action of entacapone is believed to be through its ability to inhibit COMT in peripheral tissues, altering 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 a greater reduction in the manifestations of parkinsonian syndrome.

Dosage

Comtan dosage

200 mg with each levodopa/dopa decarboxylase inhibitor dose. Max: 200 mg 10 times daily (2,000 mg daily). Gradually reduce levodopa dose by approx 10-30% or increase dosing interval w/in the 1st few wk of starting treatment.

May be taken with or without food.

Side Effects

Abdominal pain, nausea, vomiting, diarrhoea, constipation, colitis, dry mouth, dyskinesia, dizziness, nightmares, insomnia, hallucinations, confusion, fatigue, increased sweating, behavioural disturbances; urine, skin, hair, beard and nail discolourations; cholestatic hepatitis, rhabdomyolysis. Rarely, agitation, urticaria, erythematous or maculopapular rash, anorexia, wt decrease, increased liver enzymes.

Toxicity

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

Precaution

Patient with biliary obstruction, ischaemic heart disease. Avoid abrupt withdrawal. Pregnancy and lactation.

Interaction

May interfere with metabolism of other drugs metabolised by COMT (e.g. rimiterole). May aggravate levodopa-induced orthostatic hypotension. Risk of dopaminergic effects with dopamine agonists (e.g. bromocriptine), selegiline, amantadine. May form chelates with Fe in the GI tract. Additive sedative effects with other CNS depressants.

Food Interaction

Take with or without food. The absorption is unaffected by food.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Comtan Drug Interaction

Moderate: pramipexole, pramipexole, carbidopa / levodopa, carbidopa / levodopa, carbidopa / levodopa, carbidopa / levodopa, carbidopa / levodopa, carbidopa / levodopaMinor: rasagiline, rasagilineUnknown: aspirin, aspirin, apixaban, apixaban, polyethylene glycol 3350, polyethylene glycol 3350, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol

Comtan Disease Interaction

Major: hypotension, psychosisModerate: hepatic impairment

Volume of Distribution

20 L

Elimination Route

Comtan is rapidly absorbed (approximately 1 hour). The absolute bioavailability following oral administration is 35%.

Half Life

0.4-0.7 hour

Clearance

850 mL/min

Elimination Route

Comtan is almost completely metabolized prior to excretion, with only a very small amount (0.2% of dose) found unchanged in urine. As only about 10% of the entacapone dose is excreted in urine as parent compound and conjugated glucuronide, biliary excretion appears to be the major route of excretion of this drug.

Pregnancy & Breastfeeding use

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Phaeochromocytoma, history of neuroleptic malignant syndrome and/or non-traumatic rhabdomyolysis. Hepatic impairment. Concomitant use w/ non-selective MAOIs.