Entacapone (Comtan) is a COMT (catechol-O-methyltransferase) inhibitor. COMT degrades levodopa. Entacapone, thus, prolongs the half-life of levodopa and is used to treat the end-of-dose 'wearing-off' symptoms in patients with Parkinson's disease.

Entacapone Uses:

• Parkinson disease:

  • Patients with idiopathic Parkinson disease who experience "wearing-off" symptoms at the conclusion of a dose interval may benefit from adding entacapone to their Levodopa/Carbidopa medication.

Entacapone (Comtan) Dose in adults

Entacapone (Comtan) Dose in the treatment of Parkinson disease:

• Oral: 200 mg PO with each Levodopa/Carbidopa dose, up to eight times daily, is recommended (maximum daily dose: 1600 mg daily).

Note:

• Levodopa dosage may need to be decreased or the dosing interval may need to be increased in order to maximise therapy.
• Levodopa dosages for patients receiving less than 800 mg per day or who had moderate to severe dyskinesias before to medication must typically be reduced by 25%.

Use in Children:

Not indicated.

Pregnancy Risk Category: C

• Recent studies have shown that there were side effects on the reproductive system.
• It is rare for Parkinson's disease to occur in pregnancy. Information about Entacapone use in pregnant women is limited.

Use of entacapone while breastfeeding

• It is unknown if Entacapone secretes in breast milk.
• Manufacturer recommends caution when giving Entacapone to nursing mothers and may need physician's advice.

Dose in Kidney disease:

There are no dosage adjustments provided in the manufacturer's labeling; however, renal function was not found to significantly affect the pharmacokinetics of entacapone.

Dose in Liver disease:

U.S. labeling:

• There are no dosage adjustments provided in the manufacturer's labeling in chronic kidney and liver diseases.
• However, it is advisable to administer with caution and monitor the parameters closely; AUC and C may possibly be doubled.

Canadian labeling:

• Use is contraindicated

Common Side Effects of Entacapone (Comtan):

• Gastrointestinal:

  • Nausea

• Neuromuscular & skeletal:

  • Dyskinesia

Less Common Side Effects of Entacapone (Comtan):

• Cardiovascular:

  • Syncope

• Central Nervous System:

  • Dizziness
  • Fatigue
  • Anxiety
  • Drowsiness
  • Agitation
  • Hallucination

• Dermatologic:

  • Diaphoresis

• Gastrointestinal:

  • Diarrhea
  • Abdominal Pain
  • Constipation
  • Vomiting
  • Xerostomia
  • Dyspepsia
  • Flatulence
  • Dysgeusia
  • Gastritis
  • Gastrointestinal Disease

• Genitourinary:

  • Urine Discoloration

• Hematologic & Oncologic:

  • Purpura

• Infection:

  • Bacterial Infection

• Neuromuscular & Skeletal:

  • Hyperkinesia
  • Hypokinesia
  • Back Pain
  • Weakness

• Respiratory:

  • Dyspnea

Contraindications to Entacapone (Comtan):

• In Canadian labelling, it is prohibited for people who are allergic to entacapone and any other ingredients in its composition.
• Additional warnings not listed on U.S. labelling
  • There is no clinical or laboratory evidence of uncompensated kidney, endocrine, or lung disorders.
  • History of nontraumatic rhabdomyolysis or neuroleptic malignant syndromes (NMS).
  • Hepatic impairment
  • Diverse:
    • The narrow-angle glaucoma
    • Pheochromocytoma
    • If there is a history of melanoma or a suspicious skin lesion that has not been diagnosed,
    • Concurrent use of both a selective MAO-A and selective MAO-B inhibitor as well as a nonselective Monoamine Oxase (MAO) inhibitor, such as tranylcypromine and phenelzine.
    • It is also contraindicated if it is used in conjunction with sympathomimetic anamine.

Warnings and precautions

• Abnormal behavior/thinking:

  • Reports of abnormal thinking and behavior have been made. They include aggression, confusion, delirium and delusions.

• Diarrhea

  • This product has been connected to delayed diarrheal development (usual onset within 4 to 12 weeks).
  • Patients with lower gastrointestinal disorders or those who are more likely to become dehydrated should avoid it.
  • The presence of diarrhoea may be a sign of drug-induced colitis (primarily Lympocytic).
  • Keep an eye out for weight loss.
  • Stop using if you have prolonged diarrhea.

• Dyskinesia

  • When used in conjunction with levodopa, it is possible for preexisting dyskinesia to recur or even worsen.
  • Levodopa dosage reductions may occasionally be used to lessen these side effects.

• Hallucinations

  • Could cause hallucinations.

• Impulse control disorders:

  • Pathological gambling, hypersexuality, heightened libido, extreme wants to spend money without restraint, and other intense urges have all been used to describe compulsive behaviour and/or loss of impulse control.
  • Some cases of these behaviors can be reversed by discontinuing therapy or reducing dosages.

• Melanoma

  • Patients with Parkinson's disease are at higher risk of developing melanoma. However, it is not known if there is a drug cause or other factors that contribute to the increased risk.
  • Patients must be closely monitored and should have their skin examined regularly.
  • The use of this drug in patients with unidentified, worrisome skin lesions or a melanoma history is forbidden by Canadian labelling.

• Neuroleptic malignant Syndrome:

  • Entacapone has been associated with a state mimicking neuroleptic Malignant Syndrome (hyperpyrexia, confusion - some fatal) with rapid withdrawal or dose decrease when combined with other medications that affect brain biogenic amine levels (e.g. MAO inhibitors, SSRIs).
  • Avoid taking entacapone and nonselective MAO inhibitors at the same time.

• Orthostatic hypotension

  • Syncope may result in orthostatic hypotension.

• Pleural/Retroperitoneal Fibrosis

  • Ergot-family dopaminergic medications have been associated to fibrotic side effects include retroperitoneal fibrosis and pleural effusions and thickening.
  • When the medicine is withdrawn, these issues can sometimes be fully resolved, although this is not always the case.
  • This risk may be caused by non-ergot or pro-dopaminergic drugs like Entacapone.

• Rhabdomyolysis

  • Use has been linked to severe rhabdomyolysis.

• Somnolence

  • Patients have described nodding off while going about their everyday business. This could happen up to a year after therapy started and occurred without any prior warning symptoms.
  • Check for existing sleep abnormalities and daytime somnolence.
  • When combining ethanol with CNS depressants, sedatives, psychotropic medications, or sedative agents, use caution.
  • It is important to warn patients about tasks that require mental alertness, such as driving or operating machinery.

• Cardiovascular disease

  • Canadian product labeling advises patients with heart disease to be cautious, especially if they have a history of arrhythmias or myocardial injury (MI). Clinical trials have shown that MI and other adverse events can occur in patients with heart disease.

• Hepatic impairment

  • Patients with biliary blockage and hepatic dysfunction should exercise caution.
  • When there is hepatic impairment, use is forbidden according to Canadian labelling.

• Psychotic disorders

  • Patients with severe psychotic disorders should be avoided as they may experience exacerbating psychosis.
  • Psychosis treatments can exacerbate Parkinson's disease symptoms and decrease the effectiveness Entacapone.

Entacapone: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• signs or symptoms of Parkinson's Disease.
• Blood pressure
• mental health 
• You should look out for signs such as daytime sleepiness.
• You should be aware of weight loss caused by chronic diarrhea.
• If there are signs of anemia, serum iron levels & LFTs.
• If abrupt discontinuation is required, signs and symptoms can develop. Therefore, caution is recommended.
• Regular dermatologic examination during therapy.

Canadian labeling (additional monitor recommendations):

• Patients who have Ischemic heart disease should be evaluated regularly for their cardiac function during extended therapy with Entacapone.

How to administer Entacapone (Comtan)?

• Always use Levodopa/Carbidopa in conjunction.
• You can combine it with the immediate or sustained release formulations.
• You can also take it with or without food. You should not abruptly withdraw it from the patient's treatment due to NMS and significant worsening. 

Mechanism of action of Entacapone (Comtan):

• Catechol O-methyltransferase is selectively and permanently inhibited by entacapone.
• Levodopa is maintained at a higher level for a longer period of time when taken with entacapone than when given alone.
• These increased levels of levodopa result in increased absorption across blood-brain barriers, which means that dopamine, an active metabolite, is available at higher levels in the CNS.

Onset of action:

• Rapid

Absorption:

• Rapid

Protein binding:

• 98%, primarily to albumin

Metabolism:

• Isomerization to the cis-isomer, followed by the parent and cis-isomer being directly glucuronidated

Bioavailability:

• 35%

Half-life elimination:

• Beta phase: 0.4 to 0.7 hours;
• gamma phase: 2.4 hours

Time to peak, serum:

• 1 hour

Excretion:

• Feces (90%);
• urine (10%)

International Brand Names of Entacapone:

• Comtan
• MYLAN-Entacapone
• SANDOZ Entacapone
• TEVA-Entacapone
• Adcapone
• Anxopone
• Comtade
• Comtan
• Comtapone
• Comtess
• Encapia
• Parkicapone

Entacapone Brand Names in Pakistan:

It is available in Pakistan as Dopacone. Dopacone is a combination pill of Levodopa, Carbidopa, and Entacapone.

Correct Spelling: Entacapone Incorrect Spelling: Entacapon, Entecapone, antacapone, Enticapone