Comtan

Pregnancy Category: C

Lactation: excretion in milk unknown; use with caution

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Mechanism of Action

Reversible catechol-O-methyltransferase (COMT) inhibitor that prolongs half life of levodopa in Parkinsonian patients, reducing motor fluctuations

Pharmacokinetics

Peak Plasma Time: 1 hr

Concentration: 1.2 mcg/mL

Excretion: Feces (90); urine (10%)

Bioavailability: 35%

Protein Bound: 98%

Vd: 20 L

Half-life elimination: 0.4-0.7 hr (B-phase); 2.4 hr (Y-phase)

Metabolism: Hepatic glucuronidation

Total body clearance: 850 mL/min

Serious side effects have been reported with Comtan. See the "Comtan Precautions" section.

Common side effects of Comtan include the following:

• diarrhea
• nausea
• stomach pain
• dizziness
• drowsiness
• movements you cannot control
• change in the color of urine

This is not a complete list of Comtan side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid drinking alcohol. It can increase some of the side effects of entacapone.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

When used with carbidopa and levodopa (Atamet, Parcopa, Sinemet), entacapone increases levels of levodopa in the body.

Entacapone is used together with carbidopa and levodopa to treat "wearing-off" symptoms of Parkinson's disease, such as stiffness, tremors, muscle spasms, and poor muscle control.

Entacapone may also be used for purposes not listed in this medication guide.

Taking this medicine with other drugs that make you sleepy can worsen this effect. Ask your doctor before taking entacapone with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with entacapone, especially:

• isocarboxazid;

• linezolid;

• methylene blue injection;

• phenelzine; or

• tranylcypromine.

This list is not complete. Other drugs may interact with entacapone, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Parkinsonian Syndrome

Adjunct to levodopa-carbidopa in the symptomatic treatment of idiopathic parkinsonian syndrome in patients with manifestations of end-of-dose “wearing-off.”1 4

Not evaluated systematically in patients without manifestations of end-of-dose “wearing-off.”1

Storage

Oral

25°C (may be exposed to 15–30°C).1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

• If you have an allergy to entacapone or any other part of Comtan (entacapone).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take Comtan. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• The chance of a type of skin cancer called melanoma may be raised in people with Parkinson's disease. It is not known if Comtan may also raise the chance. Have skin exams while you take this medicine. Talk with your doctor.
• Do not stop taking Comtan all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this medicine, you will want to slowly stop it as ordered by your doctor.
• It is common to have diarrhea with Comtan. Sometimes, diarrhea has been very bad and rarely has led to needing to go to the hospital. Very bad diarrhea may lead to weight loss, dehydration, or low potassium levels. Talk with your doctor.
• If you get diarrhea, you will need to make sure to avoid getting dehydrated. Drink plenty of fluids and watch for weight loss. Talk with your doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of low potassium levels like muscle pain or weakness, muscle cramps, or a heartbeat that does not feel normal.
• Very loose stools (diarrhea).
• Loose stools (diarrhea) that will not go away.
• Very bad belly pain.
• Weight loss.
• Dry eyes.
• Dry mouth.
• Very bad dizziness or passing out.
• Muscle pain or weakness.
• Feeling confused.
• Fever.
• Strong urges that are hard to control (such as eating, gambling, sex, or spending money).
• Trouble controlling body movements that is new or worse.
• Shortness of breath.
• Hallucinations (seeing or hearing things that are not there).
• Mood changes.
• Change in the way you act.
• A skin lump or growth.
• Change in color or size of a mole.
• Some people have fallen asleep during activities like driving, eating, or talking. Some people did not feel sleepy and felt alert right before falling asleep. This has happened up to 1 year after Comtan was started. If you fall asleep during activities, do not drive or do other tasks or actions that call for you to be alert while you take this medicine. Call your doctor right away if this happens or you feel very sleepy.

Because clinical studies are conducted under widely varying conditions, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction associated with treatment per total number of patients treated) observed in the clinical studies of a drug cannot be directly compared to the incidence of adverse reactions in the clinical studies of another drug and may not reflect the incidence of adverse reactions observed in practice.

A total of 1,450 patients with Parkinson's disease were treated with Comtan in premarketing clinical studies. Included were patients with fluctuating symptoms, as well as those with stable responses to levodopa therapy. All patients received concomitant treatment with levodopa preparations, however, and were similar in other clinical aspects.

The most commonly observed adverse reactions (incidence at least 3% greater than placebo) in double-blind, placebo-controlled studies (N=1,003) associated with the use of Comtan were: dyskinesia, urine discoloration, diarrhea, nausea, hyperkinesia, abdominal pain, vomiting, and dry mouth. Approximately 14% of the 603 patients given entacapone in the double-blind, placebo-controlled studies discontinued treatment due to adverse reactions, compared to 9% of the 400 patients who received placebo. The most frequent causes of discontinuation in decreasing order were: psychiatric disorders (2% vs. 1%), diarrhea (2% vs. 0%), dyskinesia and hyperkinesia (2% vs. 1%), nausea (2% vs. 1%), and abdominal pain (1% vs. 0%).

Adverse Event Incidence in Controlled Clinical Studies

Table 4 lists treatment-emergent adverse events that occurred in at least 1% of patients treated with entacapone participating in the double-blind, placebo-controlled studies and that were numerically more common in the Comtan group, compared to placebo. In these studies, either Comtan or placebo was added to levodopa and carbidopa (or levodopa and benserazide).

Effects of Gender and Age on Adverse Reactions

No differences were noted in the rate of adverse events attributable to entacapone by age or gender.

Postmarketing Reports

The following spontaneous reports of adverse events temporally associated with Comtan have been identified since market introduction and are not listed in Table 4. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish causal relationship to Comtan exposure.

Hepatitis with mainly cholestatic features has been reported.

NOVARTIS
NDC 0078-0327-05

Comtan®
(entacapone)
tablets

200 mg

100
Tablets

Rx only

AU: Use is contraindicated UK: Use is not recommended US: Caution is advised Excreted into human milk: Unknown Excreted into animal milk: Yes The effects in the nursing infant are unknown.