Carbi/levo/entocap 100 Tabs
It is used to treat Parkinson's disease.
Drug Class
Antiparkinsonian agent
Pharmacologic Class
Dopamine precursor; DOPA decarboxylase inhibitor; Catechol-O-methyltransferase (COMT) inhibitor
Pregnancy Category
Category C
FDA Approved
Jul 2003
DEA Schedule
Not Controlled
Overview
What is this medicine?
This medication is a combination of three drugs (levodopa, carbidopa, and entacapone) used to treat Parkinson's disease. Levodopa helps replace a chemical called dopamine in your brain, which is low in Parkinson's. Carbidopa helps more levodopa get to your brain and reduces side effects. Entacapone helps levodopa work longer by preventing its breakdown in the body, which can help reduce 'wearing-off' symptoms between doses.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. You can take this medication with or without food. Swallow the tablet whole - do not chew, break, or crush it.
If you take an iron supplement or a multivitamin that contains iron, consult your doctor or pharmacist about how to take it with this medication. Iron may reduce the absorption of this medication in your body.
Your diet can also affect how well your body absorbs this medication. Diets high in protein, fat, or calories, as well as acidic foods, may reduce absorption. Discuss your diet with your doctor, especially if you plan to make any changes.
Do not stop taking this medication suddenly without consulting your doctor, as this may increase your risk of side effects. If you need to stop taking this medication, your doctor will advise you on how to taper off gradually.
Continue taking this medication even when you are not experiencing symptoms. Keeping a diary of your symptoms can be helpful. Take this medication at the same time every day, as directed by your doctor or healthcare provider, even if you feel well.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom. Keep all medications out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about disposing of your medication, consult your pharmacist. You may also want to check if there are any drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. You can take this medication with or without food. Swallow the tablet whole - do not chew, break, or crush it.
If you take an iron supplement or a multivitamin that contains iron, consult your doctor or pharmacist about how to take it with this medication. Iron may reduce the absorption of this medication in your body.
Your diet can also affect how well your body absorbs this medication. Diets high in protein, fat, or calories, as well as acidic foods, may reduce absorption. Discuss your diet with your doctor, especially if you plan to make any changes.
Do not stop taking this medication suddenly without consulting your doctor, as this may increase your risk of side effects. If you need to stop taking this medication, your doctor will advise you on how to taper off gradually.
Continue taking this medication even when you are not experiencing symptoms. Keeping a diary of your symptoms can be helpful. Take this medication at the same time every day, as directed by your doctor or healthcare provider, even if you feel well.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom. Keep all medications out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about disposing of your medication, consult your pharmacist. You may also want to check if there are any drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Take exactly as prescribed, do not stop suddenly without consulting your doctor.
- May be taken with or without food, but taking with a low-protein snack may help reduce stomach upset. Avoid high-protein meals as they can reduce the absorption of levodopa.
- Do not crush or chew tablets; swallow whole.
- Rise slowly from a sitting or lying position to minimize dizziness or lightheadedness (orthostatic hypotension).
- Stay well-hydrated.
- Be aware that your urine, sweat, or saliva may turn dark (reddish-brown to black). This is a harmless effect of entacapone and its metabolites.
- Avoid driving or operating machinery if you experience sudden sleep attacks or excessive drowsiness.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Highly individualized, typically starting with a low dose and titrating up. Common initial doses are 50/12.5/200 mg (levodopa/carbidopa/entacapone) 3-4 times daily, replacing existing levodopa/carbidopa doses.
Dose Range:
50 - 200 mg
Condition-Specific Dosing:
Parkinson's Disease:
Dose should be optimized to provide the lowest effective dose of levodopa. Maximum recommended daily dose of entacapone is 1600 mg (8 tablets of 200 mg entacapone strength).
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment required.
Moderate:
No specific dose adjustment required.
Severe:
Use with caution. Entacapone excretion is primarily biliary, but a small fraction is renal. Levodopa/carbidopa are renally excreted. Monitor for adverse effects.
Dialysis:
Not well studied. Use with caution and monitor for adverse effects.
Hepatic Impairment:
Mild:
Use with caution. Entacapone exposure may be increased. Consider dose reduction.
Moderate:
Use with caution. Entacapone exposure may be increased. Consider dose reduction.
Severe:
Contraindicated or not recommended due to increased entacapone exposure and potential for hepatotoxicity.
Pharmacology
Mechanism of Action
Levodopa is a metabolic precursor of dopamine that crosses the blood-brain barrier and is converted to dopamine in the brain. Carbidopa inhibits DOPA decarboxylase, an enzyme that metabolizes levodopa in the periphery, thereby increasing the amount of levodopa available to the brain and reducing peripheral side effects. Entacapone is a reversible inhibitor of catechol-O-methyltransferase (COMT), an enzyme that metabolizes levodopa in the periphery. By inhibiting COMT, entacapone prolongs the half-life of levodopa, increasing its bioavailability and extending its therapeutic effect, particularly in patients experiencing 'wearing-off' phenomena.
Pharmacokinetics
Absorption:
Bioavailability:
Levodopa: Variable (approx. 30% when given with carbidopa); Carbidopa: approx. 50%; Entacapone: approx. 35%
Tmax:
Levodopa: 0.5-2 hours; Carbidopa: 0.5-2 hours; Entacapone: 0.5-1.5 hours
FoodEffect:
High-protein meals can reduce levodopa absorption and peak plasma concentrations. Entacapone absorption is not significantly affected by food.
Distribution:
Vd:
Levodopa: 0.9-1.6 L/kg; Carbidopa: 1.1 L/kg; Entacapone: 0.27 L/kg (low)
ProteinBinding:
Levodopa: Not significantly bound; Carbidopa: approx. 36%; Entacapone: >98% (primarily to albumin)
CnssPenetration:
Levodopa: Yes (after conversion to dopamine); Carbidopa: Limited; Entacapone: Limited
Elimination:
HalfLife:
Levodopa: 1-2 hours (with carbidopa/entacapone); Carbidopa: 2-3 hours; Entacapone: 0.4-0.7 hours (terminal half-life approx. 2.4 hours)
Clearance:
Not available
ExcretionRoute:
Levodopa: Urine (metabolites); Carbidopa: Urine (unchanged and metabolites); Entacapone: Feces (90-95%), Urine (10-20% as glucuronide conjugate)
Unchanged:
Levodopa: <1% (urine); Carbidopa: 30% (urine); Entacapone: <0.2% (urine)
Pharmacodynamics
OnsetOfAction:
Variable, typically within 30-60 minutes for levodopa effect.
PeakEffect:
Variable, typically 1-2 hours after dose.
DurationOfAction:
Extended compared to levodopa/carbidopa alone, typically 2-4 hours, but can vary significantly between individuals and with disease progression.
Safety & Warnings
Side Effects
Serious Side Effects: Seek Medical Help Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, contact your doctor or seek medical attention right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
New or worsening behavior or mood changes, including:
+ Depression
+ Thoughts of suicide
Hallucinations (seeing or hearing things that are not there)
Severe dizziness or fainting
Confusion
Vomiting blood or coffee ground-like material
Black, tarry, or bloody stools
Muscle pain or weakness, dark urine, or difficulty urinating
Skin lumps or growths
Changes in the color or size of a mole
Strong, uncontrollable urges (such as eating, gambling, sex, or spending money)
New or worsening trouble controlling body movements
Chest pain or pressure
Shortness of breath
Fever, chills, or sore throat
Unexplained bruising or bleeding
Feeling extremely tired or weak
Sudden, unexplained sleepiness, including falling asleep during activities like driving, eating, or talking
If you experience sudden sleepiness, do not drive or engage in activities that require alertness. Contact your doctor immediately.
Neuroleptic Malignant Syndrome (NMS)
NMS is a rare but potentially life-threatening condition that can occur when this medication is stopped suddenly or when the dose is lowered. If you experience any of the following symptoms, contact your doctor right away:
Fever
Muscle cramps or stiffness
Dizziness
Severe headache
Confusion
Changes in thinking
Fast or irregular heartbeat
Excessive sweating
Other Side Effects
Most people do not experience serious side effects, but some may occur. If you experience any of the following side effects, contact your doctor if they bother you or do not go away:
Dizziness
Drowsiness
Fatigue
Weakness
Constipation
Diarrhea
Stomach pain
Upset stomach
Vomiting
Dry mouth
Headache
Trouble sleeping
* Back pain
This is not a comprehensive list of all possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, contact your doctor or seek medical attention right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
New or worsening behavior or mood changes, including:
+ Depression
+ Thoughts of suicide
Hallucinations (seeing or hearing things that are not there)
Severe dizziness or fainting
Confusion
Vomiting blood or coffee ground-like material
Black, tarry, or bloody stools
Muscle pain or weakness, dark urine, or difficulty urinating
Skin lumps or growths
Changes in the color or size of a mole
Strong, uncontrollable urges (such as eating, gambling, sex, or spending money)
New or worsening trouble controlling body movements
Chest pain or pressure
Shortness of breath
Fever, chills, or sore throat
Unexplained bruising or bleeding
Feeling extremely tired or weak
Sudden, unexplained sleepiness, including falling asleep during activities like driving, eating, or talking
If you experience sudden sleepiness, do not drive or engage in activities that require alertness. Contact your doctor immediately.
Neuroleptic Malignant Syndrome (NMS)
NMS is a rare but potentially life-threatening condition that can occur when this medication is stopped suddenly or when the dose is lowered. If you experience any of the following symptoms, contact your doctor right away:
Fever
Muscle cramps or stiffness
Dizziness
Severe headache
Confusion
Changes in thinking
Fast or irregular heartbeat
Excessive sweating
Other Side Effects
Most people do not experience serious side effects, but some may occur. If you experience any of the following side effects, contact your doctor if they bother you or do not go away:
Dizziness
Drowsiness
Fatigue
Weakness
Constipation
Diarrhea
Stomach pain
Upset stomach
Vomiting
Dry mouth
Headache
Trouble sleeping
* Back pain
This is not a comprehensive list of all possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- New or worsening involuntary movements (dyskinesias)
- Increased 'off' time or return of Parkinson's symptoms
- Hallucinations, delusions, or confusion
- Excessive daytime sleepiness or sudden onset of sleep
- Unusual urges or behaviors (e.g., gambling, shopping, eating, sexual urges)
- Severe diarrhea (especially if persistent or bloody)
- Signs of liver problems (e.g., yellowing of skin/eyes, dark urine, severe stomach pain, unusual tiredness)
- Severe dizziness or fainting spells
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, including:
+ Glaucoma
+ Skin lumps or growths
+ A history of skin cancer
If you have taken specific antidepressant medications, such as isocarboxazid, phenelzine, or tranylcypromine, within the last 14 days. Taking this medication too soon after these drugs can lead to severe high blood pressure.
This list is not exhaustive, and it is crucial to discuss all your medications and health conditions with your doctor. Please inform your doctor and pharmacist about:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
Your complete medical history
To ensure your safety, always verify with your doctor that it is acceptable to take this medication with your existing medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, including:
+ Glaucoma
+ Skin lumps or growths
+ A history of skin cancer
If you have taken specific antidepressant medications, such as isocarboxazid, phenelzine, or tranylcypromine, within the last 14 days. Taking this medication too soon after these drugs can lead to severe high blood pressure.
This list is not exhaustive, and it is crucial to discuss all your medications and health conditions with your doctor. Please inform your doctor and pharmacist about:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
Your complete medical history
To ensure your safety, always verify with your doctor that it is acceptable to take this medication with your existing medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. This will help ensure they have a complete understanding of your treatment plan.
Until you know how this medication affects you, avoid driving and other activities that require your full attention. To minimize the risk of dizziness or fainting, get up slowly from a sitting or lying position, and be cautious when climbing stairs.
Regular blood tests and other laboratory evaluations are crucial while taking this medication. Follow your doctor's instructions for scheduling these tests. Additionally, inform all your healthcare providers and laboratory personnel that you are taking this medication, as it may interfere with certain lab tests.
You may experience a decrease in the medication's effectiveness as the time approaches for your next dose. If this occurs and bothers you, discuss it with your doctor. It may take several months to notice the full benefits of this medication.
Before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that can cause drowsiness, consult with your doctor.
You may notice a dark discoloration (red, brown, or black) in your saliva, urine, or sweat while taking this medication. Although this is harmless, it may stain your clothing.
If you experience diarrhea or vomiting, consult your doctor promptly. It is crucial to prevent dehydration and electrolyte imbalances.
If you are pregnant, planning to become pregnant, or breastfeeding, inform your doctor. You and your doctor will need to discuss the potential benefits and risks of this medication to you and your baby.
Until you know how this medication affects you, avoid driving and other activities that require your full attention. To minimize the risk of dizziness or fainting, get up slowly from a sitting or lying position, and be cautious when climbing stairs.
Regular blood tests and other laboratory evaluations are crucial while taking this medication. Follow your doctor's instructions for scheduling these tests. Additionally, inform all your healthcare providers and laboratory personnel that you are taking this medication, as it may interfere with certain lab tests.
You may experience a decrease in the medication's effectiveness as the time approaches for your next dose. If this occurs and bothers you, discuss it with your doctor. It may take several months to notice the full benefits of this medication.
Before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that can cause drowsiness, consult with your doctor.
You may notice a dark discoloration (red, brown, or black) in your saliva, urine, or sweat while taking this medication. Although this is harmless, it may stain your clothing.
If you experience diarrhea or vomiting, consult your doctor promptly. It is crucial to prevent dehydration and electrolyte imbalances.
If you are pregnant, planning to become pregnant, or breastfeeding, inform your doctor. You and your doctor will need to discuss the potential benefits and risks of this medication to you and your baby.
Overdose Information
Overdose Symptoms:
- Agitation
- Confusion
- Dyskinesias (severe involuntary movements)
- Orthostatic hypotension
- Tachycardia
- Arrhythmias
What to Do:
Seek immediate medical attention. Call 911 or your local emergency number. For poison control, call 1-800-222-1222.
Drug Interactions
Contraindicated Interactions
- Non-selective monoamine oxidase (MAO) inhibitors (e.g., phenelzine, tranylcypromine) - risk of hypertensive crisis. Must be discontinued at least 2 weeks prior.
Major Interactions
- Antipsychotics (e.g., haloperidol, chlorpromazine, risperidone, olanzapine) - may antagonize the effects of levodopa.
- Iron salts (ferrous sulfate, gluconate) - can chelate levodopa and carbidopa, reducing absorption. Separate administration by at least 2-3 hours.
- Metoclopramide - may increase gastric emptying and antagonize levodopa effects.
- Dopamine D2 receptor antagonists (e.g., droperidol, phenothiazines, butyrophenones, metoclopramide) - may reduce therapeutic effects.
Moderate Interactions
- Antihypertensives - increased risk of orthostatic hypotension.
- Tricyclic antidepressants (TCAs) - may increase risk of orthostatic hypotension and hypertension.
- Other drugs metabolized by COMT (e.g., isoproterenol, epinephrine, norepinephrine, dopamine, dobutamine, alpha-methyldopa, apomorphine) - may increase their systemic exposure.
- CNS depressants (e.g., alcohol, benzodiazepines, opioids) - additive sedative effects.
Minor Interactions
- High-protein diet - may reduce levodopa absorption.
Monitoring
Baseline Monitoring
Blood pressure (sitting and standing)
Rationale: To assess for orthostatic hypotension, a common side effect.
Timing: Before initiation and during titration.
Heart rate
Rationale: To assess for cardiovascular effects.
Timing: Before initiation.
Liver function tests (ALT, AST, bilirubin)
Rationale: Entacapone can rarely cause hepatotoxicity.
Timing: Before initiation.
Renal function (BUN, creatinine)
Rationale: To assess baseline kidney function, especially in patients with pre-existing impairment.
Timing: Before initiation.
Complete Blood Count (CBC)
Rationale: To assess for potential hematologic abnormalities (e.g., hemolytic anemia, thrombocytopenia) though rare.
Timing: Before initiation.
Routine Monitoring
Motor fluctuations (e.g., 'wearing-off', dyskinesias)
Frequency: Regularly during follow-up visits (e.g., every 3-6 months or as needed)
Target: Optimal motor control with minimal dyskinesia
Action Threshold: Increased 'off' time, troublesome dyskinesias, or other motor complications require dose adjustment or addition of other therapies.
Blood pressure (sitting and standing)
Frequency: Regularly, especially during dose titration and if symptoms of orthostatic hypotension occur.
Target: Stable, normotensive readings
Action Threshold: Significant drop in systolic BP (>20 mmHg) or diastolic BP (>10 mmHg) upon standing, or symptomatic hypotension.
Mental status/Neuropsychiatric symptoms (e.g., hallucinations, confusion, impulse control disorders, excessive somnolence)
Frequency: Regularly during follow-up visits.
Target: Absence or minimal severity of symptoms.
Action Threshold: New onset or worsening of these symptoms requires evaluation and potential dose adjustment or discontinuation.
Liver function tests (ALT, AST)
Frequency: Periodically (e.g., every 6-12 months) or if symptoms of liver dysfunction occur.
Target: Within normal limits
Action Threshold: Significant elevation (e.g., >3x ULN) requires investigation and potential discontinuation.
Symptom Monitoring
- Dyskinesia (involuntary movements)
- Motor fluctuations ('wearing-off', 'on-off' phenomena)
- Orthostatic hypotension (dizziness, lightheadedness upon standing)
- Nausea/vomiting
- Hallucinations/delusions
- Confusion/agitation
- Excessive daytime sleepiness/sudden sleep onset
- Impulse control disorders (e.g., pathological gambling, hypersexuality, compulsive shopping, binge eating)
- Diarrhea
- Abdominal pain
- Dark discoloration of urine, sweat, or saliva (harmless, due to entacapone metabolites)
Special Patient Groups
Pregnancy
Category C. Use only if the potential benefit justifies the potential risk to the fetus. Levodopa has been shown to be teratogenic in animals.
Trimester-Specific Risks:
First Trimester:
Potential for teratogenicity based on animal studies. Human data are limited.
Second Trimester:
Limited human data. Monitor for maternal adverse effects that could impact pregnancy.
Third Trimester:
Limited human data. Monitor for maternal adverse effects and potential impact on labor/delivery.
Lactation
Levodopa is excreted into breast milk and can inhibit lactation. Entacapone is also excreted into breast milk in animals. Due to potential for serious adverse reactions in the infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
L3 (Moderate risk). Potential for inhibition of lactation, and unknown effects of levodopa, carbidopa, and entacapone on the infant. Monitor for drowsiness, poor feeding, or unusual movements.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients. Not recommended for use in children.
Geriatric Use
No specific dose adjustment is generally required based on age alone, but elderly patients may be more sensitive to the central nervous system and cardiovascular side effects (e.g., hallucinations, orthostatic hypotension). Start with lower doses and titrate carefully.
Clinical Information
Clinical Pearls
- This combination product is particularly useful for patients with Parkinson's disease who experience 'wearing-off' phenomena on levodopa/carbidopa alone.
- Patients should be advised about the harmless discoloration of urine, sweat, and saliva (reddish-brown to black) due to entacapone metabolites.
- Impulse control disorders (e.g., pathological gambling, hypersexuality, compulsive shopping, binge eating) can occur with dopamine replacement therapies; patients and caregivers should be counselled to monitor for these.
- Sudden onset of sleep without warning has been reported; patients should be cautioned about driving or engaging in activities where sudden sleep could be dangerous.
- Severe, persistent diarrhea can be a serious side effect of entacapone and may require discontinuation. Patients should report this immediately.
- Iron supplements should be taken at least 2-3 hours apart from this medication to avoid reduced absorption.
Alternative Therapies
- Dopamine agonists (e.g., pramipexole, ropinirole, rotigotine, apomorphine)
- MAO-B inhibitors (e.g., selegiline, rasagiline, safinamide)
- Amantadine
- Anticholinergics (e.g., benztropine, trihexyphenidyl)
- COMT inhibitors (e.g., entacapone, opicapone, tolcapone - as monotherapy or with levodopa/carbidopa)
Cost & Coverage
Average Cost:
Varies widely by strength and quantity (e.g., $200-$1000+) per 30 tablets
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (preferred or non-preferred brand/generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide information about what was taken, the amount, and the time it happened.