Carbidopa/lev/entac 50-200-200mg Tb
It is used to treat Parkinson's disease.
Drug Class
Anti-Parkinson's agent
Pharmacologic Class
Dopamine precursor; DOPA decarboxylase inhibitor; COMT inhibitor
Pregnancy Category
Category C
FDA Approved
Jan 2003
DEA Schedule
Not Controlled
Overview
What is this medicine?
This medicine is a combination of three drugs 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. This combination helps reduce 'off' times when your Parkinson's symptoms return.
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 precisely. You can take this medication with or without food, but be sure to 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 in relation to this medication, as iron may interfere with the absorption of this drug. Additionally, diets high in protein, fat, or calories, as well as consuming acidic foods, may also affect how well your body absorbs this medication. Discuss your diet with your doctor, especially if you plan to make any changes.
It's essential to continue taking this medication even when you're not experiencing symptoms. Keeping a diary to track 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're feeling well.
Stopping Your Medication
Do not stop taking this medication abruptly without consulting your doctor, as this may increase your risk of side effects. If you need to stop taking this medication, your doctor will instruct you on how to taper off gradually.
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. Consult your pharmacist for guidance on the best way to dispose of medications, and ask about potential drug take-back programs in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's 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 make up for a missed one.
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 precisely. You can take this medication with or without food, but be sure to 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 in relation to this medication, as iron may interfere with the absorption of this drug. Additionally, diets high in protein, fat, or calories, as well as consuming acidic foods, may also affect how well your body absorbs this medication. Discuss your diet with your doctor, especially if you plan to make any changes.
It's essential to continue taking this medication even when you're not experiencing symptoms. Keeping a diary to track 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're feeling well.
Stopping Your Medication
Do not stop taking this medication abruptly without consulting your doctor, as this may increase your risk of side effects. If you need to stop taking this medication, your doctor will instruct you on how to taper off gradually.
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. Consult your pharmacist for guidance on the best way to dispose of medications, and ask about potential drug take-back programs in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's 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 make up for a missed one.
Lifestyle & Tips
- Take exactly as prescribed; do not stop taking suddenly without consulting your doctor, as this can lead to serious side effects.
- Swallow tablets whole; do not crush, chew, or split.
- Can be taken with or without food. Taking with food may reduce nausea but can delay absorption. Avoid high-protein meals close to dosing.
- Stand up slowly from a sitting or lying position to avoid dizziness or fainting due to orthostatic hypotension.
- Report any new or worsening involuntary movements (dyskinesia) or changes in behavior (e.g., increased gambling, shopping, sexual urges) to your doctor.
- Your urine, sweat, or saliva may turn dark reddish-brown or black. This is a harmless effect of entacapone and its metabolites.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
One tablet of Carbidopa/Levodopa/Entacapone 50-200-200mg orally, up to 8 times daily, as directed by physician.
Dose Range:
1 - 8 mg
Condition-Specific Dosing:
initial_therapy:
Not for initiation of levodopa therapy. Used for patients already on carbidopa/levodopa who experience 'wearing-off' phenomena.
max_daily_entacapone:
Maximum recommended daily dose of entacapone is 1600 mg (8 tablets of 200 mg entacapone).
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
No specific dose adjustment recommended.
Severe:
Use with caution; monitor for adverse effects. Entacapone excretion is primarily biliary, but a small portion is renal.
Dialysis:
Not well studied; use with caution and monitor closely.
Hepatic Impairment:
Mild:
Use with caution; monitor for adverse effects.
Moderate:
Consider dose reduction; monitor closely for adverse effects, especially related to entacapone.
Severe:
Not recommended due to increased exposure to entacapone.
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 peripheral DOPA decarboxylase, preventing the peripheral conversion of levodopa to dopamine, thus increasing the amount of levodopa available to the CNS. Entacapone is a reversible and selective inhibitor of catechol-O-methyltransferase (COMT), which reduces the peripheral metabolism of levodopa, leading to more sustained plasma levels of levodopa and increased brain availability.
Pharmacokinetics
Absorption:
Bioavailability:
Levodopa: variable, ~30% (with carbidopa); Carbidopa: ~50%; Entacapone: ~35%
Tmax:
Levodopa: 0.5-2 hours; Carbidopa: 0.5-2 hours; Entacapone: ~1 hour
FoodEffect:
Food delays and decreases the absorption of levodopa and entacapone. High-protein meals can reduce levodopa absorption.
Distribution:
Vd:
Levodopa: 0.36-1.6 L/kg; Carbidopa: 1.3 L/kg; Entacapone: ~20 L
ProteinBinding:
Levodopa: low; Carbidopa: ~36%; Entacapone: ~98% (primarily to albumin)
CnssPenetration:
Levodopa: Yes; Carbidopa: No (does not cross BBB); Entacapone: Limited (does not readily cross BBB)
Elimination:
HalfLife:
Levodopa: ~1-2 hours (extended to 2-3 hours with entacapone); Carbidopa: ~2 hours; Entacapone: ~2.4 hours
Clearance:
Not available for combination product; individual component clearances vary.
ExcretionRoute:
Urine (major for levodopa/carbidopa metabolites, entacapone metabolites); Feces (minor for levodopa/carbidopa, major for unchanged entacapone)
Unchanged:
Levodopa: <1%; Carbidopa: ~30%; Entacapone: 10-20% (in urine)
Pharmacodynamics
OnsetOfAction:
Typically 30-60 minutes
PeakEffect:
1-2 hours
DurationOfAction:
2-4 hours (entacapone extends levodopa's duration of action by inhibiting its metabolism)
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
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 behavioral or mood changes, including depression or 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, sore throat, unexplained bruising or bleeding, or feeling extremely tired or weak
Sudden, uncontrollable sleepiness, even during activities like driving, eating, or talking (if this occurs, do not drive or engage in tasks that require alertness)
Important Warning: Stopping this medication abruptly or reducing the dose can lead to a rare but potentially life-threatening condition called neuroleptic malignant syndrome (NMS). If you experience any of the following symptoms, contact your doctor immediately:
Fever
Muscle cramps or stiffness
Dizziness
Severe headache
Confusion
Changes in thinking or mental status
Rapid heartbeat or irregular heartbeat
Excessive sweating
Other Possible Side Effects
While many people may not experience any side effects or only minor ones, it is essential to be aware of the following potential side effects. If you are bothered by any of these symptoms or if they persist, contact your doctor:
Dizziness, drowsiness, tiredness, or weakness
Constipation, diarrhea, stomach pain, upset stomach, or vomiting
Dry mouth
Headache
Trouble sleeping
Back pain
Reporting 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 notice any of the following symptoms, contact your doctor or seek immediate medical attention:
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 behavioral or mood changes, including depression or 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, sore throat, unexplained bruising or bleeding, or feeling extremely tired or weak
Sudden, uncontrollable sleepiness, even during activities like driving, eating, or talking (if this occurs, do not drive or engage in tasks that require alertness)
Important Warning: Stopping this medication abruptly or reducing the dose can lead to a rare but potentially life-threatening condition called neuroleptic malignant syndrome (NMS). If you experience any of the following symptoms, contact your doctor immediately:
Fever
Muscle cramps or stiffness
Dizziness
Severe headache
Confusion
Changes in thinking or mental status
Rapid heartbeat or irregular heartbeat
Excessive sweating
Other Possible Side Effects
While many people may not experience any side effects or only minor ones, it is essential to be aware of the following potential side effects. If you are bothered by any of these symptoms or if they persist, contact your doctor:
Dizziness, drowsiness, tiredness, or weakness
Constipation, diarrhea, stomach pain, upset stomach, or vomiting
Dry mouth
Headache
Trouble sleeping
Back pain
Reporting 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:
- Severe dizziness or fainting spells
- New or worsening involuntary movements (dyskinesia)
- Hallucinations (seeing or hearing things that are not there), confusion, unusual thoughts
- Unusual urges or behaviors (e.g., compulsive gambling, hypersexuality, binge eating)
- Severe or persistent diarrhea
- Symptoms of liver problems (e.g., yellowing of skin or eyes, dark urine, persistent nausea/vomiting, unusual fatigue)
- Muscle stiffness, high fever, sweating, fast or irregular heartbeat, confusion (signs of neuroleptic malignant syndrome-like reaction, especially if medication is stopped suddenly)
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. Be sure to describe the allergic reaction and its symptoms.
Certain health conditions, such as:
+ Glaucoma
+ Skin lumps or growths
+ A history of skin cancer
If you have taken specific antidepressant medications, including isocarboxazid, phenelzine, or tranylcypromine, within the last 14 days. Taking this medication within 14 days of these drugs can lead to severe high blood pressure.
Please note that this is not an exhaustive list of potential interactions. To ensure your safety, it is crucial to:
Inform your doctor and pharmacist about all your medications, including prescription and over-the-counter drugs, natural products, and vitamins.
Discuss your health problems with your doctor to determine if it is safe to take this medication.
Never start, stop, or change the dose of any medication without consulting your doctor first.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction and its symptoms.
Certain health conditions, such as:
+ Glaucoma
+ Skin lumps or growths
+ A history of skin cancer
If you have taken specific antidepressant medications, including isocarboxazid, phenelzine, or tranylcypromine, within the last 14 days. Taking this medication within 14 days of these drugs can lead to severe high blood pressure.
Please note that this is not an exhaustive list of potential interactions. To ensure your safety, it is crucial to:
Inform your doctor and pharmacist about all your medications, including prescription and over-the-counter drugs, natural products, and vitamins.
Discuss your health problems with your doctor to determine if it is safe to take this medication.
Never start, stop, or change the dose of any medication without consulting your doctor first.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
When starting this medication, be cautious when driving or performing tasks that require your full attention, as it may affect your alertness. To minimize the risk of dizziness or fainting, get up slowly from a sitting or lying position, and be careful when climbing stairs.
Regular blood tests and other laboratory assessments are crucial while taking this medication. Your doctor will advise you on the frequency of these tests. It is also important to notify 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 effect as the time approaches for your next dose. If this occurs and causes you concern, discuss it with your doctor. It may take several months to feel the full benefits of this medication.
Before consuming alcohol, marijuana, or other forms of cannabis, or taking prescription or over-the-counter drugs that may 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 to prevent dehydration and electrolyte imbalances.
If you are pregnant, planning to become pregnant, or breastfeeding, inform your doctor. It is crucial to discuss the potential benefits and risks of this medication to both you and your baby.
When starting this medication, be cautious when driving or performing tasks that require your full attention, as it may affect your alertness. To minimize the risk of dizziness or fainting, get up slowly from a sitting or lying position, and be careful when climbing stairs.
Regular blood tests and other laboratory assessments are crucial while taking this medication. Your doctor will advise you on the frequency of these tests. It is also important to notify 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 effect as the time approaches for your next dose. If this occurs and causes you concern, discuss it with your doctor. It may take several months to feel the full benefits of this medication.
Before consuming alcohol, marijuana, or other forms of cannabis, or taking prescription or over-the-counter drugs that may 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 to prevent dehydration and electrolyte imbalances.
If you are pregnant, planning to become pregnant, or breastfeeding, inform your doctor. It is crucial to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Severe dyskinesia (involuntary movements)
- Agitation, confusion, hallucinations
- Orthostatic hypotension (severe dizziness, fainting)
- Cardiac arrhythmias
- Nausea, vomiting
What to Do:
Seek immediate medical attention. Call 911 or Poison Control (1-800-222-1222). Treatment is supportive, including gastric lavage, IV fluids, and careful monitoring of vital signs and cardiac rhythm.
Drug Interactions
Contraindicated Interactions
- Non-selective monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, tranylcypromine) - risk of hypertensive crisis. Discontinue MAOIs at least 2 weeks prior.
Major Interactions
- Antipsychotics (e.g., haloperidol, chlorpromazine, risperidone) - may antagonize the effects of levodopa.
- Metoclopramide - may antagonize the effects of levodopa.
- Iron salts (ferrous sulfate, gluconate) - may chelate levodopa and carbidopa, reducing absorption.
- Pyridoxine (Vitamin B6) - can reverse the effects of levodopa if not given with carbidopa (less relevant for this combination).
Moderate Interactions
- Antihypertensives - additive hypotensive effects, monitor for orthostatic hypotension.
- Tricyclic antidepressants (TCAs) - rare reports of hypertension and dyskinesia.
- Sympathomimetics (e.g., epinephrine, norepinephrine, dopamine) - increased risk of arrhythmias.
- Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, metoclopramide) - may reduce therapeutic effects.
Minor Interactions
- High-protein diet - may reduce levodopa absorption.
Monitoring
Baseline Monitoring
Neurological examination
Rationale: To establish baseline Parkinson's symptoms, motor fluctuations, and dyskinesia severity.
Timing: Prior to initiation of therapy.
Blood pressure (supine and standing)
Rationale: To assess for baseline orthostatic hypotension risk.
Timing: Prior to initiation of therapy.
Liver function tests (ALT, AST, bilirubin)
Rationale: Entacapone can cause liver injury; establish baseline liver function.
Timing: Prior to initiation of therapy.
Routine Monitoring
Neurological examination (Parkinson's symptoms, dyskinesia, 'on-off' fluctuations)
Frequency: At each follow-up visit, or as clinically indicated.
Target: Improvement in motor symptoms, reduction in 'off' time, acceptable level of dyskinesia.
Action Threshold: Worsening symptoms, new or worsening dyskinesia, significant 'off' time, or development of non-motor symptoms (e.g., hallucinations, impulse control disorders) warrant dose adjustment or further evaluation.
Blood pressure (supine and standing)
Frequency: Regularly, especially during dose titration and if symptoms of orthostatic hypotension occur.
Target: Maintain within patient's normal range, minimize symptomatic orthostasis.
Action Threshold: Symptomatic orthostatic hypotension (dizziness, lightheadedness, syncope) requires intervention (e.g., dose reduction, non-pharmacological measures).
Liver function tests (ALT, AST)
Frequency: Periodically, or if symptoms suggestive of liver dysfunction occur (e.g., unexplained fatigue, nausea, dark urine, jaundice).
Target: Within normal limits.
Action Threshold: Significant elevation (e.g., >3x ULN) warrants discontinuation or dose reduction of entacapone.
Renal function (BUN, creatinine)
Frequency: Periodically, especially in patients with pre-existing renal impairment.
Target: Within normal limits.
Action Threshold: Significant decline in renal function may necessitate dose adjustment or closer monitoring.
Complete Blood Count (CBC)
Frequency: Periodically, as rare cases of hemolytic anemia, thrombocytopenia, and leukopenia have been reported.
Target: Within normal limits.
Action Threshold: Significant abnormalities warrant further investigation and potential discontinuation.
Symptom Monitoring
- Orthostatic hypotension (dizziness, lightheadedness, fainting)
- Dyskinesia (involuntary movements)
- Hallucinations, delusions, confusion
- Impulse control disorders (e.g., pathological gambling, hypersexuality, compulsive shopping, binge eating)
- Diarrhea (can be severe and persistent)
- Nausea, vomiting
- Dark discoloration of urine, sweat, or saliva (harmless, due to entacapone metabolites)
- Symptoms of liver injury (e.g., persistent fatigue, dark urine, jaundice, right upper quadrant pain)
- Neuroleptic malignant syndrome-like symptoms (fever, muscle rigidity, altered mental status) if abruptly discontinued
Special Patient Groups
Pregnancy
Category C. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies have shown developmental toxicity with levodopa and entacapone.
Trimester-Specific Risks:
First Trimester:
Limited human data. Animal studies suggest potential for developmental toxicity (e.g., visceral and skeletal abnormalities, reduced fetal weight).
Second Trimester:
Limited human data.
Third Trimester:
Limited human data. Levodopa may inhibit lactation.
Lactation
Not recommended. Levodopa is known to inhibit prolactin secretion and may suppress lactation. It is unknown if carbidopa or entacapone are excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Potential for adverse effects on the infant, including interference with neurological development or growth, and unknown effects of entacapone.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. This medication is not indicated for use in children.
Geriatric Use
No specific dose adjustment is generally required based on age alone. However, elderly patients may be more sensitive to the central nervous system (e.g., hallucinations, confusion) and cardiovascular (e.g., orthostatic hypotension) adverse effects of levodopa. Monitor closely for these effects.
Clinical Information
Clinical Pearls
- This combination product is specifically designed for Parkinson's patients experiencing 'wearing-off' phenomena on their current carbidopa/levodopa regimen, to extend the 'on' time.
- Patients should be advised about the harmless discoloration of urine, sweat, or saliva (reddish-brown to black) due to entacapone metabolites.
- Monitor for the development or worsening of impulse control disorders (e.g., pathological gambling, hypersexuality, compulsive shopping, binge eating), which can occur with dopaminergic therapies.
- Diarrhea is a common and sometimes severe side effect of entacapone; patients should be advised to report persistent or severe diarrhea.
- Abrupt discontinuation of this medication can lead to a syndrome resembling neuroleptic malignant syndrome (NMS), characterized by fever, muscle rigidity, altered mental status, and autonomic instability. Taper slowly if discontinuation is necessary.
Alternative Therapies
- Dopamine agonists (e.g., pramipexole, ropinirole, rotigotine, apomorphine)
- MAO-B inhibitors (e.g., selegiline, rasagiline, safinamide)
- Amantadine
- Anticholinergics (e.g., benztropine, trihexyphenidyl) - primarily for tremor
- COMT inhibitors (e.g., entacapone, tolcapone) as monotherapy adjunct to carbidopa/levodopa
- Adenosine A2A receptor antagonists (e.g., istradefylline)
Cost & Coverage
Average Cost:
$150 - $600+ per 30 tablets
Generic Available:
Yes
Insurance Coverage:
Generics are typically Tier 2 or 3. Brand-name Stalevo, if available, would likely be Tier 3 or 4.
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, 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 for more information. If you have any questions or concerns about this medication, don't hesitate to discuss them with 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 details about the medication taken, including the amount and time of ingestion.