What is Carbidopa/levodopa?
Carbidopa/levodopa combination is used to treat Parkinson's disease, sometimes called shaking palsy or paralysis agitans. Parkinson's disease is a disorder of the central nervous system (brain and spinal cord).
Extended-release Carbidopa/levodopa (Carbidopa/levodopa®) is also used to treat parkinsonism caused by encephalitis, or parkinsonism caused by carbon monoxide or manganese poisoning.
Dopamine is a naturally occurring substance in the brain that helps provide control of movement and activities such as walking and talking. In patients with Parkinson's disease, there is not enough dopamine in some parts of the brain. Levodopa enters the brain and helps replace the missing dopamine, which allows people to function better. By increasing the amount of dopamine in the brain, levodopa helps control symptoms and helps you to perform daily activities such as dressing, walking, and handling utensils.
Carbidopa/levodopa is available only with your doctor's prescription.
Carbidopa/levodopa indications
Carbidopa/levodopa orally disintegrating tablets are indicated in the treatment of the symptoms of idiopathic Parkinson’s disease (paralysis agitans), postencephalitic parkinsonism, and symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication. Carbidopa/levodopa orally disintegrating tablets are indicated in these conditions to permit the administration of lower doses of levodopa with reduced nausea and vomiting, with more rapid dosage titration, with a somewhat smoother response, and with supplemental pyridoxine (vitamin B6).
In some patients, a somewhat smoother antiparkinsonian effect results from therapy with Carbidopa/levodopa than with levodopa. However, patients with markedly irregular (“on-off”) responses to levodopa have not been shown to benefit from Carbidopa/levodopa therapy.
Although the administration of carbidopa permits control of parkinsonism and Parkinson’s disease with much lower doses of levodopa, there is no conclusive evidence at present that this is beneficial other than in reducing nausea and vomiting, permitting more rapid titration, and providing a somewhat smoother response to levodopa.
Certain patients who responded poorly to levodopa have improved when Carbidopa/levodopa was substituted. This is most likely due to decreased peripheral decarboxylation of levodopa which results from administration of carbidopa rather than to a primary effect of carbidopa on the nervous system. Carbidopa has not been shown to enhance the intrinsic efficacy of levodopa in parkinsonian syndromes.
In considering whether to give Carbidopa/levodopa orally disintegrating tablets to patients already on levodopa who have nausea and/or vomiting, the practitioner should be aware that, while many patients may be expected to improve, some do not. Since one cannot predict which patients are likely to improve, this can only be determined by a trial of therapy. It should be further noted that in controlled trials comparing Carbidopa/levodopa with levodopa, about half of the patients with nausea and/or vomiting on levodopa improved spontaneously despite being retained on the same dose of levodopa during the controlled portion of the trial.
How should I use Carbidopa/levodopa?
Use Carbidopa/levodopa as directed by your doctor. Check the label on the medicine for exact dosing instructions.
- Take Carbidopa/levodopa by mouth with or without food.
- If you take an iron product or a multivitamin that contains iron, ask your doctor or pharmacist how to take it with Carbidopa/levodopa. Iron may decrease your body's ability to absorb Carbidopa/levodopa.
- Diets that are high in some contents (eg, protein, fat, calories) may decrease your body's ability to absorb Carbidopa/levodopa. Discuss any questions or concerns with your doctor. Tell your doctor if you have a diet that is high in protein, fat, or calories or if you will be changing your diet.
- Carefully follow the dosing schedule given to you by your health care provider.
- Take Carbidopa/levodopa on a regular schedule to get the most benefit from it. Taking Carbidopa/levodopa at the same times each day will help you to remember to take it.
- Continue to take Carbidopa/levodopa even if you feel well. Do not miss any doses.
- If you have been taking levodopa, do not start taking Carbidopa/levodopa until at least 12 hours after your final dose of levodopa.
- Do not suddenly stop taking Carbidopa/levodopa or lower your dose without checking with your doctor. Side effects may occur. Discuss any questions or concerns with your doctor.
- If you miss a dose of Carbidopa/levodopa, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.
Ask your health care provider any questions you may have about how to use Carbidopa/levodopa.
Uses of Carbidopa/levodopa in details
This medication is used to treat symptoms of Parkinson's disease (such as shakiness, stiffness, difficulty moving).
Parkinson's disease is thought to be caused by too little of a naturally occurring substance (dopamine) in the brain. Levodopa changes into dopamine in the brain, helping to control movement. Carbidopa prevents the breakdown of levodopa in the bloodstream so more levodopa can enter the brain. Carbidopa can also reduce some of levodopa's side effects such as nausea and vomiting.
By giving this medication as a continuous infusion, it can help reduce the amount of "off" time (periods of slow movement or stiffness).
How to use Carbidopa/levodopa
Read the Medication Guide and the Instructions for Use provided by your health care professional before you start using this medication and each time you get a refill. If you have any questions, ask your health care professional.
Give this medication as directed as a continuous infusion into the small intestine using an infusion pump. It is usually given over 16 hours a day and stopped at bedtime. At bedtime, take your dose of immediate-release Carbidopa/levodopa tablets by mouth as directed.
When you first start using this medication, it is given through a tube through the nose into the small intestine. After a few days, if the doctor decides that this product is right for you, then the medication will be given through a tube through the abdomen into the small intestine. Getting the tube through the abdomen will require surgery.
Follow all instructions from your health care professional about how to properly use this medication and the infusion pump. Take a cassette containing the medication from the refrigerator and leave it at room temperature for 20 minutes before using. Do not use a cassette for longer than 16 hours or re-use it, even if there is medication left in it. Learn how to store and discard medical supplies safely. Also learn how to properly care for the small hole in your abdomen and the skin area around the tube, and how to avoid infection.
The dosage is based on your medical condition and response to treatment. Your daily dose is made up of a morning dose, a continuous dose, and extra doses. An extra dose is a small dose of this medication that can be given as needed during the day to treat sudden "off" symptoms. Extra doses should not be given more often than one every 2 hours to avoid causing or worsening movements you cannot control.
Do not suddenly decrease the dose or suddenly stop using this medication because doing either may lead to a serious condition. If you must stop this medication, slowly reduce the dose as directed by your doctor. Contact your doctor right away if your infusion is interrupted. You may need to take the tablet form of Carbidopa/levodopa by mouth.
If you plan to be disconnected from the pump for a short period of time (less than 2 hours, for example, to shower), ask your doctor ahead of time if you should use an extra dose of this medication before you disconnect. If you plan to be disconnected from the pump for longer than 2 hours, ask your doctor what you should do and discuss how you should take Carbidopa/levodopa tablets by mouth during this time.
Avoid high-protein diets because they may reduce how much of the medication you can absorb.
Tell your doctor if your condition does not improve or if it worsens.
Carbidopa/levodopa description
The naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.
Carbidopa/levodopa dosage
Dosage in Patients Naïve to Levodopa Therapy
The recommended starting dosage of Carbidopa/levodopa in levodopa-naïve patients is 23.75 mg / 95 mg taken orally three times a day for the first 3 days. On the fourth day of treatment, the dosage of Carbidopa/levodopa may be increased to 36.25 mg / 145 mg taken three times a day.
Based upon individual patient clinical response and tolerability, the Carbidopa/levodopa dose may be increased up to a maximum recommended dose of 97.5 mg / 390 mg taken three times a day. The dosing frequency may be changed from three times a day to a maximum of five times a day if more frequent dosing is needed and if tolerated. The maximum recommended daily dose of Carbidopa/levodopa is 612.5 mg / 2450 mg.
Maintain patients on the lowest dosage required to achieve symptomatic control and to minimize adverse reactions such as dyskinesia and nausea.
Converting from Immediate-Release Carbidopa-Levodopa to Carbidopa/levodopa
To convert patients from immediate-release carbidopa-levodopa to Carbidopa/levodopa, determine the recommended starting dosage of Carbidopa/levodopa using Table 1.
The dosages of other Carbidopa/levodopa products are not interchangeable with the dosages of Carbidopa/levodopa.
Adjust the dose to maintain patient tolerance and sufficient symptomatic control. The dosing frequency may be changed from three times a day to a maximum of five times a day if more frequent dosing is needed and if tolerated. The maximum recommended daily dose of Carbidopa/levodopa is 612.5 mg / 2450 mg.
For patients currently treated with Carbidopa/levodopa plus catechol-O-methyl transferase (COMT) inhibitors (such as entacapone), the initial total daily dose of levodopa in Carbidopa/levodopa described in Table 1 may need to be increased.
Use of Carbidopa/levodopa in combination with other levodopa products has not been studied.
| Total Daily Dose of Levodopa in Immediate-Release Carbidopa-Levodopa | Recommended Starting Dosage of Carbidopa/levodopa | |
|---|---|---|
| Total Daily Dose of Levodopa in Carbidopa/levodopa | Carbidopa/levodopa Dosing Regimen | |
| ||
| 400 mg to 549 mg | 855 mg | 3 capsules Carbidopa/levodopa 23.75 mg / 95 mg taken TID* |
| 550 mg to 749 mg | 1140 mg | 4 capsules Carbidopa/levodopa 23.75 mg / 95 mg taken TID |
| 750 mg to 949 mg | 1305 mg | 3 capsules Carbidopa/levodopa 36.25 mg / 145 mg taken TID |
| 950 mg to 1249 mg | 1755 mg | 3 capsules Carbidopa/levodopa 48.75 mg / 195 mg taken TID |
| Equal to or greater than 1250 mg | 2340 mg or | 4 capsules Carbidopa/levodopa 48.75 mg / 195 mg taken TID or |
| 2205 mg | 3 capsules Carbidopa/levodopa 61.25 mg / 245 mg taken TID | |
Discontinuation of Carbidopa/levodopa
Avoid sudden discontinuation or rapid dose reduction of Carbidopa/levodopa. The daily dose of Carbidopa/levodopa should be tapered at the time of treatment discontinuation.
Administration Information
Swallow Carbidopa/levodopa whole with or without food. A high-fat, high-calorie meal may delay the absorption of levodopa by about 2 hours.
Do not chew, divide or crush Carbidopa/levodopa capsules. For patients who have difficulty swallowing intact capsules, administer Carbidopa/levodopa by carefully opening the capsule, sprinkling the entire contents on a small amount of applesauce (1 to 2 tablespoons), and consuming immediately. Do not store the drug/food mixture for future use.
Carbidopa/levodopa interactions
See also:
What other drugs will affect Carbidopa/levodopa?
Monoamine Oxidase (MAO) Inhibitors
The use of nonselective MAO inhibitors with Carbidopa/levodopa is contraindicated. Discontinue use of any nonselective MAO inhibitors at least two weeks prior to initiating Carbidopa/levodopa.
The use of selective MAO-B inhibitors (e.g., rasagiline and selegiline) with Carbidopa/levodopa may be associated with orthostatic hypotension. Monitor patients who are taking these drugs.
Antihypertensive Drugs
The concurrent use of Carbidopa/levodopa with antihypertensive medications can cause symptomatic postural hypotension. A dose reduction of the antihypertensive medication may be needed after starting or increasing the dose of Carbidopa/levodopa.
Dopamine D2 Receptor Antagonists And Isoniazid
Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone, metoclopramide, papaverine) and isoniazid may reduce the effectiveness of levodopa. Monitor patients for worsening Parkinson's symptoms.
Iron Salts
Iron salts or multi-vitamins containing iron salts can form chelates with levodopa, carbidopa, and can cause a reduction in the bioavailability of Carbidopa/levodopa. If iron salts or multi-vitamins containing iron salts are co-administered with Carbidopa/levodopa, monitor patients for worsening Parkinson's symptoms.
High-Protein Diet
Because levodopa competes with certain amino acids for transport across the gut wall, the absorption of levodopa may be decreased in patients on a high-protein diet. Advise patients that a high-protein diet may reduce the effectiveness of Carbidopa/levodopa.
Carbidopa/levodopa side effects
See also:
What are the possible side effects of Carbidopa/levodopa?
The following serious adverse reactions are discussed below and elsewhere in the labeling:
- Falling asleep during activities of daily living and somnolence
- Withdrawal-emergent hyperpyrexia and confusion
- Cardiovascular ischemic events
- Hallucinations/psychosis
- Impulse control/compulsive behaviors
- Dyskinesia
- Peptic Ulcer Disease
- Glaucoma
- Melanoma
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety population consisted of a total of 978 Parkinson's disease patients who received at least one dose of Carbidopa/levodopa, and had an average duration of exposure of 40 weeks.
Adverse Reactions In Early Parkinson's Disease
In a placebo-controlled clinical study in patients with early Parkinson's disease (Study 1), the most common adverse reactions with Carbidopa/levodopa (in at least 5% of patients and more frequently than in placebo) were nausea, dizziness, headache, insomnia, abnormal dreams, dry mouth, dyskinesia, anxiety, constipation, vomiting, and orthostatic hypotension.
Table 2 lists adverse reactions occurring in at least 5% of Carbidopa/levodopa-treated patients and at a higher rate than placebo in Study 1.
Table 2: Adverse Reactions in Study 1 in Patients with Early Stage Parkinson's Disease
| Placebo | Carbidopa/levodopa 36.25 mg carbidopa 145 mg Levodopa TID | Carbidopa/levodopa 61.25 mg carbidopa 245 mg Levodopa TID | Carbidopa/levodopa 97.5 mg carbidopa 390 mg Levodopa TID | |
| (N=92) % | (N=87) % | (N=104) % | (N=98) % | |
| Nausea | 9 | 14 | 19 | 20 |
| Dizziness | 5 | 9 | 19 | 12 |
| Headache | 11 | 7 | 13 | 17 |
| Insomnia | 3 | 2 | 9 | 6 |
| Abnormal Dreams | 0 | 2 | 6 | 5 |
| Dry Mouth | 1 | 3 | 2 | 7 |
| Dyskinesia | 0 | 2 | 4 | 5 |
| Anxiety | 0 | 2 | 3 | 5 |
| Constipation | 1 | 2 | 6 | 2 |
| Vomiting | 3 | 2 | 2 | 5 |
| Orthostatic | ||||
| Hypotension | 1 | 1 | 1 | 5 |
Adverse Reactions Leading to Discontinuation in Study 1
In Study 1, 12% of patients discontinued Carbidopa/levodopa early due to adverse reactions; a higher proportion of patients in the 61.25 mg / 245 mg Carbidopa/levodopa-treated group (14%) and in the 97.5 mg / 390 mg Carbidopa/levodopa-treated group (15%) experienced adverse reactions leading to early discontinuation compared to (4%) in the placebo group. The most common adverse reactions resulting in early discontinuation were nausea, dizziness, and vomiting.
Adverse Reactions In Advanced Parkinson's Disease
In an active-controlled clinical study in patients with advanced Parkinson's disease (Study 2), the most common adverse reactions with Carbidopa/levodopa that occurred during dose conversion or maintenance (in at least 5% of patients and more frequently than on oral immediate-release carbidopa-levodopa) were nausea and headache.
Table 3 lists adverse reactions occurring in at least 5% of Carbidopa/levodopa-treated patients and at a higher rate than oral immediate-release carbidopa-levodopa in Study 2.
Table 3: Adverse Reactions in Study 2 in Patients with Advanced Parkinson's Disease
| Period | Carbidopa/levodopa (N=201) | Immediate-Release carbidopa-levodopa (N=192) | ||
| Dose Convers ion* | Maintenance | Dose Convers ion* | Maintenance | |
| % | % | % | % | |
| Nausea | 4 | 3 | 6 | 2 |
| Headache | 5 | 1 | 3 | 2 |
| *All patients were converted to Carbidopa/levodopa in the open label Dose Conversion period and then received randomized treatment during maintenance. |
Adverse Reactions Leading to Discontinuation in Study 2
In Study 2, 5% of patients discontinued treatment due to adverse reactions during conversion to Carbidopa/levodopa. The common adverse reactions leading to discontinuation during dose conversion were dyskinesia, anxiety, dizziness, and on and off phenomenon.
Carbidopa/levodopa contraindications
See also:
What is the most important information I should know about Carbidopa/levodopa?
Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with Carbidopa/levodopa orally disintegrating tablets. These inhibitors must be discontinued at least two weeks prior to initiating therapy with Carbidopa/levodopa orally disintegrating tablets. Carbidopa/levodopa orally disintegrating tablets may be administered concomitantly with the manufacturer’s recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline HCI).
Carbidopa/levodopa orally disintegrating tablets are contraindicated in patients with known hypersensitivity to any component of this drug, and in patients with narrow-angle glaucoma.
Because levodopa may activate a malignant melanoma, Carbidopa/levodopa orally disintegrating tablets should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma.
Active ingredient matches for Carbidopa/levodopa:
Carbidopa/levodopa
List of Carbidopa/levodopa substitutes (brand and generic names) | Sort by popularity |
| Unit description / dosage (Manufacturer) | Price, USD |
| Carbidopa/ levodopa sustained-release tablets | |
| Carbidopa/Levodopa Biosintetica (Brazil) | |
| Carbidopa/Levodopa Bristol (Netherlands) | |
| Carbidopa/Levodopa Fair-Med (Malta, Netherlands, Sweden) | |
| Carbidopa/Levodopa Orally Disintegrating Tablets | |
| Carbidopa/Levodopa Remedica (Macedonia) | |
| Carbidopa/Levodopa Sandoz (Netherlands) | |
| Carbidopa/Levodopa Sandoz CR (Switzerland) | |
| Carbidopa/Levodopa Sandoz CR 25/100mg (Switzerland) | |
| Carbidopa/Levodopa Sandoz CR 50/200mg (Switzerland) | |
| Carbidopa/Levodopa Sustained-Release Tablets | |
| Carbidopa/Levodopa Teva (Italy) | |
| Carbidopa; Levodopa | |
| Tablet; Oral; Carbidopa 10 mg; Levodopa 100 mg | |
| Tablet; Oral; Carbidopa 25 mg; Levodopa 100 mg | |
| Tablet; Oral; Carbidopa 25 mg; Levodopa 250 mg | |
| Tablet, Extended Release; Oral; Carbidopa 10 mg; Levodopa 100 mg | |
| Tablet, Extended Release; Oral; Carbidopa 25 mg; Levodopa 100 mg | |
| Tablet, Extended Release; Oral; Carbidopa 25 mg; Levodopa 250 mg | |
| Tablet, Extended Release; Oral; Carbidopa 50 mg; Levodopa 200 mg | |
| Tablet; Oral; Carbidopa 50 mg; Levodopa 200 mg | |
| Carbidopa; Levodopa CR | |
| Tablet, Controlled Release; Oral; Carbidopa 25 mg; Levodopa 100 mg | |
| Tablet, Controlled Release; Oral; Carbidopa 50 mg; Levodopa 200 mg | |
| Carbidopa; Levodopa LP | |
| Tablet, Prolonged Release; Oral; Carbidopa Monohydrate 25 mg; Levodopa 100 mg | |
| Tablet, Prolonged Release; Oral; Carbidopa Monohydrate 50 mg; Levodopa 200 mg | |
| Carbilev (South Africa, United States) | |
| Carcopa (Japan) | |
| Cardopar (Singapore) | |
| Cardopar 200's (Dha) | |
| Carlevod (Argentina) | |
| Cenimed 100 | |
| Cenimed 250 | |
| Cloisone (Mexico) | |
| Tablet; Oral; Carbidopa 25 mg; Levodopa 250 mg (Psicofarma) | |
| Cloteks (Vietnam) | |
| Cloteks 2 Blister x 10 Tablet | |
| Co-Careldopa (Malta) | |
| Credanil (Malta, Romania) | |
| Credanil 1's (Remedica) | |
| Cronomet (Brazil) | |
| D-Dopa (Bangladesh) | |
| D-Dopa Plus (Bangladesh) | |
| Damar (Bosnia & Herzegowina) | |
| Darpott (Peru) | |
| Dom-Levo-Carbidopa | |
| Tablet; Oral; Carbidopa 25 mg; Levodopa 100 mg | |
| Domtab (Cyprus) | |
| Dopacol (Japan) | |
See 480 substitutes for Carbidopa/levodopa | |
References
- DailyMed. "CARBIDOPA; ENTACAPONE; LEVODOPA: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- PubChem. "levodopa". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
- PubChem. "carbidopa". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
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Information checked by Dr. Sachin Kumar, MD Pharmacology
