Drug Detail:Carbidopa and levodopa (Carbidopa and levodopa [ kar-bi-doe-pa-and-lee-voe-doe-pa ])
Drug Class: Dopaminergic antiparkinsonism agents
Usual Adult Dose for Parkinson's Disease
Optimum dosage is determined by careful individual titration: All doses expressed as CARBIDOPA-LEVODOPA
Immediate-release including Oral disintegrating tablets:
Initial dose: 25 mg-100 mg orally three times a day or 10 mg-100 mg orally 3 or 4 times a day
- Increase by 1 tablet every day or every other day as needed until a dose of 8 tablets is reached; may use a combination of tablets from both ratios (1:4 or 1:10) to provide the optimum dose.
- Levodopa should be discontinued at least 12 hours before starting carbidopa-levodopa; initiate with approximately 25% of the previous levodopa dose.
- Suggested dose for patients receiving less than levodopa 1500 mg per day: 25 mg-100 mg orally 3 or 4 times a day.
- Suggested dose for patients receiving more than levodopa 1500 mg per day: 25 mg-250 mg orally 3 or 4 times a day.
Sustained-Release Tablets (SINEMET CR):
- Initial dose (levodopa-naive): 50 mg-200 mg orally twice a day; initial dosage should be given at intervals of more than 6 hours
- Dose and dosing interval may be increased or decreased at intervals of at least 3 days based on therapeutic response
- Dose range: Most patients will require levodopa 400 to 1600 mg/day in divided doses every 4 to 8 hours during waking hours; doses of 2400 mg/day at intervals of less than 4 hours have been used, but are generally not recommended.
- For patients receiving levodopa with a decarboxylase inhibitor: Dosage with Sinemet CR should be approximately 10% higher than previous levodopa dosage; this may need to be increased to up to 30% higher depending on clinical response.
- For patients receiving levodopa without a decarboxylase inhibitor: Dosage with sustained release should be approximately 25% of previous levodopa dosage; levodopa should be discontinued at least 12 hours before starting carbidopa-levodopa
Extended-Release Capsules (RYTARY):
- Initial dose (levodopa-naive): 23.75 mg-95 mg orally 3 times a day for 3 days; on the fourth day, may increase to 36.25 mg-145 mg 3 times a day
- Dosing interval may be increased up to a maximum of 5 times a day, if tolerated
- Maximum daily dose: 612.5 mg-2450 mg
- For patients receiving levodopa 400 to 549 mg/day: RYTARY levodopa dose should be 855 mg/day
- For patients receiving levodopa 550 to 749 mg/day: RYTARY levodopa dose should be 1140 mg/day
- For patients receiving levodopa 750 to 949 mg/day: RYTARY levodopa dose should be 1305 mg/day
- For patients receiving levodopa 950 to 1249 mg/day: RYTARY levodopa dose should be 1755 mg/day
- For patients receiving levodopa equal or greater than 1250 mg/day: RYTARY levodopa dose should be 2205 or 2340 mg/day
Comments:
- Peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 to 100 mg/day; patient's receiving less than this amount of carbidopa are more likely to experience nausea and vomiting; experience with carbidopa doses greater than 200 mg/day is limited.
- RYTARY products are not interchangeable with other carbidopa-levodopa products; for patients receiving carbidopa-levodopa plus catechol-O-methyl transferase (COMT) inhibitors, the initial recommended total daily dose of levodopa may need to be increased.
Use: For the treatment of the symptoms of idiopathic Parkinson's disease, postencephalitic parkinsonism, and symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication.
DUOPA Enteral Suspension (carbidopa 4.63 mg-levodopa 20 mg per mL) is indicated for the treatment of motor fluctuations in patients with advanced Parkinson's disease.
- Administered into the jejunum through a PEG-J tube using a CADD-Legacy 1400 portable infusion pump; for short term administration, a naso-jejunal tube may be used.
- Total dose is composed of 3 individually adjusted doses: the MORNING bolus dose, the CONTINUOUS maintenance dose, and EXTRA BOLUS doses.
Initiation: Convert all forms of levodopa to oral immediate-release carbidopa-levodopa tablets using 1:4 ratio tablets.
- Day 1 morning dose: Provide a dose of levodopa equivalent to previous day's first levodopa dose; calculate by converting levodopa dose from mg to milliliters and add 3 milliliters of volume to prime the intestinal tube; administer over 10 to 30 minutes.
- Day 1 continuous dose: Provide levodopa dose necessary for 16 waking hours; calculate by determining the amount of levodopa received the previous day, omitting the morning and night dose.
- Extra bolus dose function is available to manage acute "off" symptoms; initially it should be set to 20 mg (1 mL), may titrate in 0.2 mL increments; extra doses should be limited to once every 2 hours.
MORNING DOSE is administered rapidly (over 10 to 30 minutes) to achieve a therapeutic dose level; this dose should be adjusted if there is an inadequate clinical response within 1 hour of the morning dose on the preceding day:
- For doses less than or equal to 6 mL (excluding the 3 mL to prime the tube): increase by 1 mL.
- For doses greater than 6 mL (excluding the 3 mL to prime the tube): increase by 2 mL.
- If dyskinesia or levodopa-related adverse reactions occur within 1 hour of the morning dose on the preceding day, decrease morning dose by 1 mL.
- Consider increasing the dose based on the number and volume of extra doses provided on the previous day and the patient's clinical response.
- Consider decreasing the dose for troublesome dyskinesia or other adverse reactions; for reactions lasting for a period of 1 hour or more decrease by 0.3 mL/hr; for reactions lasting for periods of 2 hours or more decrease by 0.6 mL/hr.
Renal Dose Adjustments
Use with caution.
Liver Dose Adjustments
Use with caution.
Dose Adjustments
When initiating this drug, administration of other standard antiparkinsonian drugs may continue; however, dose adjustments of these drugs may be needed.
RYTARY (carbidopa-levodopa extended-release capsule) is not interchangeable with other carbidopa-levodopa products.
Precautions
Safety and efficacy have not been established in patients younger than 18 years.
Consult WARNINGS section for additional precautions.
Dialysis
Data not available.
Other Comments
Administration advice:
Oral Disintegrating Tablets:
- Remove tablet from bottle with dry hands just prior to administration
- Place on tongue, then swallow with saliva; administration of liquid is not necessary
Sinemet CR(R) Tablets:
- Swallow whole; do not crush or chew
Rytary(R) Extended-Release Capsules:
- Swallow whole; may also sprinkle the contents of the capsule onto 1 to 2 tablespoons of applesauce and take immediately.
- Consider taking the first dose of the day 1 to 2 hours prior to eating; high-fat, high calorie meals may delay absorption of levodopa up to 2 to 3 hours.
Intestinal Suspension (DUOPA):
- Cassettes should be brought to room temperature prior to use; see product information for complete administration instructions.
- Cassettes are specifically designed to be connected to the CADD(R) Legacy 1400 pump.
- Cassettes are for single-use only, do not use for longer than 16 hours
Storage requirements: DUOPA Cassettes:
- Store in freezer at -20C (-4F) prior to dispensing
- Upon dispensing, cassettes should be fully thawed in refrigerator at 2C to 8C (36F to 46F); take cartons out of transport box and separate from each other to allow even thawing (thawing may take up to 96 hours); once thawed, cartons may be repacked in a closer configuration.
- Assign a 12-week use by date once placed in refrigerator to thaw.
- Cassettes should be protected from light and kept in carton prior to use.
Stability:
- Stable for 24 months at -20C and 15 weeks at 5C; 16 hours once outside the refrigerator.
General:
- This drug is indicated for the treatment of idiopathic parkinsonism, it is useful in relieving many of the symptoms particularly rigidity and bradykinesia; it is frequently helpful in the management of tremor, dysphagia, sialorrhea, and postural instability.
- The addition of carbidopa to levodopa will reduce the peripheral effects of levodopa; however, since carbidopa does not cross the blood brain barrier, the adverse reactions due to the central effects may occur sooner and at lower doses than levodopa alone.
- Avoid sudden discontinuation or rapid dose reduction of this drug.
- Because levodopa competes with certain amino acids for gut wall transport, the absorption of levodopa may be decreased in patients on high-protein diets.
Monitoring:
- Cardiovascular: Monitor for signs and symptoms of orthostatic hypotension, particularly during dose escalation; for patients with a history of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias, cardiac function should be monitored in an intensive cardiac care facility during drug initiation.
- Nervous System: Monitor for dyskinesias, somnolence and drowsiness
- Dermatologic: Monitor for melanomas; consider periodic skin examinations by dermatologists.
- Ocular: Monitor intraocular pressure in patients with chronic wide-angle glaucoma closely during therapy; blepharospasm is a useful early sign of excess dose in some patients.
- Psychiatric: Question patients about new or increased gambling urges, sexual urges, uncontrolled spending, binge or compulsive eating, or other urges; monitor for new or worsening mental status and behavioral changes.
- Laboratory: During chronic therapy, periodic evaluations of hepatic, hematopoietic, and renal function are recommended.
Patient advice:
- Tell patients that this drug may cause a brownish orange discoloration in saliva, urine, or sweat; may discolor their garments.
- This drug frequently causes drowsiness; patients should not drive a car or operate machinery or other potentially dangerous activities until it is determined how this drug affects their mental and/or motor performance; for patients who experience continued drowsiness, they should discuss with their physician the safety of driving.
- Patients or caregivers should be instructed to report episodes of sudden onset of sleep, new or worsening dyskinesia, new or worsening compulsive behaviors and/or unusual urges, suicide attempts or suicidal ideation.
- Patients should be instructed to report changes in the size, shape, or color of moles on their skin and should have their skin checked on a regular basis for melanomas.
- Patients should be aware that this drug may cause orthostatic blood pressure changes including fainting and dizziness and patients are advised to avoid standing rapidly after sitting or lying down.
- Patients should speak to their physician or health care provider if they become pregnant, intend to become pregnant, or are breastfeeding.
Frequently asked questions
- How long does it take carbidopa levodopa to work?
- How often should carbidopa/levodopa be taken?
- What foods should be avoided when taking levodopa?
- Is Rytary better than Sinemet?
- Can carbidopa/levodopa cause high blood pressure?
- What is the difference between carbidopa, levodopa, and Rytary?
- How long does it take for Rytary to start working?
- How long does Rytary stay in your system?
