Carbidopa/Levodopa

Carbidopa/levodopais a combination of an inhibitor of aromaticamino aciddecarboxylation and an aromatic amino acid used to treat Parkinson symptoms such as muscle stiffness, tremors, spasms, and poor muscle control.

Carbidopa/levodopa is also used to treat Parkinson's symptoms caused by carbon monoxidepoisoningormanganeseintoxication.

Carbidopa/levodopa is available under the following different brand names:Sinemet,SinemetCR,Rytary, andDuopa.

剂型和力量

Tablet (Sinemet)

• 10mg/100mg
• 25mg/100mg
• 25mg/250mg

Tablet, disintegrating (Parcopa)

• 10/100mg
• 25/100mg
• 25/250mg

Tablet, extended release (Sinemet CR)

• 25mg/100mg
• 50mg/200mg

胶囊,延长release (Rytary)

• 23.75mg/95mg
• 36.25mg/145mg
• 48.75mg/195mg
• 61.25mg/245mg

Enteralsuspension, extended release (Duopa)

• (4.63mg/20mg)/mL in a single-usecassette
• Each cassette contains approximately 100 mL

Dosage Considerations – Should be Given as Follows:

Parkinson Disease and Parkinson-like Disorders

Indicated for Parkinson disease, postencephaliticparkinsonism, and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication

Maintain patients on the lowest dosage required to achieve symptomatic control and to minimize adverse reactions such asdyskinesiaand nausea

Sinemet

• Immediate release and oral disintegrating tablets: 25 mg/100 mg every 8 hours or 10 mg/100 mg orally every 6-8 hours initially; levodopa may be increased by 100 mg/day every 1-2 days
• Carbidopa should be 70-100 mg/day but not to exceed 200 mg/day; levodopa not to exceed 800 mg/day
• SinemetCR: 50 mg/200 mg orally every 12 hours initially; may be increased up to 1600 mg/day of levodopa; doses must be given at least 6 hours apart

Dosing considerations

• 立即释放(IR):当卡比多巴是要求的uired, substitute one 25 mg/100 mg tablet for each 10 mg/100 mg tablet; if necessary, dosage of 25 mg/250 mg tablet may be increased by one half or by 1 tablet every 1-2 days to maximum of 8 tablets daily; experience with total daily carbidopa doses higher than 200 mg is limited
• Extended release (ER): Doses and dosing intervals may be increased or decreased according to response; most patients are adequately treated with regimens providing levodopa 400-1600 mg/day divided every 4-8 hours while awake; higher levodopa dosages (2400 mg/day or greater) and shorter intervals (less than 4 hours) are used but not usually recommended; if interval less than 4 hours is used or if divided doses are not equal, give smaller doses at end of day; allow at least 3 days between dosage adjustments

Conversion from immediate-release to Sinemet CR

• 300-400 mg/day IR = 200 mg ER every 12 hours
• 500-600 mg/day IR = 300 mg ER every 12 hours or 200 mg ER every 8 hours
• 700-800 mg/day IR = 800 mg ER divided every 8 hours
• 900-1000 mg/day IR = 1000 ER divided every 8 hours

Rytary

• Contains immediate-release and extended-release beads
• Levodopa-naïve: 23.75 mg/95 mg orally three times daily initially; on treatment day 4, may increase to 36.25 mg/145 mg three times daily
• Dose may be increased up to a maximum recommended dose of 97.5 mg/390 mg three times daily
• The dosing frequency may be changed from 3x/day to a maximum of 5 times/day if more frequent dosing is needed and if tolerated, up to a maximum recommended daily dose 612.5 mg/2450 mg

Converting from immediate-release (IR) to Rytary

• Doses of other carbidopa/levodopa products are not interchangeable
• For patients currently treated with carbidopa/levodopa plus catechol-O-methyl transferase (COMT) inhibitors (e.g., entacapone), the initial total daily dose of levodopa in Rytary may need to be increased
• The dosing frequency may be changed from 3 times/day to a maximum of 5 times/day if more frequent dosing is needed and if tolerated, up to a maximum recommended daily dose 612.5 mg/2450 mg

Dose conversion from IR

• 400-549 mg IR: 3 caps 23.75mg/95mg three times daily
• 550-749 mg IR: 4 caps 23.75mg/95mg three times daily
• 750-949 mg IR: 3 caps 36.25mg/145mg three times daily
• 950-1249 mg IR: 3 caps 48.75 mg/195 mg three times daily
• =1250 mg IR: 4 caps 48.75 mg/195 mg three times daily, OR 3 caps 61.25 mg/245 mg three times daily

Advanced Parkinson Disease (Duopa)

Duopa: Extended-release enteral solution for indicated for treatment of motor fluctuations in patients with advanced Parkinson disease

Administer enteral suspension by intrajejunal infusion over 16 hours

Individualize daily dose by taking into consideration the morning dose, continuous dose, and extra doses that a patient is taking Maximum daily dose 2000 mg of the levodopa component (i.e., 1 cassette/day) administered over 16 hours; at the end of the daily 16 hour infusion, patients will disconnect the pump from jejunal tubing and take their night-time dose of oral immediate-release carbidopa-levodopa tablets

Treatment initiated in 3 steps

• Conversion of patients to oral immediate-release carbidopa-levodopa tablets in preparation for Duopa treatment
• Calculation and administration of the Duopa starting dose (i.e., morning dose and continuous dose) for Day 1
• Titration of the dose as needed based on individual clinical response and tolerability

Extra doses

• Duopa has an extra dose function that can be used to manage acute “Off” symptoms that are not controlled by the morning dose and the continuous dose administered over 16 hours
• The extra dose function should be set at 1 mL (20 mg of levodopa) when starting Duopa
• If the amount of the extra dose needs to be adjusted, it is typically done in 0.2 mL increments
• The extra dose frequency should be limited to 1 extra dose every 2 hours
• Administration of frequent extra doses may cause or worsen dyskinesia
• Once no further adjustments are required to the morning dose, continuous dose, or extra dose, this dosing regimen should be administered daily
• Over time, additional changes may be necessary based on the patient's clinical response and tolerability

Prepare for Duopa treatment

• Prior to initiating, convert patients from all other forms of levodopa to oral immediate-release carbidopa-levodopa tablets (1:4 ratio)
• Patients should remain on a stable dose of their concomitant medications taken for the treatment of Parkinson disease before initiation of Duopa enteral infusion
• Healthcare providers should ensure patients take their oral Parkinson disease medications the morning of the PEG-J procedure

Determine Duopa starting dose for Day 1

Step 1: Calculate Duopa Morning Dose for Day 1

• Determine the total amount of levodopa (mg) in the first dose of orally immediate-release carbidopa-levodopa that was taken by the patient on the previous day
• Convert the orally levodopa dose from mg-to-mg by multiplying the orally dose by 0.8 and dividing by 20 mg/mL; this calculation will provide the Morning Dose of Duopa in mL
• Add 3 mL to the morning dose to fill (prime) the intestinal tube to obtain the 'Total Morning Dose'
• The total morning dose is usually administered over 10-30 minutes
• Program the pump to deliver the total morning dose

Step 2: Calculate and Administer the Duopa Continuous Dose for Day 1

• Determine the amount of orally immediate-release levodopa that the patient received from orally immediate-release carbidopa-levodopa doses throughout the previous day (i.e., 16 waking hours), in mg; do not include the doses of orally immediate-release carbidopa-levodopa taken at night when calculating the levodopa amount
• 减去第一个口服左旋多巴的剂量mg taken by the patient on the previous day (determined in Step 1a from the total orally levodopa dose in mg taken over 16 waking hours; divide the result by 20 mg/mL; this is the dose of Duopa administered as an enteral Continuous Dose (in mL) over 16 hours
• The hourly infusion rate (mL/hour) is obtained by dividing the Continuous Dose by 16 (hours); program this value into the pump as the continuous rate
• If persistent or numerous “Off” periods occur during the 16 hour infusion, consider increasing the Continuous Dose or using the Extra Dose function; if dyskinesia or levodopa-related adverse reactions occur, consider decreasing the Continuous Dose or stopping the infusion until the adverse reactions subside

Duopa titration

• In the controlled trial, the average number of titration days required to establish a stable Morning and Continuous Dose was 5 days
• Additional dose adjustments may be necessary over time based on the patient level of activity and disease progression
• Morning dose adjustment
  • If the patient experienced dyskinesia or levodopa-related adverse reactions within 1 hour of the Morning Dose on the preceding day, decrease the Morning Dose by 1 mL
  • For an inadequate clinical response within 1 hour of the Morning Dose on the preceding day, adjust the Morning Dose (excluding the 3 mL to fill the tube) as follows:
  • If the Morning Dose on the preceding day was up to 6 mL: Increase the Morning Dose by 1 mL
  • If the Morning Dose on the preceding day was greater than 6 mL: Increase the Morning Dose by 2 mL
• Continuous dose adjustment
  • Consider decreasing the Continuous Dose if the patient experienced troublesome dyskinesia, or other adverse reactions on the preceding day:
  • a. Adverse reactions for a period lasting 1 hour or greater: Decrease the Continuous Dose by 0.3 mL/hour
  • b. Adverse reactions lasting for 2 periods or more of 1 hour or greater : Decrease the Continuous Dose by 0.6 mL/hour

Dosage Modifications

Renal impairment: Safety and efficacy not established; use with caution

Hepatic impairment: Safety and efficacy not established; use with caution

Pediatric: Safety and efficacy not established

Side effects of Carbidopa/Levodopa include:

• Abdominal pain and discomfort
• Agitation
• Anxiety
• Bloating/gas
• Blood in the urine
• Blurred vision
• Burning feeling in tongue
• Changes in taste
• Cold symptoms
• Complete or partial lung collapse
• Confusion
• Constipation
• Cough
• Dark urine
• Daytime drowsiness
• Decreased attention span
• Diarrhea
• Difficulty swallowing
• Dizziness
• Double vision or dilatedpupil
• Dry mouth
• Euphoria
• Excessive salivation
• Fainting
• Fatigue
• Feelingunwell(malaise)
• Hair loss
• Headache
• Heartburn
• Hiccups
• Hot flashes
• Incontinence
• Increased or dark perspiration
• Increased trembling of hands
• Indifference
• Involuntarymuscle movements/contractions
• Itching
• Lockjaw
• Loss of appetite
• Loss of control of bodily movements
• Memory loss
• Muscle cramps, pain, spasms
• Nausea
• Nervousness
• Nightmares
• Numbness or tingly feeling
• Prolonged or painful erections
• Restlessness
• Skin rash
• Sneezing
• Stuffy nose
• Swelling (edema)
• Teeth grinding or jaw clenching
• Trouble sleeping (insomnia or strangedreams)
• Uncontrollable eye movements
• Urine retention
• Vivid dreams
• Vomiting
• Weight loss

Rare but serious side effects of Carbidopa/Levodopa include:

• Greatly increased eye blinking/twitching
• Fainting
• Mental/mood changes (e.g., confusion, depression, hallucinations, thoughts of suicide)
• Unusual strong urges (such as increased gambling, increased sexual urges)
• Worsening of involuntary movements/spasms

Postmarketing side effects of carbidopa/levodopa reported include:

• Suicide attempt, suicidal ideation

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Severe interactions of Carbidopa/Levodopa include:
  • isocarboxazid
  • phenelzine
  • procarbazine
  • selegiline
  • selegiline transdermal
  • tranylcypromine
• Carbidopa/levodopa has serious interactions with at least 25 different drugs.
• Carbidopa/Levodopa has moderate interactions with at least 141 different drugs.
• Carbidopa/Levodopa has mild interactions with at least 21 different drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

• This medication contains carbidopa/levodopa. Do not take Sinemet, Sinemet CR, Rytary, or Duopa if you are allergic to carbidopa/levodopa or any ingredients contained in this drug.
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity
• Narrow-angleglaucoma(tablets)
• Concurrent administration of nonselective monoamine oxidase inhibitors (MAOIs) or use within last 14 days

Effects of Drug Abuse

• No information available

Short-Term Effects

• Levodopa may cause patients to fall asleep while engaging in activities of daily living; caution regarding use of machinery and driving.
• See "What Are Side Effects Associated with Using Carbidopa/Levodopa?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Carbidopa/Levodopa?"

Cautions

• Use caution in history ofheart attack(myocardial infarction[MI]) withresidualatrial, nodal, orventricular arrhythmias,peptic ulcer, orseizure.
• Use caution in severecardiovascular, respiratory disease, renal, hepatic, or endocrine disease; monitor disease parameters.
• Use caution in bronchialasthmapatients taking sympathomimetics.
• Levodopa may cause patients to fall asleep while engaging in activities of daily living; caution regarding use of machinery and driving.
• Avoid use in patients with a major psychotic disorder; therapy may exacerbatepsychosis;幻觉和发展的风险增加t of psychosis; other psychiatric symptoms include decreased impulse control and compulsive behaviors, depression, and suicidality; observe patients for symptoms of depression with concomitant suicidal tendencies.
• May exacerbate dyskinesia; reduce dose to control symptoms.
• Peripheral neuropathyreported with use; evaluate patients for history ofneuropathyand known risk factors prior to initiating therapy; assess patients for peripheral neuropathy periodically during therapy.
• Low blood pressureand dizziness upon standing (orthostatic hypotension) may occur (more common with immediate-release formulation).
• Use caution in patients with glaucoma; monitorintraocular pressurecarefully; some formulations are contraindicated in patients with narrow-angle glaucoma.
• Observe patients carefully if discontinued abruptly; risk of syndrome resemblingneurolepticmalignantsyndrome.
• Controlled-release formulation is less bioavailable than conventional formulation.
• Gastrointestinalcomplications from PEG-J ornaso-jejunal tube can occur (e.g., bezoar,ileus, intussusception, implant siteerosion/ulcer, intestinalhemorrhage, intestinalischemia,intestinal obstruction, intestinal perforation,pancreatitis, peritonitis, pneumoperitoneum, and post-operative wound infection); these complications may result in serious outcomes (e.g., need for surgery, death).
• Parkinson's disease patients are at increased risk of developingmelanoma;monitor patients closely and perform periodic skin examinations.

Pregnancy and Lactation

• Use carbidopa/levodopa with caution during pregnancy if benefits outweigh risks. Animal studies show risk and human studies are not available or neither animal nor human studies were done.
• Carbidopa/levodopa inhibits lactation. Use with caution if breastfeeding.