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Carbidopa and levodopa: Drug information

Carbidopa and levodopa: Drug information
(For additional information see "Carbidopa and levodopa: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Dhivy;
  • Duopa;
  • Rytary;
  • Sinemet;
  • Sinemet CR [DSC]
Brand Names: Canada
  • AA-Levocarb CR;
  • APO-Levocarb;
  • APO-Levocarb 100/25;
  • APO-Levocarb 250/25;
  • DOM-Levo-Carbidopa;
  • Duodopa;
  • MINT-Levocarb;
  • PMS-Levocarb CR;
  • Pro-Lecarb;
  • PRO-Levocarb-100/25 [DSC];
  • Sinemet 100/25;
  • Sinemet 250/25;
  • Sinemet CR 200/50 [DSC];
  • Sinemet CR [DSC];
  • TEVA-Levocarbidopa
Pharmacologic Category
  • Anti-Parkinson Agent, Decarboxylase Inhibitor;
  • Anti-Parkinson Agent, Dopamine Precursor
Dosing: Adult

Parkinson disease:

Immediate-release tablet, orally disintegrating tablet:

Note: Tablets are available in carbidopa 25 mg/levodopa 100 mg, carbidopa 10 mg/levodopa 100 mg, and carbidopa 25 mg/levodopa 250 mg strengths. For patients with daily levodopa requirements ≤400 mg/day, tablets with carbidopa 25 mg/levodopa 100 mg should be used to decrease the risk of adverse effects from peripheral dopamine. For those with higher daily levodopa requirements, different strength tablets may be given to provide the optimum dosage, as long as a carbidopa dose ≥75 mg/day is maintained (Hoehn 1980; Kaakkola 1985).

Oral: Initial: Carbidopa 12.5 mg/levodopa 50 mg or carbidopa 25 mg/levodopa 100 mg 2 to 3 times daily (Block 1997; Fahn 2004); may increase daily dose by 1 tablet of carbidopa 25 mg/levodopa 100 mg every 1 to 2 days. For patients who require higher doses of levodopa for symptom control, titrating with a tablet that has a carbidopa:levodopa ratio of 1:10 may allow for better symptom control without exceeding the usual maximum dosage of carbidopa. Usual maximum daily dose: Carbidopa 200 mg/day and levodopa 2 g/day; dosing frequency ≥4 times daily may be required. Note: Many experts use a slower titration, over weeks to months, to improve tolerability and establish the lowest dose of levodopa that provides a satisfactory clinical response (Espay 2017; Spindler 2021).

Controlled-release tablet:

Note: Intervals between doses should be 4 to 8 hours while awake; when divided doses are not equal, the smaller doses should be given toward the end of the day.

For patients initiating levodopa therapy:

Note: Controlled-release carbidopa/levodopa may exhibit erratic pharmacokinetics; therefore, controlled-release formulations are not recommended for initial therapy in Parkinson disease (Espay 2017; Grimes 2019; Spindler 2021).

Oral: Initial: Carbidopa 50 mg/levodopa 200 mg 2 times daily, at intervals not <6 hours; may adjust dose no faster than every 3 days to a maximum dose of levodopa 2.4 g/day.

Conversion from immediate release to controlled release: Oral: Initial: Substitute controlled-release dosage at an amount that provides ~10% more levodopa/day; total calculated dosage is administered in divided doses 2 to 3 times/day (or ≥3 times/day for patients maintained on levodopa ≥700 mg). Depending on clinical response, dosage may need to be increased to provide up to 30% more levodopa/day. May adjust dose every 3 days to a maximum dose of levodopa 2.4 g/day.

Extended-release capsule:

Note: Carbidopa/levodopa ER capsules are not interchangeable with other carbidopa/levodopa products on a 1:1 basis.

For patients initiating levodopa therapy: Oral: Initial: Carbidopa 23.75 mg/levodopa 95 mg 3 times daily for 3 days; on day 4, may increase to carbidopa 36.25 mg/levodopa 145 mg 3 times daily (Espay 2017; Pahwa 2014). May increase dose further based on response and tolerability in levodopa 50 mg increments at intervals ≥1 week up to carbidopa 97.5 mg/levodopa 390 mg 3 times daily (Espay 2017). Frequency of dosing may be increased to a maximum of 5 times daily if needed and tolerated (maximum: carbidopa 612.5 mg/levodopa 2.45 g per day).

Conversion from immediate release to extended release: Oral: Initial: Dose based on current total daily dose of levodopa in immediate-release carbidopa/levodopa as follows:

Conversion From Immediate-release to Extended-release Carbidopa/Levodopa (Capsules)

Total daily dose of levodopa in immediate-release carbidopa/levodopa

Recommended starting dosage of extended-release carbidopa/levodopaa

Total daily dose of levodopa in extended-release carbidopa/levodopa

Initial extended-release carbidopa/levodopa dosing regimenb

aFor patients currently treated with IR carbidopa/levodopa plus catechol-O-methyl transferase (COMT) inhibitors (eg, entacapone) and converting to monotherapy with carbidopa/levodopa ER capsules, the initial total daily dose of carbidopa/levodopa ER capsules may need to be increased.

bAdjust dose as needed; frequency of dosing may be increased to a maximum of 5 times daily if needed and tolerated (maximum dose: carbidopa 612.5 mg/levodopa 2.45 g per day) (Espay 2017).

400 to 549 mg

855 mg

3 capsules ER carbidopa 23.75 mg/levodopa 95 mg 3 times daily

550 to 749 mg

1.14 g

4 capsules ER carbidopa 23.75 mg/levodopa 95 mg 3 times daily

750 to 949 mg

1.305 g

3 capsules ER carbidopa 36.25 mg/levodopa 145 mg 3 times daily

950 mg to 1.249 g

1.755 g

3 capsules ER carbidopa 48.75 mg/levodopa 195 mg 3 times daily

≥1.25 g

2.205 g

3 capsules ER carbidopa 61.25 mg/levodopa 245 mg 3 times daily

or

2.34 g

4 capsules ER carbidopa 48.75 mg/levodopa 195 mg 3 times daily

Intestinal suspension (Duopa), intestinal gel (Duodopa [Canadian product]):

Note: Prior to initiation of therapy, convert patients from all forms of levodopa to oral IR carbidopa/levodopa tablets. Total daily dose of intestinal infusion (expressed in terms of levodopa) consists of a morning dose, a continuous dose, and extra doses. Maximum daily dose is levodopa 2 g (ie, one cassette per day) administered over 16 hours. Following the daily 16-hour infusion, some patients may require a routine nighttime dosage of oral carbidopa/levodopa. Nighttime intestinal infusion dosing may be necessary in certain rare situations (eg, nocturnal akinesia) (Ricciardi 2016).

Intestinal infusion via PEG-J tube: Initial:

Morning bolus dose: Day 1: Determine levodopa dose by using previous day's first oral IR carbidopa/levodopa dose. Reduce this dose to 60% to 80% of first oral IR carbidopa/levodopa dose and administer this amount over 10 to 30 minutes; usual levodopa dose: 100 to 200 mg (Burack 2018; Fernandez 2013; Lew 2015; Olanow 2014; Pahwa 2014; manufacturer's labeling).

Continuous dose: Day 1: Determine the amount of oral IR levodopa received in previous day's total waking hours. Do not include nighttime or first oral IR carbidopa/levodopa doses. Divide by 16 hours (usual duration of infusion) for hourly infusion rate (Burack 2018; Olanow 2014; Pahwa 2014; manufacturer's labeling). Usual levodopa dose: 20 to 120 mg/hour (Lew 2015; Nyholm 2003).

Extra bolus doses: Usual levodopa dose: 10 to 40 mg every 1 to 2 hours as needed (Lew 2015; Pahwa 2014). Note: Frequent extra doses may cause or worsen dyskinesias.

Day 2 and subsequent dosage adjustment: After day 1 of intestinal infusion, adjust as needed based on response and tolerability.

Restless legs syndrome, intermittent (alternative agent) (off-label use):

Note: Due to risk of augmentation (worsening symptoms during dopaminergic therapy), limit frequency to 2 to 3 administrations per week. May also be taken as needed prior to specific restless legs syndrome (RLS) triggers, such as prolonged immobility (IRLSSG/EURLSSG/RLS-F [Garcia-Borreguero 2016]).

Immediate-release tablet: Oral: Initial: Carbidopa 12.5 mg/levodopa 50 mg to carbidopa 25 mg/levodopa 100 mg as needed in the evening, at bedtime, or upon waking during the night due to RLS symptoms; may adjust dose (based on levodopa component) no faster than every 3 days to a maximum of 200 mg/day (Earley 1996; EFNS/ENS/ESRS [Garcia-Borreguero 2012]; Silber 2004).

Controlled-release tablet: Oral: Initial: Carbidopa 25 mg/levodopa 100 mg as needed before bedtime for RLS symptoms that awaken patient during the night; may adjust dose (based on levodopa component) no faster than every 3 days to a maximum dose of 200 mg/day (Earley 1996; EFNS/ENS/ESRS [Garcia-Borreguero 2012]; Silber 2004).

Discontinuation of therapy: Discontinuation of therapy may result in neuroleptic malignant-like syndrome (Grimes 2019; Serrano-Dueñas 2003). Avoid sudden discontinuation or rapid dose reduction; some experts recommend a gradual taper over several weeks or more (Oliver 2021).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

Intestinal suspension (Duopa):

Dyskinesias or levodopa-related adverse reactions within 1 hour of morning dose on preceding day: Decrease morning levodopa dose by 20 mg.

Dyskinesias or adverse reactions lasting ≥1 hour on the preceding day: Decrease continuous levodopa dose by 6 mg per hour.

Dyskinesias or adverse reactions lasting for 2 or more periods of ≥1 hour on the preceding day: Decrease continuous levodopa dose by 12 mg per hour.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Extended Release, Oral:

Rytary: Carbidopa 23.75 mg and levodopa 95 mg, Carbidopa 36.25 mg and levodopa 145 mg, Carbidopa 48.75 mg and levodopa 195 mg, Carbidopa 61.25 mg and levodopa 245 mg [contains fd&c blue #2 (indigotine)]

Suspension, Enteral:

Duopa: Carbidopa 5 mg and levodopa 20 mg per mL (100 mL)

Tablet, Oral:

Dhivy: Carbidopa 25 mg and levodopa 100 mg [scored]

Sinemet: Carbidopa 10 mg and levodopa 100 mg [scored; contains corn starch, fd&c blue #2 (indigotine)]

Sinemet: Carbidopa 25 mg and levodopa 100 mg [scored; contains corn starch, fd&c yellow #10 (quinoline yellow)]

Sinemet: Carbidopa 10 mg and levodopa 100 mg [DSC], Carbidopa 25 mg and levodopa 250 mg [DSC] [contains fd&c blue #2 aluminum lake]

Sinemet: Carbidopa 25 mg and levodopa 100 mg [DSC] [contains fd&c yellow #10 aluminum lake]

Generic: Carbidopa 10 mg and levodopa 100 mg, Carbidopa 25 mg and levodopa 100 mg, Carbidopa 25 mg and levodopa 250 mg

Tablet Disintegrating, Oral:

Generic: Carbidopa 10 mg and levodopa 100 mg, Carbidopa 25 mg and levodopa 100 mg, Carbidopa 25 mg and levodopa 250 mg

Tablet Extended Release, Oral:

Sinemet CR: Carbidopa 25 mg and levodopa 100 mg [DSC], Carbidopa 50 mg and levodopa 200 mg [DSC] [contains fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake]

Generic: Carbidopa 25 mg and levodopa 100 mg, Carbidopa 50 mg and levodopa 200 mg

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Gel, Enteral:

Duodopa: Carbidopa 5 mg and levodopa 20 mg per mL (100 mL)

Tablet, Oral:

Sinemet 250/25: Carbidopa 25 mg and levodopa 250 mg [contains fd&c blue #2 (indigotine)]

Sinemet 100/25: Carbidopa 25 mg and levodopa 100 mg [contains fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]

Generic: Carbidopa 10 mg and levodopa 100 mg, Carbidopa 25 mg and levodopa 100 mg, Carbidopa 25 mg and levodopa 250 mg

Tablet Extended Release, Oral:

Sinemet CR: Carbidopa 25 mg and levodopa 100 mg [DSC]

Sinemet CR 200/50: Carbidopa 50 mg and levodopa 200 mg [DSC] [contains fd&c yellow #10 aluminum lake]

Generic: Carbidopa 25 mg and levodopa 100 mg, Carbidopa 50 mg and levodopa 200 mg

Prescribing and Access Restrictions

Duodopa intestinal gel [Canadian product]: In Canada, the Duodopa Education Program is a risk mitigation program established to provide safe and effective use of Duodopa in advanced Parkinson patients. The program involves:

- Education of prescribing neurologists and other health care providers on suitable candidates for treatment, surgical procedures (PEG tube placement), and follow-up care including infusion device education.

- Distribution of educational materials to patients and caregivers describing Duodopa intestinal gel and its proper use, PEG tube placement, and complications associated with the mode of administration and/or PEG tube placement.

Administration: Adult

Intestinal suspension (Duopa): Remove one cassette from refrigerator 20 minutes prior to use (failure to use at room temperature may result in inaccurate dosage). Administer as a 16-hour infusion through either a nasojejunal tube (temporary administration) or through a percutaneous endoscopic gastrostomy-jejunostomy (PEG-J) tube (long-term administration) connected to the CADD-Legacy 1400 pump. At the end of administration, disconnect the tube from the pump at the end of the infusion and flush with room-temperature drinking water with a syringe. Following discontinuation of the daily infusion, patients should administer their routine night-time dosage of oral immediate-release carbidopa/levodopa.

Intestinal gel (Duodopa [Canadian product]): Gel is administered directly to the jejunum via a portable infusion pump (CADD-legacy Duodopa pump). Administer through a temporary nasojejunal tube for a short-term test period to evaluate patient response and for dose optimization. Long-term administration requires placement of PEG-J tube for intestinal infusion. Continuous maintenance dose is infused throughout the day for up to 16 hours; if necessary, may administer at night (eg, nocturnal akinesia). Disconnect PEG-J tube from infusion pump at end of infusion and flush with room temperature water to prevent occlusion of tubing. Following discontinuation of the daily infusion, patients should administer their routine night-time dosage of oral levodopa/carbidopa.

Oral:

Extended-release capsule: Administer with or without food; a high-fat, high-calorie meal may delay the absorption of levodopa by ~2 hours. Swallow capsules whole; do not chew, divide, or crush capsules. Patients who have difficulty swallowing intact capsules may open the capsule, sprinkle entire contents on a small amount of applesauce (1 to 2 tablespoons) and consume immediately (do not store for future use).

Oral tablet formulations: Space doses evenly over the waking hours. Administer with meals to decrease GI upset. Controlled release product should not be chewed or crushed. Orally disintegrating tablets do not require water; the tablet should disintegrate on the tongue's surface before swallowing.

Dhivy: Administer without regard to food; tablets may be broken at score lines if patient has difficulty swallowing large tablets.

Bariatric surgery: Capsule and tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Do not cut, crush, or chew. Switch to immediate-release formulation (tablet or orally disintegrating tablet) or capsule may be opened and contents sprinkled onto soft food of choice. Patient should be instructed to swallow the mixture without biting down or chewing.

Use: Labeled Indications

Parkinson disease: Treatment of Parkinson disease, postencephalitic parkinsonism, and symptomatic parkinsonism that may follow carbon monoxide and/or manganese intoxication; treatment of motor fluctuations in advanced Parkinson disease (intestinal suspension [Duopa] only).

Use: Off-Label: Adult

Parkinsonism (including corticobasal degeneration, dementia with Lewy bodies, drug-induced parkinsonism, multiple system atrophy, and progressive supranuclear palsy); Restless legs syndrome, intermittent

Medication Safety Issues
Sound-alike/look-alike issues:

Sinemet may be confused with Janumet, Serevent

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.

International issues:

Zimox: Brand name for carbidopa and levodopa [Greece], but also the brand name for amoxicillin [Italy]

Zimox [Greece] may be confused with Diamox which is a brand name for acetazolamide [Canada and multiple international markets]

Adverse Reactions (Significant): Considerations
Dyskinesia

Carbidopa and levodopa may cause or exacerbate dyskinesia. Peak-dose dyskinesia typically occurs (during maximal plasma concentrations), but diphasic dyskinesia may also occur (beginning and end of a dose cycle). Off-period dystonia may also occur; commonly affects the foot and can be painful. Off-period dystonia tends to occur early in the day, precipitated by anxiety or attempts to walk (Ref).

Mechanism: Dose- and time-related; appears to involve multiple neuronal pathways and neurotransmitter systems. The primary mechanism involves intermittent or pulsatile stimulation of striatal dopamine (D1) receptors linked to intermittent levodopa delivery to the brain. Off-period dystonia results from low levodopa concentrations (Ref).

Onset: Varied; may occur early or later with chronic levodopa use. Peak-dose dyskinesias occur early. Off-period dystonia occurs after months or years of chronic levodopa use (Ref).

Risk factors:

• Higher levodopa doses (Ref)

• Long treatment duration (Ref)

• Anxious-depressed subtype (Ref)

• Asymmetry of caudate binding on DaTscan (Ref)

• Females (Ref)

• Low bodyweight (Ref)

• Motor fluctuations (Ref)

• Non-smoker (Ref)

• Non-tremor dominant phenotype (Ref)

• Young age at onset of Parkinson disease (Ref)

GI effects

Nausea and vomiting are frequently reported in Parkinson disease patients taking carbidopa and levodopa; however, the incidence of nausea and vomiting with carbidopa and levodopa is lower than with levodopa alone (Ref).

Mechanism: May be dose-related (Ref); attributed to dopamine in peripheral tissues. Peripheral levodopa decarboxylation is inhibited by carbidopa, contributing to less nausea and vomiting than with levodopa alone.

Onset: Varied (based on data from individual components); may occur with the first dose, high doses, or with dose increases of levodopa (Ref) and may occur with doses of carbidopa ≤70 to 100 mg/day.

Risk factors:

• Treatment initiation (Ref)

• High doses (Ref)

• Dose increases (Ref)

Impulse control disorders

Dopaminergic medications have been associated with impulse control disorder, including pathological gambling, compulsive shopping, binge eating disorder, punding, and compulsive sexual behavior (increased libido [including hypersexuality]) (Ref). Most reports have occurred with dopamine agonist therapy (eg, pramipexole, ropinirole) concurrently with carbidopa/levodopa. Risk with carbidopa/levodopa monotherapy is low (Ref).

Mechanism: In susceptible individuals with a hypersensitivity to rewards, impulse control disorders may develop with dopamine replacement therapy (Ref).

Onset: Varied; in case reports, onset ranged from months to years after initiation (Ref).

Risk factors:

• Young age at the onset of Parkinson disease (Ref)

• Greater use of caffeine and cigarettes (Ref)

• High novelty seeking and impulsivity personality traits (Ref)

• Motor complications (Ref)

• Personal or family history of alcohol or substance use disorder (Ref)

• Personal or family history of gambling (Ref)

• Females (compulsive shopping and eating) (Ref)

• Males (hypersexuality) (Ref)

Orthostatic hypotension

Orthostatic hypotension may occur with carbidopa and levodopa. Neurogenic orthostatic hypotension may occur independently with the pathophysiology of Parkinson disease; dopaminergic medications may contribute (non-neurogenic). Levodopa may contribute less than other dopaminergic medications (Ref).

Mechanism: Dose-related; may be related to the baroreflex dysfunction caused by levodopa (Ref). A direct dopamine agonist effect by levodopa may also play a role (Ref).

Risk factors:

General:

• Cardiac dysfunction (Ref)

• Combined therapies (eg, dopamine agonists, monoamine oxidase inhibitors [MAOIs]) (Ref)

• Concurrent medications that may decrease blood pressure (eg, alpha-blockers, antihypertensives, diuretics, sildenafil) (Ref)

• Dehydration (Ref)

Drug-related:

• Higher doses (Ref)

Peripheral neuropathy

Peripheral neuropathy may occur with carbidopa and levodopa (Ref).

Mechanism: Exact mechanism unclear; may be related to the metabolic pathway of levodopa, resulting in the accumulation of neurotoxins such as homocysteine (Hcy) and methylmalonic acid (MMA) (Ref). Immune-mediated inflammatory mechanisms, possibly triggered by the PEG-J tube or by the gel formulation, may also play a role (Ref).

Onset: Varied; most cases are delayed but some intestinal gel cases are acute or subacute onset (Ref).

Risk factors:

• Chronic exposure to levodopa (Ref)

• Genetic factors (eg, quantitative or functional deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR) (Ref)

• Older adults (Ref)

Psychiatric behavior abnormalities

Psychiatric behavior abnormalities such as agitation, confusion, delirium, delusion, disorientation, hallucination (visual and/or auditory), paranoid ideation, and psychosis may occur (Ref). These behaviors are generally reversible with dose adjustment; discontinuation rarely required (Ref).

Mechanism: Dose-related; may induce hypersensitivity of limbic dopamine receptors (Ref).

Onset: Varied; may progress over weeks to months (Ref).

Risk factors:

• Higher doses of levodopa (Ref)

• History of a major psychotic disorder (Ref)

• Older adults with prior history of dementia (Ref)

• Younger patients (mania) (Ref)

Withdrawal syndrome/Parkinsonism-hyperpyrexia syndrome

Withdrawal syndrome, also known as Parkinsonism-hyperpyrexia syndrome (PHS), is a rare but potentially fatal condition in patients with Parkinson disease (PD) and is manifested by pyrexia, muscle rigidity, a reduced level of consciousness, and autonomic instability. It is generally believed that rapid withdrawal of antiparkinsonian drugs or abrupt changes in medication regimens is the primary cause of this syndrome (Ref).

Mechanism: Withdrawal; most likely sudden suppression of central dopaminergic activity. May also include changes in peripheral and central sympathetic outflow and alteration in central serotonin metabolism (Ref).

Onset: Varied; typically within 18 hours to 7 days following trigger (Ref).

Risk factors:

• Altered absorption/bioavailability of levodopa (Ref)

• Concurrent antipsychotics (Ref)

• Dehydration and excessively hot weather (Ref)

• Physiological stressors (eg, infection, injury, surgery, trauma) (Ref)

• Rapid withdrawal of levodopa (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Orthostatic hypotension (enteral suspension: 70% to 73%; oral: 1% to 5% [placebo: 1%])

Gastrointestinal: Constipation (enteral suspension: 22%; oral: ≤6%), nausea (enteral suspension: 30%; oral: 3% to 20% [placebo: 9%])

Nervous system: Depression (enteral suspension: 11%; oral: 1% to 2%), dizziness (2% to 19%), headache (oral: 1% to 17%)

Neuromuscular & skeletal: Dyskinesia (2% to 17% [placebo: 0%]), increased creatine phosphokinase in blood specimen (enteral suspension: ≤17%)

Renal: Increased blood urea nitrogen (enteral suspension: ≤13%)

1% to 10%:

Cardiovascular: Chest pain (oral: ≤1%), hypertension (enteral suspension: 8%), ischemia (oral: ≤2%), peripheral edema (enteral suspension: 8%)

Dermatologic: Skin rash (enteral suspension: 5%)

Endocrine & metabolic: Increased serum glucose (≥1%)

Gastrointestinal: Anorexia (oral: 1%), diarrhea (≤5%), dyspepsia (≤5%), vomiting (oral: 2% to 5% [placebo: 3%]), xerostomia (oral: 1% to 7%)

Genitourinary: Bacteriuria (enteral suspension: 5%; oral: ≥1%), hematuria (oral: ≥1%), urinary frequency (oral: ≤1%), urinary tract infection (oral: 2%)

Hematologic & oncologic: Decreased hematocrit (oral: ≥1%), decreased hemoglobin (oral: ≥1%), leukocyturia (enteral suspension: 5%; oral: ≥1%)

Nervous system: Abnormal dreams (oral: ≤6%), anxiety (2% to 8%), confusion (2% to 8%), dystonia (oral: ≤2%), hallucination (≤5%, visual and/or auditory) (Spieker 1995), insomnia (oral: 1% to 9%), on-off phenomenon (oral: 1% to 2%), paresthesia (oral: ≤1%), polyneuropathy (enteral suspension: 5%), psychosis (≤5%), sleep disorder (enteral suspension: 5%)

Neuromuscular & skeletal: Back pain (oral: ≤2%), muscle cramps (oral: ≤1%), shoulder pain (oral: ≤1%)

Respiratory: Atelectasis (enteral suspension: 8%), dyspnea (oral: ≤2%), oropharyngeal pain (enteral suspension: 8%), upper respiratory tract infection (enteral suspension: 8%; oral: 1% to 2%)

Miscellaneous: Fever (enteral suspension: 5%)

<1%: Hematologic & oncologic: Malignant melanoma (causation not established; melanoma more common in Parkinson disease than the general population) (Bertoni 2010)

Postmarketing:

Cardiovascular: Acute myocardial infarction (Ng 2019), cardiac arrhythmia (Simsek 2005), phlebitis

Dermatologic: Alopecia (Marshall 1971), bullous rash (including pemphigus-like reactions) (Forschner 2005), diaphoresis, discoloration of sweat, urticaria (Anang 2018)

Endocrine & metabolic: Glycosuria, hot flash, increased libido (including hypersexuality) (Bostwick 2009), weight gain, weight loss

Gastrointestinal: Abdominal pain, bruxism, discoloration of saliva, duodenal ulcer, dysgeusia, dysphagia, flatulence, gastrointestinal hemorrhage, heartburn, hiccups, sialorrhea

Genitourinary: Priapism, proteinuria, urinary incontinence, urinary retention, urine discoloration

Hematologic & oncologic: Agranulocytosis, anemia, hemolytic anemia (Linström 1977), Henoch-Schonlein purpura (Niedermaier 1997), leukopenia (Cordano 2015), positive direct Coombs test (Joseph 1972), thrombocytopenia (Lee 2013)

Hepatic: Increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate transaminase, increased serum bilirubin

Hypersensitivity: Angioedema

Nervous system: Abnormal behavior, abnormal gait, abnormality in thinking, agitation, ataxia, decreased mental acuity, delirium, delusion (Spieker 1995), dementia, disorientation, drowsiness, euphoria, extrapyramidal reaction, falling, fatigue, glossopyrosis, Horner’s syndrome, impulse control disorder (Bostwick 2009), malaise, memory impairment, narcolepsy, nervousness, nightmares, numbness, paranoid ideation (Spieker 1995), pathological gambling (Bostwick 2009), peripheral neuropathy, seizure, sense of stimulation, suicidal ideation (Ayobello 2019), suicidal tendencies (Ayobello 2019), trismus, withdrawal syndrome (Parkinsonism-hyperpyrexia syndrome) (Newman 2009, Simonet 2020)

Neuromuscular & skeletal: Asthenia, lower extremity pain

Ophthalmic: Blepharospasm (Ramirez-Gomez 2019), blurred vision, diplopia, mydriasis, oculogyric crisis (Kondo 1995)

Respiratory: Cough, hoarseness

Contraindications

Hypersensitivity to levodopa, carbidopa, or any component of the formulation; concurrent use with nonselective monoamine oxidase inhibitors (MAOIs) or use within the last 14 days

Tablets: Additional contraindications: Narrow angle glaucoma

Canadian labeling: Additional contraindications (not in US labeling): Clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hepatic, hematologic or pulmonary disease (eg, including bronchial asthma), or renal disease; concomitant administration of a sympathomimetic amine (eg, epinephrine, norepinephrine, isoproterenol); in the presence of a suspicious, undiagnosed skin lesion or history of melanoma; intestinal gel therapy in patients with any condition preventing the required placement of a PEG tube for administration (ie, pathological changes of gastric wall, inability to bring gastric and abdominal wall together, blood coagulation disorders, peritonitis, acute pancreatitis, paralytic ileus).

Warnings/Precautions

Concerns related to adverse effects:

• Somnolence: Somnolence and falling asleep while engaged in activities of daily living (including operation of motor vehicles) have been reported; some cases reported that there were no warning signs for the onset of symptoms. Symptom onset may occur well after initiation of treatment; some events have occurred more than 1 year after start of therapy. Prior to treatment initiation, evaluate for factors that may increase these risks such as concomitant sedating medications, and the presence of sleep disorders. Monitor for drowsiness or sleepiness. If significant daytime sleepiness or episodes of falling asleep during activities that require active participation occurs (eg, driving, conversations, eating), discontinue the medication. There is insufficient information to suggest that dose reductions will eliminate these symptoms. If therapy is continued, advise patient to avoid driving and other potentially dangerous activities.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with severe cardiovascular disease, including a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias.

• Endocrine disease: Use with caution in patients with endocrine disease and when interpreting plasma/urine catecholamine levels; falsely diagnosed pheochromocytoma has been rarely reported.

• Glaucoma: Use with caution in patients with glaucoma; monitor IOP carefully; some formulations are contraindicated in patients with narrow-angle glaucoma.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Peptic ulcer disease: Oral products: Use with caution in patients with a history of peptic ulcer disease; risk of GI hemorrhage may be increased.

• Renal impairment: Use with caution in patients with renal impairment.

• Respiratory disease: Use with caution in patients with respiratory disease.

Special populations:

• Elderly: Use with caution in elderly patients; may be more sensitive to CNS effects (eg, hallucinations) of levodopa.

Dosage forms specific issues:

• Intestinal suspension (Duopa): GI complications (eg, bezoar, ileus, implant-site erosion/ulcer, intestinal hemorrhage, intestinal ischemia, intestinal obstruction, intestinal perforation, pancreatitis, peritonitis, pneumoperitoneum, postoperative wound infection) may occur (may be fatal). Patients should notify their health care provider immediately if abdominal pain, prolonged constipation, nausea, vomiting, fever, and/or melanotic stool occur.

• Intestinal gel (Duodopa [Canadian product]): Product should be prescribed only by neurologists experienced in the treatment of Parkinson disease and who have completed the Duodopa Education Program. Response to levodopa/carbidopa intestinal gel therapy should be assessed with a short-term test period of administration via a temporary nasojejunal tube prior to placement of a percutaneous endoscopic gastrostomy-jejunostomy (PEG-J) tube for permanent access and administration. Sudden deterioration in therapy response with recurring motor symptoms may indicate PEG-J tube complications (eg, displacement) or obstruction of the infusion device. Tube or infusion device complications may require initiation of oral levodopa/carbidopa therapy until complications are resolved.

Other warnings/precautions:

• Body fluid discoloration: Urine, saliva, or sweat may appear dark in color (red, brown, black) during therapy.

• Dietary protein: Distribute dietary protein throughout the day to avoid fluctuations in levodopa absorption. A high-protein diet may reduce the effectiveness of the enteral formulations.

Metabolism/Transport Effects

None known.

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Alizapride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amisulpride (Injection): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Amisulpride (Oral): Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Amisulpride (Oral). Amisulpride (Oral) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Antipsychotic Agents (First Generation [Typical]): Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Antipsychotic Agents (First Generation [Typical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Avoid concomitant therapy if possible. If antipsychotic use is necessary, consider using atypical antipsychotics such as clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Biperiden: May enhance the adverse/toxic effect of Levodopa-Containing Products. Specifically, the risk of choreic movements or dyskinesias may be increased. Risk C: Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Brivudine [INT]: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Specifically, the risk of chorea may be increased. Risk C: Monitor therapy

Bromopride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

BuPROPion: Anti-Parkinson Agents (Dopamine Agonist) may enhance the adverse/toxic effect of BuPROPion. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Droxidopa: Carbidopa may diminish the therapeutic effect of Droxidopa. Carbidopa may decrease serum concentrations of the active metabolite(s) of Droxidopa. Carbidopa may increase the serum concentration of Droxidopa. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: May diminish the therapeutic effect of Levodopa-Containing Products. Risk C: Monitor therapy

Glycopyrrolate (Systemic): May decrease the serum concentration of Levodopa-Containing Products. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Iron Preparations: May decrease the serum concentration of Levodopa. Only applies to oral iron preparations. Management: Consider separating doses of the agents by 2 or more hours to minimize the effects of this interaction. Monitor for decreased therapeutic effects of levodopa during concomitant therapy, particularly if doses cannot be separated. Risk D: Consider therapy modification

Isoniazid: May diminish the therapeutic effect of Levodopa-Containing Products. Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Kava Kava may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Macimorelin: Levodopa-Containing Products may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination

Methionine: May diminish the therapeutic effect of Levodopa-Containing Products. Management: Avoid large daily doses of methionine in patients receiving levodopa (clinical studies showing interaction used 4.5 g methionine daily). More typical doses of methionine (eg, 500 mg) may not cause a problem. Risk D: Consider therapy modification

Methotrimeprazine: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Methotrimeprazine. Risk X: Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy

Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: Levodopa-Containing Products may enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. Risk X: Avoid combination

Monoamine Oxidase Inhibitors (Type B): Levodopa-Containing Products may enhance the orthostatic hypotensive effect of Monoamine Oxidase Inhibitors (Type B). Risk C: Monitor therapy

Multivitamins/Fluoride (with ADE): May diminish the therapeutic effect of Levodopa-Containing Products. Management: Concurrent use of a multivitamin and levodopa (without carbidopa) should be avoided. Risk D: Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): May diminish the therapeutic effect of Levodopa. Multivitamins/Minerals (with ADEK, Folate, Iron) may decrease the serum concentration of Levodopa. Only applies to oral iron-containing preparations. Management: Separate doses of these agents by 2 or more hours. Monitor for decreased levodopa effects, particularly if doses cannot be separated. Concurrent use of a multivitamin and levodopa (without carbidopa) should be avoided. Risk D: Consider therapy modification

Multivitamins/Minerals (with AE, No Iron): May diminish the therapeutic effect of Levodopa-Containing Products. Management: Concurrent use of a multivitamin and levodopa (without carbidopa) should be avoided. Risk D: Consider therapy modification

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Papaverine: May enhance the hypotensive effect of Levodopa-Containing Products. Papaverine may diminish the therapeutic effect of Levodopa-Containing Products. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pyridoxine: May diminish the therapeutic effect of Levodopa-Containing Products. Management: The concomitant use of pyridoxine and levodopa (in the absence of a dopa decarboxylase inhibitor (DDI)) should be avoided. Use of a DDI (eg, carbidopa) with levodopa will essentially eliminate the risk of this interaction. Risk D: Consider therapy modification

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Reserpine: Carbidopa may enhance the hypotensive effect of Reserpine. Reserpine may diminish the therapeutic effect of Carbidopa. Risk X: Avoid combination

Sapropterin: May enhance the adverse/toxic effect of Levodopa-Containing Products. Risk C: Monitor therapy

Solriamfetol: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy

Spiramycin: May decrease the serum concentration of Carbidopa. And thus may decrease the effectiveness of levodopa. Risk C: Monitor therapy

Sulpiride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Tetrabenazine: May diminish the therapeutic effect of Carbidopa. Risk X: Avoid combination

Food Interactions

High protein diets have the potential to impair levodopa absorption; levodopa competes with certain amino acids for transport across the gut wall or across the blood-brain barrier. Management: Avoid high protein diets.

Pregnancy Considerations

Carbidopa can be detected in the umbilical cord, but absorption in fetal tissue is minimal. Levodopa crosses the placenta and can be metabolized by the fetus and detected in fetal tissue (Merchant 1995).

The incidence of Parkinson disease in pregnancy is relatively rare, and although information related to the use of carbidopa/levodopa in pregnant women is limited (Ball 1995; Cook 1985; Golbe 1987; Serikawa 2011; Shulman 2000; Tüfekçioğlu 2018; Zlotnik 2014), this combination has the most outcome information available for the treatment of pregnant women (Seier 2017). Current guidelines note that the available information is insufficient to make a recommendation for the treatment of restless legs syndrome in pregnant women (Aurora 2012).

Breastfeeding Considerations

Levodopa is present in breast milk.

A study was done in one breastfeeding woman at 4.5 months postpartum who had been taking carbidopa/levodopa for several years. Regardless of the formulation (sustained release or immediate release), peak levodopa concentrations in the breast milk were found ~3 hours after the maternal dose and returned to baseline ~6 hours after the dose. The highest milk concentration (3.47 nmol/L) was found following the immediate release tablet, and this was 27% of the peak maternal plasma concentration (occurring 30 minutes after the dose) and ~40% of the simultaneous plasma concentration. Carbidopa was not evaluated (Thulin 1998).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Lactation may be inhibited by levodopa.

Dietary Considerations

Avoid high protein diets (>2 g/kg) which may decrease the efficacy of levodopa via competition with amino acids in crossing the blood-brain barrier. Some products may contain phenylalanine.

Monitoring Parameters

Signs and symptoms of Parkinson disease; periodic hepatic function tests, BUN, creatinine, and CBC; periodic skin examinations; signs and symptoms of postural hypotension (eg, BP, standing and sitting/supine; especially during dose escalation); symptoms of dyskinesias, mental status changes; cardiac function (particularly during initial dosage adjustment), IOP (in patients with glaucoma); signs and symptoms of Parkinsonism-hyperpyrexia syndrome, especially if abrupt dose reduction or discontinuation required (as with surgery); drowsiness or sleepiness; signs of depression (including suicidal thoughts); signs and symptoms of peripheral neuropathy prior to therapy and periodically during therapy; risk factors for neuropathy prior to initiation (eg, deficiency of vitamin B6 and/or B12, diabetes mellitus, hypothyroidism). Monitor closely for melanoma.

Additional Canadian labeling recommendations include vitamin B12, vitamin B6, folic acid, homocysteine, and methylmalonic acid levels prior to initiation and regularly thereafter (Duodopa Canadian product monograph).

Mechanism of Action

Parkinson disease symptoms are due to a lack of striatal dopamine; levodopa circulates in the plasma to the blood-brain-barrier (BBB), where it crosses, to be converted by striatal enzymes to dopamine; carbidopa inhibits the peripheral plasma breakdown of levodopa by inhibiting its decarboxylation, and thereby increases available levodopa at the BBB

Pharmacokinetics

Absorption: Absorption of levodopa may be decreased with high-fat, high-calorie, or high-protein meal.

Distribution: Levodopa: 0.9 to 1.6 L/kg (in presence of carbidopa), crosses the blood-brain barrier; Carbidopa: Does not cross the blood-brain barrier.

Protein binding: Levodopa: 10% to 30%; Carbidopa: ~36%.

Metabolism: Levodopa has two major pathways (decarboxylation and O-methylation) and two minor pathways (transamination and oxidation) of metabolism; Carbidopa inhibits the decarboxylation of levodopa to dopamine in the peripheral tissue to allow greater levodopa distribution into the CNS.

Bioavailability:

Controlled and extended release: Levodopa: Bioavailability is ~70% to 75% relative to availability from IR formulation; Carbidopa: Bioavailability is ~50% to 58% relative to availability from IR formulation.

Intestinal gel [Canadian product]: Levodopa: Similar bioavailability relative to oral administration of tablet formulations (81% to 98%).

Intestinal suspension: Levodopa: 97% relative to oral IR tablets.

Half-life elimination: Levodopa (in presence of carbidopa): Immediate release: 1.5 to 2 hours; controlled release: 1.6 hours; extended release: 1.9 hours (Hsu 2015; manufacturer's labeling).

Time to peak (levodopa component): Immediate release: 0.5 to 1 hour; controlled release: 1.5 to 2 hours; extended release: 1 to 4.5 hours (Hsu 2015; manufacturer's labeling). Intestinal gel [Canadian product]: 2.9 hours with therapeutic plasma levels reached 10 to 30 minutes following morning bolus dose; intestinal suspension: 2.5 hours.

Excretion: Urine.

Pharmacokinetics: Additional Considerations

Geriatric: The AUC and Cmax of levodopa may be increased in elderly patients.

Gender: Increased carbidopa and levodopa peak concentrations and systemic exposure in females compared with males.

Pricing: US

Capsule, controlled release (Rytary Oral)

23.75-95 mg (per each): $4.62

36.25-145 mg (per each): $4.62

48.75-195 mg (per each): $4.62

61.25-245 mg (per each): $5.80

Suspension (Duopa Enteral)

4.63-20 mg/mL (per mL): $2.42

Tablet, controlled release (Carbidopa-Levodopa ER Oral)

25-100 mg (per each): $0.93 - $0.99

50-200 mg (per each): $1.74 - $1.90

Tablet, orally-disintegrating (Carbidopa-Levodopa Oral)

10-100 mg (per each): $1.22

25-100 mg (per each): $1.38

25-250 mg (per each): $1.75

Tablets (Carbidopa-Levodopa Oral)

10-100 mg (per each): $0.71 - $0.77

25-100 mg (per each): $0.60 - $1.18

25-250 mg (per each): $0.86 - $1.11

Tablets (Dhivy Oral)

100-25 mg (per each): $3.90

Tablets (Sinemet Oral)

10-100 mg (per each): $1.25

25-100 mg (per each): $1.40

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Aldopa (BD);
  • Apo-Levotard (MY);
  • Apodespan (IE);
  • Bidopar (TW);
  • Carbidel (PH);
  • Carbidol (BR);
  • Carbilev (ZA);
  • Cardopar (SG);
  • Carlevod (AR);
  • Cinemet CR (BD);
  • Conrayen (EG);
  • Corbilta (BE);
  • Credanil (MT);
  • Dopadura (DE);
  • Dopicar (IL);
  • Duodopa (AU, IL, JP, RO, TH);
  • DuoDopa (BE, GB, IE);
  • Enpalevo (TW);
  • Grifoparkin (CL, PE);
  • Half Sinemet (IE);
  • Istonil (PY);
  • Kinson (AU);
  • Lavida (PH);
  • Lebocar (AR);
  • Ledocar (PH);
  • Levocar (EG, JO);
  • Levomed (MY);
  • Levomet (HK, SG, TH);
  • Levopa (BD);
  • Nakom (EE, PL, RO, RU, SI, SK);
  • Numient (BE, HR);
  • Pardopa (IN);
  • Parken (CO);
  • Parkimet (PH);
  • Parkimet CR (PH);
  • Parkomet (AE, BH, CY, IQ, IR, JO, KW, LY, OM, SY, YE);
  • Perkin (KR);
  • Racovel (MX);
  • Saniter (CL);
  • Sindopa (NZ);
  • Sinedin (PH);
  • Sinedopa (HK, MY);
  • Sinedopa Mite (MY);
  • Sinemet (AT, AU, BB, BR, CH, CY, CZ, DE, DK, EC, EE, EG, ES, FI, FR, GB, GR, HK, IE, IS, IT, JO, KR, KW, LB, LT, MT, MX, MY, NL, NO, NZ, PK, PL, PT, PY, RU, SA, SE, SK, TH, TR, TW, UY, VE);
  • Sinemet 25 100 (HK, MY, PH);
  • Sinemet CR (AU, BB, BG, CH, CN, CY, CZ, EG, GB, GR, HK, IL, IT, KR, KW, LT, MY, NL, NZ, PE, PH, PT);
  • Sinemet Retard (ES);
  • Stalevo (AU);
  • Sulconar (PE);
  • Syndopa (BD, VN);
  • Tidomet (PH, TH);
  • Tidomet CR (PH);
  • Tidomet Forte (IN);
  • Tidomet L.S. (IN);
  • Tidomet Plus (IN);
  • Vedilma (VN);
  • Wendica (VN);
  • Zuades (BE)


For country abbreviations used in Lexicomp (show table)

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